Management of arthropod pathogen vectors in North America: Minimizing adverse effects on pollinators

USGS Publications Warehouse

Ginsberg, Howard; Bargar, Timothy A.; Hladik, Michelle L.; Lubelczyk, Charles

2017-01-01

Tick and mosquito management is important to public health protection. At the same time, growing concerns about declines of pollinator species raise the question of whether vector control practices might affect pollinator populations. We report the results of a task force of the North American Pollinator Protection Campaign (NAPPC) that examined potential effects of vector management practices on pollinators, and how these programs could be adjusted to minimize negative effects on pollinating species. The main types of vector control practices that might affect pollinators are landscape manipulation, biocontrol, and pesticide applications. Some current practices already minimize effects of vector control on pollinators (e.g., short-lived pesticides and application-targeting technologies). Nontarget effects can be further diminished by taking pollinator protection into account in the planning stages of vector management programs. Effects of vector control on pollinator species often depend on specific local conditions (e.g., proximity of locations with abundant vectors to concentrations of floral resources), so planning is most effective when it includes collaborations of local vector management professionals with local experts on pollinators. Interventions can then be designed to avoid pollinators (e.g., targeting applications to avoid blooming times and pollinator nesting habitats), while still optimizing public health protection. Research on efficient targeting of interventions, and on effects on pollinators of emerging technologies, will help mitigate potential deleterious effects on pollinators in future management programs. In particular, models that can predict effects of integrated pest management on vector-borne pathogen transmission, along with effects on pollinator populations, would be useful for collaborative decision-making.

APOBEC3-mediated hypermutation of retroviral vectors produced from some retrovirus packaging cell lines.

PubMed

Miller, A D; Metzger, M J

2011-05-01

APOBEC3 proteins are packaged into retrovirus virions and can hypermutate retroviruses during reverse transcription. We found that HT-1080 human fibrosarcoma cells hypermutate retroviruses, and that the HT-1080 cell-derived FLYA13 retrovirus packaging cells also hypermutate a retrovirus vector produced using these cells. We found no hypermutation of the same vector produced by the mouse cell-derived packaging line PT67 or by human 293 cells transfected with the vector and retrovirus packaging plasmids. We expect that avoidance of vector hypermutation will be particularly important for vectors used in gene therapy, wherein mutant proteins might stimulate deleterious immune responses.

Adenoviral Vector Immunity: Its Implications and circumvention strategies

PubMed Central

Ahi, Yadvinder S.; Bangari, Dinesh S.; Mittal, Suresh K.

2014-01-01

Adenoviral (Ad) vectors have emerged as a promising gene delivery platform for a variety of therapeutic and vaccine purposes during last two decades. However, the presence of preexisting Ad immunity and the rapid development of Ad vector immunity still pose significant challenges to the clinical use of these vectors. Innate inflammatory response following Ad vector administration may lead to systemic toxicity, drastically limit vector transduction efficiency and significantly abbreviate the duration of transgene expression. Currently, a number of approaches are being extensively pursued to overcome these drawbacks by strategies that target either the host or the Ad vector. In addition, significant progress has been made in the development of novel Ad vectors based on less prevalent human Ad serotypes and nonhuman Ad. This review provides an update on our current understanding of immune responses to Ad vectors and delineates various approaches for eluding Ad vector immunity. Approaches targeting the host and those targeting the vector are discussed in light of their promises and limitations. PMID:21453277

Tyrosine Mutation in AAV9 Capsid Improves Gene Transfer to the Mouse Lung.

PubMed

Martini, Sabrina V; Silva, Adriana L; Ferreira, Debora; Rabelo, Rafael; Ornellas, Felipe M; Gomes, Karina; Rocco, Patricia R M; Petrs-Silva, Hilda; Morales, Marcelo M

2016-01-01

Adeno-associated virus (AAV) vectors are being increasingly used as the vector of choice for in vivo gene delivery and gene therapy for many pulmonary diseases. Recently, it was shown that phosphorylation of surface-exposed tyrosine residues from AAV capsid targets the viral particles for ubiquitination and proteasome-mediated degradation, and mutations of these tyrosine residues lead to highly efficient vector transduction in vitro and in vivo in different organs. In this study, we evaluated the pulmonary transgene expression efficacy of AAV9 vectors containing point mutations in surface-exposed capsid tyrosine residues. Eighteen C57BL/6 mice were randomly assigned into three groups: (1) a control group (CTRL) animals underwent intratracheal (i.t.) instillation of saline, (2) the wild-type AAV9 group (WT-AAV9, 1010 vg), and (3) the tyrosine-mutant Y731F AAV9 group (M-AAV9, 1010 vg), which received (i.t.) self-complementary AAV9 vectors containing the DNA sequence of enhanced green fluorescence protein (eGFP). Four weeks after instillation, lung mechanics, morphometry, tissue cellularity, gene expression, inflammatory cytokines, and growth factor expression were analyzed. No significant differences were observed in lung mechanics and morphometry among the experimental groups. However, the number of polymorphonuclear cells was higher in the WT-AAV9 group than in the CTRL and M-AAV9 groups, suggesting that the administration of tyrosine-mutant AAV9 vectors was better tolerated. Tyrosine-mutant AAV9 vectors significantly improved transgene delivery to the lung (30%) compared with their wild-type counterparts, without eliciting an inflammatory response. Our results provide the impetus for further studies to exploit the use of AAV9 vectors as a tool for pulmonary gene therapy. © 2016 The Author(s) Published by S. Karger AG, Basel.

Helper-dependent adenoviral vectors for liver-directed gene therapy

PubMed Central

Brunetti-Pierri, Nicola; Ng, Philip

2011-01-01

Helper-dependent adenoviral (HDAd) vectors devoid of all viral-coding sequences are promising non-integrating vectors for liver-directed gene therapy because they have a large cloning capacity, can efficiently transduce a wide variety of cell types from various species independent of the cell cycle and can result in long-term transgene expression without chronic toxicity. The main obstacle preventing clinical applications of HDAd for liver-directed gene therapy is the host innate inflammatory response against the vector capsid proteins that occurs shortly after intravascular vector administration resulting in acute toxicity, the severity of which is dependent on vector dose. Intense efforts have been focused on elucidating the factors involved in this acute response and various strategies have been investigated to improve the therapeutic index of HDAd vectors. These strategies have yielded encouraging results with the potential for clinical translation. PMID:21470977

Autonomous dynamic obstacle avoidance for bacteria-powered microrobots (BPMs) with modified vector field histogram

PubMed Central

Kim, Hoyeon; Cheang, U. Kei

2017-01-01

In order to broaden the use of microrobots in practical fields, autonomous control algorithms such as obstacle avoidance must be further developed. However, most previous studies of microrobots used manual motion control to navigate past tight spaces and obstacles while very few studies demonstrated the use of autonomous motion. In this paper, we demonstrated a dynamic obstacle avoidance algorithm for bacteria-powered microrobots (BPMs) using electric field in fluidic environments. A BPM consists of an artificial body, which is made of SU-8, and a high dense layer of harnessed bacteria. BPMs can be controlled using externally applied electric fields due to the electrokinetic property of bacteria. For developing dynamic obstacle avoidance for BPMs, a kinematic model of BPMs was utilized to prevent collision and a finite element model was used to characteristic the deformation of an electric field near the obstacle walls. In order to avoid fast moving obstacles, we modified our previously static obstacle avoidance approach using a modified vector field histogram (VFH) method. To validate the advanced algorithm in experiments, magnetically controlled moving obstacles were used to intercept the BPMs as the BPMs move from the initial position to final position. The algorithm was able to successfully guide the BPMs to reach their respective goal positions while avoiding the dynamic obstacles. PMID:29020016

Autonomous dynamic obstacle avoidance for bacteria-powered microrobots (BPMs) with modified vector field histogram.

PubMed

Kim, Hoyeon; Cheang, U Kei; Kim, Min Jun

2017-01-01

In order to broaden the use of microrobots in practical fields, autonomous control algorithms such as obstacle avoidance must be further developed. However, most previous studies of microrobots used manual motion control to navigate past tight spaces and obstacles while very few studies demonstrated the use of autonomous motion. In this paper, we demonstrated a dynamic obstacle avoidance algorithm for bacteria-powered microrobots (BPMs) using electric field in fluidic environments. A BPM consists of an artificial body, which is made of SU-8, and a high dense layer of harnessed bacteria. BPMs can be controlled using externally applied electric fields due to the electrokinetic property of bacteria. For developing dynamic obstacle avoidance for BPMs, a kinematic model of BPMs was utilized to prevent collision and a finite element model was used to characteristic the deformation of an electric field near the obstacle walls. In order to avoid fast moving obstacles, we modified our previously static obstacle avoidance approach using a modified vector field histogram (VFH) method. To validate the advanced algorithm in experiments, magnetically controlled moving obstacles were used to intercept the BPMs as the BPMs move from the initial position to final position. The algorithm was able to successfully guide the BPMs to reach their respective goal positions while avoiding the dynamic obstacles.

UAV formation control design with obstacle avoidance in dynamic three-dimensional environment.

PubMed

Chang, Kai; Xia, Yuanqing; Huang, Kaoli

2016-01-01

This paper considers the artificial potential field method combined with rotational vectors for a general problem of multi-unmanned aerial vehicle (UAV) systems tracking a moving target in dynamic three-dimensional environment. An attractive potential field is generated between the leader and the target. It drives the leader to track the target based on the relative position of them. The other UAVs in the formation are controlled to follow the leader by the attractive control force. The repulsive force affects among the UAVs to avoid collisions and distribute the UAVs evenly on the spherical surface whose center is the leader-UAV. Specific orders or positions of the UAVs are not required. The trajectories of avoidance obstacle can be obtained through two kinds of potential field with rotation vectors. Every UAV can choose the optimal trajectory to avoid the obstacle and reconfigure the formation after passing the obstacle. Simulations study on UAV are presented to demonstrate the effectiveness of proposed method.

A novel profit-allocation strategy for SDN enterprises

NASA Astrophysics Data System (ADS)

Hu, Wei; Hou, Ye; Tian, Longwei; Li, Yuan

2017-01-01

Aiming to solve the problem of profit allocation for supply and demand network (SDN) enterprises that ignores risk factors and generates low satisfaction, a novel profit-allocation model based on cooperative game theory and TOPSIS is proposed. This new model avoids the defect of the single-profit allocation model by introducing risk factors, compromise coefficients and high negotiation points. By measuring the Euclidean distance between the ideal solution vector and the negative ideal solution vector, every node's satisfaction problem for the SDN was resolved, and the mess phenomenon was avoided. Finally, the rationality and effectiveness of the proposed model was verified using a numerical example.

Overexpression of Annexin A1 Suppresses Pro-Inflammatory Factors in PC12 Cells Induced by 1-Methyl-4-Phenylpyridinium

PubMed Central

Kiani-Esfahani, Abbas; Kazemi Sheykhshabani, Sedigheh; Peymani, Maryam; Hashemi, Motahare-Sadat; Ghaedi, Kamran; Nasr-Esfahani, Mohammad Hossein

2016-01-01

Objective Annexin A1 (ANXA1) is suggested to have anti-inflammatory function. However, the precise function of ANXA1 has remained unclear. In this study, we therefore examined the potency of ANXA1 in regulating reactive oxygen species (ROS) production and suppressing pro-inflammatory responses in PC12 cells induced by 1-methyl-4-phenylpyridinium (MPP+). Materials and Methods In this experimental study, cDNA of ANXA1 was cloned and inserted to the PGL268 pEpi-FGM18F vector to produce a recombinant PGL/ANXA1 vector for transfection into the PC12 cells. ANXA1 transfected cells were then treated with MPP+. Apoptosis and the content of pro-inflammatory factors including ROS, Interlukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) were assessed by flow-cytometry, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in ANXA1-transfected cells and the data were compared with those obtained from mock and control cells. Results Data revealed that overexpression of ANXA1 is associated with decreased levels of ROS and expression level of IL-6 and iNOS transcripts, and NF-κB protein in MPP+ treated PC12 cells. Conclusion ANXA1 may be considered as an agent for prevention of neurodegenerative or inflammatory conditions. PMID:27540524

Overexpression of Annexin A1 Suppresses Pro-Inflammatory Factors in PC12 Cells Induced by 1-Methyl-4-Phenylpyridinium.

PubMed

Kiani-Esfahani, Abbas; Kazemi Sheykhshabani, Sedigheh; Peymani, Maryam; Hashemi, Motahare-Sadat; Ghaedi, Kamran; Nasr-Esfahani, Mohammad Hossein

2016-01-01

Annexin A1 (ANXA1) is suggested to have anti-inflammatory function. However, the precise function of ANXA1 has remained unclear. In this study, we therefore examined the potency of ANXA1 in regulating reactive oxygen species (ROS) production and suppressing pro-inflammatory responses in PC12 cells induced by 1-methyl-4-phenylpyridinium (MPP+). In this experimental study, cDNA of ANXA1 was cloned and inserted to the PGL268 pEpi-FGM18F vector to produce a recombinant PGL/ANXA1 vector for transfection into the PC12 cells. ANXA1 transfected cells were then treated with MPP+. Apoptosis and the content of pro-inflammatory factors including ROS, Interlukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) were assessed by flow-cytometry, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in ANXA1-transfected cells and the data were compared with those obtained from mock and control cells. Data revealed that overexpression of ANXA1 is associated with decreased levels of ROS and expression level of IL-6 and iNOS transcripts, and NF-κB protein in MPP+ treated PC12 cells. ANXA1 may be considered as an agent for prevention of neurodegenerative or inflammatory conditions.

Ferromagnetic quantum critical point avoided by the appearance of another magnetic phase in LaCrGe 3 under pressure

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

Taufour, Valentin; Kaluarachchi, Udhara S.; Khasanov, Rustem

2016-07-13

Here, the temperature-pressure phase diagram of the ferromagnet LaCrGe 3 is determined for the first time from a combination of magnetization, muon-spin-rotation, and electrical resistivity measurements. The ferromagnetic phase is suppressed near 2.1 GPa, but quantum criticality is avoided by the appearance of a magnetic phase, likely modulated, AFMQ. Our density functional theory total energy calculations suggest a near degeneracy of antiferromagnetic states with small magnetic wave vectors Q allowing for the potential of an ordering wave vector evolving from Q=0 to finite Q, as expected from the most recent theories on ferromagnetic quantum criticality. Our findings show that LaCrGemore » 3 is a very simple example to study this scenario of avoided ferromagnetic quantum criticality and will inspire further study on this material and other itinerant ferromagnets.« less

A space-efficient quantum computer simulator suitable for high-speed FPGA implementation

NASA Astrophysics Data System (ADS)

Frank, Michael P.; Oniciuc, Liviu; Meyer-Baese, Uwe H.; Chiorescu, Irinel

2009-05-01

Conventional vector-based simulators for quantum computers are quite limited in the size of the quantum circuits they can handle, due to the worst-case exponential growth of even sparse representations of the full quantum state vector as a function of the number of quantum operations applied. However, this exponential-space requirement can be avoided by using general space-time tradeoffs long known to complexity theorists, which can be appropriately optimized for this particular problem in a way that also illustrates some interesting reformulations of quantum mechanics. In this paper, we describe the design and empirical space/time complexity measurements of a working software prototype of a quantum computer simulator that avoids excessive space requirements. Due to its space-efficiency, this design is well-suited to embedding in single-chip environments, permitting especially fast execution that avoids access latencies to main memory. We plan to prototype our design on a standard FPGA development board.

Obstacle-avoiding navigation system

DOEpatents

Borenstein, Johann; Koren, Yoram; Levine, Simon P.

1991-01-01

A system for guiding an autonomous or semi-autonomous vehicle through a field of operation having obstacles thereon to be avoided employs a memory for containing data which defines an array of grid cells which correspond to respective subfields in the field of operation of the vehicle. Each grid cell in the memory contains a value which is indicative of the likelihood, or probability, that an obstacle is present in the respectively associated subfield. The values in the grid cells are incremented individually in response to each scan of the subfields, and precomputation and use of a look-up table avoids complex trigonometric functions. A further array of grid cells is fixed with respect to the vehicle form a conceptual active window which overlies the incremented grid cells. Thus, when the cells in the active window overly grid cell having values which are indicative of the presence of obstacles, the value therein is used as a multiplier of the precomputed vectorial values. The resulting plurality of vectorial values are summed vectorially in one embodiment of the invention to produce a virtual composite repulsive vector which is then summed vectorially with a target-directed vector for producing a resultant vector for guiding the vehicle. In an alternative embodiment, a plurality of vectors surrounding the vehicle are computed, each having a value corresponding to obstacle density. In such an embodiment, target location information is used to select between alternative directions of travel having low associated obstacle densities.

Data-Rate Performance and Coverage of the Sub-Band Vectoring for VDSL 35b Profile

NASA Astrophysics Data System (ADS)

Giuliano, Romeo; Mazzenga, Franco; Vatalaro, Francesco

2017-05-01

Vectoring, used in VDSL2 to counteract FEXT, becomes less effective, or even ineffective, when users belong to different vectoring groups. This situation is common when the Regulator imposes sub-loop unbundling and users of uncoordinated service providers cause alien-FEXT. The sub-band vectoring (SBV) technique introduced here, avoids this situation and retains the vectoring benefits. We show SBV allows achieving up to 150 Mbit/s per user in downstream at 200 m from cabinet for VDSL2 profile-35b, with two concurrent service providers. We also introduce the concept of data-rate coverage representing the users' percentage served at a given data-rate in the area.

A multistage motion vector processing method for motion-compensated frame interpolation.

PubMed

Huang, Ai- Mei; Nguyen, Truong Q

2008-05-01

In this paper, a novel, low-complexity motion vector processing algorithm at the decoder is proposed for motion-compensated frame interpolation or frame rate up-conversion. We address the problems of having broken edges and deformed structures in an interpolated frame by hierarchically refining motion vectors on different block sizes. Our method explicitly considers the reliability of each received motion vector and has the capability of preserving the structure information. This is achieved by analyzing the distribution of residual energies and effectively merging blocks that have unreliable motion vectors. The motion vector reliability information is also used as a prior knowledge in motion vector refinement using a constrained vector median filter to avoid choosing identical unreliable one. We also propose using chrominance information in our method. Experimental results show that the proposed scheme has better visual quality and is also robust, even in video sequences with complex scenes and fast motion.

Robust model predictive control for satellite formation keeping with eccentricity/inclination vector separation

NASA Astrophysics Data System (ADS)

Lim, Yeerang; Jung, Youeyun; Bang, Hyochoong

2018-05-01

This study presents model predictive formation control based on an eccentricity/inclination vector separation strategy. Alternative collision avoidance can be accomplished by using eccentricity/inclination vectors and adding a simple goal function term for optimization process. Real-time control is also achievable with model predictive controller based on convex formulation. Constraint-tightening approach is address as well improve robustness of the controller, and simulation results are presented to verify performance enhancement for the proposed approach.

Automated Creation of Labeled Pointcloud Datasets in Support of Machine-Learning Based Perception

DTIC Science & Technology

2017-12-01

computationally intensive 3D vector math and took more than ten seconds to segment a single LIDAR frame from the HDL-32e with the Dell XPS15 9650’s Intel...Core i7 CPU. Depth Clustering avoids the computationally intensive 3D vector math of Euclidean Clustering-based DON segmentation and, instead

Transduction of skeletal muscles with common reporter genes can promote muscle fiber degeneration and inflammation.

PubMed

Winbanks, Catherine E; Beyer, Claudia; Qian, Hongwei; Gregorevic, Paul

2012-01-01

Recombinant adeno-associated viral vectors (rAAV vectors) are promising tools for delivering transgenes to skeletal muscle, in order to study the mechanisms that control the muscle phenotype, and to ameliorate diseases that perturb muscle homeostasis. Many studies have employed rAAV vectors carrying reporter genes encoding for β-galactosidase (β-gal), human placental alkaline phosphatase (hPLAP), and green fluorescent protein (GFP) as experimental controls when studying the effects of manipulating other genes. However, it is not clear to what extent these reporter genes can influence signaling and gene expression signatures in skeletal muscle, which may confound the interpretation of results obtained in experimentally manipulated muscles. Herein, we report a strong pro-inflammatory effect of expressing reporter genes in skeletal muscle. Specifically, we show that the administration of rAAV6:hPLAP vectors to the hind limb muscles of mice is associated with dose- and time-dependent macrophage recruitment, and skeletal muscle damage. Dose-dependent expression of hPLAP also led to marked activity of established pro-inflammatory IL-6/Stat3, TNFα, IKKβ and JNK signaling in lysates obtained from homogenized muscles. These effects were independent of promoter type, as expression cassettes featuring hPLAP under the control of constitutive CMV and muscle-specific CK6 promoters both drove cellular responses when matched for vector dose. Importantly, the administration of rAAV6:GFP vectors did not induce muscle damage or inflammation except at the highest doses we examined, and administration of a transgene-null vector (rAAV6:MCS) did not cause damage or inflammation at any of the doses tested, demonstrating that GFP-expressing, or transgene-null vectors may be more suitable as experimental controls. The studies highlight the importance of considering the potential effects of reporter genes when designing experiments that examine gene manipulation in vivo.

Genetic modification of lymphocytes by retrovirus-based vectors.

PubMed

Suerth, Julia D; Schambach, Axel; Baum, Christopher

2012-10-01

The genetic modification of lymphocytes is an important topic in the emerging field of gene therapy. Many clinical trials targeting immunodeficiency syndromes or cancer have shown therapeutic benefit; further applications address inflammatory and infectious disorders. Retroviral vector development requires a detailed understanding of the interactions with the host. Most researchers have used simple gammaretroviral vectors to modify lymphocytes, either directly or via hematopoietic stem and progenitor cells. Lentiviral, spumaviral (foamyviral) and alpharetroviral vectors were designed to reduce the necessity for cell stimulation and to utilize potentially safer integration properties. Novel surface modifications (pseudotyping) and transgenes, built using synthetic components, expand the retroviral toolbox, altogether promising increased specificity and potency. Product consistency will be an important criterion for routine clinical use. Copyright © 2012. Published by Elsevier Ltd.

First experience of vectorizing electromagnetic physics models for detector simulation

NASA Astrophysics Data System (ADS)

Amadio, G.; Apostolakis, J.; Bandieramonte, M.; Bianchini, C.; Bitzes, G.; Brun, R.; Canal, P.; Carminati, F.; de Fine Licht, J.; Duhem, L.; Elvira, D.; Gheata, A.; Jun, S. Y.; Lima, G.; Novak, M.; Presbyterian, M.; Shadura, O.; Seghal, R.; Wenzel, S.

2015-12-01

The recent emergence of hardware architectures characterized by many-core or accelerated processors has opened new opportunities for concurrent programming models taking advantage of both SIMD and SIMT architectures. The GeantV vector prototype for detector simulations has been designed to exploit both the vector capability of mainstream CPUs and multi-threading capabilities of coprocessors including NVidia GPUs and Intel Xeon Phi. The characteristics of these architectures are very different in terms of the vectorization depth, parallelization needed to achieve optimal performance or memory access latency and speed. An additional challenge is to avoid the code duplication often inherent to supporting heterogeneous platforms. In this paper we present the first experience of vectorizing electromagnetic physics models developed for the GeantV project.

Disease Vector Ecology Profile: Ecuador

DTIC Science & Technology

1998-12-01

fleas, has not been reported since 1985; however, extensive outbreaks in neighboring Peru occurred in 1992-94. Avoid rodent -infested areas and use PPM...throughout the year ( Peru ). Heavy shade in permanent bodies of water with abundant floatage. Commonly bites humans but apparently prefers rodents ...Vectors of Arboviruses other than Dengue or Yellow Fever in the Amazon Basin and Associated Northwestern Regions of South America

Flies dynamically anti-track, rather than ballistically escape, aversive odor during flight.

PubMed

Wasserman, Sara; Lu, Patrick; Aptekar, Jacob W; Frye, Mark A

2012-08-15

Tracking distant odor sources is crucial to foraging, courtship and reproductive success for many animals including fish, flies and birds. Upon encountering a chemical plume in flight, Drosophila melanogaster integrates the spatial intensity gradient and temporal fluctuations over the two antennae, while simultaneously reducing the amplitude and frequency of rapid steering maneuvers, stabilizing the flight vector. There are infinite escape vectors away from a noxious source, in contrast to a single best tracking vector towards an attractive source. Attractive and aversive odors are segregated into parallel neuronal pathways in flies; therefore, the behavioral algorithms for avoidance may be categorically different from tracking. Do flies plot random ballistic or otherwise variable escape vectors? Or do they instead make use of temporally dynamic mechanisms for continuously and directly avoiding noxious odors in a manner similar to tracking appetitive ones? We examine this question using a magnetic tether flight simulator that permits free yaw movements, such that flies can actively orient within spatially defined odor plumes. We show that in-flight aversive flight behavior shares all of the key features of attraction such that flies continuously 'anti-track' the noxious source.

Flies dynamically anti-track, rather than ballistically escape, aversive odor during flight

PubMed Central

Wasserman, Sara; Lu, Patrick; Aptekar, Jacob W.; Frye, Mark A.

2012-01-01

SUMMARY Tracking distant odor sources is crucial to foraging, courtship and reproductive success for many animals including fish, flies and birds. Upon encountering a chemical plume in flight, Drosophila melanogaster integrates the spatial intensity gradient and temporal fluctuations over the two antennae, while simultaneously reducing the amplitude and frequency of rapid steering maneuvers, stabilizing the flight vector. There are infinite escape vectors away from a noxious source, in contrast to a single best tracking vector towards an attractive source. Attractive and aversive odors are segregated into parallel neuronal pathways in flies; therefore, the behavioral algorithms for avoidance may be categorically different from tracking. Do flies plot random ballistic or otherwise variable escape vectors? Or do they instead make use of temporally dynamic mechanisms for continuously and directly avoiding noxious odors in a manner similar to tracking appetitive ones? We examine this question using a magnetic tether flight simulator that permits free yaw movements, such that flies can actively orient within spatially defined odor plumes. We show that in-flight aversive flight behavior shares all of the key features of attraction such that flies continuously ‘anti-track’ the noxious source. PMID:22837456

Adenovirus E1B 19-Kilodalton Protein Modulates Innate Immunity through Apoptotic Mimicry

PubMed Central

Grigera, Fernando; Ucker, David S.; Cook, James L.

2014-01-01

ABSTRACT Cells that undergo apoptosis in response to chemical or physical stimuli repress inflammatory reactions, but cells that undergo nonapoptotic death in response to such stimuli lack this activity. Whether cells dying from viral infection exhibit a cell death-type modulatory effect on inflammatory reactions is unknown. We compared the effects on macrophage inflammatory responses of cells dying an apoptotic or a nonapoptotic death as a result of adenoviral infection. The results were exactly opposite to the predictions from the conventional paradigm. Cells dying by apoptosis induced by infection with an adenovirus type 5 (Ad5) E1B 19-kilodalton (E1B 19K) gene deletion mutant did not repress macrophage NF-κB activation or cytokine responses to proinflammatory stimuli, whereas cells dying a nonapoptotic death from infection with E1B 19K-competent, wild-type Ad5 repressed these macrophage inflammatory responses as well as cells undergoing classical apoptosis in response to chemical injury. The immunorepressive, E1B 19K-related cell death activity depended upon direct contact of the virally infected corpses with responder macrophages. Replacement of the viral E1B 19K gene with the mammalian Bcl-2 gene in cis restored the nonapoptotic, immunorepressive cell death activity of virally infected cells. These results define a novel function of the antiapoptotic, adenoviral E1B 19K protein that may limit local host innate immune inflammation during accumulation of virally infected cells at sites of infection and suggest that E1B 19K-deleted, replicating adenoviral vectors might induce greater inflammatory responses to virally infected cells than E1B 19K-positive vectors, because of the net effect of their loss-of-function mutation. IMPORTANCE We observed that cells dying a nonapoptotic cell death induced by adenovirus infection repressed macrophage proinflammatory responses while cells dying by apoptosis induced by infection with an E1B 19K deletion mutant virus did not repress macrophage proinflammatory responses and enhanced some cytokine responses. Our results define a new function of the antiapoptotic, adenoviral protein E1B 19K, which we have termed “apoptotic mimicry.” Our studies suggest the possibility that the presence or absence of this E1B 19K function could alter the immunological outcome of both natural and therapeutic adenoviral infections. For example, emerging, highly immunopathogenic adenovirus serotypes might induce increased host inflammatory responses as a result of altered E1B 19K function or expression. It is also possible that engineered variations in E1B 19K expression/function could be created during adenovirus vector design that would increase the therapeutic efficacy of replicating adenovirus vectors for vaccines or oncolytic viral targeting of neoplastic cells. PMID:24352454

A universal mini-vector and an annealing of PCR products (APP)-based cloning strategy for convenient molecular biological manipulations.

PubMed

Liu, Xia; Li, Tuoping; Hart, Darren J; Gao, Song; Wang, Hongling; Gao, Herui; Xu, Shumin; Zhang, Yifeng; Liu, Yifei; An, Yingfeng

2018-03-18

Currently, the most widely used strategies for molecular cloning are sticky-end ligation-based cloning, TA cloning, blunt-end ligation-based cloning and ligase-independent cloning. In this study we have developed a novel mini-vector pANY1 which can simultaneously meet the requirements of all these cloning strategies. In addition, the selection of appropriate restriction digestion sites is difficult in some cases because of the presence of internal sites. In this study, an annealing of PCR products (APP)-based sticky-end cloning strategy was introduced to avoid this issue. Additionally, false positives occur during molecular cloning, which increases the workload of isolating positive clones. The plasmid pANY1 contains a ccdB cassette between multiple cloning sites, which efficiently avoids these false positives. Therefore, this mini-vector should serve as a useful tool with wide applications in biosciences, agriculture, food technologies, etc. Copyright © 2018 Elsevier Inc. All rights reserved.

Cost-Effectiveness of the Strategies to Reduce the Incidence of Dengue in Colima, México

PubMed Central

Ochoa Diaz-Lopez, Héctor; Lugo-Radillo, Agustin; Espinoza-Gomez, Francisco; de la Cruz-Ruiz, Miriam; Sánchez-Piña, Ramón Alberto; Murillo-Zamora, Efrén

2017-01-01

Dengue fever is considered to be one of the most important arboviral diseases globally. Unsuccessful vector-control strategies might be due to the lack of sustainable community participation. The state of Colima, located in the Western region of Mexico, is a dengue-endemic area despite vector-control activities implemented, which may be due to an insufficient health economic analysis of these interventions. A randomized controlled community trial took place in five urban municipalities where 24 clusters were included. The study groups (n = 4) included an intervention to improve the community participation in vector control (A), ultra-low volume (ULV) spraying (B), both interventions (AB), and a control group. The main outcomes investigated were dengue cumulative incidence, disability-adjusted life years (DALYs), and the direct costs per intervention. The cumulative incidence of dengue was 17.4%, A; 14.3%, B; 14.4%, AB; and 30.2% in the control group. The highest efficiency and effectiveness were observed in group B (0.526 and 6.97, respectively) and intervention A was more likely to be cost-effective ($3952.84 per DALY avoided) followed by intervention B ($4472.09 per DALY avoided). Our findings suggest that efforts to improve community participation in vector control and ULV-spraying alone are cost-effective and may be useful to reduce the vector density and dengue incidence. PMID:28786919

Cost-Effectiveness of the Strategies to Reduce the Incidence of Dengue in Colima, México.

PubMed

Mendoza-Cano, Oliver; Hernandez-Suarez, Carlos Moisés; Trujillo, Xochitl; Ochoa Diaz-Lopez, Héctor; Lugo-Radillo, Agustin; Espinoza-Gomez, Francisco; de la Cruz-Ruiz, Miriam; Sánchez-Piña, Ramón Alberto; Murillo-Zamora, Efrén

2017-08-08

Dengue fever is considered to be one of the most important arboviral diseases globally. Unsuccessful vector-control strategies might be due to the lack of sustainable community participation. The state of Colima, located in the Western region of Mexico, is a dengue-endemic area despite vector-control activities implemented, which may be due to an insufficient health economic analysis of these interventions. A randomized controlled community trial took place in five urban municipalities where 24 clusters were included. The study groups ( n = 4) included an intervention to improve the community participation in vector control (A), ultra-low volume (ULV) spraying (B), both interventions (AB), and a control group. The main outcomes investigated were dengue cumulative incidence, disability-adjusted life years (DALYs), and the direct costs per intervention. The cumulative incidence of dengue was 17.4%, A; 14.3%, B; 14.4%, AB; and 30.2% in the control group. The highest efficiency and effectiveness were observed in group B (0.526 and 6.97, respectively) and intervention A was more likely to be cost-effective ($3952.84 per DALY avoided) followed by intervention B ($4472.09 per DALY avoided). Our findings suggest that efforts to improve community participation in vector control and ULV-spraying alone are cost-effective and may be useful to reduce the vector density and dengue incidence.

Self-avoiding walks that cross a square

NASA Astrophysics Data System (ADS)

Burkhardt, T. W.; Guim, I.

1991-10-01

The authors consider self-avoiding walks that traverse an L*L square lattice. Whittington and Guttmann (1990) have proved the existence of a phase transition in the infinite-L limit at a critical value of the step fugacity. They make several finite-size scaling predictions for the critical region, using the relation between self-avoiding walks and the N-vector model of magnetism. Adsorbing as well as nonadsorbing boundaries are considered. The predictions are in good agreement with numerical data for L

New Insights on the Inflammatory Role of Lutzomyia longipalpis Saliva in Leishmaniasis

PubMed Central

Prates, Deboraci Brito; Araújo-Santos, Théo; Brodskyn, Cláudia; Barral-Netto, Manoel; Barral, Aldina; Borges, Valéria Matos

2012-01-01

When an haematophagous sand fly vector insect bites a vertebrate host, it introduces its mouthparts into the skin and lacerates blood vessels, forming a hemorrhagic pool which constitutes an intricate environment of cell interactions. In this scenario, the initial performance of host, parasite, and vector “authors” will heavily influence the course of Leishmania infection. Recent advances in vector-parasite-host interaction have elucidated “co-authors” and “new roles” not yet described. We review here the stimulatory role of Lutzomyia longipalpis saliva leading to inflammation and try to connect them in an early context of Leishmania infection. PMID:22506098

Imer-product array processor for retrieval of stored images represented by bipolar binary (+1,-1) pixels using partial input trinary pixels represented by (+1,-1)

NASA Technical Reports Server (NTRS)

Liu, Hua-Kuang (Inventor); Awwal, Abdul A. S. (Inventor); Karim, Mohammad A. (Inventor)

1993-01-01

An inner-product array processor is provided with thresholding of the inner product during each iteration to make more significant the inner product employed in estimating a vector to be used as the input vector for the next iteration. While stored vectors and estimated vectors are represented in bipolar binary (1,-1), only those elements of an initial partial input vector that are believed to be common with those of a stored vector are represented in bipolar binary; the remaining elements of a partial input vector are set to 0. This mode of representation, in which the known elements of a partial input vector are in bipolar binary form and the remaining elements are set equal to 0, is referred to as trinary representation. The initial inner products corresponding to the partial input vector will then be equal to the number of known elements. Inner-product thresholding is applied to accelerate convergence and to avoid convergence to a negative input product.

Two Hop Adaptive Vector Based Quality Forwarding for Void Hole Avoidance in Underwater WSNs

PubMed Central

Javaid, Nadeem; Ahmed, Farwa; Wadud, Zahid; Alrajeh, Nabil; Alabed, Mohamad Souheil; Ilahi, Manzoor

2017-01-01

Underwater wireless sensor networks (UWSNs) facilitate a wide range of aquatic applications in various domains. However, the harsh underwater environment poses challenges like low bandwidth, long propagation delay, high bit error rate, high deployment cost, irregular topological structure, etc. Node mobility and the uneven distribution of sensor nodes create void holes in UWSNs. Void hole creation has become a critical issue in UWSNs, as it severely affects the network performance. Avoiding void hole creation benefits better coverage over an area, less energy consumption in the network and high throughput. For this purpose, minimization of void hole probability particularly in local sparse regions is focused on in this paper. The two-hop adaptive hop by hop vector-based forwarding (2hop-AHH-VBF) protocol aims to avoid the void hole with the help of two-hop neighbor node information. The other protocol, quality forwarding adaptive hop by hop vector-based forwarding (QF-AHH-VBF), selects an optimal forwarder based on the composite priority function. QF-AHH-VBF improves network good-put because of optimal forwarder selection. QF-AHH-VBF aims to reduce void hole probability by optimally selecting next hop forwarders. To attain better network performance, mathematical problem formulation based on linear programming is performed. Simulation results show that by opting these mechanisms, significant reduction in end-to-end delay and better throughput are achieved in the network. PMID:28763014

Two Hop Adaptive Vector Based Quality Forwarding for Void Hole Avoidance in Underwater WSNs.

PubMed

Javaid, Nadeem; Ahmed, Farwa; Wadud, Zahid; Alrajeh, Nabil; Alabed, Mohamad Souheil; Ilahi, Manzoor

2017-08-01

Underwater wireless sensor networks (UWSNs) facilitate a wide range of aquatic applications in various domains. However, the harsh underwater environment poses challenges like low bandwidth, long propagation delay, high bit error rate, high deployment cost, irregular topological structure, etc. Node mobility and the uneven distribution of sensor nodes create void holes in UWSNs. Void hole creation has become a critical issue in UWSNs, as it severely affects the network performance. Avoiding void hole creation benefits better coverage over an area, less energy consumption in the network and high throughput. For this purpose, minimization of void hole probability particularly in local sparse regions is focused on in this paper. The two-hop adaptive hop by hop vector-based forwarding (2hop-AHH-VBF) protocol aims to avoid the void hole with the help of two-hop neighbor node information. The other protocol, quality forwarding adaptive hop by hop vector-based forwarding (QF-AHH-VBF), selects an optimal forwarder based on the composite priority function. QF-AHH-VBF improves network good-put because of optimal forwarder selection. QF-AHH-VBF aims to reduce void hole probability by optimally selecting next hop forwarders. To attain better network performance, mathematical problem formulation based on linear programming is performed. Simulation results show that by opting these mechanisms, significant reduction in end-to-end delay and better throughput are achieved in the network.

Single-cycle adenovirus vectors in the current vaccine landscape.

PubMed

Barry, Michael

2018-02-01

Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T cell responses. Attenuated pathogen vaccines generate both, but risk causing the disease they aim to prevent. Newer gene-based vaccines drive both responses and avoid the risk of infection. While these replication-defective (RD) vaccines work well in small animals, they can be weak in humans because they do not replicate antigen genes like more potent replication-competent (RC) vaccines. RC vaccines generate substantially stronger immune responses, but also risk causing their own infections. To circumvent these problems, we developed single-cycle adenovirus (SC-Ad) vectors that amplify vaccine genes, but that avoid the risk of infection. This review will discuss these vectors and their prospects for use as vaccines. Areas covered: This review provides a background of different types of vaccines. The benefits of gene-based vaccines and their ability to replicate antigen genes are described. Adenovirus vectors are discussed and compared to other vaccine types. Replication-defective, single-cycle, and replication-competent Ad vaccines are compared. Expert commentary: The potential utility of these vaccines are discussed when used against infectious diseases and as cancer vaccines. We propose a move away from replication-defective vaccines towards more robust replication-competent or single-cycle vaccines.

Burgers Vector Analysis of Vertical Dislocations in Ge Crystals by Large-Angle Convergent Beam Electron Diffraction.

PubMed

Groiss, Heiko; Glaser, Martin; Marzegalli, Anna; Isa, Fabio; Isella, Giovanni; Miglio, Leo; Schäffler, Friedrich

2015-06-01

By transmission electron microscopy with extended Burgers vector analyses, we demonstrate the edge and screw character of vertical dislocations (VDs) in novel SiGe heterostructures. The investigated pillar-shaped Ge epilayers on prepatterned Si(001) substrates are an attempt to avoid the high defect densities of lattice mismatched heteroepitaxy. The Ge pillars are almost completely strain-relaxed and essentially defect-free, except for the rather unexpected VDs. We investigated both pillar-shaped and unstructured Ge epilayers grown either by molecular beam epitaxy or by chemical vapor deposition to derive a general picture of the underlying dislocation mechanisms. For the Burgers vector analysis we used a combination of dark field imaging and large-angle convergent beam electron diffraction (LACBED). With LACBED simulations we identify ideally suited zeroth and second order Laue zone Bragg lines for an unambiguous determination of the three-dimensional Burgers vectors. By analyzing dislocation reactions we confirm the origin of the observed types of VDs, which can be efficiently distinguished by LACBED. The screw type VDs are formed by a reaction of perfect 60° dislocations, whereas the edge types are sessile dislocations that can be formed by cross-slips and climbing processes. The understanding of these origins allows us to suggest strategies to avoid VDs.

Can antibodies against flies alter malaria transmission in birds by changing vector behavior?

PubMed

Ghosh, Suma; Waite, Jessica L; Clayton, Dale H; Adler, Frederick R

2014-10-07

Transmission of insect-borne diseases is shaped by the interactions among parasites, vectors, and hosts. Any factor that alters movement of infected vectors from infected to uninfeced hosts will in turn alter pathogen spread. In this paper, we study one such pathogen-vector-host system, avian malaria in pigeons transmitted by fly ectoparasites, where both two-way and three-way interactions play a key role in shaping disease spread. Bird immune defenses against flies can decrease malaria prevalence by reducing fly residence time on infected birds or increase disease prevalence by enhancing fly movement and thus infection transmission. We develop a mathematical model that illustrates how these changes in vector behavior influence pathogen transmission and show that malaria prevalence is maximized at an intermediate level of defense avoidance by the flies. Understanding how host immune defenses indirectly alter disease transmission by influencing vector behavior has implications for reducing the transmission of human malaria and other vectored pathogens. Published by Elsevier Ltd.

Herpes simplex virus type 1 (HSV-1)-derived recombinant vectors for gene transfer and gene therapy.

PubMed

Marconi, Peggy; Fraefel, Cornel; Epstein, Alberto L

2015-01-01

Herpes simplex virus type 1 (HSV-1 ) is a human pathogen whose lifestyle is based on a long-term dual interaction with the infected host, being able to establish both lytic and latent infections. The virus genome is a 153-kilobase pair (kbp) double-stranded DNA molecule encoding more than 80 genes. The interest of HSV-1 as gene transfer vector stems from its ability to infect many different cell types, both quiescent and proliferating cells, the very high packaging capacity of the virus capsid, the outstanding neurotropic adaptations that this virus has evolved, and the fact that it never integrates into the cellular chromosomes, thus avoiding the risk of insertional mutagenesis. Two types of vectors can be derived from HSV-1, recombinant vectors and amplicon vectors, and different methodologies have been developed to prepare large stocks of each type of vector. This chapter summarizes the approach most commonly used to prepare recombinant HSV-1 vectors through homologous recombination, either in eukaryotic cells or in bacteria.

Mosquito Avoidance Practices and Knowledge of Arboviral Diseases in Cities with Differing Recent History of Disease

PubMed Central

Haenchen, Steven D.; Hayden, Mary H.; Dickinson, Katherine L.; Walker, Kathleen; Jacobs, Elizabeth E.; Brown, Heidi E.; Gunn, Jayleen K. L.; Kohler, Lindsay N.; Ernst, Kacey C.

2016-01-01

As the range of dengue virus (DENV) transmission expands, an understanding of community uptake of prevention and control strategies is needed both in geographic areas where the virus has recently been circulating and in areas with the potential for DENV introduction. Personal protective behaviors such as the use of mosquito repellent to limit human–vector contact and the reduction of vector density through elimination of oviposition sites are the primary control methods for Aedes aegypti, the main vector of DENV. Here, we examined personal mosquito control measures taken by individuals in Key West, FL, in 2012, which had experienced a recent outbreak of DENV, and Tucson, AZ, which has a high potential for introduction but has not yet experienced autochthonous transmission. In both cities, there was a positive association between the numbers of mosquitoes noticed outdoors and the overall number of avoidance behaviors, use of repellent, and removal of standing water. Increased awareness and perceived risk of DENV were associated with increases in one of the most effective household prevention behaviors, removal of standing water, but only in Key West. PMID:27527634

Evaluation of signal transduction pathways after transient cutaneous adenoviral gene delivery

PubMed Central

2011-01-01

Background Adenoviral vectors have provided effective methods for in vivo gene delivery in therapeutic applications. However, these vectors can induce immune responses that may severely affect the ability of vector re-application. There is limited information about the mechanisms and signal transduction pathways involved in adenoviral recognition. For optimization of cutaneous gene therapy it is necessary to investigate molecular mechanisms of virus recognition in epidermal cells. The aim of this study was to investigate the signal transduction of the innate immunity after adenoviral DNA internalization in keratinocytes. Methods In vitro, keratinocytes were transfected with DNA, in the presence and absence of inhibitors for signalling molecules. In vivo, immunocompetent and athymic mice (n = 3 per group) were twice transduced with an Ad-vector. Results The results show an acute induction of type-I-interferon after in vitro transfection. Inhibition of PI3K, p38 MAPK, JNK and NFkappaB resulted in a decreased expression of type-I-interferon. In contrast to immunocompetent mice, athymic mice demonstrated a constant transgene expression and reduced inflammatory response in vivo. Conclusion The results suggest an induction of the innate immunity triggered by cytoplasm localised DNA which is mediated by PI3K-, p38 MAPK-, JNK-, NFkappaB-, JAK/STAT- and ERK1/2-dependent pathways. A stable transgene expression and a reduced inflammatory response in immunodeficient mice have been observed. These results provide potential for an effective adenoviral gene delivery into immunosupressed skin. PMID:21255430

A histogram-based technique for rapid vector extraction from PIV photographs

NASA Technical Reports Server (NTRS)

Humphreys, William M., Jr.

1991-01-01

A new analysis technique, performed totally in the image plane, is proposed which rapidly extracts all available vectors from individual interrogation regions on PIV photographs. The technique avoids the need for using Fourier transforms with the associated computational burden. The data acquisition and analysis procedure is described, and results of a preliminary simulation study to evaluate the accuracy of the technique are presented. Recently obtained PIV photographs are analyzed.

In vivo reduction or blockade of interleukin-1β in primary osteoarthritis influences expression of mediators implicated in pathogenesis

PubMed Central

Santangelo, K. S.; Nuovo, G. J.; Bertone, A. L.

2012-01-01

Summary Objective Diminish interleukin-1β (IL-1β) signaling in a model of primary osteoarthritis by RNA interference-based transcript reduction or receptor blockade, and quantify changes incurred on transcript expression of additional mediators. Methods Knees of Hartley guinea pigs were collected at 120 and 180 days of age following injection with viral vectors (N=4/treatment group/date) at 60 days. Two groups received either adeno-associated viral serotype 5 vector containing a knockdown sequence (TV), or adenoviral vector encoding for IL-1 receptor antagonist protein (Ad-IRAP); treatments were contrasted with opposite knees administered corresponding vector controls. A third group evaluated TV relative to saline-only injected knees. Chondropathy and immunohistochemistry findings were compared to untreated guinea pigs. Transcript expression levels in cartilage were calculated using the comparative CT (2−ΔΔCT) method and analyzed by one-way ANOVA with pairwise comparisons using Tukey 95% confidence intervals. Results Vector transduction was confirmed at both harvest dates. TV and Ad-IRAP, relative to vector controls, significantly decreased IL-1β. Inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interferon-γ (IFN-γ)], and catabolic matrix metalloproteinase 13 (MMP13) were also decreased, while anabolic transforming growth factor-β1 (TGF-β1) was increased. IL-1β was also decreased by TV versus saline, with a decrease in MMP13 and increase TGF-β1; TNF-α, IL-8, and IFN-γ were transiently increased. Conclusions This work confirmed that a reduction in IL-1β signaling was accomplished by either method, resulting in decreased expression of three inflammatory mediators and one catabolic agent, and increased expression of an anabolic molecule. Thus, evidence is provided that IL-1β serves a role in vivo in spontaneous osteoarthritis and that these translational tools may provide beneficial disease modification. PMID:22935786

Inflammatory nodules following soft tissue filler use: a review of causative agents, pathology and treatment options.

PubMed

Ledon, Jennifer A; Savas, Jessica A; Yang, Steven; Franca, Katlein; Camacho, Ivan; Nouri, Keyvan

2013-10-01

Nodule development is a common complication following the use of fillers for soft tissue augmentation and is commonly categorized as inflammatory or non-inflammatory in nature. Inflammatory nodules may appear anywhere from days to years after treatment, whereas non-inflammatory nodules are typically seen immediately following implantation and are usually secondary to improper placement of the filler. Although inflammatory nodules are more common with permanent fillers such as silicone, inflammatory nodule development following administration of temporary fillers such as hyaluronic acid and collagen has also been reported. Treated many times with corticosteroids due to their anti-inflammatory properties, inflammatory nodules may be secondary to infection or biofilm formation, warranting the use of alternative agents. Appropriate and prompt diagnosis is important in avoiding delay of treatment or long-term complications for the patient. This paper addresses the etiology, development, and studied treatment options available for inflammatory nodules secondary to each of the major classes of fillers. With this knowledge, practitioners may expeditiously recognize and manage this common side effect and thus maximize functional and aesthetic benefit.

Evaluation of the specificity and sensitivity of ferritin as an MRI reporter gene in the mouse brain using lentiviral and adeno-associated viral vectors.

PubMed

Vande Velde, G; Rangarajan, J R; Toelen, J; Dresselaers, T; Ibrahimi, A; Krylychkina, O; Vreys, R; Van der Linden, A; Maes, F; Debyser, Z; Himmelreich, U; Baekelandt, V

2011-06-01

The development of in vivo imaging protocols to reliably track transplanted cells or to report on gene expression is critical for treatment monitoring in (pre)clinical cell and gene therapy protocols. Therefore, we evaluated the potential of lentiviral vectors (LVs) and adeno-associated viral vectors (AAVs) to express the magnetic resonance imaging (MRI) reporter gene ferritin in the rodent brain. First, we compared the induction of background MRI contrast for both vector systems in immune-deficient and immune-competent mice. LV injection resulted in hypointense (that is, dark) changes of T(2)/T(2)(*) (spin-spin relaxation time)-weighted MRI contrast at the injection site, which can be partially explained by an inflammatory response against the vector injection. In contrast to LVs, AAV injection resulted in reduced background contrast. Moreover, AAV-mediated ferritin overexpression resulted in significantly enhanced contrast to background on T(2)(*)-weighted MRI. Although sensitivity associated with the ferritin reporter remains modest, AAVs seem to be the most promising vector system for in vivo MRI reporter gene imaging.

Gene transfer to the cerebellum.

PubMed

Louboutin, Jean-Pierre; Reyes, Beverly A S; Van Bockstaele, Elisabeth J; Strayer, David S

2010-12-01

There are several diseases for which gene transfer therapy to the cerebellum might be practicable. In these studies, we used recombinant Tag-deleted SV40-derived vectors (rSV40s) to study gene delivery targeting the cerebellum. These vectors transduce neurons and microglia very effectively in vitro and in vivo, and so we tested them to evaluate gene transfer to the cerebellum in vivo. Using a rSV40 vector carrying human immunodeficiency virus (HIV)-Nef with a C-terminal FLAG epitope, we characterized the distribution, duration, and cell types transduced. Rats received test and control vectors by stereotaxic injection into the cerebellum. Transgene expression was assessed 1, 2, and 4 weeks later by immunostaining of serial brain sections. FLAG epitope-expressing cells were seen, at all times after vector administration, principally detected in the Purkinje cells of the cerebellum, identified as immunopositive for calbindin. Occasional microglial cells were tranduced; transgene expression was not detected in astrocytes or oligodendrocytes. No inflammatory or other reaction was detected at any time. Thus, SV40-derived vectors can deliver effective, safe, and durable transgene expression to the cerebellum.

Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy

PubMed Central

Kallert, Sandra M.; Darbre, Stephanie; Bonilla, Weldy V.; Kreutzfeldt, Mario; Page, Nicolas; Müller, Philipp; Kreuzaler, Matthias; Lu, Min; Favre, Stéphanie; Kreppel, Florian; Löhning, Max; Luther, Sanjiv A.; Zippelius, Alfred; Merkler, Doron; Pinschewer, Daniel D.

2017-01-01

Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTLeff) responses. Conversely, the induction of protective tumour-specific CTLeff and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33. By triggering interleukin-33 signals, artLCMV elicits CTLeff responses of higher magnitude and functionality than those induced by replication-deficient vectors. Superior anti-tumour efficacy of artLCMV immunotherapy depends on interleukin-33 signalling, and a massive CTLeff influx triggers an inflammatory conversion of the tumour microenvironment. Our observations suggest that replicating viral delivery systems can release alarmins for improved anti-tumour efficacy. These mechanistic insights may outweigh safety concerns around replicating viral vectors in cancer immunotherapy. PMID:28548102

Enterobius Vermicularis-Associated Pelvic Inflammatory Disease in a Child.

PubMed

Mentessidou, Anastasia; Theocharides, Constantine; Patoulias, Ioannis; Panteli, Christina

2016-04-01

Enterobius vermicularis is the most highly prevalent intestinal worm in childhood and is generally considered of low pathogenicity. Little is known about the inflammatory complications of the female genital tract induced by E. vermicularis in childhood. A case of E. vermicularis-associated pelvic inflammatory disease with right salpingitis mimicking acute abdomen due to appendicitis in an 11-year-old girl is presented. E. vermicularis-related pelvic inflammatory disease should be included in the differential diagnosis of abdominal pain in children. Increased awareness is necessary to avoid an unnecessary surgery and to choose the correct antibiotic treatment. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

A new method for the prediction of chatter stability lobes based on dynamic cutting force simulation model and support vector machine

NASA Astrophysics Data System (ADS)

Peng, Chong; Wang, Lun; Liao, T. Warren

2015-10-01

Currently, chatter has become the critical factor in hindering machining quality and productivity in machining processes. To avoid cutting chatter, a new method based on dynamic cutting force simulation model and support vector machine (SVM) is presented for the prediction of chatter stability lobes. The cutting force is selected as the monitoring signal, and the wavelet energy entropy theory is used to extract the feature vectors. A support vector machine is constructed using the MATLAB LIBSVM toolbox for pattern classification based on the feature vectors derived from the experimental cutting data. Then combining with the dynamic cutting force simulation model, the stability lobes diagram (SLD) can be estimated. Finally, the predicted results are compared with existing methods such as zero-order analytical (ZOA) and semi-discretization (SD) method as well as actual cutting experimental results to confirm the validity of this new method.

Host association and the capacity of sand flies as vectors of lizard malaria in Panama.

PubMed

Kimsey, R B

1992-08-01

In this paper the capacity of sand flies (Lutzomyia) as vectors of parasites that cause malaria in anoles (Anolis limifrons) in the Zona de Canal, Panama was investigated. Inhabiting all study plots, often in local abundance, L. trinidadensis emerged as the principal candidate sand fly vector; the results of surveys did not suggest a likely mosquito vector. Although L. trinidadensis and infected anoles co-inhabited all plots, their abundances seemed unrelated. No evidence that sand flies parasitized anoles was uncovered. As anole activity patterns in daylight reciprocate with those of sand flies and at night anoles seem to avoid locations that sand flies frequent, anoles may evade sand fly bites altogether. Further, these sand flies occurred in close numerical and ecological association with Thecadactylus rapicauda, a reclusive moist forest gecko, often parasitizing these hosts in large numbers. Thus, sand flies lack capacity as vectors of malaria-causing parasites in central Panamanian anoles.

Avoiding Ticks

MedlinePlus

... ticks that bite humans How ticks spread disease Diseases transmitted by ticks Trends in tickborne diseases Tickborne diseases ... Emerging and Zoonotic Infectious Diseases (NCEZID) Division of Vector-Borne Diseases (DVBD) Email Recommend Tweet YouTube Instagram Listen Watch ...

Storage and computationally efficient permutations of factorized covariance and square-root information matrices

NASA Technical Reports Server (NTRS)

Muellerschoen, R. J.

1988-01-01

A unified method to permute vector-stored upper-triangular diagonal factorized covariance (UD) and vector stored upper-triangular square-root information filter (SRIF) arrays is presented. The method involves cyclical permutation of the rows and columns of the arrays and retriangularization with appropriate square-root-free fast Givens rotations or elementary slow Givens reflections. A minimal amount of computation is performed and only one scratch vector of size N is required, where N is the column dimension of the arrays. To make the method efficient for large SRIF arrays on a virtual memory machine, three additional scratch vectors each of size N are used to avoid expensive paging faults. The method discussed is compared with the methods and routines of Bierman's Estimation Subroutine Library (ESL).

Predictive Features of a Cockpit Traffic Display: A Workload Assessment

NASA Technical Reports Server (NTRS)

Wickens, Christopher D.; Morphew, Ephimia

1997-01-01

Eighteen pilots flew a series of traffic avoidance maneuvers in an experiment designed to assess the support offered and workload imposed by different levels of traffic display information in a free flight simulation. Three display prototypes were compared which differed in traffic information provided. A BASELINE (BL) display provided current and (2nd order) predicted information regarding ownship and current information of an intruder aircraft, represented on lateral and vertical displays in a coplanar suite. An INTRUDER PREDICTOR (IP) display, augmented the baseline display by providing lateral and vertical prediction of the intruder aircraft. A THREAT VECTOR (TV) display added to the IP display a vector that indicates the direction from ownship to the intruder at the predicted point of closest contact (POCC). The length of the vector corresponds to the radius of the protected zone, and the distance of the intersection of the vector with ownship predictor, corresponds to the time available till POCC or loss of separation. Pilots time shared the traffic avoidance task with a secondary task requiring them to monitor the top of the display for faint targets. This task simulated the visual demands of out-of-cockpit scanning, and hence was used to estimate the head-down time required by the different display formats. The results revealed that both display augmentations improved performance (safety) as assessed by predicted and actual loss of separation (i.e., penetration of the protected zone). Both enhancements also reduced workload, as assessed by the NASA TLX scale. The intruder predictor display produced these benefits with no substantial impact on the qualitative nature of the avoidance maneuvers that were selected. The threat vector produced the safety benefits by inducing a greater degree of (effective) lateral maneuvering, thus partially offsetting the benefits of reduced workload. The three displays did not differ in terms of their effect on performance of the monitoring task, used to infer head-down time, nor in the extent of vertical or airspeed maneuvering. The results are discussed in terms of their implications for 19 cognitive engineering design features.

Classification of inflammatory bowel diseases by means of Raman spectroscopic imaging of epithelium cells

NASA Astrophysics Data System (ADS)

Bielecki, Christiane; Bocklitz, Thomas W.; Schmitt, Michael; Krafft, Christoph; Marquardt, Claudio; Gharbi, Akram; Knösel, Thomas; Stallmach, Andreas; Popp, Juergen

2012-07-01

We report on a Raman microspectroscopic characterization of the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC). Therefore, Raman maps of human colon tissue sections were analyzed by utilizing innovative chemometric approaches. First, support vector machines were applied to highlight the tissue morphology (=Raman spectroscopic histopathology). In a second step, the biochemical tissue composition has been studied by analyzing the epithelium Raman spectra of sections of healthy control subjects (n=11), subjects with CD (n=14), and subjects with UC (n=13). These three groups exhibit significantly different molecular specific Raman signatures, allowing establishment of a classifier (support-vector-machine). By utilizing this classifier it was possible to separate between healthy control patients, patients with CD, and patients with UC with an accuracy of 98.90%. The automatic design of both classification steps (visualization of the tissue morphology and molecular classification of IBD) paves the way for an objective clinical diagnosis of IBD by means of Raman spectroscopy in combination with chemometric approaches.

Antibiotics during childhood and inflammatory bowel disease?

PubMed

2014-10-01

Four epidemiological studies, including two large cohort studies in children aged 17 years or under, have studied the link between antibiotic therapy and inflammatory bowel disease. The risk of inflammatory bowel disease appeared to be twice as high in children exposed to an antibiotic as in unexposed children. The risk appeared higher following exposure during the first year of life, with beta-lactam antibiotics, and with repeated antibiotic courses. One postulated mechanism is through destruction of the anaerobic intestinal flora by antibiotics. In practice, these data provide yet another reason to avoid unnecessarily exposing children to antibiotics.

Natural Products: Insights into Leishmaniasis Inflammatory Response

PubMed Central

Rodrigues, Igor A.; Mazotto, Ana Maria; Cardoso, Verônica; Alves, Renan L.; Amaral, Ana Claudia F.; Silva, Jefferson Rocha de Andrade; Pinheiro, Anderson S.; Vermelho, Alane B.

2015-01-01

Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID:26538837

Herpes simplex virus type 1-derived recombinant and amplicon vectors.

PubMed

Fraefel, Cornel; Marconi, Peggy; Epstein, Alberto L

2011-01-01

Herpes simplex virus type 1 (HSV-1) is a human pathogen whose lifestyle is based on a long-term dual interaction with the infected host, being able to establish both lytic and latent infections. The virus genome is a 153 kbp double-stranded DNA molecule encoding more than 80 genes. The interest of HSV-1 as gene transfer vector stems from its ability to infect many different cell types, both quiescent and proliferating cells, the very high packaging capacity of the virus capsid, the outstanding neurotropic adaptations that this virus has evolved, and the fact that it never integrates into the cellular chromosomes, thus avoiding the risk of insertional mutagenesis. Two types of vectors can be derived from HSV-1, recombinant vectors and amplicon vectors, and different methodologies have been developed to prepare large stocks of each type of vector. This chapter summarizes (1) the two approaches most commonly used to prepare recombinant vectors through homologous recombination, either in eukaryotic cells or in bacteria, and (2) the two methodologies currently used to generate helper-free amplicon vectors, either using a bacterial artificial chromosome (BAC)-based approach or a Cre/loxP site-specific recombination strategy.

Uterine inflammatory myofibroblastic tumor: more common than expected

PubMed Central

Mandato, Vincenzo Dario; Valli, Riccardo; Mastrofilippo, Valentina; Bisagni, Alessandra; Aguzzoli, Lorenzo; La Sala, Giovanni Battista

2017-01-01

Abstract Rationale: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm composed of spindled to epithelioid cells with prominent myxoid stroma and inflammatory infiltrate. It has a low but definite malignant potential. However, its management has never been standardized. Patient Concerns and Diagnosis: We present the first case of uterine IMT laparoscopically treated. Moreover, we reviewed the English literature regarding uterine IMT published between 1987 and June 2017. A total of 72 cases of uterine IMT were included. Clinical and pathological characteristics, treatments and outcomes were recorded. Interventions and Outcomes: A total laparoscopic hysterectomy with opportunistic bilateral salpingectomy was performed. Patient is free of disease at 6 months of follow-up. Lessons: Uterine IMT may be identified by anaplastic lymphoma kinase overexpression, its prognosis is usually good, complete excision seems to be effective to avoid relapse and mini invasive surgery seems to be effective and safe to treat uterine IMT. However, considering the age of women affected by disease, conservative management, or medical therapy could be taken in account to avoid surgical injuries and to preserve fertility. PMID:29310405

The riddle of the sphinx redux.

PubMed

Shayman, James A

2010-05-01

Understanding the mechanisms of glucocorticoid-mediated inhibition of inflammation has been challenging. This is particularly true with regard to the development of drugs that mimic the anti-inflammatory benefits of steroids while avoiding the untoward metabolic effects. Förster et al. report that the inhibition of stress-induced mesangial-cell apoptosis by dexamethasone is mediated by sphingosine-1-phosphate. These findings identify alternative pathways whereby the anti-inflammatory mechanisms of glucocorticoids can be probed.

Arm Lift (Brachioplasty)

MedlinePlus

... taken recently, including over-the-counter drugs and herbal supplements, as well as any surgeries you've had. ... to avoid taking aspirin, anti-inflammatory drugs and herbal supplements, which can increase bleeding. Arrange for help during ...

Face-Lift

MedlinePlus

... any medications, including over-the-counter drugs and herbal supplements, you're taking or have taken recently — especially ... to avoid taking aspirin, anti-inflammatory drugs and herbal supplements, which can increase bleeding. Also, if you're ...

Vector Autoregression, Structural Equation Modeling, and Their Synthesis in Neuroimaging Data Analysis

PubMed Central

Chen, Gang; Glen, Daniel R.; Saad, Ziad S.; Hamilton, J. Paul; Thomason, Moriah E.; Gotlib, Ian H.; Cox, Robert W.

2011-01-01

Vector autoregression (VAR) and structural equation modeling (SEM) are two popular brain-network modeling tools. VAR, which is a data-driven approach, assumes that connected regions exert time-lagged influences on one another. In contrast, the hypothesis-driven SEM is used to validate an existing connectivity model where connected regions have contemporaneous interactions among them. We present the two models in detail and discuss their applicability to FMRI data, and interpretational limits. We also propose a unified approach that models both lagged and contemporaneous effects. The unifying model, structural vector autoregression (SVAR), may improve statistical and explanatory power, and avoids some prevalent pitfalls that can occur when VAR and SEM are utilized separately. PMID:21975109

Gimbal-Angle Vectors of the Nonredundant CMG Cluster

NASA Astrophysics Data System (ADS)

Lee, Donghun; Bang, Hyochoong

2018-05-01

This paper deals with the method using the preferred gimbal angles of a control moment gyro (CMG) cluster for controlling spacecraft attitude. To apply the method to the nonredundant CMG cluster, analytical gimbal-angle solutions for the zero angular momentum state are derived, and the gimbal-angle vectors for the nonzero angular momentum states are studied by a numerical method. It will be shown that the number of the gimbal-angle vectors is determined from the given skew angle and the angular momentum state of the CMG cluster. Through numerical examples, it is shown that the method using the preferred gimbal-angle is an efficient approach to avoid internal singularities for the nonredundant CMG cluster.

A Deep Insight Into the Sialotranscriptome of the Chagas Disease Vector, Panstrongylus megistus (Hemiptera: Heteroptera)

PubMed Central

Ribeiro, José M. C.; Schwarz, Alexandra; Francischetti, Ivo M. B.

2015-01-01

Saliva of blood-sucking arthropods contains a complex cocktail of pharmacologically active compounds that assists feeding by counteracting their hosts’ hemostatic and inflammatory reactions. Panstrongylus megistus (Burmeister) is an important vector of Chagas disease in South America, but despite its importance there is only one salivary protein sequence publicly deposited in GenBank. In the present work, we used Illumina technology to disclose and publicly deposit 3,703 coding sequences obtained from the assembly of >70 million reads. These sequences should assist proteomic experiments aimed at identifying pharmacologically active proteins and immunological markers of vector exposure. A supplemental file of the transcriptome and deducted protein sequences can be obtained from http://exon.niaid.nih.gov/transcriptome/P_megistus/Pmeg-web.xlsx. PMID:26334808

3-D Magnetotelluric Forward Modeling And Inversion Incorporating Topography By Using Vector Finite-Element Method Combined With Divergence Corrections Based On The Magnetic Field (VFEH++)

NASA Astrophysics Data System (ADS)

Shi, X.; Utada, H.; Jiaying, W.

2009-12-01

The vector finite-element method combined with divergence corrections based on the magnetic field H, referred to as VFEH++ method, is developed to simulate the magnetotelluric (MT) responses of 3-D conductivity models. The advantages of the new VFEH++ method are the use of edge-elements to eliminate the vector parasites and the divergence corrections to explicitly guarantee the divergence-free conditions in the whole modeling domain. 3-D MT topographic responses are modeling using the new VFEH++ method, and are compared with those calculated by other numerical methods. The results show that MT responses can be modeled highly accurate using the VFEH+ +method. The VFEH++ algorithm is also employed for the 3-D MT data inversion incorporating topography. The 3-D MT inverse problem is formulated as a minimization problem of the regularized misfit function. In order to avoid the huge memory requirement and very long time for computing the Jacobian sensitivity matrix for Gauss-Newton method, we employ the conjugate gradient (CG) approach to solve the inversion equation. In each iteration of CG algorithm, the cost computation is the product of the Jacobian sensitivity matrix with a model vector x or its transpose with a data vector y, which can be transformed into two pseudo-forwarding modeling. This avoids the full explicitly Jacobian matrix calculation and storage which leads to considerable savings in the memory required by the inversion program in PC computer. The performance of CG algorithm will be illustrated by several typical 3-D models with horizontal earth surface and topographic surfaces. The results show that the VFEH++ and CG algorithms can be effectively employed to 3-D MT field data inversion.

Virus-Vectored Influenza Virus Vaccines

PubMed Central

Tripp, Ralph A.; Tompkins, S. Mark

2014-01-01

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

Effect of DSS on Bacterial Growth in Gastrointestinal Tract.

PubMed

Hlinková, J; Svobodová, H; Brachtlová, T; Gardlík, R

2016-01-01

Inflammatory bowel disease is an idiopathic autoimmune disorder that is mainly divided into ulcerative colitis and Crohn's disease. Probiotics are known for their beneficial effect and used as a treatment option in different gastrointestinal problems. The aim of our study was to find suitable bacterial vectors for gene therapy of inflammatory bowel disease. Salmonella enterica serovar Typhimurium SL7207 and Escherichia coli Nissle 1917 were investigated as potential vectors. Our results show that the growth of Escherichia coli Nissle 1917 was inhibited in the majority of samples collected from dextran sodium sulphate-treated animals compared with control growth in phosphate-buffered saline. The growth of Salmonella enterica serovar Typhimurium SL7207 in all investigated samples was enhanced or unaffected in comparison with phosphate-buffered saline; however, it did not reach the growth rates of Escherichia coli Nissle 1917. Dextran sodium sulphate treatment had a stimulating effect on the growth of both strains in homogenates of distant small intestine and proximal colon samples. The gastrointestinal tract contents and tissue homogenates did not inhibit growth of Salmonella enterica serovar Typhimurium SL7207 in comparison with the negative control, and provided more suitable environment for growth compared to Escherichia coli Nissle 1917. We therefore conclude that Salmonella enterica serovar Typhimurium SL7207 is a more suitable candidate for a potential bacterial vector, even though it has no known probiotic properties.

[Puncture scrotostomy--a treatment method in acute inflammatory diseases of the scrotal organs].

PubMed

Shapoval, V I; Asimov, D A; Lesovoĭ, V N

1989-01-01

A method for the treatment of acute inflammatory diseases of the scrotal organs by means of puncture scrotostomy, which consists in passing the indwelling micro-irrigator into a cavity of the serous sheath of the testis and epididymis and administration via this route of antibacterial and resolving preparations for 4-5 days, is suggested. A method approved in treatment of 45 patients permits to avoid surgical intervention, and is highly effective.

Mesalamine-induced myopericarditis - A case report.

PubMed

Bernardo, Sónia; Fernandes, Samuel Raimundo; Araújo-Correia, Luís

2016-11-01

Myopericarditis has occasionally been reported as a side effect of mesalamine in patients with inflammatory bowel disease. We present a 20-year-old woman with ulcerative colitis admitted with chest pain. After thorough investigation she was diagnosed with myopericarditis potentially related to mesalamine. There was complete clinical and laboratorial recovery following drug withdrawal. Although uncommon, the possibility of myopericarditis should be considered in patients with inflammatory bowel disease presenting with cardiac complaints. Early recognition can avoid potential life-threatening complications.

Corruption of genomic databases with anomalous sequence.

PubMed

Lamperti, E D; Kittelberger, J M; Smith, T F; Villa-Komaroff, L

1992-06-11

We describe evidence that DNA sequences from vectors used for cloning and sequencing have been incorporated accidentally into eukaryotic entries in the GenBank database. These incorporations were not restricted to one type of vector or to a single mechanism. Many minor instances may have been the result of simple editing errors, but some entries contained large blocks of vector sequence that had been incorporated by contamination or other accidents during cloning. Some cases involved unusual rearrangements and areas of vector distant from the normal insertion sites. Matches to vector were found in 0.23% of 20,000 sequences analyzed in GenBank Release 63. Although the possibility of anomalous sequence incorporation has been recognized since the inception of GenBank and should be easy to avoid, recent evidence suggests that this problem is increasing more quickly than the database itself. The presence of anomalous sequence may have serious consequences for the interpretation and use of database entries, and will have an impact on issues of database management. The incorporated vector fragments described here may also be useful for a crude estimate of the fidelity of sequence information in the database. In alignments with well-defined ends, the matching sequences showed 96.8% identity to vector; when poorer matches with arbitrary limits were included, the aggregate identity to vector sequence was 94.8%.

A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo.

PubMed

Tang, Yao Liang; Qian, Keping; Zhang, Y Clare; Shen, Leping; Phillips, M Ian

2005-12-01

The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector'' system that amplifies cardioprotective gene expression. Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.

Use of orbital floor steroids in the management of patients with uniocular non-necrotising scleritis.

PubMed Central

Hakin, K N; Ham, J; Lightman, S L

1991-01-01

Most cases of non-necrotising scleritis can be successfully treated with non-steroidal anti-inflammatory drugs. If these are ineffective, then high-dose systemic corticosteroids, with all their attendant side-effects, are usually required. We have used orbital floor injections of depot steroid in the management of nine patients with non-necrotising scleritis in an attempt to avoid the use of systemic steroids, or to allow the dose of steroids to be reduced while maintaining disease control. A temporary reduction in inflammation was achieved in all cases, which allowed the use of systemic steroids to be avoided altogether in two patients and delayed in the others. Non-steroidal anti-inflammatory drugs and systemic corticosteroids remain the mainstay of treatment for non-necrotising scleritis, but orbital floor injections may be a useful adjunct in certain cases. Images PMID:2043574

RNA Interference for improving the Outcome of Islet Transplantation

PubMed Central

Li, Feng; Mahato, Ram I

2010-01-01

Islet transplantation has the potential to cure type 1 diabetes. Despite recent therapeutic success, it is still not common because a large number of transpanted islets get damaged by multiple challenges including instant blood mediated inflammatory reaction, hypoxia/reperfusion injury, inflammatory cytokines, and immune rejection. RNA interference (RNAi) is an novel strategy to selectively degrade target mRNA. The use of RNAi technologies to downregulate the expression of harmful genes has the potential to improve the outcome of islet transplantation. The aim of this review is to gain a thorough understanding of biological obstacles to islet transplantation and discuss how to overcome these barriers using different RNAi technologies. This eventually will help improve islet survival and function post transplantaion. Chemically synthesized small interferring RNA (siRNA), vector based short haripin RNA (shRNA), and their critical design elements (such as sequences, promoters, backbone) are discussed. The application of combinatorial RNAi in islet transplantation is also discussed. Last but not the least, several delivery strategies for enhanced gene silencing are discussed, including chemical modification of siRNA, complex formation, bioconjugation, and viral vectors. PMID:21156190

Model Predictive Control of A Matrix-Converter Based Solid State Transformer for Utility Grid Interaction

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

Xue, Yaosuo

The matrix converter solid state transformer (MC-SST), formed from the back-to-back connection of two three-to-single-phase matrix converters, is studied for use in the interconnection of two ac grids. The matrix converter topology provides a light weight and low volume single-stage bidirectional ac-ac power conversion without the need for a dc link. Thus, the lifetime limitations of dc-bus storage capacitors are avoided. However, space vector modulation of this type of MC-SST requires to compute vectors for each of the two MCs, which must be carefully coordinated to avoid commutation failure. An additional controller is also required to control power exchange betweenmore » the two ac grids. In this paper, model predictive control (MPC) is proposed for an MC-SST connecting two different ac power grids. The proposed MPC predicts the circuit variables based on the discrete model of MC-SST system and the cost function is formulated so that the optimal switch vector for the next sample period is selected, thereby generating the required grid currents for the SST. Simulation and experimental studies are carried out to demonstrate the effectiveness and simplicity of the proposed MPC for such MC-SST-based grid interfacing systems.« less

Akt/protein kinase B activation by adenovirus vectors contributes to NFkappaB-dependent CXCL10 expression.

PubMed

Liu, Qiang; White, Lindsay R; Clark, Sharon A; Heffner, Daniel J; Winston, Brent W; Tibbles, Lee Anne; Muruve, Daniel A

2005-12-01

In gene therapy, the innate immune system is a significant barrier to the effective application of adenovirus (Ad) vectors. In kidney epithelium-derived (REC) cells, serotype 5 Ad vectors induce the expression of the chemokine CXCL10 (IP-10), a response that is dependent on NFkappaB. Compared to the parental vector AdLuc, transduction with the RGD-deleted vector AdL.PB resulted in reduced CXCL10 activation despite increasing titers, implying that RGD-alpha(V) integrin interactions contribute to adenovirus induction of inflammatory genes. Akt, a downstream effector of integrin signaling, was activated within 10 min of transduction with Ad vectors in a dose-dependent manner. Akt activation was not present following transduction with AdL.PB, confirming the importance of capsid-alpha(V) integrin interactions in Ad vector Akt activation. Inhibition of the phosphoinositide-3-OH kinase/Akt pathway by Wortmannin or Ly294002 compounds decreased Ad vector induction of CXCL10 mRNA. Similarly, adenovirus-mediated overexpression of the dominant negative AktAAA decreased CXCL10 mRNA expression compared to the reporter vector AdLacZ alone. The effect of Akt on CXCL10 mRNA expression occurred via NFkappaB-dependent transcriptional activation, since AktAAA overexpression and Ly294002 both inhibited CXCL10 and NFkappaB promoter activation in luciferase reporter experiments. These results show that Akt plays a role in the Ad vector activation of NFkappaB and CXCL10 expression. Understanding the mechanism underlying the regulation of host immunomodulatory genes by adenovirus vectors will lead to strategies that will improve the efficacy and safety of these agents for clinical use.

Amplified and persistent immune responses generated by single-cycle replicating adenovirus vaccines.

PubMed

Crosby, Catherine M; Nehete, Pramod; Sastry, K Jagannadha; Barry, Michael A

2015-01-01

Replication-competent adenoviral (RC-Ad) vectors generate exceptionally strong gene-based vaccine responses by amplifying the antigen transgenes they carry. While they are potent, they also risk causing adenovirus infections. More common replication-defective Ad (RD-Ad) vectors with deletions of E1 avoid this risk but do not replicate their transgene and generate markedly weaker vaccine responses. To amplify vaccine transgenes while avoiding production of infectious progeny viruses, we engineered "single-cycle" adenovirus (SC-Ad) vectors by deleting the gene for IIIa capsid cement protein of lower-seroprevalence adenovirus serotype 6. In mouse, human, hamster, and macaque cells, SC-Ad6 still replicated its genome but prevented genome packaging and virion maturation. When used for mucosal intranasal immunization of Syrian hamsters, both SC-Ad and RC-Ad expressed transgenes at levels hundreds of times higher than that of RD-Ad. Surprisingly, SC-Ad, but not RC-Ad, generated higher levels of transgene-specific antibody than RD-Ad, which notably climbed in serum and vaginal wash samples over 12 weeks after single mucosal immunization. When RD-Ad and SC-Ad were tested by single sublingual immunization in rhesus macaques, SC-Ad generated higher gamma interferon (IFN-γ) responses and higher transgene-specific serum antibody levels. These data suggest that SC-Ad vectors may have utility as mucosal vaccines. This work illustrates the utility of our recently developed single-cycle adenovirus (SC-Ad6) vector as a new vaccine platform. Replication-defective (RD-Ad6) vectors produce low levels of transgene protein, which leads to minimal antibody responses in vivo. This study shows that replicating SC-Ad6 produces higher levels of luciferase and induces higher levels of green fluorescent protein (GFP)-specific antibodies than RD in a permissive Syrian hamster model. Surprisingly, although a replication-competent (RC-Ad6) vector produces more luciferase than SC-Ad6, it does not elicit comparable levels of anti-GFP antibodies in permissive hamsters. When tested in the larger rhesus macaque model, SC-Ad6 induces higher transgene-specific antibody and T cell responses. Together, these data suggest that SC-Ad6 could be a more effective platform for developing vaccines against more relevant antigens. This could be especially beneficial for developing vaccines for pathogens for which traditional replication-defective adenovirus vectors have not been effective. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Patients' diets and preferences in a pediatric population with inflammatory bowel disease.

PubMed

Green, T J; Issenman, R M; Jacobson, K

1998-01-01

To determine the dietary practices of the pediatric inflammatory bowel disease population at the Children's Hospital of the Hamilton Health Sciences Corporation and the reported effectiveness of those diets. A questionnaire mailed to 153 pediatric patients was returned by 125 patients (76 Crohn's disease [CD] and 49 ulcerative colitis [UC] patients)--an 82% response rate. The median age of respondents was 13 years, and 62% were male. Ninety per cent and 71% of CD and UC patients, respectively, had changed their diets since diagnosis. Caloric supplements (eg, BOOST [Mead Johnson Nutritionals]), sole source nutrition, low fibre and lactose-free diets were used by more than 15% of CD patients, whereas lactose-free, nonspicy, low acid, additive-free, caloric supplement and low fibre diets were used by more than 15% of UC patients. A diet supplement was more commonly used in CD patients (P < 0.05) and an additive-free diet in UC patients. Corn and corn products, nuts, milk and bran were avoided by more than 20% of CD and UC patients; however, more CD than UC patients avoided corn and corn products. In addition, UC patients (more than 20%) also avoided tomato, other dairy (nonfluid milk-based products and foods containing milk products), chocolate, cheese, wheat, tomato sauces and fruit juice. A benefit was reported for 103 of 141 reported diets, with the most commonly alleviated symptoms being abdominal pain, diarrhea and flatulence. Many children with inflammatory bowel disease have altered their diets to manage their disease and have attributed symptomatic relief to these diets.

[Dermatological features of auto-inflammatory recurrent fevers].

PubMed

Escudier, A; Mauvais, F-X; Bastard, P; Boussard, C; Jaoui, A; Koskas, V; Lecoq, E; Michel, A; Orcel, M-C; Truelle, P-E; Wohrer, D; Piram, M

2018-02-01

Auto-inflammatory diseases are characterized by unexplained and recurrent attacks of systemic inflammation often involving the skin, joints, or serosal membranes. They are due to a dysfunction or dysregulation of the innate immunity, which is the first line of defense against pathogens. Early recognition of these diseases by the clinician, especially by pediatricians encountering such pathologies in pediatric patients, is primordial to avoid complications. Skin manifestations, common in most auto-inflammatory diseases, are helpful for prompt diagnosis. After a brief physiopathological review, we will describe auto-inflammatory recurrent fevers by their main dermatological presentations: urticarial lesions, neutrophilic dermatoses, panniculitis, other maculopapular eruptions, dyskeratosis, skin vasculitis, and oral aphthous. We finally suggest a decision tree to help clinicians better target genetic exams in patients with recurrent fevers and dermatological manifestations. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice.

PubMed

Ito, Naoki; Hirose, Eiji; Ishida, Tatsuya; Hori, Atsushi; Nagai, Takayuki; Kobayashi, Yoshinori; Kiyohara, Hiroaki; Oikawa, Tetsuro; Hanawa, Toshihiko; Odaguchi, Hiroshi

2017-05-03

Kososan, a Kampo (traditional Japanese herbal) medicine, has been used for the therapy of depressive mood in humans. However, evidence for the antidepressant efficacy of kososan and potential mechanisms are lacking. Recently, it has been recognized that stress triggers neuroinflammation and suppresses adult neurogenesis, leading to depression and anxiety. Here, we examined whether kososan extract affected social behavior in mice exposed to chronic social defeat stress (CSDS), an animal model of prolonged psychosocial stress, and neuroinflammation induced by CSDS. In the CSDS paradigm, C57BL/6J mice were exposed to 10 min of social defeat stress from an aggressive CD-1 mouse for 10 consecutive days (days 1-10). Kososan extract (1.0 g/kg) was administered orally once daily for 12 days (days 1-12). On day 11, the social avoidance test was performed to examine depressive- and anxious-like behaviors. To characterize the impacts of kososan on neuroinflammation and adult neurogenesis, immunochemical analyses and ex vivo microglial stimulation assay with lipopolysaccharide (LPS) were performed on days 13-15. Oral administration of kososan extract alleviated social avoidance, depression- and anxiety-like behaviors, caused by CSDS exposure. CSDS exposure resulted in neuroinflammation, as indicated by the increased accumulation of microglia, the resident immune cells of the brain, and their activation in the hippocampus, which was reversed to normal levels by treatment with kososan extract. Additionally, in ex vivo studies, CSDS exposure potentiated the microglial pro-inflammatory response to a subsequent LPS challenge, an effect that was also blunted by kososan extract treatment. Indeed, the modulatory effect of kososan extract on neuroinflammation appears to be due to a hippocampal increase in an anti-inflammatory phenotype of microglia while sparing an increased pro-inflammatory phenotype of microglia caused by CSDS. Moreover, reduced adult hippocampal neurogenesis in defeated mice was recovered by kososan extract treatment. Our findings suggest that kososan extract prevents a social avoidant behavior in socially defeated mice that is partially mediated by the downregulation of hippocampal neuroinflammation, presumably by the relative increased anti-inflammatory microglia and regulation of adult hippocampal neurogenesis. Our present study also provides novel evidence for the beneficial effects of kososan on depression/anxiety and the possible underlying mechanisms.

Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons

PubMed Central

Morral, Núria; O’Neal, Wanda; Rice, Karen; Leland, Michele; Kaplan, Johanne; Piedra, Pedro A.; Zhou, Heshan; Parks, Robin J.; Velji, Rizwan; Aguilar-Córdova, Estuardo; Wadsworth, Samuel; Graham, Frank L.; Kochanek, Stefan; Carey, K. Dee; Beaudet, Arthur L.

1999-01-01

The efficiency of first-generation adenoviral vectors as gene delivery tools is often limited by the short duration of transgene expression, which can be related to immune responses and to toxic effects of viral proteins. In addition, readministration is usually ineffective unless the animals are immunocompromised or a different adenovirus serotype is used. Recently, adenoviral vectors devoid of all viral coding sequences (helper-dependent or gutless vectors) have been developed to avoid expression of viral proteins. In mice, liver-directed gene transfer with AdSTK109, a helper-dependent adenoviral (Ad) vector containing the human α1-antitrypsin (hAAT) gene, resulted in sustained expression for longer than 10 months with negligible toxicity to the liver. In the present report, we have examined the duration of expression of AdSTK109 in the liver of baboons and compared it to first-generation vectors expressing hAAT. Transgene expression was limited to approximately 3–5 months with the first-generation vectors. In contrast, administration of AdSTK109 resulted in transgene expression for longer than a year in two of three baboons. We have also investigated the feasibility of circumventing the humoral response to the virus by sequential administration of vectors of different serotypes. We found that the ineffectiveness of readministration due to the humoral response to an Ad5 first-generation vector was overcome by use of an Ad2-based vector expressing hAAT. These data suggest that long-term expression of transgenes should be possible by combining the reduced immunogenicity and toxicity of helper-dependent vectors with sequential delivery of vectors of different serotypes. PMID:10536005

Mosquito biting activity on humans & detection of Plasmodium falciparum infection in Anopheles stephensi in Goa, India.

PubMed

Korgaonkar, Nandini S; Kumar, Ashwani; Yadav, Rajpal S; Kabadi, Dipak; Dash, Aditya P

2012-01-01

Knowledge of the bionomics of mosquitoes, especially of disease vectors, is essential to plan appropriate vector avoidance and control strategies. Information on biting activity of vectors during the night hours in different seasons is important for choosing personal protection measures. This study was carried out to find out the composition of mosquito fauna biting on humans and seasonal biting trends in Goa, India. Biting activities of all mosquitoes including vectors were studied from 1800 to 0600 h during 85 nights using human volunteers in 14 different localities of three distinct ecotypes in Goa. Seasonal biting trends of vector species were analysed and compared. Seasonal biting periodicity during different phases of night was also studied using William's mean. A total of 4,191 mosquitoes of five genera and 23 species were collected. Ten species belonged to Anopheles, eight to Culex, three to Aedes and one each to Mansonia and Armigeres. Eleven vector species had human hosts, including malaria vectors Anopheles stephensi (1.3%), An. fluviatilis (1.8%), and An. culicifacies (0.76%); filariasis vectors Culex quinquefasciatus (40.8%) and Mansonia uniformis (1.8%); Japanese encephalitis vectors Cx. tritaeniorhynchus (17.4%), Cx. vishnui (7.7%), Cx. pseudovishnui (0.1%), and Cx. gelidus (2.4%); and dengue and chikungunya vectors Aedes albopictus (0.9%) and Ae. aegypti (0.6%). Two An. stephensi of the total 831 female anophelines, were found positive for P. falciparum sporozoites. The entomological inoculation rate (EIR) of P. falciparum was 18.1 and 2.35 for Panaji city and Goa, respectively. Most of the mosquito vector species were collected in all seasons and throughout the scotophase. Biting rates of different vector species differed during different phases of night and seasons. Personal protection methods could be used to stop vector-host contact.

A Fast Reduced Kernel Extreme Learning Machine.

PubMed

Deng, Wan-Yu; Ong, Yew-Soon; Zheng, Qing-Hua

2016-04-01

In this paper, we present a fast and accurate kernel-based supervised algorithm referred to as the Reduced Kernel Extreme Learning Machine (RKELM). In contrast to the work on Support Vector Machine (SVM) or Least Square SVM (LS-SVM), which identifies the support vectors or weight vectors iteratively, the proposed RKELM randomly selects a subset of the available data samples as support vectors (or mapping samples). By avoiding the iterative steps of SVM, significant cost savings in the training process can be readily attained, especially on Big datasets. RKELM is established based on the rigorous proof of universal learning involving reduced kernel-based SLFN. In particular, we prove that RKELM can approximate any nonlinear functions accurately under the condition of support vectors sufficiency. Experimental results on a wide variety of real world small instance size and large instance size applications in the context of binary classification, multi-class problem and regression are then reported to show that RKELM can perform at competitive level of generalized performance as the SVM/LS-SVM at only a fraction of the computational effort incurred. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modified conjugate gradient method for diagonalizing large matrices.

PubMed

Jie, Quanlin; Liu, Dunhuan

2003-11-01

We present an iterative method to diagonalize large matrices. The basic idea is the same as the conjugate gradient (CG) method, i.e, minimizing the Rayleigh quotient via its gradient and avoiding reintroducing errors to the directions of previous gradients. Each iteration step is to find lowest eigenvector of the matrix in a subspace spanned by the current trial vector and the corresponding gradient of the Rayleigh quotient, as well as some previous trial vectors. The gradient, together with the previous trial vectors, play a similar role as the conjugate gradient of the original CG algorithm. Our numeric tests indicate that this method converges significantly faster than the original CG method. And the computational cost of one iteration step is about the same as the original CG method. It is suitable for first principle calculations.

A Safe Bacterial Microsyringe for In Vivo Antigen Delivery and Immunotherapy

PubMed Central

Le Gouëllec, Audrey; Chauchet, Xavier; Laurin, David; Aspord, Caroline; Verove, Julien; Wang, Yan; Genestet, Charlotte; Trocme, Candice; Ahmadi, Mitra; Martin, Sandrine; Broisat, Alexis; Cretin, François; Ghezzi, Catherine; Polack, Benoit; Plumas, Joël; Toussaint, Bertrand

2013-01-01

The industrial development of active immunotherapy based on live-attenuated bacterial vectors has matured. We developed a microsyringe for antigen delivery based on the type III secretion system (T3SS) of P. aeruginosa. We applied the “killed but metabolically active” (KBMA) attenuation strategy to make this bacterial vector suitable for human use. We demonstrate that attenuated P. aeruginosa has the potential to deliver antigens to human antigen-presenting cells in vitro via T3SS with considerable attenuated cytotoxicity as compared with the wild-type vector. In a mouse model of cancer, we demonstrate that this KBMA strain, which cannot replicate in its host, efficiently disseminates into lymphoid organs and delivers its heterologous antigen. The attenuated strain effectively induces a cellular immune response to the cancerous cells while lowering the systemic inflammatory response. Hence, a KBMA P. aeruginosa microsyringe is an efficient and safe tool for in vivo antigen delivery. PMID:23531551

Protective Immunity and Safety of a Genetically Modified Influenza Virus Vaccine

PubMed Central

Garcia, Cristiana Couto; Filho, Bruno Galvão; Gonçalves, Ana Paula de Faria; Lima, Braulio Henrique Freire; Lopes, Gabriel Augusto Oliveira; Rachid, Milene Alvarenga; Peixoto, Andiara Cristina Cardoso; de Oliveira, Danilo Bretas; Ataíde, Marco Antônio; Zirke, Carla Aparecida; Cotrim, Tatiane Marques; Costa, Érica Azevedo; Almeida, Gabriel Magno de Freitas; Russo, Remo Castro; Gazzinelli, Ricardo Tostes; Machado, Alexandre de Magalhães Vieira

2014-01-01

Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Δ) and evaluated the innate and inflammatory responses and the safety of this recombinant virus in wild type or knock-out (KO) mice with impaired innate (Myd88 -/-) or acquired (RAG -/-) immune responses. Infection using truncated neuraminidase influenza virus was harmless regarding lung and systemic inflammatory response in wild type mice and was highly attenuated in KO mice. We also demonstrated that vNA-Δ infection does not induce unbalanced cytokine production that strongly contributes to lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus-specific humoral and CD8+ T cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taken together, our findings suggest and reinforce the safety of using NA deleted influenza viruses as antigen delivery vectors against human or veterinary pathogens. PMID:24927156

Constructing storyboards based on hierarchical clustering analysis

NASA Astrophysics Data System (ADS)

Hasebe, Satoshi; Sami, Mustafa M.; Muramatsu, Shogo; Kikuchi, Hisakazu

2005-07-01

There are growing needs for quick preview of video contents for the purpose of improving accessibility of video archives as well as reducing network traffics. In this paper, a storyboard that contains a user-specified number of keyframes is produced from a given video sequence. It is based on hierarchical cluster analysis of feature vectors that are derived from wavelet coefficients of video frames. Consistent use of extracted feature vectors is the key to avoid a repetition of computationally-intensive parsing of the same video sequence. Experimental results suggest that a significant reduction in computational time is gained by this strategy.

Storage and computationally efficient permutations of factorized covariance and square-root information arrays

NASA Technical Reports Server (NTRS)

Muellerschoen, R. J.

1988-01-01

A unified method to permute vector stored Upper triangular Diagonal factorized covariance and vector stored upper triangular Square Root Information arrays is presented. The method involves cyclic permutation of the rows and columns of the arrays and retriangularization with fast (slow) Givens rotations (reflections). Minimal computation is performed, and a one dimensional scratch array is required. To make the method efficient for large arrays on a virtual memory machine, computations are arranged so as to avoid expensive paging faults. This method is potentially important for processing large volumes of radio metric data in the Deep Space Network.

The Magsat precision vector magnetometer

NASA Technical Reports Server (NTRS)

Acuna, M. H.

1980-01-01

This paper examines the Magsat precision vector magnetometer which is designed to measure projections of the ambient field in three orthogonal directions. The system contains a highly stable and linear triaxial fluxgate magnetometer with a dynamic range of + or - 2000 nT (1 nT = 10 to the -9 weber per sq m). The magnetometer electronics, analog-to-digital converter, and digitally controlled current sources are implemented with redundant designs to avoid a loss of data in case of failures. Measurements are carried out with an accuracy of + or - 1 part in 64,000 in magnitude and 5 arcsec in orientation (1 arcsec = 0.00028 deg).

Ada Namelist Package

NASA Technical Reports Server (NTRS)

Klumpp, Allan R.

1991-01-01

Ada Namelist Package, developed for Ada programming language, enables calling program to read and write FORTRAN-style namelist files. Features are: handling of any combination of types defined by user; ability to read vectors, matrices, and slices of vectors and matrices; handling of mismatches between variables in namelist file and those in programmed list of namelist variables; and ability to avoid searching entire input file for each variable. Principle benefits derived by user: ability to read and write namelist-readable files, ability to detect most file errors in initialization phase, and organization keeping number of instantiated units to few packages rather than to many subprograms.

The epoch state navigation filter. [for maximum likelihood estimates of position and velocity vectors

NASA Technical Reports Server (NTRS)

Battin, R. H.; Croopnick, S. R.; Edwards, J. A.

1977-01-01

The formulation of a recursive maximum likelihood navigation system employing reference position and velocity vectors as state variables is presented. Convenient forms of the required variational equations of motion are developed together with an explicit form of the associated state transition matrix needed to refer measurement data from the measurement time to the epoch time. Computational advantages accrue from this design in that the usual forward extrapolation of the covariance matrix of estimation errors can be avoided without incurring unacceptable system errors. Simulation data for earth orbiting satellites are provided to substantiate this assertion.

A robust interpolation procedure for producing tidal current ellipse inputs for regional and coastal ocean numerical models

NASA Astrophysics Data System (ADS)

Byun, Do-Seong; Hart, Deirdre E.

2017-04-01

Regional and/or coastal ocean models can use tidal current harmonic forcing, together with tidal harmonic forcing along open boundaries in order to successfully simulate tides and tidal currents. These inputs can be freely generated using online open-access data, but the data produced are not always at the resolution required for regional or coastal models. Subsequent interpolation procedures can produce tidal current forcing data errors for parts of the world's coastal ocean where tidal ellipse inclinations and phases move across the invisible mathematical "boundaries" between 359° and 0° degrees (or 179° and 0°). In nature, such "boundaries" are in fact smooth transitions, but if these mathematical "boundaries" are not treated correctly during interpolation, they can produce inaccurate input data and hamper the accurate simulation of tidal currents in regional and coastal ocean models. These avoidable errors arise due to procedural shortcomings involving vector embodiment problems (i.e., how a vector is represented mathematically, for example as velocities or as coordinates). Automated solutions for producing correct tidal ellipse parameter input data are possible if a series of steps are followed correctly, including the use of Cartesian coordinates during interpolation. This note comprises the first published description of scenarios where tidal ellipse parameter interpolation errors can arise, and of a procedure to successfully avoid these errors when generating tidal inputs for regional and/or coastal ocean numerical models. We explain how a straightforward sequence of data production, format conversion, interpolation, and format reconversion steps may be used to check for the potential occurrence and avoidance of tidal ellipse interpolation and phase errors. This sequence is demonstrated via a case study of the M2 tidal constituent in the seas around Korea but is designed to be universally applicable. We also recommend employing tidal ellipse parameter calculation methods that avoid the use of Foreman's (1978) "northern semi-major axis convention" since, as revealed in our analysis, this commonly used conversion can result in inclination interpolation errors even when Cartesian coordinate-based "vector embodiment" solutions are employed.

Immunomodulatory therapies for acute pancreatitis

PubMed Central

Li, Jing; Yang, Wen-Juan; Huang, Lu-Ming; Tang, Cheng-Wei

2014-01-01

It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3rd d to the 14th d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis. PMID:25493006

Avoiding and tolerating latency in large-scale next-generation shared-memory multiprocessors

NASA Technical Reports Server (NTRS)

Probst, David K.

1993-01-01

A scalable solution to the memory-latency problem is necessary to prevent the large latencies of synchronization and memory operations inherent in large-scale shared-memory multiprocessors from reducing high performance. We distinguish latency avoidance and latency tolerance. Latency is avoided when data is brought to nearby locales for future reference. Latency is tolerated when references are overlapped with other computation. Latency-avoiding locales include: processor registers, data caches used temporally, and nearby memory modules. Tolerating communication latency requires parallelism, allowing the overlap of communication and computation. Latency-tolerating techniques include: vector pipelining, data caches used spatially, prefetching in various forms, and multithreading in various forms. Relaxing the consistency model permits increased use of avoidance and tolerance techniques. Each model is a mapping from the program text to sets of partial orders on program operations; it is a convention about which temporal precedences among program operations are necessary. Information about temporal locality and parallelism constrains the use of avoidance and tolerance techniques. Suitable architectural primitives and compiler technology are required to exploit the increased freedom to reorder and overlap operations in relaxed models.

Immunogenicity of ORFV-based vectors expressing the rabies virus glycoprotein in livestock species.

PubMed

Martins, Mathias; Joshi, Lok R; Rodrigues, Fernando S; Anziliero, Deniz; Frandoloso, Rafael; Kutish, Gerald F; Rock, Daniel L; Weiblen, Rudi; Flores, Eduardo F; Diel, Diego G

2017-11-01

The parapoxvirus Orf virus (ORFV) encodes several immunomodulatory proteins (IMPs) that modulate host-innate and pro-inflammatory responses and has been proposed as a vaccine delivery vector for use in animal species. Here we describe the construction and characterization of two recombinant ORFV vectors expressing the rabies virus (RABV) glycoprotein (G). The RABV-G gene was inserted in the ORFV024 or ORFV121 gene loci, which encode for IMPs that are unique to parapoxviruses and inhibit activation of the NF-κB signaling pathway. The immunogenicity of the resultant recombinant viruses (ORFV ∆024 RABV-G or ORFV ∆121 RABV-G, respectively) was evaluated in pigs and cattle. Immunization of the target species with ORFV ∆024 RABV-G and ORFV ∆121 RABV-G elicited robust neutralizing antibody responses against RABV. Notably, neutralizing antibody titers induced in ORFV ∆121 RABV-G-immunized pigs and cattle were significantly higher than those detected in ORFV ∆024 RABV-G-immunized animals, indicating a higher immunogenicity of ORFV Δ121 -based vectors in these animal species. Copyright © 2017 Elsevier Inc. All rights reserved.

State-vector formalism and the Legendre polynomial solution for modelling guided waves in anisotropic plates

NASA Astrophysics Data System (ADS)

Zheng, Mingfang; He, Cunfu; Lu, Yan; Wu, Bin

2018-01-01

We presented a numerical method to solve phase dispersion curve in general anisotropic plates. This approach involves an exact solution to the problem in the form of the Legendre polynomial of multiple integrals, which we substituted into the state-vector formalism. In order to improve the efficiency of the proposed method, we made a special effort to demonstrate the analytical methodology. Furthermore, we analyzed the algebraic symmetries of the matrices in the state-vector formalism for anisotropic plates. The basic feature of the proposed method was the expansion of field quantities by Legendre polynomials. The Legendre polynomial method avoid to solve the transcendental dispersion equation, which can only be solved numerically. This state-vector formalism combined with Legendre polynomial expansion distinguished the adjacent dispersion mode clearly, even when the modes were very close. We then illustrated the theoretical solutions of the dispersion curves by this method for isotropic and anisotropic plates. Finally, we compared the proposed method with the global matrix method (GMM), which shows excellent agreement.

Molecular design for recombinant adeno-associated virus (rAAV) vector production.

PubMed

Aponte-Ubillus, Juan Jose; Barajas, Daniel; Peltier, Joseph; Bardliving, Cameron; Shamlou, Parviz; Gold, Daniel

2018-02-01

Recombinant adeno-associated virus (rAAV) vectors are increasingly popular tools for gene therapy applications. Their non-pathogenic status, low inflammatory potential, availability of viral serotypes with different tissue tropisms, and prospective long-lasting gene expression are important attributes that make rAAVs safe and efficient therapeutic options. Over the last three decades, several groups have engineered recombinant AAV-producing platforms, yielding high titers of transducing vector particles. Current specific productivity yields from different platforms range from 10 3 to 10 5 vector genomes (vg) per cell, and there is an ongoing effort to improve vector yields in order to satisfy high product demands required for clinical trials and future commercialization.Crucial aspects of vector production include the molecular design of the rAAV-producing host cell line along with the design of AAV genes, promoters, and regulatory elements. Appropriately, configuring and balancing the expression of these elements not only contributes toward high productivity, it also improves process robustness and product quality. In this mini-review, the rational design of rAAV-producing expression systems is discussed, with special attention to molecular strategies that contribute to high-yielding, biomanufacturing-amenable rAAV production processes. Details on molecular optimization from four rAAV expression systems are covered: adenovirus, herpesvirus, and baculovirus complementation systems, as well as a recently explored yeast expression system.

Effects of angiopoietin-1 on inflammatory injury in endothelial progenitor cells and blood vessels.

PubMed

Wang, Yi-Qing; Song, Jing-Jin; Han, Xiao; Liu, Yi-Ye; Wang, Xi-Huang; Li, Zhi-Ming; Tzeng, Chi-Meng

2014-01-01

Endothelial progenitor cells (EPCs) and angiopoietin-1 (Ang-1) play important roles in vasculogenesis and angiogenesis, respectively. Thus, targeting both aspects of cardiovascular tissue regeneration may offer promising therapeutic options for cardiovascular disorders. To this end, we constructed a lentiviral vector (pNL) with the Ang-1 gene and transfected EPCs with it (Ang-1-EPCs) to investigate vasculogenesis in both cellular and animal models. Compared to controls, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) increased significantly in both untreated EPCs and in the pNL vector group. After Ang-1 transcription, ICAM-1 and VCAM-1 decreased considerably in those treatment groups. Ang-1-modified EPCs alleviated inflammatory responses induced by tumor-necrosis factor-α (TNF-α) in vitro. Moreover, Ang-1-EPC implantation inhibited neointimal hyperplasia after balloon catheter injury in rats, dramatically diminishing the intimal-media (I/M) ratio and decreasing the neointimal area. Proliferating cell nuclear antigen expression in the Ang-1-EPC group was lower than the EPC non-treatment group as well, suggesting that Ang-1-EPC improved cell survival during inflammation and promoted endothelialization in damaged blood vessels.

Creating an arsenal of Adeno-associated virus (AAV) gene delivery stealth vehicles.

PubMed

Smith, J Kennon; Agbandje-McKenna, Mavis

2018-05-01

The Adeno-associated virus (AAV) gene delivery system is ushering in a new and exciting era in the United States; following the first approved gene therapy (Glybera) in Europe, the FDA has approved a second therapy, Luxturna [1]. However, challenges to this system remain. In viral gene therapy, the surface of the capsid is an important determinant of tissue tropism, impacts gene transfer efficiency, and is targeted by the human immune system. Preexisting immunity is a significant challenge to this approach, and the ability to visualize areas of antibody binding ("footprints") can inform efforts to improve the efficacy of viral vectors. Atomic resolution, smaller proteins, and asymmetric structures are the goals to attain in cryo-electron microscopy and image reconstruction (cryo-EM) as of late. The versatility of the technique and the ability to vitrify a wide range of heterogeneous molecules in solution allow structural biologists to characterize a variety of protein-DNA and protein-protein interactions at lower resolution. Cryo-EM has served as an important means to study key surface areas of the AAV gene delivery vehicle-specifically, those involved with binding neutralizing antibodies (NAbs) [2-4]. This method offers a unique opportunity for visualizing antibody binding "hotspots" on the surface of these and other viral vectors. When combined with mutagenesis, one can eliminate these hotspots to create viral vectors with the ability to avoid preexisting host immune recognition during gene delivery and genetic defect correction in disease treatment. Here, we discuss the use of structure-guided site-directed mutagenesis and directed evolution to create "stealth" AAV vectors with modified surface amino acid sequences that allow NAb avoidance while maintaining natural capsid functions or gaining desired novel tropisms.

Creating an arsenal of Adeno-associated virus (AAV) gene delivery stealth vehicles

PubMed Central

Agbandje-McKenna, Mavis

2018-01-01

The Adeno-associated virus (AAV) gene delivery system is ushering in a new and exciting era in the United States; following the first approved gene therapy (Glybera) in Europe, the FDA has approved a second therapy, Luxturna [1]. However, challenges to this system remain. In viral gene therapy, the surface of the capsid is an important determinant of tissue tropism, impacts gene transfer efficiency, and is targeted by the human immune system. Preexisting immunity is a significant challenge to this approach, and the ability to visualize areas of antibody binding (“footprints”) can inform efforts to improve the efficacy of viral vectors. Atomic resolution, smaller proteins, and asymmetric structures are the goals to attain in cryo-electron microscopy and image reconstruction (cryo-EM) as of late. The versatility of the technique and the ability to vitrify a wide range of heterogeneous molecules in solution allow structural biologists to characterize a variety of protein–DNA and protein–protein interactions at lower resolution. Cryo-EM has served as an important means to study key surface areas of the AAV gene delivery vehicle—specifically, those involved with binding neutralizing antibodies (NAbs) [2–4]. This method offers a unique opportunity for visualizing antibody binding “hotspots” on the surface of these and other viral vectors. When combined with mutagenesis, one can eliminate these hotspots to create viral vectors with the ability to avoid preexisting host immune recognition during gene delivery and genetic defect correction in disease treatment. Here, we discuss the use of structure-guided site-directed mutagenesis and directed evolution to create “stealth” AAV vectors with modified surface amino acid sequences that allow NAb avoidance while maintaining natural capsid functions or gaining desired novel tropisms. PMID:29723270

A survey of people with inflammatory bowel disease to investigate their views of food and nutritional issues.

PubMed

Kinsey, L; Burden, S

2016-07-01

Survey aims were to investigate the dietary concerns, beliefs and opinions of people with inflammatory bowel disease (IBD), and differences between those with Crohn's disease (CD) or ulcerative colitis (UC). A cross-sectional postal questionnaire was sent to people with IBD who were booked into an adult IBD or Gastroenterology clinic over a 6-week period. There were 416 eligible people and 168 (40%) responded. Sixty-four (42%) people indicated that food affects their symptoms a lot or severely. Eighty (51%) respondents indicated that diet was important or extremely important in controlling symptoms. Significantly more people with CD reported meat, fatty foods, chocolate and salad as a trigger than people with UC. Significantly more people with UC reported wheat as a trigger. More people with CD avoided meat and chocolate than UC. This survey highlights the importance of nutrition and diet to people with IBD. Frequent food avoidance was reported. This may impact on nutrition-related health problems.

Assaying the Stability and Inactivation of AAV Serotype 1 Vectors

PubMed Central

Howard, Douglas B.; Harvey, Brandon K.

2017-01-01

Adeno-associated virus (AAV) vectors are a commonplace tool for gene delivery ranging from cell culture to human gene therapy. One feature that makes AAV a desirable vector is its stability, in regard to both the duration of transgene expression and retention of infectivity as a viral particle. This study examined the stability of AAV serotype 1 (AAV1) vectors under different conditions. First, transducibility after storage at 4°C decreased 20% over 7 weeks. Over 10 freeze–thaw cycles, the resulting transduction efficiency became variable at 60–120% of a single thaw. Using small stainless steel slugs to mimic a biosafety cabinet or metal lab bench surface, it was found that an AAV1 vector can be reconstituted after 6 days of storage at room temperature. The stability of AAV is a desired feature, but effective decontamination procedures must be available for safety and experimental integrity. Multiple disinfectants commonly used in the laboratory for ability to inactivate an AAV1 vector were tested, and it was found that autoclaving, 0.25% peracetic acid, iodine, or 10% Clorox bleach completely prevented AAV-mediated transgene expression. These data suggest that peracetic acid should be used for inactivating AAV1 vectors on metal-based surfaces or instruments in order to avoid inadvertent transgene expression in human cells or cross-contamination of instruments. PMID:28192678

A comparative study of surface EMG classification by fuzzy relevance vector machine and fuzzy support vector machine.

PubMed

Xie, Hong-Bo; Huang, Hu; Wu, Jianhua; Liu, Lei

2015-02-01

We present a multiclass fuzzy relevance vector machine (FRVM) learning mechanism and evaluate its performance to classify multiple hand motions using surface electromyographic (sEMG) signals. The relevance vector machine (RVM) is a sparse Bayesian kernel method which avoids some limitations of the support vector machine (SVM). However, RVM still suffers the difficulty of possible unclassifiable regions in multiclass problems. We propose two fuzzy membership function-based FRVM algorithms to solve such problems, based on experiments conducted on seven healthy subjects and two amputees with six hand motions. Two feature sets, namely, AR model coefficients and room mean square value (AR-RMS), and wavelet transform (WT) features, are extracted from the recorded sEMG signals. Fuzzy support vector machine (FSVM) analysis was also conducted for wide comparison in terms of accuracy, sparsity, training and testing time, as well as the effect of training sample sizes. FRVM yielded comparable classification accuracy with dramatically fewer support vectors in comparison with FSVM. Furthermore, the processing delay of FRVM was much less than that of FSVM, whilst training time of FSVM much faster than FRVM. The results indicate that FRVM classifier trained using sufficient samples can achieve comparable generalization capability as FSVM with significant sparsity in multi-channel sEMG classification, which is more suitable for sEMG-based real-time control applications.

AAV viral vector delivery to the brain by shape-conforming MR-guided infusions.

PubMed

Bankiewicz, Krystof S; Sudhakar, Vivek; Samaranch, Lluis; San Sebastian, Waldy; Bringas, John; Forsayeth, John

2016-10-28

Gene transfer technology offers great promise as a potential therapeutic approach to the brain but has to be viewed as a very complex technology. Success of ongoing clinical gene therapy trials depends on many factors such as selection of the correct genetic and anatomical target in the brain. In addition, selection of the viral vector capable of transfer of therapeutic gene into target cells, along with long-term expression that avoids immunotoxicity has to be established. As with any drug development strategy, delivery of gene therapy has to be consistent and predictable in each study subject. Failed drug and vector delivery will lead to failed clinical trials. In this article, we describe our experience with AAV viral vector delivery system, that allows us to optimize and monitor in real time viral vector administration into affected regions of the brain. In addition to discussing MRI-guided technology for administration of AAV vectors we have developed and now employ in current clinical trials, we also describe ways in which infusion cannula design and stereotactic trajectory may be used to maximize the anatomical coverage by using fluid backflow. This innovative approach enables more precise coverage by fitting the shape of the infusion to the shape of the anatomical target. Copyright © 2016 Elsevier B.V. All rights reserved.

A Semi-Vectorization Algorithm to Synthesis of Gravitational Anomaly Quantities on the Earth

NASA Astrophysics Data System (ADS)

Abdollahzadeh, M.; Eshagh, M.; Najafi Alamdari, M.

2009-04-01

The Earth's gravitational potential can be expressed by the well-known spherical harmonic expansion. The computational time of summing up this expansion is an important practical issue which can be reduced by an efficient numerical algorithm. This paper proposes such a method for block-wise synthesizing the anomaly quantities on the Earth surface using vectorization. Fully-vectorization means transformation of the summations to the simple matrix and vector products. It is not a practical for the matrices with large dimensions. Here a semi-vectorization algorithm is proposed to avoid working with large vectors and matrices. It speeds up the computations by using one loop for the summation either on degrees or on orders. The former is a good option to synthesize the anomaly quantities on the Earth surface considering a digital elevation model (DEM). This approach is more efficient than the two-step method which computes the quantities on the reference ellipsoid and continues them upward to the Earth surface. The algorithm has been coded in MATLAB which synthesizes a global grid of 5′Ã- 5′ (corresponding 9 million points) of gravity anomaly or geoid height using a geopotential model to degree 360 in 10000 seconds by an ordinary computer with 2G RAM.

Tripartite polyionic complex (PIC) micelles as non-viral vectors for mesenchymal stem cell siRNA transfection.

PubMed

Raisin, Sophie; Morille, Marie; Bony, Claire; Noël, Danièle; Devoisselle, Jean-Marie; Belamie, Emmanuel

2017-08-22

In the context of regenerative medicine, the use of RNA interference mechanisms has already proven its efficiency in targeting specific gene expression with the aim of enhancing, accelerating or, more generally, directing stem cell differentiation. However, achievement of good transfection levels requires the use of a gene vector. For in vivo applications, synthetic vectors are an interesting option to avoid possible issues associated with viral vectors (safety, production costs, etc.). Herein, we report on the design of tripartite polyionic complex micelles as original non-viral polymeric vectors suited for mesenchymal stem cell transfection with siRNA. Three micelle formulations were designed to exhibit pH-triggered disassembly in an acidic pH range comparable to that of endosomes. One formulation was selected as the most promising with the highest siRNA loading capacity while clearly maintaining pH-triggered disassembly properties. A thorough investigation of the internalization pathway of micelles into cells with tagged siRNA was made before showing an efficient inhibition of Runx2 expression in primary bone marrow-derived stem cells. This work evidenced PIC micelles as promising synthetic vectors that allow efficient MSC transfection and control over their behavior, from the perspective of their clinical use.

[Orthogonal Vector Projection Algorithm for Spectral Unmixing].

PubMed

Song, Mei-ping; Xu, Xing-wei; Chang, Chein-I; An, Ju-bai; Yao, Li

2015-12-01

Spectrum unmixing is an important part of hyperspectral technologies, which is essential for material quantity analysis in hyperspectral imagery. Most linear unmixing algorithms require computations of matrix multiplication and matrix inversion or matrix determination. These are difficult for programming, especially hard for realization on hardware. At the same time, the computation costs of the algorithms increase significantly as the number of endmembers grows. Here, based on the traditional algorithm Orthogonal Subspace Projection, a new method called. Orthogonal Vector Projection is prompted using orthogonal principle. It simplifies this process by avoiding matrix multiplication and inversion. It firstly computes the final orthogonal vector via Gram-Schmidt process for each endmember spectrum. And then, these orthogonal vectors are used as projection vector for the pixel signature. The unconstrained abundance can be obtained directly by projecting the signature to the projection vectors, and computing the ratio of projected vector length and orthogonal vector length. Compared to the Orthogonal Subspace Projection and Least Squares Error algorithms, this method does not need matrix inversion, which is much computation costing and hard to implement on hardware. It just completes the orthogonalization process by repeated vector operations, easy for application on both parallel computation and hardware. The reasonability of the algorithm is proved by its relationship with Orthogonal Sub-space Projection and Least Squares Error algorithms. And its computational complexity is also compared with the other two algorithms', which is the lowest one. At last, the experimental results on synthetic image and real image are also provided, giving another evidence for effectiveness of the method.

A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies.

PubMed

White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A

2017-08-01

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy.

A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies

PubMed Central

White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A.

2017-01-01

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy. PMID:28817344

Treatment of collagenase-induced osteoarthritis with a viral vector encoding TSG-6 results in ectopic bone formation.

PubMed

Broeren, Mathijs G A; Di Ceglie, Irene; Bennink, Miranda B; van Lent, Peter L E M; van den Berg, Wim B; Koenders, Marije I; Blaney Davidson, Esmeralda N; van der Kraan, Peter M; van de Loo, Fons A J

2018-01-01

Tumor necrosis factor-inducible gene 6 (TSG-6) has anti-inflammatory and chondroprotective effects in mouse models of inflammatory arthritis. Because cartilage damage and inflammation are also observed in osteoarthritis (OA), we determined the effect of viral overexpression of TSG-6 in experimental osteoarthritis. Bone marrow-derived cells were differentiated to multinucleated osteoclasts in the presence of recombinant TSG-6 or after transduction with a lentiviral TSG-6 expression vector. Multi-nucleated osteoclasts were analyzed after tartrate resistant acid phosphatase staining and resorption activity was determined on dentin slices. Collagenase-induced osteoarthritis (CIOA) was induced in C57BL/6 mice after intra-articular injection of an adenoviral TSG-6 or control luciferase expression vector. Inflammation-related protease activity was measured using bioluminescent Prosense probes. After a second adenovirus injection, cartilage damage was assessed in histological sections stained with Safranin-O. Ectopic bone formation was scored in X-ray images of the affected knees. TSG-6 did not inhibit the formation of multi-nucleated osteoclasts, but caused a significant reduction in the resorption activity on dentin slices. Adenoviral TSG-6 gene therapy in CIOA could not reduce the cartilage damage compared to the luciferase control virus and no significant difference in inflammation-related protease activity was noted between the TSG-6 and control treated group. Instead, X-ray analysis and histological analysis revealed the presence of ectopic bone formation in the TSG-6 treated group. Gene therapy based on the expression of TSG-6 could not provide cartilage protection in experimental osteoarthritis, but instead resulted in increased ectopic bone formation.

Age-related pathology after adenoviral overexpression of the leucine-rich repeat kinase 2 in the mouse striatum.

PubMed

Kritzinger, Astrid; Ferger, Boris; Gillardon, Frank; Stierstorfer, Birgit; Birk, Gerald; Kochanek, Stefan; Ciossek, Thomas

2018-06-01

Mutations in leucine-rich repeat kinase 2 (LRRK2) age-dependently cause Parkinson's disease and are associated with several inflammatory diseases. So far, the potential role of LRRK2 expression in glial cells as mediators of neuroinflammation and the influence of aging have not been investigated in viral vector-based LRRK2 animal models. In this study, we compared the effect of striatal injection of high-capacity adenoviral vectors expressing either a kinase-overactive LRRK2 with the familial G2019S mutation or a kinase-inactive LRRK2 variant in young and old C57BL/6J mice. The intrinsic adenovirus tropism guided preferentially glial transduction, and the vector design led to stable expression for at least 6 months. In histopathological analysis, young mice expressing either LRRK2 variant presented with transient vacuolization of striatal white fiber tracts accompanied by accumulation of microglial cells and astrogliosis, but inflammation resolved without permanent damage. Old mice had a stronger and prolonged inflammatory reaction and experienced permanent damage in form of partial neuron loss after 3 months exclusively in case of LRRK2_G2019S expression. The autophagic receptor p62 accumulated in cells with high levels of either LRRK2 variant, even more so in old mice. We conclude that the aging mouse brain is more susceptible to LRRK2-associated pathology, and in this model, glial LRRK2 expression significantly contributed to neuroinflammation, ultimately causing neurodegeneration. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Reanalyzing the "far medial" (transcondylar-transtubercular) approach based on three anatomical vectors: the ventral posterolateral corridor.

PubMed

Chakravarthi, Srikant; Monroy-Sosa, Alejandro; Gonen, Lior; Fukui, Melanie; Rovin, Richard; Kojis, Nathaniel; Lindsay, Mark; Khalili, Sammy; Celix, Juanita; Corsten, Martin; Kassam, Amin B

2018-06-01

Endoscopic endonasal access to the jugular foramen and occipital condyle - the transcondylar-transtubercular approach - is anatomically complex and requires detailed knowledge of the relative position of critical neurovascular structures, in order to avoid inadvertent injury and resultant complications. However, access to this region can be confusing as the orientation and relationships of osseous, vascular, and neural structures are very much different from traditional dorsal approaches. This review aims at providing an organizational construct for a more understandable framework in accessing the transcondylar-transtubercular window. The region can be conceptualized using a three-vector coordinate system: vector 1 represents a dorsal or ventral corridor, vector 2 represents the outer and inner circumferential anatomical limits; in an "onion-skin" fashion, key osseous, vascular, and neural landmarks are organized based on a 360-degree skull base model, and vector 3 represents the final core or target of the surgical corridor. The creation of an organized "global-positioning system" may better guide the surgeon in accessing the far-medial transcondylar-transtubercular region, and related pathologies, and help understand the surgical limits to the occipital condyle and jugular foramen - the ventral posterolateral corridor - via the endoscopic endonasal approach.

Web Extensible Display Manager

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

Slominski, Ryan; Larrieu, Theodore L.

Jefferson Lab's Web Extensible Display Manager (WEDM) allows staff to access EDM control system screens from a web browser in remote offices and from mobile devices. Native browser technologies are leveraged to avoid installing and managing software on remote clients such as browser plugins, tunnel applications, or an EDM environment. Since standard network ports are used firewall exceptions are minimized. To avoid security concerns from remote users modifying a control system, WEDM exposes read-only access and basic web authentication can be used to further restrict access. Updates of monitored EPICS channels are delivered via a Web Socket using a webmore » gateway. The software translates EDM description files (denoted with the edl suffix) to HTML with Scalable Vector Graphics (SVG) following the EDM's edl file vector drawing rules to create faithful screen renderings. The WEDM server parses edl files and creates the HTML equivalent in real-time allowing existing screens to work without modification. Alternatively, the familiar drag and drop EDM screen creation tool can be used to create optimized screens sized specifically for smart phones and then rendered by WEDM.« less

AZTEC. Parallel Iterative method Software for Solving Linear Systems

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

Hutchinson, S.; Shadid, J.; Tuminaro, R.

1995-07-01

AZTEC is an interactive library that greatly simplifies the parrallelization process when solving the linear systems of equations Ax=b where A is a user supplied n X n sparse matrix, b is a user supplied vector of length n and x is a vector of length n to be computed. AZTEC is intended as a software tool for users who want to avoid cumbersome parallel programming details but who have large sparse linear systems which require an efficiently utilized parallel processing system. A collection of data transformation tools are provided that allow for easy creation of distributed sparse unstructured matricesmore » for parallel solutions.« less

Vector Observation-Aided/Attitude-Rate Estimation Using Global Positioning System Signals

NASA Technical Reports Server (NTRS)

Oshman, Yaakov; Markley, F. Landis

1997-01-01

A sequential filtering algorithm is presented for attitude and attitude-rate estimation from Global Positioning System (GPS) differential carrier phase measurements. A third-order, minimal-parameter method for solving the attitude matrix kinematic equation is used to parameterize the filter's state, which renders the resulting estimator computationally efficient. Borrowing from tracking theory concepts, the angular acceleration is modeled as an exponentially autocorrelated stochastic process, thus avoiding the use of the uncertain spacecraft dynamic model. The new formulation facilitates the use of aiding vector observations in a unified filtering algorithm, which can enhance the method's robustness and accuracy. Numerical examples are used to demonstrate the performance of the method.

An iterative technique to stabilize a linear time invariant multivariable system with output feedback

NASA Technical Reports Server (NTRS)

Sankaran, V.

1974-01-01

An iterative procedure for determining the constant gain matrix that will stabilize a linear constant multivariable system using output feedback is described. The use of this procedure avoids the transformation of variables which is required in other procedures. For the case in which the product of the output and input vector dimensions is greater than the number of states of the plant, general solution is given. In the case in which the states exceed the product of input and output vector dimensions, a least square solution which may not be stable in all cases is presented. The results are illustrated with examples.

Animal models of the cancer anorexia-cachexia syndrome.

PubMed

Bennani-Baiti, Nabila; Walsh, Declan

2011-09-01

Cancer cachexia, a complex wasting syndrome, is common in palliative medicine. Animal models expand our understanding of its mechanisms. A review of cancer cachexia and anorexia animal models will help investigators make an informed choice of the study model. Cancer-anorexia cachexia animal models are numerous. No one is ideal. The choice should depend on the research question. To investigate cancer-anorexia cachexia independent of pro-inflammatory cytokine effects, the MAC16 ADK and XK1 are useful. MAC16 ADK helps study the host's tumor metabolic effects, independent of any anorexia or inflammation. XK1 is both anorectic and cachectic, but data about it is limited. All other models induce a host inflammatory response. The Walker 256 ADK and MCG 101 are best avoided due to excessive tumor growth. Since individual models do not address all aspects of the syndrome, use of a combination seems wise. Suggested combinations: MAC16-ADK (non-inflammatory and non-anorectic) with YAH-130 (inflammatory, anorectic, and cachectic), Lewis lung carcinoma (slow onset anorexia) or prostate adenocarcinoma (inflammatory, anorectic but not cachectic) with YAH-130.

Optimization of a nonviral transfection system to evaluate Cox-2 controlled interleukin-4 expression for osteoarthritis gene therapy in vitro.

PubMed

Lang, Annemarie; Neuhaus, Johannes; Pfeiffenberger, Moritz; Schröder, Erik; Ponomarev, Igor; Weber, Yvonne; Gaber, Timo; Schmidt, Michael F G

2014-01-01

Gene therapy appears to have the potential for achieving a long-term remedy for osteoarthritis (OA). However, there is a risk of adverse reactions, especially when using cytomegalovirus-controlled expression. To provide a safe application, we focused on the expression of therapeutic cytokines [e.g. interleukin (IL)-4] in a disease-responsive manner by use of the previously cloned Cox-2 promoter as 'genetic switch'. In the present study, we report the functionality of a controlled gene therapeutic system in an equine osteoarthritic cell model. Different nonviral transfection reagents were tested for their efficiency on equine chondrocytes stimulated with equine IL-1β or lipopolysaccharide to create an inflammatory environment. To optimize the transfection, we successfully redesigned the vector by excluding the internal ribosomal entry site (IRES). The functionality of our Cox-2 promoter construct with respect to expressing IL-4 was proven at the mRNA and protein levels and the anti-inflammatory potential of IL-4 was confirmed by analyzing the expression of IL-1β, IL-6, IL-8, matrix metalloproteinase (MMP)-1, MMP-3 and tumor necrosis factor (TNF)-α using a quantitative polymerase chain reaction. Nonviral transfection reagents yielded transfection rates from 21% to 44% with control vectors with and without IRES, respectively. Stimulation of equine chondrocytes resulted in a 20-fold increase of mRNA expression of IL-1β. Such exogenous stimulation of chondrocytes transfected with pNCox2-IL4 led to an increase of IL-4 mRNA expression, whereas expression of inflammatory mediators decreased. The timely link between these events confirms the anti-inflammatory potential of synthesized IL-4. We consider that this approach has significant potential for translation into a useful anti-inflammation therapy. Molecular tools such as the described therapeutic plasmid pave the way for a local-controlled, self-limiting gene therapy. Copyright © 2014 John Wiley & Sons, Ltd.

“Stealth” Adenoviruses Blunt Cell-Mediated and Humoral Immune Responses against the Virus and Allow for Significant Gene Expression upon Readministration in the Lung

PubMed Central

Croyle, Maria A.; Chirmule, Narendra; Zhang, Yi; Wilson, James M.

2001-01-01

Most of the early gene therapy trials for cystic fibrosis have been with adenovirus vectors. First-generation viruses with E1a and E1b deleted are limited by transient expression of the transgene and substantial inflammatory responses. Gene transfer is also significantly curtailed following a second dose of virus. In an effort to reduce adenovirus-associated inflammation, capsids of first-generation vectors were modified with various activated monomethoxypolyethylene glycols. Cytotoxic T-lymphocyte production was significantly reduced in C57BL/6 mice after a single intratracheal administration of modified vectors, and length of gene expression was extended from 4 to 42 days. T-cell subsets from mice exposed to the conjugated vectors demonstrated a marked decrease in Th1 responses and slight enhancement of Th2 responses compared to animals dosed with native virus. Neutralizing antibodies (NAB) against adenovirus capsid proteins were reduced in serum and bronchoalveolar lavage fluid of animals after a single dose of modified virus, allowing significant levels of gene expression upon rechallenge with native adenovirus. Modification with polyethylene glycol (PEG) also allowed substantial gene expression from the new vectors in animals previously immunized with unmodified virus. However, gene expression was significantly reduced after two doses of the same PEG-conjugated vector. Alternating the activation group of PEG between doses did produce significant gene expression upon readministration. This technology in combination with second-generation or helper-dependent adenovirus could produce dosing strategies which promote successful readministration of vector in clinical trials and marked expression in patients with significant anti-adenovirus NAB levels and reduce the possibility of immune reactions against viral vectors for gene therapy. PMID:11312351

Aerosolized Surfactants, Anti-Inflammatory Drugs, and Analgesics.

PubMed

Willson, Douglas F

2015-06-01

Drug delivery by aerosol may have several advantages over other modes, particularly if the lung is the target organ. Aerosol delivery may allow achievement of higher concentrations while minimizing systemic effects and offers convenience, rapid onset of action, and avoidance of the needles and sterile technique necessary with intravenous drug administration. Aerosol delivery may change the pharmacokinetics of many drugs, however, and an awareness of the caveats of aerosolized drug delivery is mandatory to ensure both safety and adequate drug delivery. This paper discusses the administration of surfactants, anti-inflammatory agents, and analgesics by the aerosol route. Copyright © 2015 by Daedalus Enterprises.

Novel Strategies to Enhance Vaccine Immunity against Coccidioidomycosis

DTIC Science & Technology

2013-12-19

Mexico and Central and South America [1]. Coccidioides is a dimorphic ascomycetous fungus with distinct saprobic and parasitic phases and is classified in...lethal spore inoculum. However, sterile immunity was not achieved and pulmonary tissue damage associated with a persistent host inflammatory response...observation will translate to humans. A recent vector-based vaccine against tuberculosis intended to protect by eliciting strong CMI failed in humans despite

Quantifying and resolving multiple vector transformants in S. cerevisiae plasmid libraries.

PubMed

Scanlon, Thomas C; Gray, Elizabeth C; Griswold, Karl E

2009-11-20

In addition to providing the molecular machinery for transcription and translation, recombinant microbial expression hosts maintain the critical genotype-phenotype link that is essential for high throughput screening and recovery of proteins encoded by plasmid libraries. It is known that Escherichia coli cells can be simultaneously transformed with multiple unique plasmids and thusly complicate recombinant library screening experiments. As a result of their potential to yield misleading results, bacterial multiple vector transformants have been thoroughly characterized in previous model studies. In contrast to bacterial systems, there is little quantitative information available regarding multiple vector transformants in yeast. Saccharomyces cerevisiae is the most widely used eukaryotic platform for cell surface display, combinatorial protein engineering, and other recombinant library screens. In order to characterize the extent and nature of multiple vector transformants in this important host, plasmid-born gene libraries constructed by yeast homologous recombination were analyzed by DNA sequencing. It was found that up to 90% of clones in yeast homologous recombination libraries may be multiple vector transformants, that on average these clones bear four or more unique mutant genes, and that these multiple vector cells persist as a significant proportion of library populations for greater than 24 hours during liquid outgrowth. Both vector concentration and vector to insert ratio influenced the library proportion of multiple vector transformants, but their population frequency was independent of transformation efficiency. Interestingly, the average number of plasmids born by multiple vector transformants did not vary with their library population proportion. These results highlight the potential for multiple vector transformants to dominate yeast libraries constructed by homologous recombination. The previously unrecognized prevalence and persistence of multiply transformed yeast cells have important implications for yeast library screens. The quantitative information described herein should increase awareness of this issue, and the rapid sequencing approach developed for these studies should be widely useful for identifying multiple vector transformants and avoiding complications associated with cells that have acquired more than one unique plasmid.

76 FR 79196 - Gluten in Drug Products; Request for Information and Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

... ingestion of wheat grain proteins collectively known as glutens (Ref. 3). The consumption of wheat gluten and similar proteins in barley and rye stimulates the production of antibodies and inflammatory cells... gluten-containing products from the diet (Ref. 1). Over time, strict avoidance of gluten from wheat...

A Self-Alignment Algorithm for SINS Based on Gravitational Apparent Motion and Sensor Data Denoising

PubMed Central

Liu, Yiting; Xu, Xiaosu; Liu, Xixiang; Yao, Yiqing; Wu, Liang; Sun, Jin

2015-01-01

Initial alignment is always a key topic and difficult to achieve in an inertial navigation system (INS). In this paper a novel self-initial alignment algorithm is proposed using gravitational apparent motion vectors at three different moments and vector-operation. Simulation and analysis showed that this method easily suffers from the random noise contained in accelerometer measurements which are used to construct apparent motion directly. Aiming to resolve this problem, an online sensor data denoising method based on a Kalman filter is proposed and a novel reconstruction method for apparent motion is designed to avoid the collinearity among vectors participating in the alignment solution. Simulation, turntable tests and vehicle tests indicate that the proposed alignment algorithm can fulfill initial alignment of strapdown INS (SINS) under both static and swinging conditions. The accuracy can either reach or approach the theoretical values determined by sensor precision under static or swinging conditions. PMID:25923932

Methods for control of tick vectors of Lyme Borreliosis

USGS Publications Warehouse

Jaenson, T.G.T.; Fish, D.; Ginsberg, H.S.; Gray, J.S.; Mather, T.N.; Piesman, J.

1991-01-01

During the IVth International Conference on Lyme Borreliosis in Stockholm, 1990, a workshop on control of Lyme disease vectors briefly reviewed: basic ecological principles for tick control; biocontrol of ticks; chemical control, including the use of repellents and use of permethrin-treated rodent nest material; tick control by habitat modification; and reduction of tick host availability. It was concluded that, although much research work remains, Lyme borreliosis is to a large extent a preventable infection. Avoidance of heavily tick-infested areas, personal protection using proper clothing, and prompt removal of attached ticks remain the most effective protective measures. Many other prophylactic measures are available and could be efficiently integrated into schemes to reduce the abundance of vectors. However, since the ecology of the infection varies greatly between different localities it may be necessary to apply different combinations of control methods in different endemic regions.

Synergistic inhibition of PARP-1 and NF-κB signaling downregulates immune response against recombinant AAV2 vectors during hepatic gene therapy.

PubMed

Hareendran, Sangeetha; Ramakrishna, Banumathi; Jayandharan, Giridhara R

2016-01-01

Host immune response remains a key obstacle to widespread application of adeno-associated virus (AAV) based gene therapy. Thus, targeted inhibition of the signaling pathways that trigger such immune responses will be beneficial. Previous studies have reported that DNA damage response proteins such as poly(ADP-ribose) polymerase-1 (PARP-1) negatively affect the integration of AAV in the host genome. However, the role of PARP-1 in regulating AAV transduction and the immune response against these vectors has not been elucidated. In this study, we demonstrate that repression of PARP-1 improves the transduction of single-stranded AAV vectors both in vitro (∼174%) and in vivo (two- to 3.4-fold). Inhibition of PARP-1, also significantly downregulated the expression of several proinflammatory and cytokine markers such as TLRs, ILs, NF-κB subunit proteins associated with the host innate response against self-complementary AAV2 vectors. The suppression of the inflammatory response targeted against these vectors was more effective upon combined inhibition of PARP-1 and NF-κB signaling. This strategy also effectively attenuated the AAV capsid-specific cytotoxic T-cell response, with minimal effect on vector transduction, as demonstrated in normal C57BL/6 and hemophilia B mice. These data suggest that targeting specific host cellular proteins could be useful to attenuate the immune barriers to AAV-mediated gene therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An 'inflammatory' variant of solar purpura: a simulant of leukocytoclastic vasculitis and neutrophilic dermatoses.

PubMed

Wood, Benjamin A; LeBoit, Philip E

2013-08-01

To study the clinical and pathological features of cases of apparent solar purpura, with attention to the recently described phenomenon of inflammatory changes within otherwise typical lesions. We studied 95 cases diagnosed as solar purpura and identified 10 cases (10.5%) in which significant neutrophilic inflammation was present, potentially simulating a leukocytoclastic vasculitis or neutrophilic dermatosis. An additional three cases were identified in subsequent routine practice. The clinical features, including follow-up for subsequent development of vasculitis and histological features were studied. In all cases the histological features were typical of solar purpura, with the exception of inflammatory changes, typically associated with clefting of elastotic stroma. Clinical follow-up information was available for all patients and none developed subsequent evidence of a cutaneous or systemic vasculitis or neutrophilic dermatosis. Inflammatory changes appear to be more frequent in solar purpura than is generally recognised. Awareness of this histological variation and correlation with the clinical findings and evolution is important in avoiding misdiagnosis.

Error analysis in a stereo vision-based pedestrian detection sensor for collision avoidance applications.

PubMed

Llorca, David F; Sotelo, Miguel A; Parra, Ignacio; Ocaña, Manuel; Bergasa, Luis M

2010-01-01

This paper presents an analytical study of the depth estimation error of a stereo vision-based pedestrian detection sensor for automotive applications such as pedestrian collision avoidance and/or mitigation. The sensor comprises two synchronized and calibrated low-cost cameras. Pedestrians are detected by combining a 3D clustering method with Support Vector Machine-based (SVM) classification. The influence of the sensor parameters in the stereo quantization errors is analyzed in detail providing a point of reference for choosing the sensor setup according to the application requirements. The sensor is then validated in real experiments. Collision avoidance maneuvers by steering are carried out by manual driving. A real time kinematic differential global positioning system (RTK-DGPS) is used to provide ground truth data corresponding to both the pedestrian and the host vehicle locations. The performed field test provided encouraging results and proved the validity of the proposed sensor for being used in the automotive sector towards applications such as autonomous pedestrian collision avoidance.

Error Analysis in a Stereo Vision-Based Pedestrian Detection Sensor for Collision Avoidance Applications

PubMed Central

Llorca, David F.; Sotelo, Miguel A.; Parra, Ignacio; Ocaña, Manuel; Bergasa, Luis M.

2010-01-01

This paper presents an analytical study of the depth estimation error of a stereo vision-based pedestrian detection sensor for automotive applications such as pedestrian collision avoidance and/or mitigation. The sensor comprises two synchronized and calibrated low-cost cameras. Pedestrians are detected by combining a 3D clustering method with Support Vector Machine-based (SVM) classification. The influence of the sensor parameters in the stereo quantization errors is analyzed in detail providing a point of reference for choosing the sensor setup according to the application requirements. The sensor is then validated in real experiments. Collision avoidance maneuvers by steering are carried out by manual driving. A real time kinematic differential global positioning system (RTK-DGPS) is used to provide ground truth data corresponding to both the pedestrian and the host vehicle locations. The performed field test provided encouraging results and proved the validity of the proposed sensor for being used in the automotive sector towards applications such as autonomous pedestrian collision avoidance. PMID:22319323

Discrimination of crop and weeds on visible and visible/near-infrared spectrums using support vector machines, artificial neural network and decision tree

USDA-ARS?s Scientific Manuscript database

Weeds are regarded as farmers' natural enemy. In order to avoid excessive pesticide residues, the destruction of ecological environment, and to guarantee the quality and safety of agricultural products, it is urgent to develop highly-efficient weed management methods. Amongst, weed discrimination is...

Geographic Information Systems: A Primer

DTIC Science & Technology

1990-10-01

AVAILABILITY OF REPORT Approved for public release; distribution 2b DECLASSjFICATION/ DOWNGRADING SCHEDULE unlimited. 4 PERFORMING ORGANIZATION REPORT...utilizing sophisticated integrated databases (usually vector-based), avoid the indirect value coding scheme by recognizing names or direct magnitudes...intricate involvement required by the operator in order to establish a functional coding scheme . A simple raster system, in which cell values indicate

Off-pump CABG surgery reduces systemic inflammation compared with on-pump surgery but does not change systemic endothelial responses: a prospective randomized study.

PubMed

Jongman, Rianne M; Zijlstra, Jan G; Kok, Wendelinde F; van Harten, Annemarie E; Mariani, Massimo A; Moser, Jill; Struys, Michel M R F; Absalom, Anthony R; Molema, Grietje; Scheeren, Thomas W L; van Meurs, Matijs

2014-08-01

Coronary artery bypass graft (CABG) surgery can result in severe postoperative organ failure. During CABG surgery, cardiopulmonary bypass (CPB) with cardiac arrest is often used (on-pump CABG), which often results in a systemic inflammatory response. To reduce this inflammatory response, off-pump CABG was reintroduced, thereby avoiding CPB. There is increasing evidence that the endothelium plays an important role in the pathophysiology of organ failure after CABG surgery. In this study, 60 patients who were scheduled for elective CABG surgery were randomized to have surgery for on-pump or off-pump CABG. Blood was collected at four time points: start, end, 6 h, and 24 h postoperatively. Levels of inflammatory cytokines, soluble adhesion molecules, and angiogenic factors and their receptors were measured in the plasma. No differences were found in preoperative characteristics between the patient groups. The levels of tumor necrosis factor-α, interleukin 10, and myeloperoxidase, but not interleukin 6, were increased to a greater extent in the on-pump CABG compared with off-pump CABG after sternum closure. The soluble endothelial adhesion molecules E-selectin, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 were not elevated in the plasma during and after CABG surgery in both on-pump and off-pump CABG. Angiopoietin 2 was only increased 24 h after surgery in both on-pump and off-pump CABG. Higher levels of sFlt-1 were found after sternum closure in off-pump CABG compared with on-pump CABG. Avoiding CPB and aortic cross clamping in CABG surgery reduces the systemic inflammatory response. On-pump CABG does not lead to an increased release of soluble endothelial adhesion molecules in the circulation compared with off-pump CABG.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Induced Dyspepsia.

PubMed

Yap, Paul Ray-Yee; Goh, Khean-Lee

2015-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed group of drugs in the world. They are used primarily for pain relief in chronic inflammatory joint disease and act by inhibiting enzymes COX1 and COX2 and ultimately preventing the production of active prostanoids which are required for the innate inflammatory pathway. The use of NSAIDs have been associated with the development of gastrointestinal (GI) symptoms ranging from simple dyspepsia to life threatening GI bleeds and perforations. The definition of dyspepsia has evolved over the years and this has hampered accurate studies on the prevalence of dyspepsia as different studies used varying criteria to define dyspepsia. It is now known that NSAIDs significantly increase the risk of dyspepsia.The risk of developing peptic ulcer disease vary with specific NSAIDs and dosages but there is no correlation between the symptoms of dyspepsia and underlying peptic ulcers. The pathogenesis of dyspepsia with NSAIDs is not completely understood. Peptic ulceration alone is not able to account for the majority of dyspepsia symptoms encountered by NSAIDs users. Erosive oesophagitis secondary to NSAIDs may be contributing factor to the prevalence of dyspepsia in NSAIDs users. Altered gut permeability and changes in gastric mechanosensory function due to NSAIDs may also be a contributory factor. Management of NSAID induced dyspepsia is involves a multipronged approach. Drug avoidance if possible would be ideal. Other options include using the lowest effective dose, changing to an NSAIDs with a safer GI risk profile, avoiding concurrent use with other NSAIDs or if the patient has a previous history of peptic ulcer disease, and co-prescribing with anti-secretory medications such as proton pump inhibitors. Eradication of Helicobacter pylori has a protective role against developing peptic ulcers and may also improve symptoms of NSAIDs induced dyspepsia.

Current vector control challenges in the fight against malaria.

PubMed

Benelli, Giovanni; Beier, John C

2017-10-01

The effective and eco-friendly control of Anopheles vectors plays a key role in any malaria management program. Integrated Vector Management (IVM) suggests making use of the full range of vector control tools available. The strategies for IVM require novel technologies to control outdoor transmission of malaria. Despite the wide number of promising control tools tested against mosquitoes, current strategies for malaria vector control used in most African countries are not sufficient to achieve successful malaria control. The majority of National Malaria Control Programs in Africa still rely on indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). These methods reduce malaria incidence but generally have little impact on malaria prevalence. In addition to outdoor transmission, growing levels of insecticide resistance in targeted vectors threaten the efficacy of LLINs and IRS. Larvicidal treatments can be useful, but are not recommended for rural areas. The research needed to improve the quality and delivery of mosquito vector control should focus on (i) optimization of processes and methods for vector control delivery; (ii) monitoring of vector populations and biting activity with reliable techniques; (iii) the development of effective and eco-friendly tools to reduce the burden or locally eliminate malaria and other mosquito-borne diseases; (iv) the careful evaluation of field suitability and efficacy of new mosquito control tools to prove their epidemiological impact; (v) the continuous monitoring of environmental changes which potentially affect malaria vector populations; (vi) the cooperation among different disciplines, with main emphasis on parasitology, tropical medicine, ecology, entomology, and ecotoxicology. A better understanding of behavioral ecology of malaria vectors is required. Key ecological obstacles that limit the effectiveness of vector control include the variation in mosquito behavior, development of insecticide resistance, presence of behavioral avoidance, high vector biodiversity, competitive and food web interactions, lack of insights on mosquito dispersal and mating behavior, and the impact of environmental changes on mosquito ecological traits. Overall, the trans-disciplinary cooperation among parasitologists and entomologists is crucial to ensure proper evaluation of the epidemiological impact triggered by novel mosquito vector control strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

Habitat discrimination by gravid Anopheles gambiae sensu lato – a push-pull system

PubMed Central

2014-01-01

Background The non-random distribution of anopheline larvae in natural habitats suggests that gravid females discriminate between habitats of different quality. Whilst physical and chemical cues used by Culex and Aedes vector mosquitoes for selecting an oviposition site have been extensively studied, those for Anopheles remain poorly explored. Here the habitat selection by Anopheles gambiae sensu lato (s.l.), the principal African malaria vector, was investigated when presented with a choice of two infusions made from rabbit food pellets, or soil. Methods Natural colonization and larval survival was evaluated in artificial ponds filled randomly with either infusion. Dual-choice, egg-count bioassays evaluated the responses of caged gravid females to (1) two- to six-day old infusions versus lake water; (2) autoclaved versus non-autoclaved soil infusions; and assessed (3) the olfactory memory of gravid females conditioned in pellet infusion as larvae. Results Wild Anopheles exclusively colonized ponds with soil infusion and avoided those with pellet infusion. When the individual infusions were tested in comparison with lake water, caged An. gambiae sensu stricto (s.s.) showed a dose response: females increasingly avoided the pellet infusion with increasing infusion age (six-day versus lake water: odds ratio (OR) 0.22; 95% confidence interval (CI) 0.1-0.5) and showed increasing preference to lay eggs as soil infusion age increased (six-day versus lake water: OR 2.1; 95% CI 1.4-3.3). Larvae survived in soil infusions equally well as in lake water but died in pellet infusions. Anopheles gambiae s.s. preferred to lay eggs in the non-autoclaved soil (OR 2.6; 95% CI 1.8-3.7) compared with autoclaved soil. There was no change in the avoidance of pellet infusion by individuals reared in the infusion compared with those reared in lake water. Conclusion Wild and caged An. gambiae s.l. females discriminate between potential aquatic habitats for oviposition. These choices benefit the survival of the offspring. Although the study was not designed to distinguish between stimuli that acted over a distance or on contact, it could be demonstrated that the choice of habitat is mediated by chemical cues based on both preference and avoidance. These cues, if identified, might be developed for ‘push-pull’ strategies to improve malaria vector monitoring and control. PMID:24693951

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses.

PubMed

Crosby, Catherine M; Matchett, William E; Anguiano-Zarate, Stephanie S; Parks, Christopher A; Weaver, Eric A; Pease, Larry R; Webby, Richard J; Barry, Michael A

2017-01-15

Head-to-head comparisons of conventional influenza vaccines with adenovirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we developed "single-cycle" adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than RD-Ad vectors in Syrian hamsters and rhesus macaques. To test them as potential vaccines, we engineered RD and SC versions of adenovirus serotype 6 (Ad6) to express the hemagglutinin (HA) gene from influenza A/PR/8/34 virus. We show here that it takes approximately 33 times less SC-Ad6 than RD-Ad6 to produce equal amounts of HA antigen in vitro SC-Ad produced markedly higher HA binding and hemagglutination inhibition (HAI) titers than RD-Ad in Syrian hamsters. SC-Ad-vaccinated cotton rats had markedly lower influenza titers than RD-Ad-vaccinated animals after challenge with influenza A/PR/8/34 virus. These data suggest that SC-Ads may be more potent vaccine platforms than conventional RD-Ad vectors and may have utility as "needle-free" mucosal vaccines. Most adenovirus vaccines that are being tested are replication-defective adenoviruses (RD-Ads). This work describes testing newer single-cycle adenovirus (SC-Ad) vectors that replicate transgenes to amplify protein production and immune responses. We show that SC-Ads generate markedly more influenza virus hemagglutinin protein and require substantially less vector to generate the same immune responses as RD-Ad vectors. SC-Ads therefore hold promise to be more potent vectors and vaccines than current RD-Ad vectors. Copyright © 2017 Crosby et al.

Unfavourable results with distraction in craniofacial skeleton

PubMed Central

Agarwal, Rajiv

2013-01-01

Distraction osteogenesis has revolutionised the management of craniofacial abnormalities. The technique however requires precise planning, patient selection, execution and follow-up to achieve consistent and positive results and to avoid unfavourable results. The unfavourable results with craniofacial distraction stem from many factors ranging from improper patient selection, planning and use of inappropriate distraction device and vector. The present study analyses the current standards and techniques of distraction and details in depth the various errors and complications that may occur due to this technique. The commonly observed complications of distraction have been detailed along with measures and suggestions to avoid them in clinical practice. PMID:24501455

Guillain-Barré syndrome during adalimumab therapy for Crohn´s disease: coincidence or consequence?

PubMed

Cançado, Guilherme Grossi Lopes; Vilela, Eduardo Garcia

2017-04-01

We report the case of a 64-year-old patient diagnosed with extensive ileal Crohn´s disease who developed Guillain-Barré syndrome after starting biological therapy with adalimumab. Neurologic involvement associated with inflammatory bowel diseases is recognized as an extra-intestinal manifestation. After the breakthrough of antitumor necrosis factor alpha (anti-TNF-α) agents, an increasing number of cases of acute inflammatory demyelinating polyneuropathies have been reported; however, only one case has been described in a patient with Crohn´s disease. Although a causal relationship between Guillain-Barré syndrome and TNF-α antagonist therapy cannot be proven, this report emphasizes the need to monitor for neurologic signs and symptoms in patients with inflammatory bowel diseases, with or without biological therapy, to avoid severe and irreversible complications associated with demyelinating diseases.

Novel redox nanomedicine improves gene expression of polyion complex vector

NASA Astrophysics Data System (ADS)

Toh, Kazuko; Yoshitomi, Toru; Ikeda, Yutaka; Nagasaki, Yukio

2011-12-01

Gene therapy has generated worldwide attention as a new medical technology. While non-viral gene vectors are promising candidates as gene carriers, they have several issues such as toxicity and low transfection efficiency. We have hypothesized that the generation of reactive oxygen species (ROS) affects gene expression in polyplex supported gene delivery systems. The effect of ROS on the gene expression of polyplex was evaluated using a nitroxide radical-containing nanoparticle (RNP) as an ROS scavenger. When polyethyleneimine (PEI)/pGL3 or PEI alone was added to the HeLa cells, ROS levels increased significantly. In contrast, when (PEI)/pGL3 or PEI was added with RNP, the ROS levels were suppressed. The luciferase expression was increased by the treatment with RNP in a dose-dependent manner and the cellular uptake of pDNA was also increased. Inflammatory cytokines play an important role in ROS generation in vivo. In particular, tumor necrosis factor (TNF)-α caused intracellular ROS generation in HeLa cells and decreased gene expression. RNP treatment suppressed ROS production even in the presence of TNF-α and increased gene expression. This anti-inflammatory property of RNP suggests that it may be used as an effective adjuvant for non-viral gene delivery systems.

Smart-Divert Powered Descent Guidance to Avoid the Backshell Landing Dispersion Ellipse

NASA Technical Reports Server (NTRS)

Carson, John M.; Acikmese, Behcet

2013-01-01

A smart-divert capability has been added into the Powered Descent Guidance (PDG) software originally developed for Mars pinpoint and precision landing. The smart-divert algorithm accounts for the landing dispersions of the entry backshell, which separates from the lander vehicle at the end of the parachute descent phase and prior to powered descent. The smart-divert PDG algorithm utilizes the onboard fuel and vehicle thrust vectoring to mitigate landing error in an intelligent way: ensuring that the lander touches down with minimum- fuel usage at the minimum distance from the desired landing location that also avoids impact by the descending backshell. The smart-divert PDG software implements a computationally efficient, convex formulation of the powered-descent guidance problem to provide pinpoint or precision-landing guidance solutions that are fuel-optimal and satisfy physical thrust bound and pointing constraints, as well as position and speed constraints. The initial smart-divert implementation enforced a lateral-divert corridor parallel to the ground velocity vector; this was based on guidance requirements for MSL (Mars Science Laboratory) landings. This initial method was overly conservative since the divert corridor was infinite in the down-range direction despite the backshell landing inside a calculable dispersion ellipse. Basing the divert constraint instead on a local tangent to the backshell dispersion ellipse in the direction of the desired landing site provides a far less conservative constraint. The resulting enhanced smart-divert PDG algorithm avoids impact with the descending backshell and has reduced conservatism.

Ixodes scapularis saliva mitigates inflammatory cytokine secretion during Anaplasma phagocytophilum stimulation of immune cells

PubMed Central

2012-01-01

Background Ixodes scapularis saliva enables the transmission of infectious agents to the mammalian host due to its immunomodulatory, anesthetic and anti-coagulant properties. However, how I. scapularis saliva influences host cytokine secretion in the presence of the obligate intracellular rickettsial pathogen Anaplasma phagocytophilum remains elusive. Methods Bone marrow derived macrophages (BMDMs) were stimulated with pathogen associated molecular patterns (PAMPs) and A. phagocytophilum. Cytokine secretion was measured in the presence and absence of I. scapularis saliva. Human peripheral blood mononuclear cells (PBMCs) were also stimulated with Tumor Necrosis Factor (TNF)-α in the presence and absence of I. scapularis saliva and interleukin (IL)-8 was measured. Results I. scapularis saliva inhibits inflammatory cytokine secretion by macrophages during stimulation of Toll-like (TLR) and Nod-like receptor (NLR) signaling pathways. The effect of I. scapularis saliva on immune cells is not restricted to murine macrophages because decreasing levels of interleukin (IL)-8 were observed after TNF-α stimulation of human peripheral blood mononuclear cells. I. scapularis saliva also mitigates pro-inflammatory cytokine response by murine macrophages during challenge with A. phagocytophilum. Conclusions These findings suggest that I. scapularis may inhibit inflammatory cytokine secretion during rickettsial transmission at the vector-host interface. PMID:23050849

Cloning of Pf3, a filamentous bacteriophage of Pseudomonas aeruginosa, into the pBD214 vector of Bacillus subtilis.

PubMed Central

Putterman, D G; Gryczan, T J; Dubnau, D; Day, L A

1983-01-01

The genome of Pf3, a filamentous single-stranded DNA bacteriophage of Pseudomonas aeruginosa (a gram-negative organism) was cloned into pBD214, a plasmid cloning vector of Bacillus subtilis (a gram-positive organism). Cloning in the gram-positive organism was done to avoid anticipated lethal effects. The entire Pf3 genome was inserted in each orientation at a unique Bc/I site within a thymidylate synthetase gene (from B. subtilis phage beta 22) on the plasmid. Additional clones were made by inserting EcoRI fragments of Pf3 DNA into a unique EcoRI site within this gene. Images PMID:6306273

Comparison of Computational-Model and Experimental-Example Trained Neural Networks for Processing Speckled Fringe Patterns

NASA Technical Reports Server (NTRS)

Decker, A. J.; Fite, E. B.; Thorp, S. A.; Mehmed, O.

1998-01-01

The responses of artificial neural networks to experimental and model-generated inputs are compared for detection of damage in twisted fan blades using electronic holography. The training-set inputs, for this work, are experimentally generated characteristic patterns of the vibrating blades. The outputs are damage-flag indicators or second derivatives of the sensitivity-vector-projected displacement vectors from a finite element model. Artificial neural networks have been trained in the past with computational-model-generated training sets. This approach avoids the difficult inverse calculations traditionally used to compare interference fringes with the models. But the high modeling standards are hard to achieve, even with fan-blade finite-element models.

Comparison of Computational, Model and Experimental, Example Trained Neural Networks for Processing Speckled Fringe Patterns

NASA Technical Reports Server (NTRS)

Decker, A. J.; Fite, E. B.; Thorp, S. A.; Mehmed, O.

1998-01-01

The responses of artificial neural networks to experimental and model-generated inputs are compared for detection of damage in twisted fan blades using electronic holography. The training-set inputs, for this work, are experimentally generated characteristic patterns of the vibrating blades. The outputs are damage-flag indicators or second derivatives of the sensitivity-vector-projected displacement vectors from a finite element model. Artificial neural networks have been trained in the past with computational-model- generated training sets. This approach avoids the difficult inverse calculations traditionally used to compare interference fringes with the models. But the high modeling standards are hard to achieve, even with fan-blade finite-element models.

Ranging through Gabor logons-a consistent, hierarchical approach.

PubMed

Chang, C; Chatterjee, S

1993-01-01

In this work, the correspondence problem in stereo vision is handled by matching two sets of dense feature vectors. Inspired by biological evidence, these feature vectors are generated by a correlation between a bank of Gabor sensors and the intensity image. The sensors consist of two-dimensional Gabor filters at various scales (spatial frequencies) and orientations, which bear close resemblance to the receptive field profiles of simple V1 cells in visual cortex. A hierarchical, stochastic relaxation method is then used to obtain the dense stereo disparities. Unlike traditional hierarchical methods for stereo, feature based hierarchical processing yields consistent disparities. To avoid false matchings due to static occlusion, a dual matching, based on the imaging geometry, is used.

A fingerprint key binding algorithm based on vector quantization and error correction

NASA Astrophysics Data System (ADS)

Li, Liang; Wang, Qian; Lv, Ke; He, Ning

2012-04-01

In recent years, researches on seamless combination cryptosystem with biometric technologies, e.g. fingerprint recognition, are conducted by many researchers. In this paper, we propose a binding algorithm of fingerprint template and cryptographic key to protect and access the key by fingerprint verification. In order to avoid the intrinsic fuzziness of variant fingerprints, vector quantization and error correction technique are introduced to transform fingerprint template and then bind with key, after a process of fingerprint registration and extracting global ridge pattern of fingerprint. The key itself is secure because only hash value is stored and it is released only when fingerprint verification succeeds. Experimental results demonstrate the effectiveness of our ideas.

Humanlike agents with posture planning ability

NASA Astrophysics Data System (ADS)

Jung, Moon R.; Badler, Norman I.

1992-11-01

Human body models are geometric structures which may be ultimately controlled by kinematically manipulating their joints, but for animation, it is desirable to control them in terms of task-level goals. We address a fundamental problem in achieving task-level postural goals: controlling massively redundant degrees of freedom. We reduce the degrees of freedom by introducing significant control points and vectors, e.g., pelvis forward vector, palm up vector, and torso up vector, etc. This reduced set of parameters are used to enumerate primitive motions and motion dependencies among them, and thus to select from a small set of alternative postures (e.g., bend versus squat to lower shoulder height). A plan for a given goal is found by incrementally constructing a goal/constraint set based on the given goal, motion dependencies, collision avoidance requirements, and discovered failures. Global postures satisfying a given goal/constraint set are determined with the help of incremental mental simulation which uses a robust inverse kinematics algorithm. The contributions of the present work are: (1) There is no need to specify beforehand the final goal configuration, which is unrealistic for the human body, and (2) the degrees of freedom problem becomes easier by representing body configurations in terms of `lumped' control parameters, that is, control points and vectors.

Human-like agents with posture planning ability

NASA Technical Reports Server (NTRS)

Jung, Moon R.; Badler, Norman

1992-01-01

Human body models are geometric structures which may be ultimately controlled by kinematically manipulating their joints, but for animation, it is desirable to control them in terms of task-level goals. We address a fundamental problem in achieving task-level postural goals: controlling massively redundant degrees of freedom. We reduce the degrees of freedom by introducing significant control points and vectors, e.g., pelvis forward vector, palm up vector, and torso up vector, etc. This reduced set of parameters are used to enumerate primitive motions and motion dependencies among them, and thus to select from a small set of alternative postures (e.g., bend vs. squat to lower shoulder height). A plan for a given goal is found by incrementally constructing a goal/constraint set based on the given goal, motion dependencies, collision avoidance requirements, and discovered failures. Global postures satisfying a given goal/constraint set are determined with the help of incremental mental simulation which uses a robust inverse kinematics algorithm. The contributions of the present work are: (1) There is no need to specify beforehand the final goal configuration, which is unrealistic for the human body, and (2) the degrees of freedom problem becomes easier by representing body configurations in terms of 'lumped' control parameters, that is, control points and vectors.

Neonatal handling (resilience) attenuates water-avoidance stress induced enhancement of chronic mechanical hyperalgesia in the rat

PubMed Central

Alvarez, Pedro; Levine, Jon D.; Green, Paul G.

2015-01-01

Chronic stress is well known to exacerbate pain. We tested the hypothesis that neonatal handling, which induces resilience to the negative impact of stress by increasing the quality and quantity of maternal care, attenuates the mechanical hyperalgesia produced by water-avoidance stress in the adult rat. Neonatal male rats underwent the handling protocol on postnatal days 2–9, weaned at 21 days and tested for muscle mechanical nociceptive threshold at postnatal days 50–75. Decrease in mechanical nociceptive threshold in skeletal muscle in adult rats, produced by exposure to water-avoidance stress, was significantly attenuated by neonatal handling. Neonatal handling also attenuated the mechanical hyperalgesia produced by intramuscular administration of the pronociceptive inflammatory mediator, prostaglandin E2 in rats exposed as adults to water-avoidance stress. Neonatal handling, which induces a smaller corticosterone response in adult rats exposed to a stressor as well as changes in central nervous system neurotransmitter systems, attenuates mechanical hyperalgesia produced by water-avoidance stress and enhanced prostaglandin hyperalgesia in adult animals. PMID:25637700

Local Delivery of Gene Vectors From Bare-Metal Stents by Use of a Biodegradable Synthetic Complex Inhibits In-Stent Restenosis in Rat Carotid Arteries

PubMed Central

Fishbein, Ilia; Alferiev, Ivan; Bakay, Marina; Stachelek, Stanley J.; Sobolewski, Peter; Lai, Meizan; Choi, Hoon; Chen, I.-W.; Levy, Robert J.

2012-01-01

Background Local drug delivery from polymer-coated stents has demonstrated efficacy for preventing in-stent restenosis; however, both the inflammatory effects of polymer coatings and concerns about late outcomes of drug-eluting stent use indicate the need to investigate innovative approaches, such as combining localized gene therapy with stent angioplasty. Thus, we investigated the hypothesis that adenoviral vectors (Ad) could be delivered from the bare-metal surfaces of stents with a synthetic complex for reversible vector binding. Methods and Results We synthesized the 3 components of a gene vector binding complex: (1) A polyallylamine bisphosphonate with latent thiol groups (PABT), (2) a polyethyleneimine (PEI) with pyridyldithio groups for amplification of attachment sites [PEI(PDT)], and (3) a bifunctional (amine- and thiol-reactive) cross-linker with a labile ester bond (HL). HL-modified Ad attached to PABT/PEI(PDT)-treated steel surfaces demonstrated both sustained release in vitro over 30 days and localized green fluorescent protein expression in rat arterial smooth muscle cell cultures, which were not sensitive to either inhibition by neutralizing anti-Ad antibodies or inactivation after storage at 37°C. In rat carotid studies, deployment of steel stents configured with PABT/PEI(PDT)/HL-tethered adenoviral vectors demonstrated both site-specific arterial AdGFP expression and adenovirus-luciferase transgene activity per optical imaging. Rat carotid stent delivery of adenovirus encoding inducible nitric oxide synthase resulted in significant inhibition of restenosis. Conclusions Reversible immobilization of adenovirus vectors on the bare-metal surfaces of endovascular stents via a synthetic complex represents an efficient, tunable method for sustained release of gene vectors to the vasculature. PMID:18413497

Generation and characterization of a novel candidate gene therapy and vaccination vector based on human species D adenovirus type 56.

PubMed

Duffy, Margaret R; Alonso-Padilla, Julio; John, Lijo; Chandra, Naresh; Khan, Selina; Ballmann, Monika Z; Lipiec, Agnieszka; Heemskerk, Evert; Custers, Jerome; Arnberg, Niklas; Havenga, Menzo; Baker, Andrew H; Lemckert, Angelique

2018-01-01

The vectorization of rare human adenovirus (HAdV) types will widen our knowledge of this family and their interaction with cells, tissues and organs. In this study we focus on HAdV-56, a member of human Ad species D, and create ease-of-use cloning systems to generate recombinant HAdV-56 vectors carrying foreign genes. We present in vitro transduction profiles for HAdV-56 in direct comparison to the most commonly used HAdV-5-based vector. In vivo characterizations demonstrate that when it is delivered intravenously (i.v.) HAdV-56 mainly targets the spleen and, to a lesser extent, the lungs, whilst largely bypassing liver transduction in mice. HAdV-56 triggered robust inflammatory and cellular immune responses, with higher induction of IFNγ, TNFα, IL5, IL6, IP10, MCP1 and MIG1 compared to HAdV-5 following i.v. administration. We also investigated its potential as a vaccine vector candidate by performing prime immunizations in mice with HAdV-56 encoding luciferase (HAdV-56-Luc). Direct comparisons were made to HAdV-26, a highly potent human vaccine vector currently in phase II clinical trials. HAdV-56-Luc induced luciferase 'antigen'-specific IFNγ-producing cells and anti-HAdV-56 neutralizing antibodies in Balb/c mice, demonstrating a near identical profile to that of HAdV-26. Taken together, the data presented provides further insight into human Ad receptor/co-receptor usage, and the first report on HAdV-56 vectors and their potential for gene therapy and vaccine applications.

Diet and Anthropometrics of Children With Inflammatory Bowel Disease: A Comparison With the General Population.

PubMed

Diederen, Kay; Krom, Hilde; Koole, Jeffrey C D; Benninga, Marc A; Kindermann, Angelika

2018-04-25

There is a lack of knowledge regarding the diet of children with inflammatory bowel disease (IBD). Therefore, we investigated dietary intake in pediatric IBD compared to the general population and assessed anthropometrics and food avoidance. In this cross-sectional cohort study, patients younger than 18 years with IBD were included (2014-2017). Dietary intake (total energy, macro nutrients, food types) was assessed using a Food Frequency Questionnaire (FFQ) and compared with a matched reference population (n = 306). There were 102 patients included (55% male, median age 15.0 years). Median height Z-score was -0.39 (interquartile range [IQR]: -1.17 to 0.26). Growth failure (height Z-scores<-1.64) was present in 11% of patients. Median BMI Z-score was 0.36 (IQR: -0.70 to 0.96). Acute malnutrition (weight-for-height Z-score<-2) was present in 3% of patients. Energy intake was lower in pediatric IBD compared to the reference population (mean kilojoule/day: 8286 vs 9794, P < 0.001). Protein intake did not differ, while fat intake was higher in pediatric IBD (mean gram/day: 101 vs 91, P < 0.001), with higher intake of vegetable oils/fats. Carbohydrate intake was lower in pediatric IBD (mean gram/day: 267 vs 305, P < 0.001), with lower intake of food types high in sugar. Food avoidance was reported in 53% of patients, with frequent avoidance of spicy (46%), high-fat food (30%), and dairy (30%). The diet of children with IBD differs from the general pediatric population, with lower energy intake and high rates of food avoidance. Evaluation of the dietary intake alongside anthropometrics may be important to prevent nutrition deficiencies and promote health.

Protective effect of vitamin E in an animal model of LPS-induced inflammation.

PubMed

Mayorga, M; Iborra, A; Estany, S; Martínez, P

2004-12-01

Many sterility outcomes may be associated to the presence of an inflammatory response that would lead to an inability of the endometrium to support implantation and maintain viable embryos. We have established an animal model of inflammation in which the systemic administration of lipopolysaccharyde (LPS) results in a low embryo implantation rate. The purpose of this work was to investigate the effect of the inflammatory agent LPS on embryo viability and to verify the ability of vitamin E to modulate the inflammatory effect of LPS on embryo viability. For pre-implantation studies B6CBAF1 mice, which were intraperitoneally inoculated with LPS (4-10 mg/kg), were used. Mice were also treated with vitamin E (4-10 mg/kg) before or after LPS injection. Embryos were obtained from the oviduct after each treatment. The LPS produces a decrease in the number of pre-implantational embryos in a concentration dependent manner. The LPS effect can be partially reversed or prevented by vitamin E. Preliminary results show that inflammatory cytokines are secreted by intraperitoneal macrophages in LPS treated mice. Our results demonstrate the ability of vitamin E to avoid an inflammatory environment and to allow viability of embryos. (c) Blackwell Munksgaard, 2004

Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

PubMed Central

Goodman, S. B.; Gibon, E.; Pajarinen, J.; Lin, T.-H.; Keeney, M.; Ren, P.-G.; Nich, C.; Yao, Z.; Egashira, K.; Yang, F.; Konttinen, Y. T.

2014-01-01

Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 (pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-κB) by delivery of an NF-κB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants. PMID:24478281

Influence of vector dose on factor IX-specific T and B cell responses in muscle-directed gene therapy.

PubMed

Herzog, Roland W; Fields, Paul A; Arruda, Valder R; Brubaker, Jeff O; Armstrong, Elina; McClintock, Darryl; Bellinger, Dwight A; Couto, Linda B; Nichols, Timothy C; High, Katherine A

2002-07-20

Intramuscular injection of an adeno-associated virus (AAV) vector has resulted in vector dose-dependent, stable expression of canine factor IX (cF.IX) in hemophilia B dogs with an F.IX missense mutation (Herzog et al., Nat. Med. 1999;5:56-63). The use of a species-specific transgene allowed us to study risks and characteristics of antibody formation against the therapeutic transgene product. We analyzed seven dogs that had been injected at a single time point at multiple intramuscular sites with varying vector doses (dose per kilogram, dose per animal, dose per site). Comparison of individual animals suggests an increased likelihood of inhibitory anti-cF.IX (inhibitor) development with increased vector doses, with dose per site showing the strongest correlation with the risk of inhibitor formation. In six of seven animals, such immune responses were either absent or transient, and therefore did not prevent sustained systemic expression of cF.IX. Transient inhibitory/neutralizing anti-cF.IX responses occurred at vector doses of 2 x 10(12)/site, whereas a 6-fold higher dose resulted in a longer lasting, higher titer inhibitor. Anti-cF.IX was efficiently blocked in an eighth animal that was injected with a high vector dose per site, but in addition received transient immune suppression. Inhibitor formation was characterized by synthesis of two IgG subclasses and in vitro proliferation of lymphocytes to cF.IX antigen, indicating a helper T cell-dependent mechanism. Anti-cF.IX formation is likely influenced by the extent of local antigen presentation and may be avoided by limited vector doses or by transient immune modulation.

Interleukin 10 mediated by herpes simplex virus vectors suppresses neuropathic pain induced by human immunodeficiency virus gp120 in rats.

PubMed

Zheng, Wenwen; Huang, Wan; Liu, Shue; Levitt, Roy C; Candiotti, Keith A; Lubarsky, David A; Hao, Shuanglin

2014-09-01

Human immunodeficiency virus (HIV)-associated sensory neuropathy is a common neurological complication of HIV infection affecting up to 30% of HIV-positive individuals. However, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments for HIV-related neuropathic pain (NP). In this study, we tested the hypothesis that inhibition of proinflammatory factors with overexpression of interleukin (IL)-10 reduces HIV-related NP in a rat model. NP was induced by the application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve. The hindpaws of rats were inoculated with nonreplicating herpes simplex virus (HSV) vectors expressing anti-inflammatory cytokine IL-10 or control vector. Mechanical threshold was tested using von Frey filaments before and after treatments with the vectors. The mechanical threshold response was assessed over time using the area under curves. The expression of phosphorylated p38 mitogen-activated kinase, tumor necrosis factor-α, stromal cell-derived factor-1α, and C-X-C chemokine receptor type 4 in both the lumbar spinal cord and the L4/5 dorsal root ganglia (DRG), was examined at 14 and 28 days after vector inoculation using Western blots. We found that in the gp120-induced NP model, IL-10 overexpression mediated by the HSV vector resulted in a significant elevation of the mechanical threshold that was apparent on day 3 after vector inoculation compared with the control vector (P < 0.001). The antiallodynic effect of the single HSV vector inoculation expressing IL-10 lasted >28 days. The area under curve in the HSV vector expressing IL-10 was increased compared with that in the control vector (P < 0.0001). HSV vectors expressing IL-10 reversed the upregulation of phosphorylated p38 mitogen-activated kinase, tumor necrosis factor-α, stromal cell-derived factor-1α, and C-X-C chemokine receptor type 4 expression at 14 and/or 28 days in the DRG and/or the spinal dorsal horn. Our studies demonstrate that blocking the signaling of these proinflammatory molecules in the DRG and/or the spinal cord using the HSV vector expressing IL-10 is able to reduce HIV-related NP. These results provide new insights on the potential mechanisms of HIV-associated NP and a proof of concept for treating painful HIV sensory neuropathy with this type of gene therapy.

Quantitative Measurement of Cationic Polymer Vector and Polymer-pDNA Polyplex Intercalation into the Cell Plasma Membrane.

PubMed

Vaidyanathan, Sriram; Anderson, Kevin B; Merzel, Rachel L; Jacobovitz, Binyamin; Kaushik, Milan P; Kelly, Christina N; van Dongen, Mallory A; Dougherty, Casey A; Orr, Bradford G; Banaszak Holl, Mark M

2015-06-23

Cationic gene delivery agents (vectors) are important for delivering nucleotides, but are also responsible for cytotoxicity. Cationic polymers (L-PEI, jetPEI, and G5 PAMAM) at 1× to 100× the concentrations required for translational activity (protein expression) induced the same increase in plasma membrane current of HEK 293A cells (30-50 nA) as measured by whole cell patch-clamp. This indicates saturation of the cell membrane by the cationic polymers. The increased currents induced by the polymers are not reversible for over 15 min. Irreversibility on this time scale is consistent with a polymer-supported pore or carpet model and indicates that the cell is unable to clear the polymer from the membrane. For polyplexes, although the charge concentration was the same (at N/P ratio of 10:1), G5 PAMAM and jetPEI polyplexes induced a much larger current increase (40-50 nA) than L-PEI polyplexes (<20 nA). Both free cationic lipid and lipid polyplexes induced a lower increase in current than cationic polymers (<20 nA). To quantify the membrane bound material, partition constants were measured for both free vectors and polyplexes into the HEK 293A cell membrane using a dye influx assay. The partition constants of free vectors increased with charge density of the vectors. Polyplex partition constants did not show such a trend. The long lasting cell plasma permeability induced by exposure to the polymer vectors or the polyplexes provides a plausible mechanism for the toxicity and inflammatory response induced by exposure to these materials.

Anaesthesia for children with bronchial asthma and respiratory infections.

PubMed

Rajesh, M C

2015-09-01

Asthma represents one of the most common chronic diseases in children with an increasing incidence reported worldwide. The key to successful anaesthetic outcome involves thorough pre-operative assessment and optimisation of the child's pulmonary status. Judicious application of proper anti-inflammatory and bronchodilatory regimes should be instituted as part of pre-operative preparation. Bronchospasm triggering agents should be carefully probed and meticulously avoided. A calm and properly sedated child at the time of induction is ideal, so also is extubation in a deep plane with an unobstructed airway. Wherever possible, regional anaesthesia should be employed. This will avoid airway manipulations, with additional benefit of excellent peri-operative analgesia. Agents with a potential for histamine release and techniques that can increase airway resistance should be diligently avoided. Emphasis must be given to proper post-operative care including respiratory monitoring, analgesia and breathing exercises.

Rescue strategies against non-steroidal anti-inflammatory drug-induced gastroduodenal damage.

PubMed

Lim, Yun Jeong; Lee, Jeong Sang; Ku, Yang Suh; Hahm, Ki-Baik

2009-07-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs worldwide, which attests to their efficacy as analgesic, antipyretic and anti-inflammatory agents as well as anticancer drugs. However, NSAID use also carries a risk of major gastroduodenal events, including symptomatic ulcers and their serious complications that can lead to fatal outcomes. The development of "coxibs" (selective cyclooxygenase-2 [COX-2] inhibitors) offered similar efficacy with reduced toxicity, but this promise of gastroduodenal safety has only partially been fulfilled, and is now dented with associated risks of cardiovascular or intestinal complications. Recent advances in basic science and biotechnology have given insights into molecular mechanisms of NSAID-induced gastroduodenal damage beyond COX-2 inhibition. The emergence of newer kinds of NSAIDs should alleviate gastroduodenal toxicity without compromising innate drug efficacy. In this review, novel strategies for avoiding NSAID-associated gastroduodenal damage will be described.

Lipid nanostructured Hydrogels for Topical Delivery of Anti-inflammatory Drugs: Preparation and Characterization

NASA Astrophysics Data System (ADS)

Acevedo-Robles, Noelia

Diclofenac sodium is a nonsteroidal anti-inflammatory drugs (NSAID) used to treat sign or symptoms of osteoarthritis and rheumatoid arthritis. However, its clinical usage is limited to some extent due to its toxicity and systemic side effects, including gastrointestinal lesions. The development of lipid nanostructured hydrogel for topical application will solve the problems of first pass metabolism minimize systemic side effect of the anti-inflammatory drugs. Two types of nanotechnologies were used: Lipid Nanostructured Lipid carrier (NLC) and Solid Lipid Nanoparticles (SLN). The difference between both nanotechnologies is that NLC carrier contain liquid and solid lipid, however, the SLN contains solid lipid. Both nanostructured lipid carrier is prepared by high pressure micro-fluidizer technology avoiding solvents use. The use of liquid lipid with solid lipid leads us to imperfection in the matrix which can provide more space for the accommodation of the drug, therefore NLC is the more efficient formulation in drug entrapment.

Temporal relationships of emotional avoidance in a patient with anorexia nervosa--a time series analysis.

PubMed

Stroe-Kunold, Esther; Wesche, Daniela; Friederich, Hans-Christoph; Herzog, Wolfgang; Zastrow, Arne; Wild, Beate

2012-01-01

Anorexia nervosa (AN) is a serious eating disorder marked by self-induced underweight. In patients with AN, the avoidance of emotions appears to be a central feature that is reinforced during the acute state of the disorder. This single case study investigated the role of emotional avoidance of a 25-year-old patient with AN during her inpatient treatment. Throughout the course of 96 days, the patient answered questions daily about her emotional avoidance, pro-anorectic beliefs, perfectionism, and further variables on an electronic diary. The patient's daily self-assessment of emotional avoidance was described in terms of mean value, range, and variability for the various treatment phases. Temporal relationships between emotional avoidance and further variables were determined using a time series approach (vector autoregressive (VAR) modelling). Diary data reflect that the patient's ability to tolerate unpleasant emotions appeared to undergo a process of change during inpatient treatment. Results of the time series analysis indicate that the more the patient was able to deal with negative emotions on any one day (t-1), the less she would be socially avoidant, cognitively confined to food and eating, as well as feeling less secure with her AN, and less depressive on the following day (t). The findings show that for this patient emotional avoidance plays a central role in the interacting system of various psychosocial variables. Replication of these results in other patients with AN would support the recommendation to focus more on emotional regulation in the treatment of AN.

Correcting prominent ears with the island technique.

PubMed

DeMoura, L F

1977-01-01

A surgical procedure is described which corrects the ansiform ear by repositioning and reconstructing the anthelix and the anterior crus with the formation of the triangular fossa. This corrects the scaphoconchal angle and improves the cephaloauricular angle, overcoming the problem of prominent ears. Correction in early childhood is recommended in order to avoid personality problems that may result from the deformity, particularly in boys. The technique employed yields important advantages: (1) prolonged use of the helmet-type of surgical dressing is unnecessary; (2) scars are less conspicuous; (3) the outcome is attractive and normal; (4) bleeding and inflammatory complications are avoided; and (5) recurrence of the malformation is unlikely.

A Case of Familial Mediterranean Fever Having Intermittent Leukopenia.

PubMed

Beyitler, Ilke; Kavukcu, Salih

2018-03-01

Familial Mediterranean fever (FMF) is a genetically inherited autoinflammatory disorder characterized by inflammatory attacks and may result in amyloidosis as a severe complication. Elevation of acute phase reactants, including leukocytosis, is seen during attack periods. Here we describe a 13-year-old female patient with a very rare clinical presentation of FMF, who would experience FMF attacks when she did not regularly take her colchicine. During these attacks she had leukopenia and neutropenia instead of leukocytosis. The leukocyte count returned to normal when she continued the medication and avoided attacks. Ethnicity and clinical signs are important in leukopenic patientsand should be investigated for FMF to avoid unnecessary procedures and complications.

Nuclease-free Adeno-Associated Virus-Mediated Il2rg Gene Editing in X-SCID Mice.

PubMed

Hiramoto, Takafumi; Li, Li B; Funk, Sarah E; Hirata, Roli K; Russell, David W

2018-05-02

X-linked severe combined immunodeficiency (X-SCID) has been successfully treated by hematopoietic stem cell (HSC) transduction with retroviral vectors expressing the interleukin-2 receptor subunit gamma gene (IL2RG), but several patients developed malignancies due to vector integration near cellular oncogenes. This adverse side effect could in principle be avoided by accurate IL2RG gene editing with a vector that does not contain a functional promoter or IL2RG gene. Here, we show that adeno-associated virus (AAV) gene editing vectors can insert a partial Il2rg cDNA at the endogenous Il2rg locus in X-SCID murine bone marrow cells and that these ex vivo-edited cells repopulate transplant recipients and produce CD4 + and CD8 + T cells. Circulating, edited lymphocytes increased over time and appeared in secondary transplant recipients, demonstrating successful editing in long-term repopulating cells. Random vector integration events were nearly undetectable, and malignant transformation of the transplanted cells was not observed. Similar editing frequencies were observed in human hematopoietic cells. Our results demonstrate that therapeutically relevant HSC gene editing can be achieved by AAV vectors in the absence of site-specific nucleases and suggest that this may be a safe and effective therapy for hematopoietic diseases where in vivo selection can increase edited cell numbers. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Treatment of toxicodendron dermatitis (poison ivy and poison oak).

PubMed

Guin, J D

2001-04-01

Toxicodendron dermatitis results from a reaction to an oil soluble oleoresin that is present in many parts of the poison ivy and poison oak plants. Prophylactic measures include avoidance, protective clothing, barrier creams and hyposensitization. Treatments include washing the area immediately with a solvent suitable for lipids and the use of anti-inflammatory agents, especially corticosteroids.

The inflammatory response between miniaturised and conventional cardiopulmonary bypass after cardiac surgery in an Asian population.

PubMed

Ng, R R G; Chew, S T H; Liu, W; Ong, P; Caleb, M G; Ti, L K

2015-09-01

We compared the systemic inflammatory response of the MCPB system to the CCPB system with cell salvage and phosphorylcholine-coated tubing amongst Asian patients undergoing coronary artery bypass grafting. Seventy-eight patients were randomly assigned to the MCPB or the CCPB groups equally and followed up in a prospective, single-blinded, randomised, controlled trial. Levels of TNF-α, IL-6, CRP and LDH were measured peri-operatively. The systemic inflammatory response was similar in both groups (TNF-α: p=0.222; IL-6: p=0.991; CRP: p=0.258). Only haemolysis was significantly higher in the CCPB group (LDH: p=0.011). The MCPB system was twice more expensive, but had a near 4-fold cost saving in tranfusions. Overall, the MCPB system cost 20% more than the modified CCPB system. These results corroborate with studies that demonstrated the avoidance of cardiotomy suction rather than the MCPB system, itself, leads to an attenuated inflammatory response. The absence of obvious clinical benefit and the higher costs involved with the MCPB system would preclude its routine use. © The Author(s) 2014.

Continuous-wave THz vector imaging system utilizing two-tone signal generation and self-mixing detection.

PubMed

Song, Hajun; Hwang, Sejin; An, Hongsung; Song, Ho-Jin; Song, Jong-In

2017-08-21

We propose and demonstrate a continuous-wave vector THz imaging system utilizing a photonic generation of two-tone THz signals and self-mixing detection. The proposed system measures amplitude and phase information simultaneously without the local oscillator reference or phase rotation scheme that is required for heterodyne or homodyne detection. In addition, 2π phase ambiguity that occurs when the sample is thicker than the wavelength of THz radiation can be avoided. In this work, THz signal having two frequency components was generated with a uni-traveling-carrier photodiode and electro-optic modulator on the emitter side and detected with a Schottky barrier diode detector used as a self-mixer on the receiver side. The proposed THz vector imaging system exhibited a 50-dB signal to noise ratio and 0.012-rad phase fluctuation with 100-μs integration time at 325-GHz. With the system, we demonstrate two-dimensional THz phase contrast imaging. Considering the recent use of two-dimensional arrays of Schottky barrier diodes as a THz image sensor, the proposed system is greatly advantageous for realizing a real-time THz vector imaging system due to its simple receiver configuration.

Method of Menu Selection by Gaze Movement Using AC EOG Signals

NASA Astrophysics Data System (ADS)

Kanoh, Shin'ichiro; Futami, Ryoko; Yoshinobu, Tatsuo; Hoshimiya, Nozomu

A method to detect the direction and the distance of voluntary eye gaze movement from EOG (electrooculogram) signals was proposed and tested. In this method, AC-amplified vertical and horizontal transient EOG signals were classified into 8-class directions and 2-class distances of voluntary eye gaze movements. A horizontal and a vertical EOGs during eye gaze movement at each sampling time were treated as a two-dimensional vector, and the center of gravity of the sample vectors whose norms were more than 80% of the maximum norm was used as a feature vector to be classified. By the classification using the k-nearest neighbor algorithm, it was shown that the averaged correct detection rates on each subject were 98.9%, 98.7%, 94.4%, respectively. This method can avoid strict EOG-based eye tracking which requires DC amplification of very small signal. It would be useful to develop robust human interfacing systems based on menu selection for severely paralyzed patients.

Beyond generalized Proca theories

NASA Astrophysics Data System (ADS)

Heisenberg, Lavinia; Kase, Ryotaro; Tsujikawa, Shinji

2016-09-01

We consider higher-order derivative interactions beyond second-order generalized Proca theories that propagate only the three desired polarizations of a massive vector field besides the two tensor polarizations from gravity. These new interactions follow the similar construction criteria to those arising in the extension of scalar-tensor Horndeski theories to Gleyzes-Langlois-Piazza-Vernizzi (GLPV) theories. On the isotropic cosmological background, we show the existence of a constraint with a vanishing Hamiltonian that removes the would-be Ostrogradski ghost. We study the behavior of linear perturbations on top of the isotropic cosmological background in the presence of a matter perfect fluid and find the same number of propagating degrees of freedom as in generalized Proca theories (two tensor polarizations, two transverse vector modes, and two scalar modes). Moreover, we obtain the conditions for the avoidance of ghosts and Laplacian instabilities of tensor, vector, and scalar perturbations. We observe key differences in the scalar sound speed, which is mixed with the matter sound speed outside the domain of generalized Proca theories.

Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses

NASA Astrophysics Data System (ADS)

Moon, James J.; Suh, Heikyung; Bershteyn, Anna; Stephan, Matthias T.; Liu, Haipeng; Huang, Bonnie; Sohail, Mashaal; Luo, Samantha; Ho Um, Soong; Khant, Htet; Goodwin, Jessica T.; Ramos, Jenelyn; Chiu, Wah; Irvine, Darrell J.

2011-03-01

Vaccines based on recombinant proteins avoid the toxicity and antivector immunity associated with live vaccine (for example, viral) vectors, but their immunogenicity is poor, particularly for CD8+ T-cell responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8+ T-cell responses comparable to those for live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. Interbilayer-crosslinked vesicles stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying vesicles form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to those for the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for therapeutic protein delivery.

Anti-inflammatory effects of EMD in the presence of biomechanical loading and interleukin-1β in vitro.

PubMed

Nokhbehsaim, Marjan; Deschner, Birgit; Winter, Jochen; Bourauel, Christoph; Jäger, Andreas; Jepsen, Søren; Deschner, James

2012-02-01

Enamel matrix derivative (EMD) used to promote periodontal regeneration has been shown to exert anti-inflammatory effects. This in vitro study was performed to investigate if the anti-inflammatory actions of EMD are modulated by the local cellular environment, such as inflammation or occlusal, i.e., biomechanical, loading. Human periodontal ligament cells were seeded on BioFlex plates and incubated with EMD under normal, inflammatory, and biomechanical loading conditions for 1 and 6 days. In order to mimic inflammatory and biomechanical loading conditions in vitro, cells were stimulated with interleukin (IL)-1β and exposed to dynamic tensile strain, respectively. The gene expression of IL-1β, IL-1 receptor antagonist (IL-1RN), IL-6, IL-8, IL-10, and cyclooxygenase (COX)-2 was analyzed by real-time RT-PCR and the IL-6 protein synthesis by enzyme-linked immunoassay. For statistical analysis, Student's t test, ANOVA, and post-hoc comparison tests were applied (p < 0.05). EMD downregulated significantly the expression of IL-1β and COX-2 at 1 day and of IL-6, IL-8, and COX-2 at 6 days in normal condition. In an inflammatory environment, the anti-inflammatory actions of EMD were significantly enhanced at 6 days. In the presence of low biomechanical loading, EMD caused a downregulation of IL-1β and IL-8, whereas high biomechanical loading significantly abrogated the anti-inflammatory effects of EMD at both days. Neither IL-1RN nor IL-10 was upregulated by EMD. These data suggest that high occlusal forces may abrogate anti-inflammatory effects of EMD and should, therefore, be avoided immediately after the application of EMD to achieve best healing results.

Therapeutic action of ghrelin in a mouse model of colitis.

PubMed

Gonzalez-Rey, Elena; Chorny, Alejo; Delgado, Mario

2006-05-01

Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis. We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Diverse clinical signs of the disease were evaluated, including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of ghrelin, such as inflammatory cytokines and chemokines, Th1-type response, and regulatory factors. Ghrelin ameliorated significantly the clinical and histopathologic severity of the trinitrobenzene sulfonic acid-induced colitis; abrogating body weight loss, diarrhea, and inflammation; and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response through the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of interluekin-10/transforming growth factor-beta1-secreting regulatory T cells in this therapeutic effect was demonstrated. Importantly, the ghrelin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. Our data demonstrate novel anti-inflammatory actions for ghrelin in the gastrointestinal tract, ie, the capacity to deactivate the intestinal inflammatory response and to restore mucosal immune tolerance at multiple levels. Consequently, ghrelin administration represents a novel possible therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis.

Adaptation and optimization of a line-by-line radiative transfer program for the STAR-100 (STARSMART)

NASA Technical Reports Server (NTRS)

Rarig, P. L.

1980-01-01

A program to calculate upwelling infrared radiation was modified to operate efficiently on the STAR-100. The modified software processes specific test cases significantly faster than the initial STAR-100 code. For example, a midlatitude summer atmospheric model is executed in less than 2% of the time originally required on the STAR-100. Furthermore, the optimized program performs extra operations to save the calculated absorption coefficients. Some of the advantages and pitfalls of virtual memory and vector processing are discussed along with strategies used to avoid loss of accuracy and computing power. Results from the vectorized code, in terms of speed, cost, and relative error with respect to serial code solutions are encouraging.

Global constraints on vector-like WIMP effective interactions

DOE PAGES

Blennow, Mattias; Coloma, Pilar; Fernandez-Martinez, Enrique; ...

2016-04-07

In this work we combine information from relic abundance, direct detection, cosmic microwave background, positron fraction, gamma rays, and colliders to explore the existing constraints on couplings between Dark Matter and Standard Model constituents when no underlying model or correlation is assumed. For definiteness, we include independent vector-like effective interactions for each Standard Model fermion. Our results show that low Dark Matter masses below 20 GeV are disfavoured at the 3 σ  level with respect to higher masses, due to the tension between the relic abundance requirement and upper constraints on the Dark Matter couplings. Lastly, large couplings are typically onlymore » allowed in combinations which avoid effective couplings to the nuclei used in direct detection experiments.« less

Regular and Chaotic Spatial Distribution of Bose-Einstein Condensed Atoms in a Ratchet Potential

NASA Astrophysics Data System (ADS)

Li, Fei; Xu, Lan; Li, Wenwu

2018-02-01

We study the regular and chaotic spatial distribution of Bose-Einstein condensed atoms with a space-dependent nonlinear interaction in a ratchet potential. There exists in the system a space-dependent atomic current that can be tuned via Feshbach resonance technique. In the presence of the space-dependent atomic current and a weak ratchet potential, the Smale-horseshoe chaos is studied and the Melnikov chaotic criterion is obtained. Numerical simulations show that the ratio between the intensities of optical potentials forming the ratchet potential, the wave vector of the laser producing the ratchet potential or the wave vector of the modulating laser can be chosen as the controlling parameters to result in or avoid chaotic spatial distributional states.

Generalizing on Multiple Grounds: Performance Learning in Model-Based Troubleshooting

DTIC Science & Technology

1989-02-01

Aritificial Intelligence , 24, 1984. [Ble88] Guy E. Blelloch. Scan Primitives and Parallel Vector Models. PhD thesis, Artificial Intelligence Laboratory...Diagnostic reasoning based on strcture and behavior. Aritificial Intelligence , 24, 1984. [dK86] J. de Kleer. An assumption-based truth maintenance system...diagnosis. Aritificial Intelligence , 24. �. )3 94 BIBLIOGRAPHY [Ham87] Kristian J. Hammond. Learning to anticipate and avoid planning prob- lems

A 41-Year-Old Patient with a Rare Cause of Severe Abdominal Sepsis Misdiagnosed as PID.

PubMed

Mikuscheva, Anastasia; Becker, David; Thompson-Fawcett, Mark

2018-01-01

Infectious pelvic inflammatory disease is a common condition and a frequent cause of abdominal pain in a young female patient. In a patient who has not completed family planning, the diagnosis is often made with a low threshold and treatment started on a low suspicion of diagnosis to avoid a negative impact on fertility. Here, we present a case of a 41-year-old woman who was misdiagnosed with infectious pelvic inflammatory disease and treated ineffectively with antibiotics when the underlying condition of her persistent abdominal pain was a midgut neuroendocrine tumor that had caused bowel perforation and formation of an abscess in the pouch of Douglas.

A 41-Year-Old Patient with a Rare Cause of Severe Abdominal Sepsis Misdiagnosed as PID

PubMed Central

Becker, David; Thompson-Fawcett, Mark

2018-01-01

Infectious pelvic inflammatory disease is a common condition and a frequent cause of abdominal pain in a young female patient. In a patient who has not completed family planning, the diagnosis is often made with a low threshold and treatment started on a low suspicion of diagnosis to avoid a negative impact on fertility. Here, we present a case of a 41-year-old woman who was misdiagnosed with infectious pelvic inflammatory disease and treated ineffectively with antibiotics when the underlying condition of her persistent abdominal pain was a midgut neuroendocrine tumor that had caused bowel perforation and formation of an abscess in the pouch of Douglas. PMID:29850363

Differential Diagnosis of Benign Spindle Cell Lesions.

PubMed

Magro, Gaetano

2018-03-01

Spindle cell lesions of the breast cover a wide spectrum of diseases ranging from reactive tumor-like lesions to high-grade malignant tumors. The recognition of the benign spindle cell tumor-like lesions (nodular fasciitis; reactive spindle cell nodule after biopsy, inflammatory pseudotumor/inflammatory myofibroblastic tumor; fascicular variant of pseudoangiomatous stromal hyperplasia) and tumors (myofibroblastoma, benign fibroblastic spindle cell tumor, leiomyoma, schwannoma, spindle cell lipoma, solitary fibrous tumor, myxoma) is crucial to avoid confusion with morphologically similar but more aggressive bland-appearing spindle cell tumors, such as desmoid-type fibromatosis, low-grade (fibromatosis-like) spindle cell carcinoma, low-grade fibrosarcoma/myofibroblastic sarcoma and dermatofibrosarcoma protuberans. Copyright © 2017 Elsevier Inc. All rights reserved.

Ankle injuries in athletes.

PubMed

Wilkerson, L A

1992-06-01

Ankle injuries are the most frequent cause of physician evaluation in a sports-oriented environment. The lateral ligaments are most commonly injured. With a detailed history, physical and radiographic examination to avoid missing underlying pathology, the primary care physician can diagnose and treat the majority of ankle injuries. Occasionally, stress radiographs, arthograms, or magnetic resonance imaging (MRI) is needed. The vast majority of ankle sprains can be treated with adhesive tape strapping or semirigid orthotics and nonsteroidal anti-inflammatory medication followed by rehabilitation. Key points of rehabilitation are control of pain and swelling acutely with nonsteroidal anti-inflammatories and RICE (rest, ice, compression, and elevation), then restoring normal range of motion, strengthening muscle groups, and retraining proprioception of the ankle joint.

Relative efficacy of repellent-treated wristbands against three major mosquito (Diptera: Culicidae) vectors of disease, under laboratory conditions.

PubMed

Karunamoorthi, Kaliyaperumal; Sabesan, Shanmugavelu

2009-12-01

A laboratory study was carried out to evaluate the relative efficacy of N-N-diethyl-m-toluamide (DEET)- and N,N-diethyl phenylacetamide (DEPA)-treated wristbands against three major vector mosquitoes viz., Anopheles stephensi Liston, Culex quinquefasciatus Say and Aedes aegypti (L.), at two different concentrations viz., 1.5 and 2.0 mg/cm(2). Overall, both DEET and DEPA have shown various degrees of repellency impact against all three vector mosquitoes. DEET offered the highest 317.0 min mean complete protection against An. stephensi and DEPA provided 275.6 min complete protection to Cx. quinquefasciatus at 2.0 mg/cm(2). However, DEPA-treated wristbands did not show any significant differences in terms of reduction of human landing rate and mean complete protection time against An. stephensi and Ae. aegypti between 1.5 and 2.0 mg/cm(2). DEET demonstrated relatively higher repellency impact to vector mosquitoes than DEPA. However, χ(2) analysis revealed that there was no statistically significant difference found in repellent efficiency between DEET and DEPA (P = 0.924). The present study result suggests that repellent-treated wristbands could serve as a means of potential personal protection expedient to avoid insect's annoyance and reduce vector-borne disease transmission. They are extremely valuable whenever and wherever other kinds of personal protection measures are unfeasible.

Developing an expanded vector control toolbox for malaria elimination

PubMed Central

Tatarsky, Allison; Diabate, Abdoulaye; Chaccour, Carlos J; Marshall, John M; Okumu, Fredros O; Brunner, Shannon; Newby, Gretchen; Williams, Yasmin A; Malone, David; Tusting, Lucy S; Gosling, Roland D

2017-01-01

Vector control using long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) accounts for most of the malaria burden reductions achieved recently in low and middle-income countries (LMICs). LLINs and IRS are highly effective, but are insufficient to eliminate malaria transmission in many settings because of operational constraints, growing resistance to available insecticides and mosquitoes that behaviourally avoid contact with these interventions. However, a number of substantive opportunities now exist for rapidly developing and implementing more diverse, effective and sustainable malaria vector control strategies for LMICs. For example, mosquito control in high-income countries is predominantly achieved with a combination of mosquito-proofed housing and environmental management, supplemented with large-scale insecticide applications to larval habitats and outdoor spaces that kill off vector populations en masse, but all these interventions remain underused in LMICs. Programmatic development and evaluation of decentralised, locally managed systems for delivering these proactive mosquito population abatement practices in LMICs could therefore enable broader scale-up. Furthermore, a diverse range of emerging or repurposed technologies are becoming available for targeting mosquitoes when they enter houses, feed outdoors, attack livestock, feed on sugar or aggregate into mating swarms. Global policy must now be realigned to mobilise the political and financial support necessary to exploit these opportunities over the decade ahead, so that national malaria control and elimination programmes can access a much broader, more effective set of vector control interventions. PMID:28589022

Zinc-finger nuclease-mediated gene correction using single AAV vector transduction and enhancement by Food and Drug Administration-approved drugs

PubMed Central

Ellis, BL; Hirsch, ML; Porter, SN; Samulski, RJ; Porteus, MH

2016-01-01

An emerging strategy for the treatment of monogenic diseases uses genetic engineering to precisely correct the mutation(s) at the genome level. Recent advancements in this technology have demonstrated therapeutic levels of gene correction using a zinc-finger nuclease (ZFN)-induced DNA double-strand break in conjunction with an exogenous DNA donor substrate. This strategy requires efficient nucleic acid delivery and among viral vectors, recombinant adeno-associated virus (rAAV) has demonstrated clinical success without pathology. However, a major limitation of rAAV is the small DNA packaging capacity and to date, the use of rAAV for ZFN gene delivery has yet to be reported. Theoretically, an ideal situation is to deliver both ZFNs and the repair substrate in a single vector to avoid inefficient gene targeting and unwanted mutagenesis, both complications of a rAAV co-transduction strategy. Therefore, a rAAV format was generated in which a single polypeptide encodes the ZFN monomers connected by a ribosome skipping 2A peptide and furin cleavage sequence. On the basis of this arrangement, a DNA repair substrate of 750 nucleotides was also included in this vector. Efficient polypeptide processing to discrete ZFNs is demonstrated, as well as the ability of this single vector format to stimulate efficient gene targeting in a human cell line and mouse model derived fibroblasts. Additionally, we increased rAAV-mediated gene correction up to sixfold using a combination of Food and Drug Administration-approved drugs, which act at the level of AAV vector transduction. Collectively, these experiments demonstrate the ability to deliver ZFNs and a repair substrate by a single AAV vector and offer insights for the optimization of rAAV-mediated gene correction using drug therapy. PMID:22257934

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma

PubMed Central

Xie, Yuran; Merkel, Olivia M

2015-01-01

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues has limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases and costimulatory factors that have been reported as targets of siRNA mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages and dendritic cells, which could potentially be applied in asthma therapy. PMID:26148454

Effects of Ghrelin miRNA on Inflammation and Calcium Pathway in Pancreatic Acinar Cells of Acute Pancreatitis.

PubMed

Tang, Xiping; Tang, Guodu; Liang, Zhihai; Qin, Mengbin; Fang, Chunyun; Zhang, Luyi

The study investigated the effects of endogenous targeted inhibition of ghrelin gene on inflammation and calcium pathway in an in vitro pancreatic acinar cell model of acute pancreatitis. Lentiviral expression vector against ghrelin gene was constructed and transfected into AR42J cells. The mRNA and protein expression of each gene were detected by reverse transcription polymerase chain reaction, Western blotting, or enzyme-linked immunosorbent assay. The concentration of intracellular calcium ([Ca]i) was determined by calcium fluorescence mark probe combined with laser scanning confocal microscopy. Compared with the control group, cerulein could upregulate mRNA and protein expression of inflammatory factors, calcium pathway, ghrelin, and [Ca]i. mRNA and protein expression of inflammatory factors increased significantly in cells transfected with ghrelin miRNA compared with the other groups. Intracellular calcium and expression of some calcium pathway proteins decreased significantly in cells transfected with ghrelin miRNA compared with the other groups. Targeted inhibition of ghrelin gene in pancreatic acinar cells of acute pancreatitis can upregulate the expression of the intracellular inflammatory factors and alleviate the intracellular calcium overload.

Effects of indole-3-carbinol on steroid hormone profile and tumor progression in a mice model of canine inflammatory mammarycancer.

PubMed

Martín-Ruiz, Asunción; Peña, Laura; González-Gil, Alfredo; Díez-Córdova, Lucía Teresa; Cáceres, Sara; Illera, Juan Carlos

2018-06-04

Indole-3-carbinol, derived from Cruciferous vegetables is an estrogen receptor antagonist considered a preventive agent that is naturally present in diet. There are no previous studies on its effects in human inflammatory breast cancer or canine inflammatory mammary cancer that is the most aggressive type of breast cancer. The aim of this study was to analyze the effect of indole-3-carbinol on a SCID mice xenograft model of canine inflammatory mammary cancer, using equivalent human oral dose as a preventive therapy in humans for 3 weeks. Indole-3-carbinol treatment decreased tumor proliferation and increased apoptosis, although tumor embolization and liver metastasis were observed in some animals. There was a characteristic subpopulation of lipid-rich cells and increased contents of select steroid hormones in tumor homogenates and serum. Our data reveal for the first time that the ingestion of indole-3-carbinol, as administered, diminishes proliferation and increases apoptosis of tumor cells in an experimental model of inflammatory breast cancer, although this effect could not be enough to avoid the appearance of tumor embolization and metastasis. Future clinical trials will be needed to clarify the usefulness of indole-3-carbinol in this cancer and to understand the molecular mechanisms involved.

An interesting case of inflammatory myofibroblastic tumor presenting as cholangiocarcinoma.

PubMed

Karimi, Mehrdad; Tizmaghz, Adnan; Shabestanipour, Ghazaal

2018-04-06

Inflammatory myofibroblastic tumor (IMT) is a reactive or inflammatory state mostly affecting the pulmonary system and commonly occurs in children and young adults. IMT presentation in the hepatic duct bifurcation is very rare and has sporadically been reported before. A 12-year-old girl presented with jaundice, pruritus which had begun 5 weeks previously. Ultrasound revealed intrahepatic biliary ductal dilation and an isoechoic 25*30 mm lesion at or near the confluence of the right and left hepatic ducts that were suggestive of a hilar cholangiocarcinoma. Limited resection was decided intraoperatively because the intraoperative frozen section assessment of the CBD, right and left hepatic duct wall samples and porta hepatis lymph nodes was normal. Histologically the tumor proved an inflammatory myofibroblastic tumor (IMT). Almost all patients with resectable IMT should be managed with radical surgical resection or single nonsteroidal anti-inflammatory drugs. In addition, conservative treatments with NSAIDs, corticosteroids or chemotherapeutic agents could not be started in many cases due to the lack of definitive diagnosis of the mass preoperatively. Thus, surgical removal is frequently unavoidable. Biliary IBT is extremely rare and should be considered by all hepatobiliary surgeons dealing with the teens with cholangiocarcinoma, to avoid unnecessary major surgical resections. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Steam cautery of the cornea in microbial keratitis].

PubMed

Maier, P; Birnbaum, F; Reinhard, T

2008-01-01

In some cases topical antimicrobial treatment of microbial keratitis or corneal ulcers remains unsuccessful, with increasing infiltration of the corneal stroma. In this situation the steam cautery procedure developed by Karl Wessely in 1911 can lead to rapid healing of the inflammatory process, avoiding further corneal surgery. In this article we describe the steam cautery technique and discuss its indications for microbial keratitis.

Effective reduction of the interleukin-1β transcript in osteoarthritis-prone guinea pig chondrocytes via short hairpin RNA mediated RNA interference influences gene expression of mediators implicated in disease pathogenesis

PubMed Central

Santangeloyz, K.S.; Bertoneyz, A.L.

2011-01-01

summary Objective To ascertain a viral vector-based short hairpin RNA (shRNA) capable of reducing the interleukin-1β (IL-1β) transcript in osteoarthritis (OA)-prone chondrocytes and detect corresponding changes in the expression patterns of several critical disease mediators. Methods Cultured chondrocytes from 2-month-old Hartley guinea pigs were screened for reduction of the IL-1β transcript following plasmid-based delivery of U6-driven shRNA sequences. A successful plasmid/shRNA knockdown combination was identified and used to construct an adeno-associated virus serotype 5 (AAV5) vector for further evaluation. Relative real-time reverse transcription polymerase chain reaction (RTPCR) was used to quantify in vitro transcript changes of IL-1β and an additional nine genes following transduction with this targeting knockdown vector. To validate in vitro findings, this AAV5 vector was injected into one knee, while either an equivalent volume of saline vehicle (three animals) or non-targeting control vector (three animals) were injected into opposite knees. Fold differences and subsequent percent gene expression levels relative to control groups were calculated using the comparative CT (2−ΔΔCT) method. Results Statistically significant decreases in IL-1β expression were achieved by the targeting knockdown vector relative to both the mock-transduced control and non-targeting vector control groups in vitro. Transcript levels of anabolic transforming growth factor-β (TGF-β) were significantly increased by use of this targeting knockdown vector. Transduction with this targeting AAV5 vector also significantly decreased the transcript levels of key inflammatory cytokines [tumor necrosis factor-α (TNF-α), IL-2, IL-8, and IL-12] and catabolic agents [matrix metalloproteinase (MMP)13, MMP2, interferon-γ (IFN-γ), and inducible nitrous oxide synthase (iNOS)] relative to both mock-transduced and non-targeting vector control groups. In vivo application of this targeting knockdown vector resulted in a >50% reduction (P= 0.0045) or >90% (P= 0.0001) of the IL-1β transcript relative to vehicle-only or non-targeting vector control exposed cartilage, respectively. Conclusions Successful reduction of the IL-1β transcript was achieved via RNA interference (RNAi) techniques. Importantly, this alteration significantly influenced the transcript levels of several major players involved in OA pathogenesis in the direction of disease modification. Investigations to characterize additional gene expression changes influenced by targeting knockdown AAV5 vector-based diminution of the IL-1β transcript in vivo are warranted. PMID:21945742

Understanding the type 1 reactional state for early diagnosis and treatment: a way to avoid disability in leprosy.

PubMed

Nery, José Augusto da Costa; Bernardes Filho, Fred; Quintanilha, Juliana; Machado, Alice Miranda; Oliveira, Soraya de Souza Chantre; Sales, Anna Maria

2013-01-01

A type 1 reaction or reversal reaction is expressed clinically by inflammatory exacerbation of the skin lesions and nerve trunks, consequently leading to sensory and motor alterations. It occurs in non-polar forms of leprosy, although it can occur in a small percentage of sub-polar LL treated patients. Disabilities, deformities and morbidity, still present in leprosy, are mainly caused by these acute episodes. The recognition of reactional states is imperative for an early approach and efficient management, to avoid the emergence of disabilities that stigmatize the disease. This review aims to describe the clinical aspects, immunopathogenesis, epidemiology, histopathological features and therapeutics of type 1 reactions.

Influence of conversion on the location of points and lines: The change of location entropy and the probability of a vector point inside the converted grid point

NASA Astrophysics Data System (ADS)

Chen, Nan

2018-03-01

Conversion of points or lines from vector to grid format, or vice versa, is the first operation required for most spatial analysis. Conversion, however, usually causes the location of points or lines to change, which influences the reliability of the results of spatial analysis or even results in analysis errors. The purpose of this paper is to evaluate the change of the location of points and lines during conversion using the concepts of probability and entropy. This paper shows that when a vector point is converted to a grid point, the vector point may be outside or inside the grid point. This paper deduces a formula for computing the probability that the vector point is inside the grid point. It was found that the probability increased with the side length of the grid and with the variances of the coordinates of the vector point. In addition, the location entropy of points and lines are defined in this paper. Formulae for computing the change of the location entropy during conversion are deduced. The probability mentioned above and the change of location entropy may be used to evaluate the location reliability of points and lines in Geographic Information Systems and may be used to choose an appropriate range of the side length of grids before conversion. The results of this study may help scientists and users to avoid mistakes caused by the change of location during conversion as well as in spatial decision and analysis.

Post-inflammatory fatigue in sarcoidosis: personality profiles, psychological symptoms and stress hormones.

PubMed

Korenromp, Ingrid H E; Grutters, Jan C; van den Bosch, Jules M M; Heijnen, Cobi J

2012-02-01

Chronic fatigue following inflammatory diseases has been well documented. However, little is known about possible risk factors of chronic post-inflammatory fatigue. The aim of this study was to investigate whether chronic post-inflammatory fatigue after clinical remission of the disease sarcoidosis is associated with specific dimensions of personality, psychological symptoms and baseline levels of stress hormones. Thirty-seven non-fatigued and 33 fatigued patients in clinical remission of sarcoidosis were evaluated with the Temperament and Character Inventory-short form (TCI); the Symptom CheckList-90 (SCL), and the Checklist Individual Strength (CIS). Baseline levels of ACTH and cortisol were measured in plasma. Principal component analysis with orthogonal rotation (varimax) was conducted on all personality, psychological and stress hormone data in order to obtain a smaller set of components. Logistic regression was performed to associate these components with chronic post-inflammatory fatigue. Principal component analyses identified 5 components, of which two components were significantly associated with chronic post-inflammatory fatigue. The first component comprised the personality trait Harm Avoidance and all SCL-subscales except Sleep. The second component consisted of baseline levels ACTH and cortisol, and showed an inverse association with chronic post-inflammatory fatigue. The 3 other components, consisting of respectively SCL-Sleep, TCI-Novelty Seeking-Reward Dependence-Self Transcendence, and TCI-Persistence, were not significantly associated with chronic fatigue. Chronic post-inflammatory fatigue after clinical remission of sarcoidosis is associated with a triad of risk factors: a specific personality profile with profound neurotic characteristics in combination with high levels of psychological distress, and decreased baseline ACTH/cortisol levels. Copyright © 2011 Elsevier Inc. All rights reserved.

Whole arm manipulation planning based on feedback velocity fields and sampling-based techniques.

PubMed

Talaei, B; Abdollahi, F; Talebi, H A; Omidi Karkani, E

2013-09-01

Changing the configuration of a cooperative whole arm manipulator is not easy while enclosing an object. This difficulty is mainly because of risk of jamming caused by kinematic constraints. To reduce this risk, this paper proposes a feedback manipulation planning algorithm that takes grasp kinematics into account. The idea is based on a vector field that imposes perturbation in object motion inducing directions when the movement is considerably along manipulator redundant directions. Obstacle avoidance problem is then considered by combining the algorithm with sampling-based techniques. As experimental results confirm, the proposed algorithm is effective in avoiding jamming as well as obstacles for a 6-DOF dual arm whole arm manipulator. Copyright © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

SAMPEX science pointing with velocity avoidance. [solar anomalous and magnetospheric particle explorer

NASA Technical Reports Server (NTRS)

Frakes, Joseph P.; Henretty, Debra A.; Flatley, Thomas W.; Markley, F. L.; San, Josephine K.; Lightsey, E. G.

1992-01-01

The Solar, Anomalous, and Magnetospheric Particle Explorer (SAMPEX) science pointing mode is presented with the additional constraint of velocity avoidance. This constraint has been added in light of the orbital debris and micrometeoroid fluxes that have been revealed by the Long Duration Exposure Facility (LDEF) recovered in January 1990. These fluxes are 50-100 times higher than the flux tables that were used in the September 1988 proposal to NASA for the SAMPEX mission. The SAMPEX Heavey Ion Large Telescope (HILT) sensor includes a flow-through isobutane proportional counter that is susceptible to penetration by orbital debris and micrometeoroids. Thus, keeping the HILT sensor pointed away from the velocity vector, the direction of maximum flux, will compensate for the higher than expected fluxes. Using an orbital debris model and a micrometeoroid model developed at the Johnson Space Center (JSC), and a SAMPEX dynamic simulator developed by the Guidance and Control Branch at the Goddard Space Flight Center (GSFC), an 'optimal' minimum ram angle (the angle between the HILT boresight and the velocity vector) of 90 degrees has been determined. It is optimal in the sense of minimizing the science pointing performance degradation while providing approximately an 89 percent chance of survival for the HILT sensor over a three year period.

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

PubMed Central

Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Background The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. New Method The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Results Injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in males and females. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Comparison with Existing Methods Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. Conclusions The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men. PMID:26891874

MIC-SVM: Designing A Highly Efficient Support Vector Machine For Advanced Modern Multi-Core and Many-Core Architectures

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

You, Yang; Song, Shuaiwen; Fu, Haohuan

2014-08-16

Support Vector Machine (SVM) has been widely used in data-mining and Big Data applications as modern commercial databases start to attach an increasing importance to the analytic capabilities. In recent years, SVM was adapted to the field of High Performance Computing for power/performance prediction, auto-tuning, and runtime scheduling. However, even at the risk of losing prediction accuracy due to insufficient runtime information, researchers can only afford to apply offline model training to avoid significant runtime training overhead. To address the challenges above, we designed and implemented MICSVM, a highly efficient parallel SVM for x86 based multi-core and many core architectures,more » such as the Intel Ivy Bridge CPUs and Intel Xeon Phi coprocessor (MIC).« less

Diptera vectors of avian Haemosporidian parasites: untangling parasite life cycles and their taxonomy.

PubMed

Santiago-Alarcon, Diego; Palinauskas, Vaidas; Schaefer, Hinrich Martin

2012-11-01

Haemosporida is a large group of vector-borne intracellular parasites that infect amphibians, reptiles, birds, and mammals. This group includes the different malaria parasites (Plasmodium spp.) that infect humans around the world. Our knowledge on the full life cycle of these parasites is most complete for those parasites that infect humans and, to some extent, birds. However, our current knowledge on haemosporidian life cycles is characterized by a paucity of information concerning the vector species responsible for their transmission among vertebrates. Moreover, our taxonomic and systematic knowledge of haemosporidians is far from complete, in particular because of insufficient sampling in wild vertebrates and in tropical regions. Detailed experimental studies to identify avian haemosporidian vectors are uncommon, with only a few published during the last 25 years. As such, little knowledge has accumulated on haemosporidian life cycles during the last three decades, hindering progress in ecology, evolution, and systematic studies of these avian parasites. Nonetheless, recently developed molecular tools have facilitated advances in haemosporidian research. DNA can now be extracted from vectors' blood meals and the vertebrate host identified; if the blood meal is infected by haemosporidians, the parasite's genetic lineage can also be identified. While this molecular tool should help to identify putative vector species, detailed experimental studies on vector competence are still needed. Furthermore, molecular tools have helped to refine our knowledge on Haemosporida taxonomy and systematics. Herein we review studies conducted on Diptera vectors transmitting avian haemosporidians from the late 1800s to the present. We also review work on Haemosporida taxonomy and systematics since the first application of molecular techniques and provide recommendations and suggest future research directions. Because human encroachment on natural environments brings human populations into contact with novel parasite sources, we stress that the best way to avoid emergent and reemergent diseases is through a program encompassing ecological restoration, environmental education, and enhanced understanding of the value of ecosystem services. © 2012 The Authors. Biological Reviews © 2012 Cambridge Philosophical Society.

ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leucocyte trans-endothelial migration.

PubMed

Hortelano, Sonsoles; López-Fontal, Raquel; Través, Paqui G; Villa, Natividad; Grashoff, Carsten; Boscá, Lisardo; Luque, Alfonso

2010-05-01

The inflammatory response to injurious agents is tightly regulated to avoid adverse consequences of inappropriate leucocyte accumulation or failed resolution. Lipopolysaccharide (LPS)-activated endothelium recruits leucocytes to the inflamed tissue through controlled expression of membrane-associated adhesion molecules. LPS responses in macrophages are known to be regulated by integrin-linked kinase (ILK); in this study, we investigated the role of ILK in the regulation of the LPS-elicited inflammatory response in endothelium. This study was performed on immortalized mouse endothelial cells (EC) isolated from lung and coronary vasculature. Cells were thoroughly characterized and the role of ILK in the regulation of the LPS response was investigated by suppressing ILK expression using siRNA and shRNA technologies. Phenotypic and functional analyses confirmed that the immortalized cells behaved as true EC. LPS induced the expression of the inflammatory genes E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). ILK knockdown impaired LPS-mediated endothelial activation by preventing the induction of ICAM-1 and VCAM-1. Blockade of the LPS-induced response inhibited the inflammatory-related processes of firm adhesion and trans-endothelial migration of leucocytes. ILK is involved in the expression of cell adhesion molecules by EC activated with the inflammatory stimulus LPS. This reduced expression modulates leucocyte adhesion to the endothelium and the extravasation process. This finding suggests ILK as a potential anti-inflammatory target for the development of vascular-specific treatments for inflammation-related diseases.

Effects of miR-33a-5P on ABCA1/G1-Mediated Cholesterol Efflux under Inflammatory Stress in THP-1 Macrophages

PubMed Central

Mao, Min; Lei, Han; Liu, Qing; Chen, Yaxi; Zhao, Lei; Li, Qing; Luo, Suxin; Zuo, Zhong; He, Quan; Huang, Wei; Zhang, Nan; Zhou, Chao; Ruan, Xiong Z.

2014-01-01

The present study is to investigate whether inflammatory cytokines inhibit ABCA1/ABCG1-mediated cholesterol efflux by regulating miR-33a-5P in THP-1 macrophages. We used interleukin-6 and tumor necrosis factor-alpha in the presence or absence of native low density lipoprotein (LDL) to stimulate THP-1 macrophages. THP-1 macrophages were infected by either control lentivirus vectors or lentivirus encoding miR-33a-5P or antisense miR-33a-5P. The effects of inflammatory cytokines, miR-33a-5P and antisense miR-33a-5P on intracellular lipids accumulation and intracellular cholesterol contents were assessed by oil red O staining and quantitative intracellular cholesterol assay. ApoA-I-mediated cholesterol efflux was examined using the fluorescent sterol (BODIPY-cholesterol). The gene and protein expressions of the molecules involved in cholesterol trafficking were examined using quantitative real-time polymerase chain reaction and Western blotting. Inflammatory cytokines or miR-33a-5P increased intracellular lipid accumulation and decreased apoA-I-mediated cholesterol efflux via decreasing the expression of ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. However, antisense miR-33a-5P reversed the effects of inflammatory cytokines on intracellular lipid accumulation, cholesterol efflux, and the expression of miR-33a-5P, ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. This study indicated that inflammatory cytokines inhibited ABCA1/ABCG1-mediated cholesterol efflux by up-regulating miR-33a-5P in THP-1 macrophages. PMID:25329888

Effects of miR-33a-5P on ABCA1/G1-mediated cholesterol efflux under inflammatory stress in THP-1 macrophages.

PubMed

Mao, Min; Lei, Han; Liu, Qing; Chen, Yaxi; Zhao, Lei; Li, Qing; Luo, Suxin; Zuo, Zhong; He, Quan; Huang, Wei; Zhang, Nan; Zhou, Chao; Ruan, Xiong Z

2014-01-01

The present study is to investigate whether inflammatory cytokines inhibit ABCA1/ABCG1-mediated cholesterol efflux by regulating miR-33a-5P in THP-1 macrophages. We used interleukin-6 and tumor necrosis factor-alpha in the presence or absence of native low density lipoprotein (LDL) to stimulate THP-1 macrophages. THP-1 macrophages were infected by either control lentivirus vectors or lentivirus encoding miR-33a-5P or antisense miR-33a-5P. The effects of inflammatory cytokines, miR-33a-5P and antisense miR-33a-5P on intracellular lipids accumulation and intracellular cholesterol contents were assessed by oil red O staining and quantitative intracellular cholesterol assay. ApoA-I-mediated cholesterol efflux was examined using the fluorescent sterol (BODIPY-cholesterol). The gene and protein expressions of the molecules involved in cholesterol trafficking were examined using quantitative real-time polymerase chain reaction and Western blotting. Inflammatory cytokines or miR-33a-5P increased intracellular lipid accumulation and decreased apoA-I-mediated cholesterol efflux via decreasing the expression of ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. However, antisense miR-33a-5P reversed the effects of inflammatory cytokines on intracellular lipid accumulation, cholesterol efflux, and the expression of miR-33a-5P, ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. This study indicated that inflammatory cytokines inhibited ABCA1/ABCG1-mediated cholesterol efflux by up-regulating miR-33a-5P in THP-1 macrophages.

Autoimmune pancreatitis associated with renal lesions mimicking metastatic tumours

PubMed Central

Rudmik, Lucas; Trpkov, Kiril; Nash, Carla; Kinnear, Susan; Falck, Vincent; Dushinski, John; Dixon, Elijah

2006-01-01

Autoimmune pancreatitis is a chronic inflammatory disorder that is often misdiagnosed as pancreatic cancer. Since autoimmune pancreatitis is benign and responds to steroid management, it is important to diagnose it to avoid unnecessary surgical intervention. We describe a novel case of IgG4-associated autoimmune pancreatitis presenting with tubulointerstitial nephritis as renal lesions mimicking metastatic tumours but with no change in renal function. PMID:16908897

An Energy Scaled and Expanded Vector-Based Forwarding Scheme for Industrial Underwater Acoustic Sensor Networks with Sink Mobility.

PubMed

Wadud, Zahid; Hussain, Sajjad; Javaid, Nadeem; Bouk, Safdar Hussain; Alrajeh, Nabil; Alabed, Mohamad Souheil; Guizani, Nadra

2017-09-30

Industrial Underwater Acoustic Sensor Networks (IUASNs) come with intrinsic challenges like long propagation delay, small bandwidth, large energy consumption, three-dimensional deployment, and high deployment and battery replacement cost. Any routing strategy proposed for IUASN must take into account these constraints. The vector based forwarding schemes in literature forward data packets to sink using holding time and location information of the sender, forwarder, and sink nodes. Holding time suppresses data broadcasts; however, it fails to keep energy and delay fairness in the network. To achieve this, we propose an Energy Scaled and Expanded Vector-Based Forwarding (ESEVBF) scheme. ESEVBF uses the residual energy of the node to scale and vector pipeline distance ratio to expand the holding time. Resulting scaled and expanded holding time of all forwarding nodes has a significant difference to avoid multiple forwarding, which reduces energy consumption and energy balancing in the network. If a node has a minimum holding time among its neighbors, it shrinks the holding time and quickly forwards the data packets upstream. The performance of ESEVBF is analyzed through in network scenario with and without node mobility to ensure its effectiveness. Simulation results show that ESEVBF has low energy consumption, reduces forwarded data copies, and less end-to-end delay.

Pre-existing immunity against Ad vectors: humoral, cellular, and innate response, what's important?.

PubMed

Fausther-Bovendo, Hugues; Kobinger, Gary P

2014-01-01

Pre-existing immunity against human adenovirus (HAd) serotype 5 derived vector in the human population is widespread, thus hampering its clinical use. Various components of the immune system, including neutralizing antibodies (nAbs), Ad specific T cells and type I IFN activated NK cells, contribute to dampening the efficacy of Ad vectors in individuals with pre-existing Ad immunity. In order to circumvent pre-existing immunity to adenovirus, numerous strategies, such as developing alternative Ad serotypes, varying immunization routes and utilizing prime-boost regimens, are under pre-clinical or clinical phases of development. However, these strategies mainly focus on one arm of pre-existing immunity. Selection of alternative serotypes has been largely driven by the absence in the human population of nAbs against them with little attention paid to cross-reactive Ad specific T cells. Conversely, varying the route of immunization appears to mainly rely on avoiding Ad specific tissue-resident T cells. Finally, prime-boost regimens do not actually circumvent pre-existing immunity but instead generate immune responses of sufficient magnitude to confer protection despite pre-existing immunity. Combining the above strategies and thus taking into account all components regulating pre-existing Ad immunity will help further improve the development of Ad vectors for animal and human use.

v-src induces clonal sarcomas and rapid metastasis following transduction with a replication-defective retrovirus

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

Stoker, A.W.; Sieweke, M.H.

1989-12-01

v-src is an effective carcinogen when expressed from Rous sarcoma virus (RSV) in vivo. Whereas RSV tumors require sustained oncogene expression, their growth is largely a balance between viral recruitment of tissues and host immune destruction of infected cells. The authors have therefore examined the tumorigenic potential of v-src in the absence of viral recruitment and viral antigen expression. v-src was introduced with high efficiency into chicken wing web tissues using replication-defective (rd) retroviral vectors. Clonal sarcomas were induced rapidly, and furthermore, v-src potentiated metastatic progression in {approx} 0.1%-1% of tumor clones with unexpectedly short latency. rd vectors proved effectivemore » not only in transducing v-src into tissues but also as insertional markers of tumor clonality. The rd vector present in most primary and metastatic tumors was a highly truncated form of RSV derived by viral transmission of spliced v-src mRNA; this vector should thus avoid viral recruitment and host anti-viral immune reaction through its complete lack of viral structural genes. Under such conditions v-src maintains strong carcinogenicity in vivo when restricted to clonal tumor growth and can confer rapid metastatic potential on a discrete subset of tumor clones.« less

High-quality and interactive animations of 3D time-varying vector fields.

PubMed

Helgeland, Anders; Elboth, Thomas

2006-01-01

In this paper, we present an interactive texture-based method for visualizing three-dimensional unsteady vector fields. The visualization method uses a sparse and global representation of the flow, such that it does not suffer from the same perceptual issues as is the case for visualizing dense representations. The animation is made by injecting a collection of particles evenly distributed throughout the physical domain. These particles are then tracked along their path lines. At each time step, these particles are used as seed points to generate field lines using any vector field such as the velocity field or vorticity field. In this way, the animation shows the advection of particles while each frame in the animation shows the instantaneous vector field. In order to maintain a coherent particle density and to avoid clustering as time passes, we have developed a novel particle advection strategy which produces approximately evenly-spaced field lines at each time step. To improve rendering performance, we decouple the rendering stage from the preceding stages of the visualization method. This allows interactive exploration of multiple fields simultaneously, which sets the stage for a more complete analysis of the flow field. The final display is rendered using texture-based direct volume rendering.

Vectors for co-expression of an unrestricted number of proteins

PubMed Central

Scheich, Christoph; Kümmel, Daniel; Soumailakakis, Dimitri; Heinemann, Udo; Büssow, Konrad

2007-01-01

A vector system is presented that allows generation of E. coli co-expression clones by a standardized, robust cloning procedure. The number of co-expressed proteins is not limited. Five ‘pQLink’ vectors for expression of His-tag and GST-tag fusion proteins as well as untagged proteins and for cloning by restriction enzymes or Gateway cloning were generated. The vectors allow proteins to be expressed individually; to achieve co-expression, two pQLink plasmids are combined by ligation-independent cloning. pQLink co-expression plasmids can accept an unrestricted number of genes. As an example, the co-expression of a heterotetrameric human transport protein particle (TRAPP) complex from a single plasmid, its isolation and analysis of its stoichiometry are shown. pQLink clones can be used directly for pull-down experiments if the proteins are expressed with different tags. We demonstrate pull-down experiments of human valosin-containing protein (VCP) with fragments of the autocrine motility factor receptor (AMFR). The cloning method avoids PCR or gel isolation of restriction fragments, and a single resistance marker and origin of replication are used, allowing over-expression of rare tRNAs from a second plasmid. It is expected that applications are not restricted to bacteria, but could include co-expression in other hosts such as Bacluovirus/insect cells. PMID:17311810

Recombinant AAV-directed gene therapy for type I glycogen storage diseases

PubMed Central

Chou, JY; Mansfield, BC

2011-01-01

Introduction Glycogen storage disease (GSD) type Ia and Ib are disorders of impaired glucose homeostasis affecting the liver and kidney. GSD-Ib also affects neutrophils. Current dietary therapies cannot prevent long-term complications. In animal studies, recombinant adeno-associated virus (rAAV) vector-mediated gene therapy can correct or minimize multiple aspects of the disorders, offering hope for human gene therapy. Areas covered A summary of recent progress in rAAV-mediated gene therapy for GSD-I; strategies to improve rAAV-mediated gene delivery, transduction efficiency and immune avoidance; and vector refinements that improve expression. Expert opinion rAAV-mediated gene delivery to the liver can restore glucose homeostasis in preclinical models of GSD-I, but some long-term complications of the liver and kidney remain. Gene therapy for GSD-Ib is less advanced than for GSD-Ia and only transient correction of myeloid dysfunction has been achieved. A question remains whether a single rAAV vector can meet the expression efficiency and tropism required to treat all aspects of GSD-I, or if a multi-prong approach is needed. An understanding of the strengths and weaknesses of rAAV vectors in the context of strategies to achieve efficient transduction of the liver, kidney, and hematopoietic stem cells is required for treating GSD-I. PMID:21504389

Bridging the gap between the clinician and the patient with cryopyrin-associated periodic syndromes.

PubMed

Cantarini, L; Lucherini, O M; Frediani, B; Brizi, M G; Bartolomei, B; Cimaz, R; Galeazzi, M; Rigante, D

2011-01-01

Cryopyrin-associated periodic syndromes are categorized as a spectrum of three autoinflammatory diseases, namely familial cold auto-inflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurological cutaneous articular syndrome. All are caused by mutations in the NLRP3 gene coding for cryopyrin and result in active interleukin-1 release: their rarity and shared clinical indicators involving skin, joints, central nervous system and eyes often mean that correct diagnosis is delayed. Onset occurs early in childhood, and life-long therapy with interleukin-1 blocking agents usually leads to tangible clinical remission and inflammatory marker normalization in a large number of patients, justifying the need to facilitate early diagnosis and thus avoid irreversible negative consequences for tissues and organs.

A flame burning within.

PubMed

Ferrucci, Luigi; Ble, Alessandro; Bandinelli, Stefania; Lauretani, Fulvio; Suthers, Kristen; Guralnik, Jack M

2004-06-01

Inflammation is a human being's primary defense against threats to homeostasis that are encountered every day. Especially in old age, when regulatory mechanisms responsible for inflammatory responses may be ineffective or damaged, the result can be adverse pathological conditions, and an increased risk of morbidity and mortality. The inflammation response is a plastic network composed of redundant signaling among several different mediators. These mediators have a reciprocal relationship with other biological sub-systems, including hormone regulation, the autonomic nervous system, and oxidative/anti-oxidant balance. Studying this complex architecture requires parallel and multiple research strategies from epidemiological to biochemical level, from observational studies to innovative intervention approaches. Given that the inflammatory response is a critical age-related process, understanding its regulatory action is essential in avoiding hazardous consequences in old age.

[Role of the small intestinal decompression tube and Gastrografin in the treatment of early postoperative inflammatory small bowel obstruction].

PubMed

Li, Wei; Li, Zhixia; An, Dali; Liu, Jing; Zhang, Xiaohu

2014-03-01

To evaluate the role of the small intestinal decompression tube (SIDT) and Gastrografin in the treatment of early postoperative inflammatory small bowel obstruction (EPISBO). Twelve patients presented EPISBO after abdominal surgery in our department from April 2011 to July 2012. Initially, nasogastric tube decompression and other conventional conservative treatment were administrated. After 14 days, obstruction symptom improvement was not obvious, then the SIDT was used. At the same time, Gastrografin was injected into the small bowel through the SIDT in order to demonstrate the site of obstruction of small bowel and its efficacy. In 11 patients after this management, obstruction symptoms disappeared, bowel function recovered within 3 weeks, and oral feeding occurred gradually. Another patient did not pass flatus after 4 weeks and was reoperated. After postoperative follow-up of 6 months, no case relapsed with intestinal obstruction. For severe and long course of early postoperative inflammatory intestinal obstruction, intestinal decompression tube plus Gastrografin is safe and effective, and can avoid unnecessary reoperation.

How to predict clinical relapse in inflammatory bowel disease patients

PubMed Central

Liverani, Elisa; Scaioli, Eleonora; Digby, Richard John; Bellanova, Matteo; Belluzzi, Andrea

2016-01-01

Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn’s disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse. PMID:26811644

[AA amyloidosis].

PubMed

Stojanovic, Katia Stankovic; Georgin-Lavialle, Sophie; Grateau, Gilles

2017-06-01

AA amyloidosis remains one of the three main types of systemic amyloidosis with AL and ATTR. Its incidence has been however decreasing recently in Western countries. Chronic inflammatory diseases are currently the first cause of AA amyloidosis, including rheumatoid arthritis, spondyloarthritis and autoinflammatory diseases. Castleman's disease is a specific cause of AA amyloidosis that can be cured by surgery. A chronic inflammatory response is required to develop amyloidosis. Other genetic and environmental factors are also involved. The first clinical manifestation is a chronic glomerular nephropathy, which can be detected by urine examination and serum creatinine measure. Immunohistochemistry is mandatory to confirm the clinical diagnosis of AA amyloidosis and to avoid misdiagnosis. Long-term prognosis remains poor on chronic dialysis in case of clinical gut involvement. Current treatment is based on the control of the inflammatory response. Specific treatment aimed at inhibiting amyloid formation targeting serum amyloid P component and heparan sulphate are currently evaluated. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Innate Immune Control of West Nile Virus Infection

PubMed Central

Arjona, Alvaro; Wang, Penghua; Montgomery, Ruth R.; Fikrig, Erol

2011-01-01

West Nile virus (WNV), from the Flaviviridae family, is a re-emerging zoonotic pathogen of medical importance. In humans, WNV infection may cause life-threatening meningoencephalitis or long-term neurologic sequelae. WNV is transmitted by Culex spp mosquitoes and both the arthropod vector and the mammalian host are equipped with antiviral innate immune mechanisms sharing a common phylogeny. As far as the current evidence is able to demonstrate, mosquitoes primarily rely on RNA interference, Toll, Imd and JAK-STAT signaling pathways for limiting viral infection, while mammals are provided with these and other more complex antiviral mechanisms involving antiviral effectors, inflammatory mediators, and cellular responses triggered by highly specialized pathogen detection mechanisms that often resemble their invertebrate ancestry. This mini-review summarizes our current understanding of how the innate immune systems of the vector and the mammalian host react to WNV infection and shape its pathogenesis. PMID:21790942

Plant food supplements with anti-inflammatory properties: a systematic review (I).

PubMed

Dell'Agli, Mario; Di Lorenzo, Chiara; Badea, Mihaela; Sangiovanni, Enrico; Dima, Lorena; Bosisio, Enrica; Restani, Patrizia

2013-01-01

Plant food supplements (PFS) receive great acceptance by European consumers. However, quality and efficacy of these products remain a question of concern. The aim of this systematic review is to summarize and critically evaluate the evidence for or against the efficacy of PFS for coping inflammatory conditions by considering epidemiological and human intervention studies. The review, which consists of two parts, considers Olea europea L., Camellia sinensis L., Vitis vinifera L., and Matricaria recutita L., which are herbal material frequently used also as food. The search retrieved 1251 publications. By applying the inclusion/exclusion criteria, the final number of papers was 91. Vitis vinifera L. showed promising results, but other trials should be performed in order to assessing the efficacy. Surprisingly, it was impossible to draw conclusions for the anti-inflammatory effect of Camellia sinensis L. as green tea. No studies were found on the leaves of Olea europea L. whereas more human trials are needed to assess the anti-inflammatory effect of olive oil. Only one study for Matricaria recutita L. was selected. In conclusion, it is advisable to conduct further studies with more homogeneous population and larger number of subjects by avoiding the heterogeneity of the herbal preparations considered.

Sources of Blood Meals of Sylvatic Triatoma guasayana near Zurima, Bolivia, Assayed with qPCR and 12S Cloning

PubMed Central

Lucero, David E.; Ribera, Wilma; Pizarro, Juan Carlos; Plaza, Carlos; Gordon, Levi W.; Peña, Reynaldo; Morrissey, Leslie A.; Rizzo, Donna M.; Stevens, Lori

2014-01-01

Background In this study we compared the utility of two molecular biology techniques, cloning of the mitochondrial 12S ribosomal RNA gene and hydrolysis probe-based qPCR, to identify blood meal sources of sylvatic Chagas disease insect vectors collected with live-bait mouse traps (also known as Noireau traps). Fourteen T. guasayana were collected from six georeferenced trap locations in the Andean highlands of the department of Chuquisaca, Bolivia. Methodology/Principal Findings We detected four blood meals sources with the cloning assay: seven samples were positive for human (Homo sapiens), five for chicken (Gallus gallus) and unicolored blackbird (Agelasticus cyanopus), and one for opossum (Monodelphis domestica). Using the qPCR assay we detected chicken (13 vectors), and human (14 vectors) blood meals as well as an additional blood meal source, Canis sp. (4 vectors). Conclusions/Significance We show that cloning of 12S PCR products, which avoids bias associated with developing primers based on a priori knowledge, detected blood meal sources not previously considered and that species-specific qPCR is more sensitive. All samples identified as positive for a specific blood meal source by the cloning assay were also positive by qPCR. However, not all samples positive by qPCR were positive by cloning. We show the power of combining the cloning assay with the highly sensitive hydrolysis probe-based qPCR assay provides a more complete picture of blood meal sources for insect disease vectors. PMID:25474154

Artificial Vector Calibration Method for Differencing Magnetic Gradient Tensor Systems

PubMed Central

Li, Zhining; Zhang, Yingtang; Yin, Gang

2018-01-01

The measurement error of the differencing (i.e., using two homogenous field sensors at a known baseline distance) magnetic gradient tensor system includes the biases, scale factors, nonorthogonality of the single magnetic sensor, and the misalignment error between the sensor arrays, all of which can severely affect the measurement accuracy. In this paper, we propose a low-cost artificial vector calibration method for the tensor system. Firstly, the error parameter linear equations are constructed based on the single-sensor’s system error model to obtain the artificial ideal vector output of the platform, with the total magnetic intensity (TMI) scalar as a reference by two nonlinear conversions, without any mathematical simplification. Secondly, the Levenberg–Marquardt algorithm is used to compute the integrated model of the 12 error parameters by nonlinear least-squares fitting method with the artificial vector output as a reference, and a total of 48 parameters of the system is estimated simultaneously. The calibrated system outputs along the reference platform-orthogonal coordinate system. The analysis results show that the artificial vector calibrated output can track the orientation fluctuations of TMI accurately, effectively avoiding the “overcalibration” problem. The accuracy of the error parameters’ estimation in the simulation is close to 100%. The experimental root-mean-square error (RMSE) of the TMI and tensor components is less than 3 nT and 20 nT/m, respectively, and the estimation of the parameters is highly robust. PMID:29373544

Operations of the Far Ultraviolet Spectroscopic Explorer : A `Dynamic' Flux Calibration.

NASA Astrophysics Data System (ADS)

Ehrenreich, D.; Dupuis, J.; Dixon, W. V.; Sahnow, D. J.; Kruk, J. W.

2003-05-01

The FUSE flux calibration is based on model-atmosphere predictions of the spectra of well studied white-dwarf stars. Calibration operations, however, are a highly `dynamic' process consisting of repeatedly measuring these standard stars, deriving corrections, and integrating the results into CALFUSE, the FUSE science pipeline. With suitable scheduling, those calibration observation campaigns let us characterize short term and long term variations of the sensitivity. One particular issue addressed by these observations is monitoring possible degradation of the FUSE optical coatings by atomic oxygen present in the upper atmosphere. We have attempted to minimize this by avoiding pointing close to the instantaneous velocity vector of the spacecraft (the ram vector). Prior to Cycle 3, the minimum permitted angle between the line of sight and the ram vector was 20 degrees. This was reduced to 15 degrees during Cycle 3 to increase our sky coverage, and will be further reduced to 10 degrees for Cycle 4. This relaxation of ram constraints has been preceded by a tailored calibration program in which white dwarf measurements are obtained before and after observations performed for a limited time below the current ram vector constraint. This relaxation of the ram vector constraint will considerably expand the ability of FUSE to observe sources at low declination. This work is based on data obtained for the Guaranteed Time Team by the NASA-CNES-CSA FUSE mission operated by the Johns Hopkins University. Financial support to U.S. participants has been provided by NASA contract NAS5-32985.

Predicting ectotherm disease vector spread—benefits from multidisciplinary approaches and directions forward

NASA Astrophysics Data System (ADS)

Thomas, Stephanie Margarete; Beierkuhnlein, Carl

2013-05-01

The occurrence of ectotherm disease vectors outside of their previous distribution area and the emergence of vector-borne diseases can be increasingly observed at a global scale and are accompanied by a growing number of studies which investigate the vast range of determining factors and their causal links. Consequently, a broad span of scientific disciplines is involved in tackling these complex phenomena. First, we evaluate the citation behaviour of relevant scientific literature in order to clarify the question "do scientists consider results of other disciplines to extend their expertise?" We then highlight emerging tools and concepts useful for risk assessment. Correlative models (regression-based, machine-learning and profile techniques), mechanistic models (basic reproduction number R 0) and methods of spatial regression, interaction and interpolation are described. We discuss further steps towards multidisciplinary approaches regarding new tools and emerging concepts to combine existing approaches such as Bayesian geostatistical modelling, mechanistic models which avoid the need for parameter fitting, joined correlative and mechanistic models, multi-criteria decision analysis and geographic profiling. We take the quality of both occurrence data for vector, host and disease cases, and data of the predictor variables into consideration as both determine the accuracy of risk area identification. Finally, we underline the importance of multidisciplinary research approaches. Even if the establishment of communication networks between scientific disciplines and the share of specific methods is time consuming, it promises new insights for the surveillance and control of vector-borne diseases worldwide.

Highly stable maintenance of a mouse artificial chromosome in human cells and mice.

PubMed

Kazuki, Kanako; Takehara, Shoko; Uno, Narumi; Imaoka, Natsuko; Abe, Satoshi; Takiguchi, Masato; Hiramatsu, Kei; Oshimura, Mitsuo; Kazuki, Yasuhiro

2013-12-06

Human artificial chromosomes (HACs) and mouse artificial chromosomes (MACs) display several advantages as gene delivery vectors, such as stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Previously, we showed that a MAC vector developed from a natural mouse chromosome by chromosome engineering was more stably maintained in adult tissues and hematopoietic cells in mice than HAC vectors. In this study, to expand the utility for a gene delivery vector in human cells and mice, we investigated the long-term stability of the MACs in cultured human cells and transchromosomic mice. We also investigated the chromosomal copy number-dependent expression of genes on the MACs in mice. The MAC was stably maintained in human HT1080 cells in vitro during long-term culture. The MAC was stably maintained at least to the F8 and F4 generations in ICR and C57BL/6 backgrounds, respectively. The MAC was also stably maintained in hematopoietic cells and tissues derived from old mice. Transchromosomic mice containing two or four copies of the MAC were generated by breeding. The DNA contents were comparable to the copy number of the MACs in each tissue examined, and the expression of the EGFP gene on the MAC was dependent on the chromosomal copy number. Therefore, the MAC vector may be useful not only for gene delivery in mammalian cells but also for animal transgenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Gokumakulapalle, Madhuri; Mei, Ya-Fang, E-mail: ya-fang.mei@umu.se

The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were asmore » capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. - Highlights: • Africa green monkey cell lines were monitored for human adenovirus 11p GFP vector infection. • Human CD46 molecules were detectable in these monkey cell lines. • Adenovirus 11p GFP vector can be propagated in Vero cells increases the safety of Ad11p-based vectors for clinical trials. • To use Vero cells for preparation of Ad11p vector avoids the potential inclusion of oncogenes from tumor cells.« less

An Improved TA-SVM Method Without Matrix Inversion and Its Fast Implementation for Nonstationary Datasets.

PubMed

Shi, Yingzhong; Chung, Fu-Lai; Wang, Shitong

2015-09-01

Recently, a time-adaptive support vector machine (TA-SVM) is proposed for handling nonstationary datasets. While attractive performance has been reported and the new classifier is distinctive in simultaneously solving several SVM subclassifiers locally and globally by using an elegant SVM formulation in an alternative kernel space, the coupling of subclassifiers brings in the computation of matrix inversion, thus resulting to suffer from high computational burden in large nonstationary dataset applications. To overcome this shortcoming, an improved TA-SVM (ITA-SVM) is proposed using a common vector shared by all the SVM subclassifiers involved. ITA-SVM not only keeps an SVM formulation, but also avoids the computation of matrix inversion. Thus, we can realize its fast version, that is, improved time-adaptive core vector machine (ITA-CVM) for large nonstationary datasets by using the CVM technique. ITA-CVM has the merit of asymptotic linear time complexity for large nonstationary datasets as well as inherits the advantage of TA-SVM. The effectiveness of the proposed classifiers ITA-SVM and ITA-CVM is also experimentally confirmed.

Strong coupling constant from Adler function in lattice QCD

NASA Astrophysics Data System (ADS)

Hudspith, Renwick J.; Lewis, Randy; Maltman, Kim; Shintani, Eigo

2016-09-01

We compute the QCD coupling constant, αs, from the Adler function with vector hadronic vacuum polarization (HVP) function. On the lattice, Adler function can be measured by the differential of HVP at two different momentum scales. HVP is measured from the conserved-local vector current correlator using nf = 2 + 1 flavor Domain Wall lattice data with three different lattice cutoffs, up to a-1 ≈ 3.14 GeV. To avoid the lattice artifact due to O(4) symmetry breaking, we set the cylinder cut on the lattice momentum with reflection projection onto vector current correlator, and it then provides smooth function of momentum scale for extracted HVP. We present a global fit of the lattice data at a justified momentum scale with three lattice cutoffs using continuum perturbation theory at 𝒪(αs4) to obtain the coupling in the continuum limit at arbitrary scale. We take the running to Z boson mass through the appropriate thresholds, and obtain αs(5)(MZ) = 0.1191(24)(37) where the first is statistical error and the second is systematic one.

Asymptotic stability of spectral-based PDF modeling for homogeneous turbulent flows

NASA Astrophysics Data System (ADS)

Campos, Alejandro; Duraisamy, Karthik; Iaccarino, Gianluca

2015-11-01

Engineering models of turbulence, based on one-point statistics, neglect spectral information inherent in a turbulence field. It is well known, however, that the evolution of turbulence is dictated by a complex interplay between the spectral modes of velocity. For example, for homogeneous turbulence, the pressure-rate-of-strain depends on the integrated energy spectrum weighted by components of the wave vectors. The Interacting Particle Representation Model (IPRM) (Kassinos & Reynolds, 1996) and the Velocity/Wave-Vector PDF model (Van Slooten & Pope, 1997) emulate spectral information in an attempt to improve the modeling of turbulence. We investigate the evolution and asymptotic stability of the IPRM using three different approaches. The first approach considers the Lagrangian evolution of individual realizations (idealized as particles) of the stochastic process defined by the IPRM. The second solves Lagrangian evolution equations for clusters of realizations conditional on a given wave vector. The third evolves the solution of the Eulerian conditional PDF corresponding to the aforementioned clusters. This last method avoids issues related to discrete particle noise and slow convergence associated with Lagrangian particle-based simulations.

Color and Vector Flow Imaging in Parallel Ultrasound With Sub-Nyquist Sampling.

PubMed

Madiena, Craig; Faurie, Julia; Poree, Jonathan; Garcia, Damien; Garcia, Damien; Madiena, Craig; Faurie, Julia; Poree, Jonathan

2018-05-01

RF acquisition with a high-performance multichannel ultrasound system generates massive data sets in short periods of time, especially in "ultrafast" ultrasound when digital receive beamforming is required. Sampling at a rate four times the carrier frequency is the standard procedure since this rule complies with the Nyquist-Shannon sampling theorem and simplifies quadrature sampling. Bandpass sampling (or undersampling) outputs a bandpass signal at a rate lower than the maximal frequency without harmful aliasing. Advantages over Nyquist sampling are reduced storage volumes and data workflow, and simplified digital signal processing tasks. We used RF undersampling in color flow imaging (CFI) and vector flow imaging (VFI) to decrease data volume significantly (factor of 3 to 13 in our configurations). CFI and VFI with Nyquist and sub-Nyquist samplings were compared in vitro and in vivo. The estimate errors due to undersampling were small or marginal, which illustrates that Doppler and vector Doppler images can be correctly computed with a drastically reduced amount of RF samples. Undersampling can be a method of choice in CFI and VFI to avoid information overload and reduce data transfer and storage.

From medical herbalism to phytotherapy in dermatology: back to the future.

PubMed

Dattner, Alan M

2003-01-01

Plant-based therapeutic preparations are cyclically returning to complement dermatologic therapy. They serve as therapeutic alternatives, safer choices, or in some cases, as the only effective treatment. Folk medicine tradition provides different indicators for use than the medical disease model. Advantages of multiple synergistic components of crude extracts are discussed, as well as herbs already used in dermatology. Bitter digestive stimulants are used for vitiligo. Bioflavinoids from buckwheat and horse chestnut are used for varicose veins, and silymarin is used for liver protection. Gotu kola and sarsaparilla are used for inflammatory skin conditions. Oregon grape root has synergistic antibacterial, anti-inflammatory, and bile-stimulating properties which make the crude extract useful in acne. Philosophical differences in herbology compared to medicine exist in the application of science toward improving elimination and strengthening the host as opposed to destroying the vector or manifestation of the disease.

Gene Therapy for Neuropathic Pain by Silencing of TNF-α Expression with Lentiviral Vectors Targeting the Dorsal Root Ganglion in Mice

PubMed Central

Ogawa, Nobuhiro; Kawai, Hiromichi; Terashima, Tomoya; Kojima, Hideto; Oka, Kazuhiro; Chan, Lawrence; Maegawa, Hiroshi

2014-01-01

Neuropathic pain can be a debilitating condition. Many types of drugs that have been used to treat neuropathic pain have only limited efficacy. Recent studies indicate that pro-inflammatory mediators including tumor necrosis factor α (TNF-α) are involved in the pathogenesis of neuropathic pain. In the present study, we engineered a gene therapy strategy to relieve neuropathic pain by silencing TNF-α expression in the dorsal root ganglion (DRG) using lentiviral vectors expressing TNF short hairpin RNA1-4 (LV-TNF-shRNA1-4) in mice. First, based on its efficacy in silencing TNF-α in vitro, we selected shRNA3 to construct LV-TNF-shRNA3 for in vivo study. We used L5 spinal nerve transection (SNT) mice as a neuropathic pain model. These animals were found to display up-regulated mRNA expression of activating transcription factor 3 (ATF3) and neuropeptide Y (NPY), injury markers, and interleukin (IL)-6, an inflammatory cytokine in the ipsilateral L5 DRG. Injection of LV-TNF-shRNA3 onto the proximal transected site suppressed significantly the mRNA levels of ATF3, NPY and IL-6, reduced mechanical allodynia and neuronal cell death of DRG neurons. These results suggest that lentiviral-mediated silencing of TNF-α in DRG relieves neuropathic pain and reduces neuronal cell death, and may constitute a novel therapeutic option for neuropathic pain. PMID:24642694

Lactococcus lactis carrying the pValac eukaryotic expression vector coding for IL-4 reduces chemically-induced intestinal inflammation by increasing the levels of IL-10-producing regulatory cells.

PubMed

Souza, Bianca Mendes; Preisser, Tatiane Melo; Pereira, Vanessa Bastos; Zurita-Turk, Meritxell; de Castro, Camila Prósperi; da Cunha, Vanessa Pecini; de Oliveira, Rafael Pires; Gomes-Santos, Ana Cristina; de Faria, Ana Maria Caetano; Machado, Denise Carmona Cara; Chatel, Jean-Marc; Azevedo, Vasco Ariston de Carvalho; Langella, Philippe; Miyoshi, Anderson

2016-08-30

Inflammatory bowel diseases are characterized by chronic intestinal inflammation that leads to severe destruction of the intestinal mucosa. Therefore, the understanding of their aetiology as well as the development of new medicines is an important step for the treatment of such diseases. Consequently, the development of Lactococcus lactis strains capable of delivering a eukaryotic expression vector encoding the interleukin 4 (IL-4) of Mus musculus would represent a new strategy for the elaboration of a more effective alternative therapy against Crohn's disease. The murine IL-4 ORF was cloned into the eukaryotic expression vector pValac::dts. The resulting plasmid-pValac::dts::IL-4-was transfected into CHO cells so that its functionality could be evaluated in vitro. With fluorescent confocal microscopy, flow cytometry and ELISA, it was observed that pValac::dts::IL-4-transfected cells produced IL-4, while non-transfected cells and cells transfected with the empty vector did not. Then, pValac::dts::IL-4 was inserted into L. lactis MG1363 FnBPA(+) in order to evaluate the therapeutic potential of the recombinant strain against TNBS-induced colitis. Intragastric administration of L. lactis MG1363 FnBPA(+) (pValac::dts::IL-4) was able to decrease the severity of colitis, with animals showing decreased levels of IL-12, IL-6 and MPO activity; and increased levels of IL-4 and IL-10. Finally, LP-isolated cells from mice administered TNBS were immunophenotyped so that the main IL-4 and IL-10 producers were identified. Mice administered the recombinant strain presented significantly higher percentages of F4/80(+)MHCII(+)Ly6C(-)IL-4(+), F4/80(+)MHCII(+)Ly6C(-)IL-10(+), F4/80(+)MHCII(+)Ly6C(-)CD206(+)CD124(+)IL-10(+) and CD4(+)Foxp3(+)IL10(+) cells compared to the other groups. This study shows that L. lactis MG1363 FnBPA(+) (pValac::dts::IL-4) is a good candidate to maintain the anti-inflammatory and proinflammatory balance in the gastrointestinal tract, increasing the levels of IL-10-secreting regulatory cells and, thus, demonstrating the effectiveness of this novel DNA delivery-based strategy.

Three-dimensional tool radius compensation for multi-axis peripheral milling

NASA Astrophysics Data System (ADS)

Chen, Youdong; Wang, Tianmiao

2013-05-01

Few function about 3D tool radius compensation is applied to generating executable motion control commands in the existing computer numerical control (CNC) systems. Once the tool radius is changed, especially in the case of tool size changing with tool wear in machining, a new NC program has to be recreated. A generic 3D tool radius compensation method for multi-axis peripheral milling in CNC systems is presented. The offset path is calculated by offsetting the tool path along the direction of the offset vector with a given distance. The offset vector is perpendicular to both the tangent vector of the tool path and the orientation vector of the tool axis relative to the workpiece. The orientation vector equations of the tool axis relative to the workpiece are obtained through homogeneous coordinate transformation matrix and forward kinematics of generalized kinematics model of multi-axis machine tools. To avoid cutting into the corner formed by the two adjacent tool paths, the coordinates of offset path at the intersection point have been calculated according to the transition type that is determined by the angle between the two tool path tangent vectors at the corner. Through the verification by the solid cutting simulation software VERICUT® with different tool radiuses on a table-tilting type five-axis machine tool, and by the real machining experiment of machining a soup spoon on a five-axis machine tool with the developed CNC system, the effectiveness of the proposed 3D tool radius compensation method is confirmed. The proposed compensation method can be suitable for all kinds of three- to five-axis machine tools as a general form.

Effective reduction of the interleukin-1β transcript in osteoarthritis-prone guinea pig chondrocytes via short hairpin RNA mediated RNA interference influences gene expression of mediators implicated in disease pathogenesis.

PubMed

Santangelo, K S; Bertone, A L

2011-12-01

To ascertain a viral vector-based short hairpin RNA (shRNA) capable of reducing the interleukin-1β (IL-1β) transcript in osteoarthritis (OA)-prone chondrocytes and detect corresponding changes in the expression patterns of several critical disease mediators. Cultured chondrocytes from 2-month-old Hartley guinea pigs were screened for reduction of the IL-1β transcript following plasmid-based delivery of U6-driven shRNA sequences. A successful plasmid/shRNA knockdown combination was identified and used to construct an adeno-associated virus serotype 5 (AAV5) vector for further evaluation. Relative real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify in vitro transcript changes of IL-1β and an additional nine genes following transduction with this targeting knockdown vector. To validate in vitro findings, this AAV5 vector was injected into one knee, while either an equivalent volume of saline vehicle (three animals) or non-targeting control vector (three animals) were injected into opposite knees. Fold differences and subsequent percent gene expression levels relative to control groups were calculated using the comparative CT (2(-ΔΔCT)) method. Statistically significant decreases in IL-1β expression were achieved by the targeting knockdown vector relative to both the mock-transduced control and non-targeting vector control groups in vitro. Transcript levels of anabolic transforming growth factor-β (TGF-β) were significantly increased by use of this targeting knockdown vector. Transduction with this targeting AAV5 vector also significantly decreased the transcript levels of key inflammatory cytokines [tumor necrosis factor-α (TNF-α), IL-2, IL-8, and IL-12] and catabolic agents [matrix metalloproteinase (MMP)13, MMP2, interferon-γ (IFN-γ), and inducible nitrous oxide synthase (iNOS)] relative to both mock-transduced and non-targeting vector control groups. In vivo application of this targeting knockdown vector resulted in a >50% reduction (P=0.0045) or >90% (P=0.0001) of the IL-1β transcript relative to vehicle-only or non-targeting vector control exposed cartilage, respectively. Successful reduction of the IL-1β transcript was achieved via RNA interference (RNAi) techniques. Importantly, this alteration significantly influenced the transcript levels of several major players involved in OA pathogenesis in the direction of disease modification. Investigations to characterize additional gene expression changes influenced by targeting knockdown AAV5 vector-based diminution of the IL-1β transcript in vivo are warranted. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effect of Circular ANRIL on the Inflammatory Response of Vascular Endothelial Cells in a Rat Model of Coronary Atherosclerosis.

PubMed

Song, Chun-Li; Wang, Jin-Peng; Xue, Xin; Liu, Ning; Zhang, Xiao-Hao; Zhao, Zhuo; Liu, Jian-Gen; Zhang, Chun-Peng; Piao, Zhe-Hao; Liu, Yang; Yang, Yi-Bo

2017-01-01

This study aims to investigate the role of circular antisense non-coding RNA at the INK4 locus (cANRIL) in the inflammatory response of vascular endothelial cells (ECs) in a rat model of coronary atherosclerosis (AS). A rat model of AS was established with rats that were injected with a large dose of vitamin D3 and fed a high-fat diet. Sixty Wistar rats were randomly assigned into control, model, empty vector, over-expressed cANRIL and low-expressed cANRIL groups (12 rats in each group). Sixteen weeks later, the ultrastructure of their coronary arteries was observed via transmission electron microscopy. Rat serum lipid levels were analyzed using an automatic biochemical analyzer, and their atherogenic index (AI) values were calculated. Hematoxylin and eosin staining was used to observe the endothelial morphology of rats. Additionally, rat EC apoptosis was tested via a TUNEL assay. Enzyme-linked immunosorbent assays (ELISAs) were applied to measure serum levels of interleukin-1 (IL-1), IL-6, matrix metalloproteinase-9 (MMP-9) and C-reactive protein (CRP). The cANRIL, Bax, bcl-2 and caspase-3 mRNA expression levels were measured with a quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of Bax, bcl-2 and caspase-3 were detected using immunohistochemistry. In the control group, ECs were closely arranged with normal structures, and there was no proliferation. In the model, empty vector and over-expressed cANRIL groups, some cells were not present, and atherosclerotic plaques and thrombi appeared. However, in the under-expressed cANRIL group, the cells had a normal structure. Compared with the model and empty vector groups, the levels of total cholesterol (CHOL), triglycerides (TGs), low density lipoprotein (LDL), IL-1, IL-6, MMP-9, CRP, cANRIL, Bax, and caspase-3, AI values, and rates of EC apoptosis decreased in the low-expressed cANRIL group, while HDL (high density lipoprotein) levels and mRNA and protein expression levels of bcl-2 were increased. The changes in expression levels in the over-expressed cANRIL group were the opposite of those in the low-expressed cANRIL group. Our study provides evidence that reduced cANRIL expression could prevent coronary AS by reducing vascular EC apoptosis and inflammatory factor expression. © 2017 The Author(s). Published by S. Karger AG, Basel.

Laboratory Diagnosis of Sepsis? No SIRS, Not Just Yet

PubMed Central

2015-01-01

In order to maximize the benefit of prompt antimicrobial therapy and avoid the risk associated with inappropriate use of antimicrobial agents, patients with suspected sepsis must be rapidly differentiated from patients with systemic inflammatory response syndrome (SIRS). In combination with standard microbiological testing, a number of biomarkers have been recently evaluated for this purpose, and the performance characteristics of the most promising of these are reviewed. PMID:25631808

Dietary strategies to attenuate muscle loss during recovery from injury.

PubMed

Tipton, Kevin D

2013-01-01

Injuries are an unavoidable aspect of participation in physical activity. Nutrition is important for optimal wound healing and recovery, but little information about nutritional support for injuries exists. Immediately following injury, wound healing begins with an inflammatory response. Excessive anti-inflammatory measures may impair recovery. Many injuries result in limb immobilization. Immobilization results in muscle loss due to increased periods of negative muscle protein balance from decreased basal muscle protein synthesis and resistance to anabolic stimuli, including protein ingestion. Oxidative capacity of muscle is also decreased. Nutrient and energy deficiencies should be avoided. Energy expenditure may be reduced during immobilization, but inflammation, wound healing and the energy cost of ambulation limit the reduction of energy expenditure. There is a theoretical rationale for leucine and omega-3 fatty acid supplementation to help reduce muscle atrophy. During rehabilitation and recovery from immobilization, increased activity, in particular resistance exercise will increase muscle protein synthesis and restore sensitivity to anabolic stimuli. Ample, but not excessive, protein and energy must be consumed to support muscle growth. During rehabilitation and recovery, nutritional needs are very much like those for any athlete desiring muscle growth. The most important consideration is to avoid malnutrition and to apply a risk/benefit approach. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

Cordylobia rodhaini infestation of the breast: Report of a case mimicking a breast abscess.

PubMed

Grassi, Veronica; Butterworth, James William; Latiffi, Layloma

2016-01-01

Myiasis, parasitic infestation of the body by fly larvae, caused by the Cordylobia rodhaini is very rare with only fourteen cases published since 1970. We present a rare case of myiasis mimicking a breast abscess. A 17-year-old female presented with a nodular ulcerative lesion in her left breast 14days following a trip to Ghana. She had been initially unsuccessfully treated with the antibiotic flucloxacillin following a misdiagnosis of a breast abscess. Following application of Vaseline to the breast wound, covering the wound for 2h and gentle manipulation the larvae was removed successfully and the patient made a good recovery. Presenting as an inflammatory papule with central opening oozing serosanguinous fluid myiasis secondary to C. rodhaini can easily be mistaken for a breast abscess, often avoiding detection by unsuspecting surgeons on initial assessment. In turn ineffective antibiotic treatment is often prescribed leading to further disease progression and associated morbidity. Myiasis secondary to C. rodhaini is a rare but important differential surgeons should consider in women presenting with an inflammatory breast lesion with a recent history of foreign travel to ensure timely diagnosis and treatment. Ultrasound imaging can be useful in confirming diagnosis and avoiding treatment delays. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma.

PubMed

Xie, Yuran; Merkel, Olivia M

2015-10-01

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues have limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases, and costimulatory factors that have been reported as targets of siRNA-mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages, and dendritic cells, which could potentially be applied in asthma therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Symmetry-preserving contact interaction model for heavy-light mesons

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

Serna, F. E.; Brito, M. A.; Krein, G.

2016-01-22

We use a symmetry-preserving regularization method of ultraviolet divergences in a vector-vector contact interaction model for low-energy QCD. The contact interaction is a representation of nonperturbative kernels used Dyson-Schwinger and Bethe-Salpeter equations. The regularization method is based on a subtraction scheme that avoids standard steps in the evaluation of divergent integrals that invariably lead to symmetry violation. Aiming at the study of heavy-light mesons, we have implemented the method to the pseudoscalar π and K mesons. We have solved the Dyson-Schwinger equation for the u, d and s quark propagators, and obtained the bound-state Bethe-Salpeter amplitudes in a way thatmore » the Ward-Green-Takahashi identities reflecting global symmetries of the model are satisfied for arbitrary routing of the momenta running in loop integrals.« less

A parallel-vector algorithm for rapid structural analysis on high-performance computers

NASA Technical Reports Server (NTRS)

Storaasli, Olaf O.; Nguyen, Duc T.; Agarwal, Tarun K.

1990-01-01

A fast, accurate Choleski method for the solution of symmetric systems of linear equations is presented. This direct method is based on a variable-band storage scheme and takes advantage of column heights to reduce the number of operations in the Choleski factorization. The method employs parallel computation in the outermost DO-loop and vector computation via the 'loop unrolling' technique in the innermost DO-loop. The method avoids computations with zeros outside the column heights, and as an option, zeros inside the band. The close relationship between Choleski and Gauss elimination methods is examined. The minor changes required to convert the Choleski code to a Gauss code to solve non-positive-definite symmetric systems of equations are identified. The results for two large-scale structural analyses performed on supercomputers, demonstrate the accuracy and speed of the method.

A parallel-vector algorithm for rapid structural analysis on high-performance computers

NASA Technical Reports Server (NTRS)

Storaasli, Olaf O.; Nguyen, Duc T.; Agarwal, Tarun K.

1990-01-01

A fast, accurate Choleski method for the solution of symmetric systems of linear equations is presented. This direct method is based on a variable-band storage scheme and takes advantage of column heights to reduce the number of operations in the Choleski factorization. The method employs parallel computation in the outermost DO-loop and vector computation via the loop unrolling technique in the innermost DO-loop. The method avoids computations with zeros outside the column heights, and as an option, zeros inside the band. The close relationship between Choleski and Gauss elimination methods is examined. The minor changes required to convert the Choleski code to a Gauss code to solve non-positive-definite symmetric systems of equations are identified. The results for two large scale structural analyses performed on supercomputers, demonstrate the accuracy and speed of the method.

Update on gene therapy for immunodeficiencies.

PubMed

Kohn, Donald B

2010-05-01

Primary immune deficiencies (PID) are due to blood cell defects and can be treated with transplantation of normal hematopoietic stem cells (HSC) from another person (allogeneic). Gene therapy in which a patient's autologous HSC are genetically corrected represents an alternative treatment for patients with PID, which could avoid the immunologic risks of allogeneic HSCT and confer similar benefits. Recent clinical trials using gene therapy have led to immune restoration in patients with X-linked severe combined immune deficiency (XSCID), adenosine deaminase (ADA)-deficient SCID and chronic granulomatous disease (CGD). However, severe complications arose in several of the patients in whom the integrated retroviral vectors led to leukoproliferative disorders. New approaches using safer integrating vectors or direct correction of the defective gene underlying the PID are being developed and may lead to safer and effective gene therapy for PID. Copyright 2009 Elsevier Inc. All rights reserved.

Navigation Doppler lidar sensor for precision altitude and vector velocity measurements: flight test results

NASA Astrophysics Data System (ADS)

Pierrottet, Diego; Amzajerdian, Farzin; Petway, Larry; Barnes, Bruce; Lockard, George; Hines, Glenn

2011-06-01

An all fiber Navigation Doppler Lidar (NDL) system is under development at NASA Langley Research Center (LaRC) for precision descent and landing applications on planetary bodies. The sensor produces high-resolution line of sight range, altitude above ground, ground relative attitude, and high precision velocity vector measurements. Previous helicopter flight test results demonstrated the NDL measurement concepts, including measurement precision, accuracies, and operational range. This paper discusses the results obtained from a recent campaign to test the improved sensor hardware, and various signal processing algorithms applicable to real-time processing. The NDL was mounted in an instrumentation pod aboard an Erickson Air-Crane helicopter and flown over various terrains. The sensor was one of several sensors tested in this field test by NASA's Autonomous Landing and Hazard Avoidance Technology (ALHAT) project.

Study of modal coupling procedures for the shuttle: A matrix method for damping synthesis

NASA Technical Reports Server (NTRS)

Hasselman, T. K.

1972-01-01

The damping method was applied successfully to real structures as well as analytical models. It depends on the ability to determine an appropriate modal damping matrix for each substructure. In the past, modal damping matrices were assumed diagonal for lack of being able to determine the coupling terms which are significant in the general case of nonproportional damping. This problem was overcome by formulating the damped equations of motion as a linear perturbation of the undamped equations for light structural damping. Damped modes are defined as complex vectors derived from the complex frequency response vectors of each substructure and are obtained directly from sinusoidal vibration tests. The damped modes are used to compute first order approximations to the modal damping matrices. The perturbation approach avoids ever having to solve a complex eigenvalue problem.

Navigation Doppler Lidar Sensor for Precision Altitude and Vector Velocity Measurements Flight Test Results

NASA Technical Reports Server (NTRS)

Pierrottet, Diego F.; Lockhard, George; Amzajerdian, Farzin; Petway, Larry B.; Barnes, Bruce; Hines, Glenn D.

2011-01-01

An all fiber Navigation Doppler Lidar (NDL) system is under development at NASA Langley Research Center (LaRC) for precision descent and landing applications on planetary bodies. The sensor produces high resolution line of sight range, altitude above ground, ground relative attitude, and high precision velocity vector measurements. Previous helicopter flight test results demonstrated the NDL measurement concepts, including measurement precision, accuracies, and operational range. This paper discusses the results obtained from a recent campaign to test the improved sensor hardware, and various signal processing algorithms applicable to real-time processing. The NDL was mounted in an instrumentation pod aboard an Erickson Air-Crane helicopter and flown over vegetation free terrain. The sensor was one of several sensors tested in this field test by NASA?s Autonomous Landing and Hazard Avoidance Technology (ALHAT) project.

A consensus least squares support vector regression (LS-SVR) for analysis of near-infrared spectra of plant samples.

PubMed

Li, Yankun; Shao, Xueguang; Cai, Wensheng

2007-04-15

Consensus modeling of combining the results of multiple independent models to produce a single prediction avoids the instability of single model. Based on the principle of consensus modeling, a consensus least squares support vector regression (LS-SVR) method for calibrating the near-infrared (NIR) spectra was proposed. In the proposed approach, NIR spectra of plant samples were firstly preprocessed using discrete wavelet transform (DWT) for filtering the spectral background and noise, then, consensus LS-SVR technique was used for building the calibration model. With an optimization of the parameters involved in the modeling, a satisfied model was achieved for predicting the content of reducing sugar in plant samples. The predicted results show that consensus LS-SVR model is more robust and reliable than the conventional partial least squares (PLS) and LS-SVR methods.

Death of Military Working Dogs Due to Bartonella vinsonii Subspecies berkhoffii Genotype III Endocarditis and Myocarditis.

PubMed

Shelnutt, Leslie M; Balakrishnan, Nandhakumar; DeVanna, Justin; Batey, Kenneth L; Breitschwerdt, Edward B

2017-03-01

As a result of extensive field-related activities, military working dogs (MWDs) have an increased occupational risk for acquiring vector-borne infectious diseases. Indirect fluorescent antibody, Bartonella alpha-proteobacteria growth medium enrichment culture, and 16-23S Bartonella intergenic transcribed spacer polymerase chain reaction were performed using blood, serum, or tissue specimens. Endocarditis was diagnosed in three MWDs infected with Bartonella vinsonii subspecies (subsp.) berkhoffii genotype III. One dog was also infected with Bartonella rochalimae. B. vinsonii subsp. berkhoffii genotype III may represent an occupational risk for MWDs that develop endocarditis or myocarditis. Comprehensive periodic screening for canine vector-borne infections, in particular occult infections caused by Bartonella spp, is prudent to avoid serious or life-threating illnesses. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Identification of repellent odorants to the body louse, Pediculus humanus corporis, in clove essential oil.

PubMed

Iwamatsu, Takuma; Miyamoto, Daisuke; Mitsuno, Hidefumi; Yoshioka, Yoshiaki; Fujii, Takeshi; Sakurai, Takeshi; Ishikawa, Yukio; Kanzaki, Ryohei

2016-04-01

The control of body lice is an important issue for human health and welfare because lice act as vectors of disease such as typhus, relapsing fever, and trench fever. Body lice exhibit avoidance behavior to some essential oils, including clove essential oil. Therefore, odorants containing clove essential oil components may potentially be useful in the development of repellents to body lice. However, such odorants that induce avoidance behavior in body lice have not yet been identified from clove essential oil. Here, we established an analysis method to evaluate the avoidance behavior of body lice to specific odorants. The behavioral analysis of the body lice in response to clove essential oil and its constituents revealed that eugenol, a major component of clove essential oil, has strong repellent effect on body lice, whereas the other components failed to induce obvious avoidance behavior. A comparison of the repellent effects of eugenol with those of other structurally related odorants revealed possible moieties that are important for the avoidance effects to body lice. The repellent effect of eugenol to body lice was enhanced by combining it with the other major component of clove essential oil, β-caryophyllene. We conclude that a synthetic blend of eugenol and β-caryophyllene is the most effective repellent to body lice. This finding will be valuable as the potential use of eugenol as body lice repellent.

[Lymphoplasmacytic inflammatory pseudotumor of the liver].

PubMed

Valdivielso Córtazar, E; Yáñez López, J A; Yáñez Gónzalez-Dopeso, L; Diz-Lois Palomares, M; González Conde, B; Alonso Aguirre, P

2016-01-01

We present the case of a middle-aged woman with antecedents of cholecystectomy and several episodes of resi-dual coledocolitiasis resolved endoscopically. She attended Emergency Services due to a new clinical picture of abdo-minal pain and alteration of hepatic enzymes. Image tests showed lesions that suggested hepatic abscesses without ruling out a malign origin. Given this doubt it was decided to carry out a thick needle biopsy obtaining a diagnosis of an inflammatory pseudotumour of the liver related to IgG4-related disease. This is an infrequent entity but must be taken into consideration because - unlike malign pathology, which is the main differential diagnosis - its behaviour is benign, with a good evolution with medical treatment. That is why a suitable diagnosis is vital to avoid aggressive, diagnostic-therapeutic procedures.

[Complex regional pain syndrome (CRPS) : An update].

PubMed

Dimova, V; Birklein, F

2018-04-17

The acute phase of complex regional pain syndrome (CRPS) is pathophysiologically characterized by an activation of the immune system and its associated inflammatory response. During the course of CRPS, central nervous symptoms like mechanical hyperalgesia, loss of sensation, and body perception disorders develop. Psychological factors such as pain-related anxiety and traumatic events might have a negative effect on the treatment outcome. While the visible inflammatory symptoms improve, the pain often persists. A stage adapted, targeted treatment could improve the prognosis. Effective multidisciplinary treatment includes the following: pharmacotherapy with steroids, bisphosphonates, or dimethylsulfoxide cream (acute phase), and antineuropathic analgesics (all phases); physiotherapy and behavioral therapy for pain-related anxiety and avoidance of movement; and interventional treatment like spinal cord or dorsal root ganglion stimulation if noninvasive options failed.

Chronic idiopathic inflammatory bowel diseases: the histology report.

PubMed

Cornaggia, Matteo; Leutner, Monica; Mescoli, Claudia; Sturniolo, Giacomo Carlo; Gullotta, Renzo

2011-03-01

The incidence of chronic idiopathic inflammatory bowel diseases (IBD) is growing in western countries, making their histological diagnosis an everyday task for all pathologists. Reviews from the literature strongly suggest that such diagnosis cannot be performed on the histological ground alone but requires a clinical-pathological approach. Moreover, bewildering variations can be observed in the terminology employed to report either individual lesions or diagnostic categories. The aim of the present paper is to suggest a practical diagnostic algorithm summarizing the main data from the literature. Particular emphasis has been placed on minimum clinical information required and the accurate definition of individual lesions. Diagnostic categories to employ and to avoid in daily practice have furthermore been stressed. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

The combined geodetic network adjusted on the reference ellipsoid - a comparison of three functional models for GNSS observations

NASA Astrophysics Data System (ADS)

Kadaj, Roman

2016-12-01

The adjustment problem of the so-called combined (hybrid, integrated) network created with GNSS vectors and terrestrial observations has been the subject of many theoretical and applied works. The network adjustment in various mathematical spaces was considered: in the Cartesian geocentric system on a reference ellipsoid and on a mapping plane. For practical reasons, it often takes a geodetic coordinate system associated with the reference ellipsoid. In this case, the Cartesian GNSS vectors are converted, for example, into geodesic parameters (azimuth and length) on the ellipsoid, but the simple form of converted pseudo-observations are the direct differences of the geodetic coordinates. Unfortunately, such an approach may be essentially distorted by a systematic error resulting from the position error of the GNSS vector, before its projection on the ellipsoid surface. In this paper, an analysis of the impact of this error on the determined measures of geometric ellipsoid elements, including the differences of geodetic coordinates or geodesic parameters is presented. Assuming that the adjustment of a combined network on the ellipsoid shows that the optimal functional approach in relation to the satellite observation, is to create the observational equations directly for the original GNSS Cartesian vector components, writing them directly as a function of the geodetic coordinates (in numerical applications, we use the linearized forms of observational equations with explicitly specified coefficients). While retaining the original character of the Cartesian vector, one avoids any systematic errors that may occur in the conversion of the original GNSS vectors to ellipsoid elements, for example the vector of the geodesic parameters. The problem is theoretically developed and numerically tested. An example of the adjustment of a subnet loaded from the database of reference stations of the ASG-EUPOS system was considered for the preferred functional model of the GNSS observations.

Current Good Manufacturing Practice Production of an Oncolytic Recombinant Vesicular Stomatitis Viral Vector for Cancer Treatment

PubMed Central

Meseck, M.; Derecho, I.; Lopez, P.; Knoblauch, C.; McMahon, R.; Anderson, J.; Dunphy, N.; Quezada, V.; Khan, R.; Huang, P.; Dang, W.; Luo, M.; Hsu, D.; Woo, S.L.C.; Couture, L.

2011-01-01

Abstract Vesicular stomatitis virus (VSV) is an oncolytic virus currently being investigated as a promising tool to treat cancer because of its ability to selectively replicate in cancer cells. To enhance the oncolytic property of the nonpathologic laboratory strain of VSV, we generated a recombinant vector [rVSV(MΔ51)-M3] expressing murine gammaherpesvirus M3, a secreted viral chemokine-binding protein that binds to a broad range of mammalian chemokines with high affinity. As previously reported, when rVSV(MΔ51)-M3 was used in an orthotopic model of hepatocellular carcinoma (HCC) in rats, it suppressed inflammatory cell migration to the virus-infected tumor site, which allowed for enhanced intratumoral virus replication leading to increased tumor necrosis and substantially prolonged survival. These encouraging results led to the development of this vector for clinical translation in patients with HCC. However, a scalable current Good Manufacturing Practice (cGMP)-compliant manufacturing process has not been described for this vector. To produce the quantities of high-titer virus required for clinical trials, a process that is amenable to GMP manufacturing and scale-up was developed. We describe here a large-scale (50-liter) vector production process capable of achieving crude titers on the order of 109 plaque-forming units (PFU)/ml under cGMP. This process was used to generate a master virus seed stock and a clinical lot of the clinical trial agent under cGMP with an infectious viral titer of approximately 2 × 1010 PFU/ml (total yield, 1 × 1013 PFU). The lot has passed all U.S. Food and Drug Administration-mandated release testing and will be used in a phase 1 clinical translational trial in patients with advanced HCC. PMID:21083425

Current good manufacturing practice production of an oncolytic recombinant vesicular stomatitis viral vector for cancer treatment.

PubMed

Ausubel, L J; Meseck, M; Derecho, I; Lopez, P; Knoblauch, C; McMahon, R; Anderson, J; Dunphy, N; Quezada, V; Khan, R; Huang, P; Dang, W; Luo, M; Hsu, D; Woo, S L C; Couture, L

2011-04-01

Vesicular stomatitis virus (VSV) is an oncolytic virus currently being investigated as a promising tool to treat cancer because of its ability to selectively replicate in cancer cells. To enhance the oncolytic property of the nonpathologic laboratory strain of VSV, we generated a recombinant vector [rVSV(MΔ51)-M3] expressing murine gammaherpesvirus M3, a secreted viral chemokine-binding protein that binds to a broad range of mammalian chemokines with high affinity. As previously reported, when rVSV(MΔ51)-M3 was used in an orthotopic model of hepatocellular carcinoma (HCC) in rats, it suppressed inflammatory cell migration to the virus-infected tumor site, which allowed for enhanced intratumoral virus replication leading to increased tumor necrosis and substantially prolonged survival. These encouraging results led to the development of this vector for clinical translation in patients with HCC. However, a scalable current Good Manufacturing Practice (cGMP)-compliant manufacturing process has not been described for this vector. To produce the quantities of high-titer virus required for clinical trials, a process that is amenable to GMP manufacturing and scale-up was developed. We describe here a large-scale (50-liter) vector production process capable of achieving crude titers on the order of 10(9) plaque-forming units (PFU)/ml under cGMP. This process was used to generate a master virus seed stock and a clinical lot of the clinical trial agent under cGMP with an infectious viral titer of approximately 2 × 10(10) PFU/ml (total yield, 1 × 10(13) PFU). The lot has passed all U.S. Food and Drug Administration-mandated release testing and will be used in a phase 1 clinical translational trial in patients with advanced HCC.

Loganin enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments.

PubMed

Hwang, Eun-Sang; Kim, Hyun-Bum; Lee, Seok; Kim, Min-Ji; Lee, Sung-Ok; Han, Seung-Moo; Maeng, Sungho; Park, Ji-Ho

2017-03-15

Although the incidence rate of dementia is rapidly growing in the aged population, therapeutic and preventive reagents are still suboptimal. Various model systems are used for the development of such reagents in which scopolamine is one of the favorable pharmacological tools widely applied. Loganin is a major iridoid glycoside obtained from Corni fructus (Cornusofficinalis et Zucc) and demonstrated to have anti-inflammatory, anti-tumor and osteoporosis prevention effects. It has also been found to attenuate Aβ-induced inflammatory reactions and ameliorate memory deficits induced by scopolamine. However, there has been limited information available on how loganin affects learning and memory both electrophysiologically and behaviorally. To assess its effect on learning and memory, we investigated the influence of acute loganin administration on long-term potentiation (LTP) using organotypic cultured hippocampal tissues. In addition, we measured the effects of loganin on the behavior performance related to avoidance memory, short-term spatial navigation memory and long-term spatial learning and memory in the passive avoidance, Y-maze, and Morris water maze learning paradigms, respectively. Loganin dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In accordance with these findings, loganin behaviorally attenuated scopolamine-induced shortening of step-through latency in the passive avoidance test, reduced the percent alternation in the Y-maze, and increased memory retention in the Morris water maze test. These results indicate that loganin can effectively block cholinergic muscarinic receptor blockade -induced deterioration of LTP and memory related behavioral performance. Based on these findings, loganin may aid in the prevention and treatment of Alzheimer's disease and learning and memory-deficit disorders in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment of irritable bowel syndrome in outpatients with inflammatory bowel disease using a food and beverage intolerance, food and beverage avoidance diet.

PubMed

MacDermott, Richard P

2007-01-01

Irritable bowel syndrome (IBS) in the outpatient with chronic inflammatory bowel disease (IBD) is a difficult but important challenge to recognize and treat. It is very helpful to have effective treatment approaches for IBS that are practical and use minimal medications. Because of the underlying chronic inflammation in IBD, IBS symptoms occur with increased frequency and severity, secondary to increased hypersensitivity to foods and beverages that stimulate the gastrointestinal tract. This paper discusses how to treat IBS in the IBD outpatient, with emphasis on using a food and beverage intolerance, avoidance diet. The adverse effects of many foods and beverages are amount dependent and can be delayed, additive, and cumulative. The specific types of foods and beverages that can induce IBS symptoms include milk and milk containing products; caffeine containing products; alcoholic beverages; fruits; fruit juices; spices; seasonings; diet beverages; diet foods; diet candies; diet gum; fast foods; condiments; fried foods; fatty foods; multigrain breads; sourdough breads; bagels; salads; salad dressings; vegetables; beans; red meats; gravies; spaghetti sauce; stews; nuts; popcorn; high fiber; and cookies, crackers, pretzels, cakes, and pies. The types of foods and beverages that are better tolerated include water; rice; plain pasta or noodles; baked or broiled potatoes; white breads; plain fish, chicken, turkey, or ham; eggs; dry cereals; soy or rice based products; peas; applesauce; cantaloupe; watermelon; fruit cocktail; margarine; jams; jellies; and peanut butter. Handouts that were developed based upon what worsens or helps IBS symptoms in patients are included to help patients learn which foods and beverages to avoid and which are better tolerated.

Deciphering Babesia-Vector Interactions.

PubMed

Antunes, Sandra; Rosa, Catarina; Couto, Joana; Ferrolho, Joana; Domingos, Ana

2017-01-01

Understanding host-pathogen-tick interactions remains a vitally important issue that might be better understood by basic research focused on each of the dyad interplays. Pathogens gain access to either the vector or host during tick feeding when ticks are confronted with strong hemostatic, inflammatory and immune responses. A prominent example of this is the Babesia spp.-tick-vertebrate host relationship. Babesia spp. are intraerythrocytic apicomplexan organisms spread worldwide, with a complex life cycle. The presence of transovarial transmission in almost all the Babesia species is the main difference between their life cycle and that of other piroplasmida. With more than 100 species described so far, Babesia are the second most commonly found blood parasite of mammals after trypanosomes. The prevalence of Babesia spp. infection is increasing worldwide and is currently classified as an emerging zoonosis. Babesia microti and Babesia divergens are the most frequent etiological agents associated with human babesiosis in North America and Europe, respectively. Although the Babesia -tick system has been extensively researched, the currently available prophylactic and control methods are not efficient, and chemotherapeutic treatment is limited. Studying the molecular changes induced by the presence of Babesia in the vector will not only elucidate the strategies used by the protozoa to overcome mechanical and immune barriers, but will also contribute toward the discovery of important tick molecules that have a role in vector capacity. This review provides an overview of the identified molecules involved in Babesia -tick interactions, with an emphasis on the fundamentally important ones for pathogen acquisition and transmission.

Deciphering Babesia-Vector Interactions

PubMed Central

Antunes, Sandra; Rosa, Catarina; Couto, Joana; Ferrolho, Joana; Domingos, Ana

2017-01-01

Understanding host-pathogen-tick interactions remains a vitally important issue that might be better understood by basic research focused on each of the dyad interplays. Pathogens gain access to either the vector or host during tick feeding when ticks are confronted with strong hemostatic, inflammatory and immune responses. A prominent example of this is the Babesia spp.—tick—vertebrate host relationship. Babesia spp. are intraerythrocytic apicomplexan organisms spread worldwide, with a complex life cycle. The presence of transovarial transmission in almost all the Babesia species is the main difference between their life cycle and that of other piroplasmida. With more than 100 species described so far, Babesia are the second most commonly found blood parasite of mammals after trypanosomes. The prevalence of Babesia spp. infection is increasing worldwide and is currently classified as an emerging zoonosis. Babesia microti and Babesia divergens are the most frequent etiological agents associated with human babesiosis in North America and Europe, respectively. Although the Babesia-tick system has been extensively researched, the currently available prophylactic and control methods are not efficient, and chemotherapeutic treatment is limited. Studying the molecular changes induced by the presence of Babesia in the vector will not only elucidate the strategies used by the protozoa to overcome mechanical and immune barriers, but will also contribute toward the discovery of important tick molecules that have a role in vector capacity. This review provides an overview of the identified molecules involved in Babesia-tick interactions, with an emphasis on the fundamentally important ones for pathogen acquisition and transmission. PMID:29034218

Transcriptome analysis of a tau overexpression model in rats implicates an early pro-inflammatory response

PubMed Central

Wang, David B.; Dayton, Robert D.; Zweig, Richard M.; Klein, Ronald L.

2010-01-01

Neurofibrillary tangles comprised of the microtubule-associated protein tau are pathological features of Alzheimer's disease and several other neurodegenerative diseases, such as progressive supranuclear palsy. We previously overexpressed tau in the substantia nigra of rats and mimicked some of the neurodegenerative sequelae that occur in humans such as tangle formation, loss of dopamine neurons, and microgliosis. To study molecular changes involved in the tau-induced disease state, we used DNA microarrays at an early stage of the disease process. A range of adeno-associated virus (AAV9) vector doses for tau were injected in groups of rats with a survival interval of two weeks. Specific decreases in messages for dopamine related genes validated the technique with respect to the dopaminergic cell loss observed. Of the mRNAs upregulated, there was a dose-dependent effect on multiple genes involved in immune response such as chemokines, interferon-inducible genes and leukocyte markers, only in the tau vector groups and not in dose-matched controls of either transgene-less empty vector or control green fluorescent protein vector. Histological staining for dopamine neurons and microglia matched the loss of dopaminergic markers and upregulation of immune response mRNAs in the microarray data, respectively. RT-PCR for selected markers confirmed the microarray results, with similar changes found by either technique. The mRNA data correlate well with previous findings, and underscore microgliosis and immune response in the degenerative process following tau overexpression. PMID:20346943

Overexpression of IL-10 in C2D macrophages promotes a macrophage phenotypic switch in adipose tissue environments.

PubMed

Xie, Linglin; Fu, Qiang; Ortega, Teresa M; Zhou, Lun; Rasmussen, Dane; O'Keefe, Jacy; Zhang, Ke K; Chapes, Stephen K

2014-01-01

Adipose tissue macrophages are a heterogeneous collection of classically activated (M1) and alternatively activated (M2) macrophages. Interleukin 10 (IL-10) is an anti-inflammatory cytokine, secreted by a variety of cell types including M2 macrophages. We generated a macrophage cell line stably overexpressing IL-10 (C2D-IL10) and analyzed the C2D-IL10 cells for several macrophage markers after exposure to adipocytes compared to C2D cells transfected with an empty vector (C2D-vector). C2D-IL10 macrophage cells expressed more CD206 when co-cultured with adipocytes than C2D-vector cells; while the co-cultured cell mixture also expressed higher levels of Il4, Il10, Il1β and Tnf. Since regular C2D cells traffic to adipose tissue after adoptive transfer, we explored the impact of constitutive IL-10 expression on C2D-IL10 macrophages in adipose tissue in vivo. Adipose tissue-isolated C2D-IL10 cells increased the percentage of CD206(+), CD301(+), CD11c(-)CD206(+) (M2) and CD11c(+)CD206(+) (M1b) on their cell surface, compared to isolated C2D-vector cells. These data suggest that the expression of IL-10 remains stable, alters the C2D-IL10 macrophage cell surface phenotype and may play a role in regulating macrophage interactions with the adipose tissue.

Reducing inappropriate non-steroidal anti-inflammatory prescription in primary care patients with chronic kidney disease.

PubMed

Keohane, David M; Dennehy, Thomas; Keohane, Kenneth P; Shanahan, Eamonn

2017-08-14

Purpose The purpose of this paper is to reduce inappropriate non-steroidal anti-inflammatory prescribing in primary care patients with chronic kidney disease (CKD). Once diagnosed, CKD management involves delaying progression to end stage renal failure and preventing complications. It is well established that non-steroidal anti-inflammatories have a negative effect on kidney function and consequently, all nephrology consensus groups suggest avoiding this drug class in CKD. Design/methodology/approach The sampling criteria included all practice patients with a known CKD risk factor. This group was refined to include those with an estimated glomerular filtration rate (eGFR)<60 ml/min per 1.73m2 (stage 3 CKD or greater). Phase one analysed how many prescriptions had occurred in this group over the preceding three months. The intervention involved creating an automated alert on at risk patient records if non-steroidal anti-inflammatories were prescribed and discussing the rationale with practice staff. The re-audit phase occurred three months' post intervention. Findings The study revealed 728/7,500 (9.7 per cent) patients at risk from CKD and 158 (2.1 per cent) who were subsequently found to have an eGFR<60 ml/min, indicating=stage 3 CKD. In phase one, 10.2 per cent of at risk patients had received a non-steroidal anti-inflammatory prescription in the preceding three months. Additionally, 6.2 per cent had received non-steroidal anti-inflammatories on repeat prescription. Phase two post intervention revealed a significant 75 per cent reduction in the total non-steroidal anti-inflammatories prescribed and a 90 per cent reduction in repeat non-steroidal anti-inflammatory prescriptions in those with CKD. Originality/value The study significantly reduced non-steroidal anti-inflammatory prescription in those with CKD in primary care settings. It also created a CKD register within the practice and an enduring medication alert system for individuals that risk nephrotoxic non-steroidal anti-inflammatory prescription. It established a safe, reliable and efficient process for reducing morbidity and mortality, improving quality of life and limiting the CKD associated health burden.

Induction of Immune Tolerance to Foreign Protein via Adeno-Associated Viral Vector Gene Transfer in Mid-Gestation Fetal Sheep

PubMed Central

Davey, Marcus G.; Riley, John S.; Andrews, Abigail; Tyminski, Alec; Limberis, Maria; Pogoriler, Jennifer E.; Partridge, Emily; Olive, Aliza; Hedrick, Holly L.; Flake, Alan W.; Peranteau, William H.

2017-01-01

A major limitation to adeno-associated virus (AAV) gene therapy is the generation of host immune responses to viral vector antigens and the transgene product. The ability to induce immune tolerance to foreign protein has the potential to overcome this host immunity. Acquisition and maintenance of tolerance to viral vector antigens and transgene products may also permit repeat administration thereby enhancing therapeutic efficacy. In utero gene transfer (IUGT) takes advantage of the immunologic immaturity of the fetus to induce immune tolerance to foreign antigens. In this large animal study, in utero administration of AAV6.2, AAV8 and AAV9 expressing green fluorescent protein (GFP) to ~60 day fetal sheep (term: ~150 days) was performed. Transgene expression and postnatal immune tolerance to GFP and viral antigens were assessed. We demonstrate 1) hepatic expression of GFP 1 month following in utero administration of AAV6.2.GFP and AAV8.GFP, 2) in utero recipients of either AAV6.2.GFP or AAV8.GFP fail to mount an anti-GFP antibody response following postnatal GFP challenge and lack inflammatory cellular infiltrates at the intramuscular site of immunization, 3) a serotype specific anti-AAV neutralizing antibody response is elicited following postnatal challenge of in utero recipients of AAV6.2 or AAV8 with the corresponding AAV serotype, and 4) durable hepatic GFP expression was observed up to 6 months after birth in recipients of AAV8.GFP but expression was lost between 1 and 6 months of age in recipients of AAV6.2.GFP. The current study demonstrates, in a preclinical large animal model, the potential of IUGT to achieve host immune tolerance to the viral vector transgene product but also suggests that a single exposure to the vector capsid proteins at the time of IUGT is inadequate to induce tolerance to viral vector antigens. PMID:28141818

Annotated Differentially Expressed Salivary Proteins of Susceptible and Insecticide-Resistant Mosquitoes of Anopheles stephensi

PubMed Central

Vijay, Sonam; Rawal, Ritu; Kadian, Kavita; Raghavendra, Kamaraju; Sharma, Arun

2015-01-01

Vector control is one of the major global strategies for control of malaria. However, the major obstacle for vector control is the development of multiple resistances to organochlorine, organophosphorus insecticides and pyrethroids that are currently being used in public health for spraying and in bednets. Salivary glands of vectors are the first target organ for human-vector contact during biting and parasite-vector contact prior to parasite development in the mosquito midguts. The salivary glands secrete anti-haemostatic, anti-inflammatory biologically active molecules to facilitate blood feeding from the host and also inadvertently inject malaria parasites into the vertebrate host. The Anopheles stephensi mosquito, an urban vector of malaria to both human and rodent species has been identified as a reference laboratory model to study mosquito—parasite interactions. In this study, we adopted a conventional proteomic approach of 2D-electrophoresis coupled with MALDI-TOF mass spectrometry and bioinformatics to identify putative differentially expressed annotated functional salivary proteins between An. stephensi susceptible and multiresistant strains with same genetic background. Our results show 2D gel profile and MALDI-TOF comparisons that identified 31 differentially expressed putative modulated proteins in deltamethrin/DDT resistant strains of An. stephensi. Among these 15 proteins were found to be upregulated and 16 proteins were downregulated. Our studies interpret that An. stephensi (multiresistant) caused an upregulated expression of proteins and enzymes like cytochrome 450, short chain dehyrdogenase reductase, phosphodiesterase etc that may have an impact in insecticide resistance and xenobiotic detoxification. Our study elucidates a proteomic response of salivary glands differentially regulated proteins in response to insecticide resistance development which include structural, redox and regulatory enzymes of several pathways. These identified proteins may play a role in regulating mosquito biting behavior patterns and may have implications in the development of malaria parasites in resistant mosquitoes during parasite transmission. PMID:25742511

Annotated differentially expressed salivary proteins of susceptible and insecticide-resistant mosquitoes of Anopheles stephensi.

PubMed

Vijay, Sonam; Rawal, Ritu; Kadian, Kavita; Raghavendra, Kamaraju; Sharma, Arun

2015-01-01

Vector control is one of the major global strategies for control of malaria. However, the major obstacle for vector control is the development of multiple resistances to organochlorine, organophosphorus insecticides and pyrethroids that are currently being used in public health for spraying and in bednets. Salivary glands of vectors are the first target organ for human-vector contact during biting and parasite-vector contact prior to parasite development in the mosquito midguts. The salivary glands secrete anti-haemostatic, anti-inflammatory biologically active molecules to facilitate blood feeding from the host and also inadvertently inject malaria parasites into the vertebrate host. The Anopheles stephensi mosquito, an urban vector of malaria to both human and rodent species has been identified as a reference laboratory model to study mosquito-parasite interactions. In this study, we adopted a conventional proteomic approach of 2D-electrophoresis coupled with MALDI-TOF mass spectrometry and bioinformatics to identify putative differentially expressed annotated functional salivary proteins between An. stephensi susceptible and multiresistant strains with same genetic background. Our results show 2D gel profile and MALDI-TOF comparisons that identified 31 differentially expressed putative modulated proteins in deltamethrin/DDT resistant strains of An. stephensi. Among these 15 proteins were found to be upregulated and 16 proteins were downregulated. Our studies interpret that An. stephensi (multiresistant) caused an upregulated expression of proteins and enzymes like cytochrome 450, short chain dehyrdogenase reductase, phosphodiesterase etc that may have an impact in insecticide resistance and xenobiotic detoxification. Our study elucidates a proteomic response of salivary glands differentially regulated proteins in response to insecticide resistance development which include structural, redox and regulatory enzymes of several pathways. These identified proteins may play a role in regulating mosquito biting behavior patterns and may have implications in the development of malaria parasites in resistant mosquitoes during parasite transmission.

Ethnopharmacological in vitro studies on Austria's folk medicine—An unexplored lore in vitro anti-inflammatory activities of 71 Austrian traditional herbal drugs☆

PubMed Central

Vogl, Sylvia; Picker, Paolo; Mihaly-Bison, Judit; Fakhrudin, Nanang; Atanasov, Atanas G.; Heiss, Elke H.; Wawrosch, Christoph; Reznicek, Gottfried; Dirsch, Verena M.; Saukel, Johannes; Kopp, Brigitte

2013-01-01

Ethnopharmacological relevance In Austria, like in most Western countries, knowledge about traditional medicinal plants is becoming scarce. Searching the literature concerning Austria's ethnomedicine reveals its scant scientific exploration. Aiming to substantiate the potential of medicinal plants traditionally used in Austria, 63 plant species or genera with claimed anti-inflammatory properties listed in the VOLKSMED database were assessed for their in vitro anti-inflammatory activity. Material and methods 71 herbal drugs from 63 plant species or genera were extracted using solvents of varying polarities and subsequently depleted from the bulk constituents, chlorophylls and tannins to avoid possible interferences with the assays. The obtained 257 extracts were assessed for their in vitro anti-inflammatory activity. The expression of the inflammatory mediators E-selectin and interleukin-8 (IL-8), induced by the inflammatory stimuli tumor necrosis factor alpha (TNF-α) and the bacterial product lipopolysaccharide (LPS) was measured in endothelial cells. The potential of the extracts to activate the nuclear factors PPARα and PPARγ and to inhibit TNF-α-induced activation of the nuclear factor-kappa B (NF-κB) in HEK293 cells was determined by luciferase reporter gene assays. Results In total, extracts from 67 of the 71 assessed herbal drugs revealed anti-inflammatory activity in the applied in vitro test systems. Thereby, 30 could downregulate E-selectin or IL-8 gene expression, 28 were strong activators of PPARα or PPARγ (inducing activation of more than 2-fold at a concentration of 10 µg/mL) and 21 evoked a strong inhibition of NF-κB (inhibition of more than 80% at 10 µg/mL). Conclusion Our research supports the efficacy of herbal drugs reported in Austrian folk medicine used for ailments associated with inflammatory processes. Hence, an ethnopharmacological screening approach is a useful tool for the discovery of new drug leads. PMID:23770053

A comparative analysis of acute-phase proteins as inflammatory biomarkers in preclinical toxicology studies: implications for preclinical to clinical translation.

PubMed

Watterson, Claire; Lanevschi, Anne; Horner, Judith; Louden, Calvert

2009-01-01

Recently, in early clinical development, a few biologics and small molecules intended as antitumor or anti-inflammatory agents have caused a severe adverse pro-inflammatory systemic reaction also known as systemic inflammatory response syndrome (SIRS). This toxicity could result from expected pharmacological effects of a therapeutic antibody and/or from interaction with antigens expressed on cells/tissues other than the intended target. Clinical monitoring of SIRS is challenging because of the narrow diagnostic window to institute a successful intervening therapeutic strategy prior to acute circulatory collapse. Furthermore, for these classes of therapeutic agents, studies in animals have low predictive ability to identify potential human hazards. In vitro screens with human cells, though promising, need further development. Therefore, identification of improved preclinical diagnostic markers of SIRS will enable clinicians to select applicable markers for clinical testing and avoid potentially catastrophic events. There is limited preclinical toxicology data describing the interspecies performance of acute-phase proteins because the response time, type, and duration of major acute-phase proteins vary significantly between species. This review will attempt to address this intellectual gap, as well as the use and applicability of acute-phase proteins as preclinical to clinical translational biomarkers of SIRS.

A Parallel Vector Machine for the PM Programming Language

NASA Astrophysics Data System (ADS)

Bellerby, Tim

2016-04-01

PM is a new programming language which aims to make the writing of computational geoscience models on parallel hardware accessible to scientists who are not themselves expert parallel programmers. It is based around the concept of communicating operators: language constructs that enable variables local to a single invocation of a parallelised loop to be viewed as if they were arrays spanning the entire loop domain. This mechanism enables different loop invocations (which may or may not be executing on different processors) to exchange information in a manner that extends the successful Communicating Sequential Processes idiom from single messages to collective communication. Communicating operators avoid the additional synchronisation mechanisms, such as atomic variables, required when programming using the Partitioned Global Address Space (PGAS) paradigm. Using a single loop invocation as the fundamental unit of concurrency enables PM to uniformly represent different levels of parallelism from vector operations through shared memory systems to distributed grids. This paper describes an implementation of PM based on a vectorised virtual machine. On a single processor node, concurrent operations are implemented using masked vector operations. Virtual machine instructions operate on vectors of values and may be unmasked, masked using a Boolean field, or masked using an array of active vector cell locations. Conditional structures (such as if-then-else or while statement implementations) calculate and apply masks to the operations they control. A shift in mask representation from Boolean to location-list occurs when active locations become sufficiently sparse. Parallel loops unfold data structures (or vectors of data structures for nested loops) into vectors of values that may additionally be distributed over multiple computational nodes and then split into micro-threads compatible with the size of the local cache. Inter-node communication is accomplished using standard OpenMP and MPI. Performance analyses of the PM vector machine, demonstrating its scaling properties with respect to domain size and the number of processor nodes will be presented for a range of hardware configurations. The PM software and language definition are being made available under unrestrictive MIT and Creative Commons Attribution licenses respectively: www.pm-lang.org.

Air Travel, Circadian Rhythms/Hormones, and Autoimmunity.

PubMed

Torres-Ruiz, J; Sulli, A; Cutolo, M; Shoenfeld, Y

2017-08-01

Biological rhythms are fundamental for homeostasis and have recently been involved in the regulatory processes of various organs and systems. Circadian cycle proteins and hormones have a direct effect on the inflammatory response and have shown pro- or anti-inflammatory effects in animal models of autoimmune diseases. The cells of the immune system have their own circadian rhythm, and the light-dark cycle directly influences the inflammatory response. On the other hand, patients with autoimmune diseases characteristically have sleep disorders and fatigue, and in certain disease, such as rheumatoid arthritis (RA), a frank periodicity in the signs and symptoms is recognized. The joint symptoms predominate in the morning, and apparently, subjects with RA have relative adrenal insufficiency, with a cortisol peak unable to control the late night load of pro-inflammatory cytokines. Transatlantic flights represent a challenge in the adjustment of biological rhythms, since they imply sleep deprivation, time zone changes, and potential difficulties for drug administration. In patients with autoimmune diseases, the use of DMARDs and prednisone at night is probably best suited to lessen morning symptoms. It is also essential to sleep during the trip to improve adaptation to the new time zone and to avoid, as far as possible, works involving flexible or nocturnal shifts. The study of proteins and hormones related to biological rhythms will demonstrate new pathophysiological pathways of autoimmune diseases, which will emphasize the use of general measures for sleep respect and methods for drug administration at key daily times to optimize their anti-inflammatory and immune modulatory effects.

Cardiac RNAi therapy using RAGE siRNA/deoxycholic acid-modified polyethylenimine complexes for myocardial infarction.

PubMed

Hong, Jueun; Ku, Sook Hee; Lee, Min Sang; Jeong, Ji Hoon; Mok, Hyejung; Choi, Donghoon; Kim, Sun Hwa

2014-08-01

Inflammatory response in myocardial ischemia-reperfusion injury plays a critical role in ventricular remodeling. To avoid deleterious effects of overwhelming inflammation, we blocked the expression of receptor for advanced glycation end-products (RAGE), a key mediator of the local and systemic inflammatory responses, via RNAi mechanism. Herein, a facial amphipathic deoxycholic acid-modified low molecular weight polyethylenimine (DA-PEI) was used as a siRNA delivery carrier to myocardium. The DA-PEI conjugate formed a stable complex with siRNA via electrostatic and hydrophobic interactions. The siRAGE/DA-PEI formulation having negligible toxicity could enhance intracellular delivery efficiency and successfully suppress RAGE expression both in vitro and in vivo. Furthermore, the cardiac administration of siRAGE/DA-PEI reduced apoptosis and inflammatory cytokine release, subsequently led to attenuation of left ventricular remodeling in rat myocardial infarction model. The potential therapeutic effects of RAGE gene silencing on myocardial ischemia-reperfusion injury may suggest that the siRAGE/DA-PEI delivery system can be considered as a promising strategy for treating myocardial infarction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Anti-inflammatory properties of drugs from saffron crocus.

PubMed

Poma, Anna; Fontecchio, Gabriella; Carlucci, Giuseppe; Chichiriccò, Giuseppe

2012-01-01

The medicinal uses of saffron (Crocus sativus Linnaeus) have a long history beginning in Asian countries since the Late Bronze Age. Recent studies have validated its potential to lower the risk of several diseases. Some metabolites derived from saffron stigmas exert numerous therapeutic effects due to hypolipidemic, antitussive, antioxidant, antidiabetic activities and many others. Water and ethanol extracts of Crocus sativus L. are cardioprotective and counteract neurodegenerative disorders. Many of these medicinal properties of saffron can be attributed to a number of its compounds such as crocetin, crocins and other substances having strong antioxidant and radical scavenger properties against a variety of radical oxygen species and pro-inflammatory cytokines. Botany, worldwide spreading of cultivars, biochemical pathways, active constituents and chemical detection methods are reviewed. Therapeutic uses of saffron principles with particular regard to those exhibiting antioxidant and thus anti-inflammatory features are discussed. To date, very few adverse health effects of saffron have been demonstrated. At high doses (more than 5 g/die day), it should be avoided in pregnancy owing to its uterine stimulation activity.

Unmanned Aircraft Systems Detect and Avoid System: End-to-End Verification and Validation Simulation Study of Minimum Operations Performance Standards for Integrating Unmanned Aircraft into the National Airspace System

NASA Technical Reports Server (NTRS)

Ghatas, Rania W.; Jack, Devin P.; Tsakpinis, Dimitrios; Sturdy, James L.; Vincent, Michael J.; Hoffler, Keith D.; Myer, Robert R.; DeHaven, Anna M.

2017-01-01

As Unmanned Aircraft Systems (UAS) make their way to mainstream aviation operations within the National Airspace System (NAS), research efforts are underway to develop a safe and effective environment for their integration into the NAS. Detect and Avoid (DAA) systems are required to account for the lack of "eyes in the sky" due to having no human on-board the aircraft. The technique, results, and lessons learned from a detailed End-to-End Verification and Validation (E2-V2) simulation study of a DAA system representative of RTCA SC-228's proposed Phase I DAA Minimum Operational Performance Standards (MOPS), based on specific test vectors and encounter cases, will be presented in this paper.

Cosmology in bimetric theory with an effective composite coupling to matter

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

Gümrükçüoğlu, A. Emir; Heisenberg, Lavinia; Mukohyama, Shinji

We study the cosmology of bimetric theory with a composite matter coupling. We find two possible branches of background evolution. We investigate the question of stability of cosmological perturbations. For the tensor and vector perturbations, we derive conditions on the absence of ghost and gradient instabilities. For the scalar modes, we obtain conditions for avoiding ghost degrees. In the first branch, we find that one of the scalar modes becomes a ghost at the late stages of the evolution. Conversely, this problem can be avoided in the second branch. However, we also find that the constraint for the second branchmore » prevents the doubly coupled matter fields from being the standard ingredients of cosmology. We thus conclude that a realistic and stable cosmological model requires additional minimally coupled matter fields.« less

Oral delivery of Lactococcus lactis that secretes bioactive heme oxygenase-1 alleviates development of acute colitis in mice.

PubMed

Shigemori, Suguru; Watanabe, Takafumi; Kudoh, Kai; Ihara, Masaki; Nigar, Shireen; Yamamoto, Yoshinari; Suda, Yoshihito; Sato, Takashi; Kitazawa, Haruki; Shimosato, Takeshi

2015-11-25

Mucosal delivery of therapeutic proteins using genetically modified strains of lactic acid bacteria (gmLAB) is being investigated as a new therapeutic strategy. We developed a strain of gmLAB, Lactococcus lactis NZ9000 (NZ-HO), which secretes the anti-inflammatory molecule recombinant mouse heme oxygenase-1 (rmHO-1). The effects of short-term continuous oral dosing with NZ-HO were evaluated in mice with dextran sulfate sodium (DSS)-induced acute colitis as a model of inflammatory bowel diseases (IBD). We identified the secretion of rmHO-1 by NZ-HO. rmHO-1 was biologically active as determined with spectroscopy. Viable NZ-HO was directly delivered to the colon via oral administration, and rmHO-1 was secreted onto the colonic mucosa in mice. Acute colitis in mice was induced by free drinking of 3 % DSS in water and was accompanied by an increase in the disease activity index score and histopathological changes. Daily oral administration of NZ-HO significantly improved these colitis-associated symptoms. In addition, NZ-HO significantly increased production of the anti-inflammatory cytokine interleukin (IL)-10 and decreased the expression of pro-inflammatory cytokines such as IL-1α and IL-6 in the colon compared to a vector control strain. Oral administration of NZ-HO alleviates DSS-induced acute colitis in mice. Our results suggest that NZ-HO may be a useful mucosal therapeutic agent for treating IBD.

Mathematical solution of multilevel fractional programming problem with fuzzy goal programming approach

NASA Astrophysics Data System (ADS)

Lachhwani, Kailash; Poonia, Mahaveer Prasad

2012-08-01

In this paper, we show a procedure for solving multilevel fractional programming problems in a large hierarchical decentralized organization using fuzzy goal programming approach. In the proposed method, the tolerance membership functions for the fuzzily described numerator and denominator part of the objective functions of all levels as well as the control vectors of the higher level decision makers are respectively defined by determining individual optimal solutions of each of the level decision makers. A possible relaxation of the higher level decision is considered for avoiding decision deadlock due to the conflicting nature of objective functions. Then, fuzzy goal programming approach is used for achieving the highest degree of each of the membership goal by minimizing negative deviational variables. We also provide sensitivity analysis with variation of tolerance values on decision vectors to show how the solution is sensitive to the change of tolerance values with the help of a numerical example.

Mathematical modelling of Bit-Level Architecture using Reciprocal Quantum Logic

NASA Astrophysics Data System (ADS)

Narendran, S.; Selvakumar, J.

2018-04-01

Efficiency of high-performance computing is on high demand with both speed and energy efficiency. Reciprocal Quantum Logic (RQL) is one of the technology which will produce high speed and zero static power dissipation. RQL uses AC power supply as input rather than DC input. RQL has three set of basic gates. Series of reciprocal transmission lines are placed in between each gate to avoid loss of power and to achieve high speed. Analytical model of Bit-Level Architecture are done through RQL. Major drawback of reciprocal Quantum Logic is area, because of lack in proper power supply. To achieve proper power supply we need to use splitters which will occupy large area. Distributed arithmetic uses vector- vector multiplication one is constant and other is signed variable and each word performs as a binary number, they rearranged and mixed to form distributed system. Distributed arithmetic is widely used in convolution and high performance computational devices.

A Relevance Vector Machine-Based Approach with Application to Oil Sand Pump Prognostics

PubMed Central

Hu, Jinfei; Tse, Peter W.

2013-01-01

Oil sand pumps are widely used in the mining industry for the delivery of mixtures of abrasive solids and liquids. Because they operate under highly adverse conditions, these pumps usually experience significant wear. Consequently, equipment owners are quite often forced to invest substantially in system maintenance to avoid unscheduled downtime. In this study, an approach combining relevance vector machines (RVMs) with a sum of two exponential functions was developed to predict the remaining useful life (RUL) of field pump impellers. To handle field vibration data, a novel feature extracting process was proposed to arrive at a feature varying with the development of damage in the pump impellers. A case study involving two field datasets demonstrated the effectiveness of the developed method. Compared with standalone exponential fitting, the proposed RVM-based model was much better able to predict the remaining useful life of pump impellers. PMID:24051527

Support vector machines and generalisation in HEP

NASA Astrophysics Data System (ADS)

Bevan, Adrian; Gamboa Goñi, Rodrigo; Hays, Jon; Stevenson, Tom

2017-10-01

We review the concept of Support Vector Machines (SVMs) and discuss examples of their use in a number of scenarios. Several SVM implementations have been used in HEP and we exemplify this algorithm using the Toolkit for Multivariate Analysis (TMVA) implementation. We discuss examples relevant to HEP including background suppression for H → τ + τ - at the LHC with several different kernel functions. Performance benchmarking leads to the issue of generalisation of hyper-parameter selection. The avoidance of fine tuning (over training or over fitting) in MVA hyper-parameter optimisation, i.e. the ability to ensure generalised performance of an MVA that is independent of the training, validation and test samples, is of utmost importance. We discuss this issue and compare and contrast performance of hold-out and k-fold cross-validation. We have extended the SVM functionality and introduced tools to facilitate cross validation in TMVA and present results based on these improvements.

Image size invariant visual cryptography for general access structures subject to display quality constraints.

PubMed

Lee, Kai-Hui; Chiu, Pei-Ling

2013-10-01

Conventional visual cryptography (VC) suffers from a pixel-expansion problem, or an uncontrollable display quality problem for recovered images, and lacks a general approach to construct visual secret sharing schemes for general access structures. We propose a general and systematic approach to address these issues without sophisticated codebook design. This approach can be used for binary secret images in non-computer-aided decryption environments. To avoid pixel expansion, we design a set of column vectors to encrypt secret pixels rather than using the conventional VC-based approach. We begin by formulating a mathematic model for the VC construction problem to find the column vectors for the optimal VC construction, after which we develop a simulated-annealing-based algorithm to solve the problem. The experimental results show that the display quality of the recovered image is superior to that of previous papers.

Real-time characterization of motion of motile microorganisms by means of a hybrid laser Doppler velocimeter technique

NASA Astrophysics Data System (ADS)

Zheng, Bin; Pleass, Charles M.; Ih, Charles S.

1993-11-01

A hybrid three-axis laser Doppler velocimeter system has been demonstrated in our laboratory. The system can monitor the motion of microorganisms in an unconstrained environment. During measurement, a computer system collects and processes time series data from the transit of a microorganism through the measurement volume. The fast Fourier transform of this data contains the motion signature of this microorganism. Because individual microorganisms can be selected from the field, ambiguity caused by multiscattering among two or more microorganisms can be avoided. Using this new system, we can obtain a feature vector that relates to features of the microorganism, such as its size, average translational velocity, rotation or wobbling, and its flagellum beat frequency. Such a vector appears to be a useful criterion for distinguishing the species using statistical pattern recognition. Successful experiments demonstrate that the new system and technique has some unique advantages.

Density-based penalty parameter optimization on C-SVM.

PubMed

Liu, Yun; Lian, Jie; Bartolacci, Michael R; Zeng, Qing-An

2014-01-01

The support vector machine (SVM) is one of the most widely used approaches for data classification and regression. SVM achieves the largest distance between the positive and negative support vectors, which neglects the remote instances away from the SVM interface. In order to avoid a position change of the SVM interface as the result of an error system outlier, C-SVM was implemented to decrease the influences of the system's outliers. Traditional C-SVM holds a uniform parameter C for both positive and negative instances; however, according to the different number proportions and the data distribution, positive and negative instances should be set with different weights for the penalty parameter of the error terms. Therefore, in this paper, we propose density-based penalty parameter optimization of C-SVM. The experiential results indicated that our proposed algorithm has outstanding performance with respect to both precision and recall.

Controllable Edge Feature Sharpening for Dental Applications

PubMed Central

2014-01-01

This paper presents a new approach to sharpen blurred edge features in scanned tooth preparation surfaces generated by structured-light scanners. It aims to efficiently enhance the edge features so that the embedded feature lines can be easily identified in dental CAD systems, and to avoid unnatural oversharpening geometry. We first separate the feature regions using graph-cut segmentation, which does not require a user-defined threshold. Then, we filter the face normal vectors to propagate the geometry from the smooth region to the feature region. In order to control the degree of the sharpness, we propose a feature distance measure which is based on normal tensor voting. Finally, the vertex positions are updated according to the modified face normal vectors. We have applied the approach to scanned tooth preparation models. The results show that the blurred edge features are enhanced without unnatural oversharpening geometry. PMID:24741376

Controllable edge feature sharpening for dental applications.

PubMed

Fan, Ran; Jin, Xiaogang

2014-01-01

This paper presents a new approach to sharpen blurred edge features in scanned tooth preparation surfaces generated by structured-light scanners. It aims to efficiently enhance the edge features so that the embedded feature lines can be easily identified in dental CAD systems, and to avoid unnatural oversharpening geometry. We first separate the feature regions using graph-cut segmentation, which does not require a user-defined threshold. Then, we filter the face normal vectors to propagate the geometry from the smooth region to the feature region. In order to control the degree of the sharpness, we propose a feature distance measure which is based on normal tensor voting. Finally, the vertex positions are updated according to the modified face normal vectors. We have applied the approach to scanned tooth preparation models. The results show that the blurred edge features are enhanced without unnatural oversharpening geometry.

A support vector machine based control application to the experimental three-tank system.

PubMed

Iplikci, Serdar

2010-07-01

This paper presents a support vector machine (SVM) approach to generalized predictive control (GPC) of multiple-input multiple-output (MIMO) nonlinear systems. The possession of higher generalization potential and at the same time avoidance of getting stuck into the local minima have motivated us to employ SVM algorithms for modeling MIMO systems. Based on the SVM model, detailed and compact formulations for calculating predictions and gradient information, which are used in the computation of the optimal control action, are given in the paper. The proposed MIMO SVM-based GPC method has been verified on an experimental three-tank liquid level control system. Experimental results have shown that the proposed method can handle the control task successfully for different reference trajectories. Moreover, a detailed discussion on data gathering, model selection and effects of the control parameters have been given in this paper. 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Annual Insecticide Loadings

EPA Pesticide Factsheets

Pesticides, Herbicides, Fungicides...etc, are used for a variety of purposes, including control of household, lawn, and garden pests; for control of mosquitoes and other insect vectors of animal and human diseases; for control of brush in rangelands, on roadsides, and along power line rights-of-way; as wood preservatives; as disinfectants; and in golf courses, parks and forest lands. The toxicity that makes pesticides useful in agriculture, silviculture, disease vector, and nuisance control can, however, also endanger humans, nontarget wildlife, and ecosystems. EPA carries the mandated responsibility for solving this policy and regulatory dilemma, first through registering pesticides so that their labels explain how to avoid unreasonable risks when using them, and second by setting allowable levels of pesticide residues to ensure the safety of drinking water and the food supply (Schierow 1996). More information about these resources, including the variables used in this study, may be found here: https://edg.epa.gov/data/Public/ORD/NERL/ReVA/ReVA_Data.zip.

Annual Fungicide Loadings

EPA Pesticide Factsheets

Pesticides, Herbicides, Fungicides...etc, are used for a variety of purposes, including control of household, lawn, and garden pests; for control of mosquitoes and other insect vectors of animal and human diseases; for control of brush in rangelands, on roadsides, and along power line rights-of-way; as wood preservatives; as disinfectants; and in golf courses, parks and forest lands. The toxicity that makes pesticides useful in agriculture, silviculture, disease vector, and nuisance control can, however, also endanger humans, nontarget wildlife, and ecosystems. EPA carries the mandated responsibility for solving this policy and regulatory dilemma, first through registering pesticides so that their labels explain how to avoid unreasonable risks when using them, and second by setting allowable levels of pesticide residues to ensure the safety of drinking water and the food supply (Schierow 1996). More information about these resources, including the variables used in this study, may be found here: https://edg.epa.gov/data/Public/ORD/NERL/ReVA/ReVA_Data.zip.

The public health planners' perfect storm: Hurricane Matthew and Zika virus.

PubMed

Ahmed, Qanta A; Memish, Ziad A

Hurricane Matthew threatened to be one of the most powerful Hurricanes to hit the United States in a century. Fortunately, it avoided making landfall on Florida, the eye of the Hurricane remaining centered 40 miles off the Florida coast. Even so it has resulted in over $7 Billion USD in damage according to initial estimates with much of the damage ongoing in severe flooding. Response to and recovery from Hurricane Matthew challenged Florida's public health services and resources just as emergency Zika-specific congressional funding to combat Zika outbreaks in Florida had become available. Hurricanes can disrupt the urban environment in a way that increases the likelihood of vector-borne illnesses and their aftermath can severely strain the very infectious disease and infection control academe needed to combat vector-borne outbreaks. This commentary attempts to examine the challenges posed by Hurricane Matthew in Florida's efforts to contain Zika. Copyright © 2016 Elsevier Ltd. All rights reserved.

A relevance vector machine-based approach with application to oil sand pump prognostics.

PubMed

Hu, Jinfei; Tse, Peter W

2013-09-18

Oil sand pumps are widely used in the mining industry for the delivery of mixtures of abrasive solids and liquids. Because they operate under highly adverse conditions, these pumps usually experience significant wear. Consequently, equipment owners are quite often forced to invest substantially in system maintenance to avoid unscheduled downtime. In this study, an approach combining relevance vector machines (RVMs) with a sum of two exponential functions was developed to predict the remaining useful life (RUL) of field pump impellers. To handle field vibration data, a novel feature extracting process was proposed to arrive at a feature varying with the development of damage in the pump impellers. A case study involving two field datasets demonstrated the effectiveness of the developed method. Compared with standalone exponential fitting, the proposed RVM-based model was much better able to predict the remaining useful life of pump impellers.

Adaptive Array for Weak Interfering Signals: Geostationary Satellite Experiments. M.S. Thesis

NASA Technical Reports Server (NTRS)

Steadman, Karl

1989-01-01

The performance of an experimental adaptive array is evaluated using signals from an existing geostationary satellite interference environment. To do this, an earth station antenna was built to receive signals from various geostationary satellites. In these experiments the received signals have a frequency of approximately 4 GHz (C-band) and have a bandwidth of over 35 MHz. These signals are downconverted to a 69 MHz intermediate frequency in the experimental system. Using the downconverted signals, the performance of the experimental system for various signal scenarios is evaluated. In this situation, due to the inherent thermal noise, qualitative instead of quantitative test results are presented. It is shown that the experimental system can null up to two interfering signals well below the noise level. However, to avoid the cancellation of the desired signal, the use a steering vector is needed. Various methods to obtain an estimate of the steering vector are proposed.

Space-time variability of citrus leprosis as strategic planning for crop management.

PubMed

Andrade, Daniel J; Lorençon, José R; Siqueira, Diego S; Novelli, Valdenice M; Bassanezi, Renato B

2018-01-31

Citrus leprosis is the most important viral disease of citrus. Knowledge of its spatiotemporal structure is fundamental to a representative sampling plan focused on the disease control approach. Such a well-crafted sampling design helps to reduce pesticide use in agriculture to control pests and diseases. Despite the use of acaricides to control citrus leprosis vector (Brevipalpus spp.) populations, the disease has spread rapidly through experimental areas. Citrus leprosis has an aggregate spatial distribution, with high dependence among symptomatic plants. Temporal variation in disease incidence increased among symptomatic plants by 4% per month. Use of acaricides alone to control the vector of leprosis is insufficient to avoid its incidence in healthy plants. Preliminary investigation into the time and space variation in the incidence of the disease is fundamental to select a sampling plan and determine effective strategies for disease management. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Inhibition of oncogene-induced inflammatory chemokines using a farnesyltransferase inhibitor

PubMed Central

DeGeorge, Katharine C; DeGeorge, Brent R; Testa, James S; Rothstein, Jay L

2008-01-01

Background Farnesyltransferase inhibitors (FTI) are small molecule agents originally formulated to inhibit the oncogenic functions of Ras. Although subsequent analysis of FTI activity revealed wider effects on other pathways, the drug has been demonstrated to reduce Ras signaling by direct measurements. The purpose of the current study was to determine if FTI could be used to inhibit the inflammatory activities of a known Ras-activating human oncoprotein, RET/PTC3. RET/PTC3 is a fusion oncoprotein expressed in the thyroid epithelium of patients afflicted with thyroid autoimmune disease and/or differentiated thyroid carcinoma. Previous studies have demonstrated that RET/PTC3 signals through Ras and can provoke nuclear translocation of NFκB and the downstream release of pro-inflammatory mediators from thyroid follicular cells in vitro and in vivo, making it an ideal target for studies using FTI. Methods For the studies described here, an in vitro assay was developed to measure FTI inhibition of RET/PTC3 pro-inflammatory effects. Rat thyrocytes transfected with RET/PTC3 or vector control cDNA were co-cultured with FTI and examined for inhibition of chemokine expression and secretion measured by RT-PCR and ELISA. Immunoblot analysis was used to confirm the level at which FTI acts on RET/PTC3-expressing cells, and Annexin V/PI staining of cells was used to assess cell death in RET/PTC3-expressing cells co-cultured with FTI. Results These analyses revealed significant mRNA and protein inhibition of chemokines Ccl2 and Cxcl1 with nanomolar doses of FTI. Neither RET/PTC3 protein expression nor apoptosis were affected at any dose of FTI investigated. Conclusion These data suggest that FTI may be applied as an effective inhibitor for RET/PTC3-oncogene induced pro-inflammatory mediators. PMID:18304343

Behavioral Responses of Catnip (Nepeta cataria) by Two Species of Mosquitoes, Aedes aegypti and Anopheles harrisoni, in Thailand

DTIC Science & Technology

2008-01-01

Ministry of Public Health (MOPH) in Thailand has recommended the use of deltamethrin in public health to control malaria and dengue haemorhagic fever...catnip oil. We investigated the activity of catnip oil against 2 species of mosquitoes, Ae. aegypti, a vector of dengue , and Anopheles harrisoni...systems. This test system was first used to test the avoidance behavior of An. abimanus from Belize , Central America (Char- eonviriyaphap et al. 1997

Synthetic lipoprotein as nano-material vehicle in the targeted drug delivery.

PubMed

Zhang, Xueqin; Huang, Gangliang

2017-12-01

High-density lipoprotein (HDL) and low-density lipoprotein (LDL), as human endogenous lipoprotein particles, have low toxicity, high selectivity, and good safety. They can avoid the recognition and clearance of human reticuloendothelial system. These synthetic lipoproteins (sLPs) have been attracted extensive attention as the nanovectors for tumor-targeted drug and gene delivery. Herein, recent advances in the field of anticancer based on these two lipid proteins and recombinant lipoproteins (rLPs) as target delivery vectors were analyzed and discussed.

Spectral functions at small energies and the electrical conductivity in hot quenched lattice QCD.

PubMed

Aarts, Gert; Allton, Chris; Foley, Justin; Hands, Simon; Kim, Seyong

2007-07-13

In lattice QCD, the maximum entropy method can be used to reconstruct spectral functions from Euclidean correlators obtained in numerical simulations. We show that at finite temperature the most commonly used algorithm, employing Bryan's method, is inherently unstable at small energies and gives a modification that avoids this. We demonstrate this approach using the vector current-current correlator obtained in quenched QCD at finite temperature. Our first results indicate a small electrical conductivity above the deconfinement transition.

Iterative Minimum Variance Beamformer with Low Complexity for Medical Ultrasound Imaging.

PubMed

Deylami, Ali Mohades; Asl, Babak Mohammadzadeh

2018-06-04

Minimum variance beamformer (MVB) improves the resolution and contrast of medical ultrasound images compared with delay and sum (DAS) beamformer. The weight vector of this beamformer should be calculated for each imaging point independently, with a cost of increasing computational complexity. The large number of necessary calculations limits this beamformer to application in real-time systems. A beamformer is proposed based on the MVB with lower computational complexity while preserving its advantages. This beamformer avoids matrix inversion, which is the most complex part of the MVB, by solving the optimization problem iteratively. The received signals from two imaging points close together do not vary much in medical ultrasound imaging. Therefore, using the previously optimized weight vector for one point as initial weight vector for the new neighboring point can improve the convergence speed and decrease the computational complexity. The proposed method was applied on several data sets, and it has been shown that the method can regenerate the results obtained by the MVB while the order of complexity is decreased from O(L 3 ) to O(L 2 ). Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Gene correction of induced pluripotent stem cells derived from a murine model of X-linked chronic granulomatous disorder.

PubMed

Mukherjee, Sayandip; Thrasher, Adrian J

2014-01-01

Gene therapy presents an attractive alternative to allogeneic haematopoietic stem cell transplantation (HSCT) for treating patients suffering from primary immunodeficiency disorder (PID). The conceptual advantage of gene correcting a patient's autologous HSCs lies in minimizing or completely avoiding immunological complications arising from allogeneic transplantation while conferring the same benefits of immune reconstitution upon long-term engraftment. Clinical trials targeting X-linked chronic granulomatous disorder (X-CGD) have shown promising results in this context. However, long-term clinical benefits in these patients have been limited by issues of poor engraftment of gene-transduced cells coupled with transgene silencing and vector induced clonal proliferation. Novel vectors incorporating safety features such as self-inactivating (SIN) mutations in the long terminal repeats (LTRs) along with synthetic promoters driving lineage-restricted sustainable expression of the gp91phox transgene are expected to resolve the current pitfalls and require rigorous preclinical testing. In this chapter, we have outlined a protocol in which X-CGD mouse model derived induced pluripotent stem cells (iPSCs) have been utilized to develop a platform for investigating the efficacy and safety profiles of novel vectors prior to clinical evaluation.

Phenotypic correction of Fanconi anemia cells in the murine bone marrow after carrier cell mediated delivery of lentiviral vector.

PubMed

Chakkaramakkil Verghese, Santhosh; Goloviznina, Natalya A; Kurre, Peter

2016-11-19

Fanconi anemia (FA) is an autosomal-recessive disorder associated with hematopoietic failure and it is a candidate for hematopoietic stem cell (HSC)-directed gene therapy. However, the characteristically reduced HSC numbers found in FA patients, their ineffective mobilization from the marrow, and re-oxygenation damage during ex vivo manipulation have precluded clinical success using conventional in vitro approaches. We previously demonstrated that lentiviral vector (LV) particles reversibly attach to the cell surface where they gain protection from serum complement neutralization. We reasoned that cellular delivery of LV to the bone marrow niche could avoid detrimental losses during FA HSC mobilization and in vitro modification. Here, we demonstrate that a VSV-G pseudotyped lentivector, carrying the FANCC transgene, can be transmitted from carrier to bystander cells. In cell culture and transplantation models of FA, we further demonstrate that LV carrier cells migrate along SDF-1α gradients and transfer vector particles that stably integrate and phenotypically correct the characteristic DNA alkylator sensitivity in murine and human FA-deficient target bystander cells. Altogether, we demonstrate that cellular homing mechanisms can be harnessed for the functional phenotype correction in murine FA hematopoietic cells.

Vector prevalence and detection of Crimean-Congo haemorrhagic fever virus in Golestan Province, Iran.

PubMed

Sedaghat, Mohammad Mehdi; Sarani, Moslem; Chinikar, Sadegh; Telmadarraiy, Zakiye; Moghaddam, Abdolreza Salahi; Azam, Kamal; Nowotny, Norbert; Fooks, Anthony R; Shahhosseini, Nariman

2017-01-01

Crimean-Congo haemorrhagic fever virus (CCHFV) causes severe disease with fatality rate of 30%. The virus is transmitted to humans through the bite of an infected tick, direct contact with the products of infected livestock as well as nosocomially. The disease occurs sporadically throughout many of African, Asian and European countries. Different species of ticks serve either as vector or reservoir for CCHFV. This study was aimed to determine the prevalence of CCHFV in hard ticks (Ixodidae) in the Golestan Province of Iran. A molecular survey was conducted on hard ticks (Ixodidae) isolated from six counties in Golestan Province, north of Iran during 2014-15. The ticks were identified using morphological characteristics and presence of CCHFV RNA was detected using RT-PCR. Data revealed the presence of CCHFV in 5.3% of the ticks selected for screening. The infected ticks belonged to Hyalomma dromedarii, Hy. anatolicum, Hy. marginatum and Rhipicephalus sanguineus species. The study demonstrated that Hyalomma ticks are the main vectors of CCHFV in Golestan Province. Thus, preventive strategies such as using acaricides and repellents in order to avoid contact with Hyalomma ticks are proposed.

Pattern classification using an olfactory model with PCA feature selection in electronic noses: study and application.

PubMed

Fu, Jun; Huang, Canqin; Xing, Jianguo; Zheng, Junbao

2012-01-01

Biologically-inspired models and algorithms are considered as promising sensor array signal processing methods for electronic noses. Feature selection is one of the most important issues for developing robust pattern recognition models in machine learning. This paper describes an investigation into the classification performance of a bionic olfactory model with the increase of the dimensions of input feature vector (outer factor) as well as its parallel channels (inner factor). The principal component analysis technique was applied for feature selection and dimension reduction. Two data sets of three classes of wine derived from different cultivars and five classes of green tea derived from five different provinces of China were used for experiments. In the former case the results showed that the average correct classification rate increased as more principal components were put in to feature vector. In the latter case the results showed that sufficient parallel channels should be reserved in the model to avoid pattern space crowding. We concluded that 6~8 channels of the model with principal component feature vector values of at least 90% cumulative variance is adequate for a classification task of 3~5 pattern classes considering the trade-off between time consumption and classification rate.

Extensions of the standard model

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

Ramond, P.

1983-01-01

In these lectures we focus on several issues that arise in theoretical extensions of the standard model. First we describe the kinds of fermions that can be added to the standard model without affecting known phenomenology. We focus in particular on three types: the vector-like completion of the existing fermions as would be predicted by a Kaluza-Klein type theory, which we find cannot be realistically achieved without some chiral symmetry; fermions which are vector-like by themselves, such as do appear in supersymmetric extensions, and finally anomaly-free chiral sets of fermions. We note that a chiral symmetry, such as the Peccei-Quinnmore » symmetry can be used to produce a vector-like theory which, at scales less than M/sub W/, appears to be chiral. Next, we turn to the analysis of the second hierarchy problem which arises in Grand Unified extensions of the standard model, and plays a crucial role in proton decay of supersymmetric extensions. We review the known mechanisms for avoiding this problem and present a new one which seems to lead to the (family) triplication of the gauge group. Finally, this being a summer school, we present a list of homework problems. 44 references.« less

A support vector regression-firefly algorithm-based model for limiting velocity prediction in sewer pipes.

PubMed

Ebtehaj, Isa; Bonakdari, Hossein

2016-01-01

Sediment transport without deposition is an essential consideration in the optimum design of sewer pipes. In this study, a novel method based on a combination of support vector regression (SVR) and the firefly algorithm (FFA) is proposed to predict the minimum velocity required to avoid sediment settling in pipe channels, which is expressed as the densimetric Froude number (Fr). The efficiency of support vector machine (SVM) models depends on the suitable selection of SVM parameters. In this particular study, FFA is used by determining these SVM parameters. The actual effective parameters on Fr calculation are generally identified by employing dimensional analysis. The different dimensionless variables along with the models are introduced. The best performance is attributed to the model that employs the sediment volumetric concentration (C(V)), ratio of relative median diameter of particles to hydraulic radius (d/R), dimensionless particle number (D(gr)) and overall sediment friction factor (λ(s)) parameters to estimate Fr. The performance of the SVR-FFA model is compared with genetic programming, artificial neural network and existing regression-based equations. The results indicate the superior performance of SVR-FFA (mean absolute percentage error = 2.123%; root mean square error =0.116) compared with other methods.

Molecular detection of six (endo-) symbiotic bacteria in Belgian mosquitoes: first step towards the selection of appropriate paratransgenesis candidates.

PubMed

Raharimalala, Fara Nantenaina; Boukraa, S; Bawin, T; Boyer, S; Francis, F

2016-04-01

Actually, the use of symbiotic bacteria is one of alternative solution to avoid vector resistance to pesticides. In Belgium, among 31 identified mosquito species, 10 were considered as potential vectors. Given to introduction risks of arbovirosis, the purpose of this study was to investigate the presence of symbiosis bacteria in potential mosquito vectors. Eleven species caught from 12 sites in Belgium were used: Culex pipiens s.l., Culex torrentium, Culex hortensis, Anopheles claviger, Anopheles maculipennis s.l., Anopheles plumbeus, Culiseta annulata, Ochlerotatus geniculatus, Ochlerotatus dorsalis, Aedes albopictus, and Coquillettidia richiardii. Six genera of symbiotic bacteria were screened: Wolbachia sp., Comamonas sp, Delftia sp., Pseudomonas sp., Acinetobacter sp., and Asaia sp. A total of 173 mosquito individuals (144 larvae and 29 adults) were used for the polymerase chain reaction screening. Wolbachia was not found in any Anopheles species nor Cx. torrentium. A total absence of Comamonas and Delftia was observed in all species. Acinetobacter, Pseudomonas, and Asaia were found in most of species with a high prevalence for Pseudomonas. These results were discussed to develop potential strategy and exploit the variable occurrence of symbiotic bacteria to focus on them to propose biological ways of mosquito control.

Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector.

PubMed

Sasaki, Makoto; Mathis, J Michael; Jennings, Merilyn H; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J Steven

2005-10-31

Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.

Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector

PubMed Central

Sasaki, Makoto; Mathis, J Michael; Jennings, Merilyn H; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J Steven

2005-01-01

Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation. PMID:16259632

Effect of radiofrequency energy emitted from monopolar "Bovie" instruments on cardiac implantable electronic devices.

PubMed

Robinson, Thomas N; Varosy, Paul D; Guillaume, Girard; Dunning, James E; Townsend, Nicole T; Jones, Edward L; Paniccia, Alessandro; Stiegmann, Greg V; Weyer, Christopher; Rozner, Marc A

2014-09-01

The monopolar "Bovie" instrument emits radiofrequency energy that can disrupt the function of other implanted electronic devices through a phenomenon termed electromagnetic interference. The purpose of this study was to quantify the electromagnetic interference occurring on cardiac implantable devices (CIEDs) resulting from monopolar instrument use in common, modifiable clinical scenarios. Three anesthetized pigs underwent CIED placement (1 pacemaker and 2 defibrillators). Electromagnetic interference was quantified when changing the monopolar instrument parameters of generator power, generator mode, surgical technique, orientation of active electrode cord, pathway of current vector, and proximity of active electrode to the CIED. Monopolar instrument parameters that decreased the electromagnetic interference occurring on the CIED included decreasing generator power from 60 W to 30 W (p < 0.001), using cut mode rather than coag mode (p < 0.001), using desiccation technique rather than fulguration technique (p < 0.001), orienting the active electrode cord from the feet rather than across the chest wall (p < 0.001), and avoiding the current vector from crossing the CIED system (p < 0.001). Increasing the distance between the active electrode tool and the CIED system decreased electromagnetic interference occurring on the CIED in a dose-response fashion up to a distance of 10 cm (ANOVA, p < 0.001), after which the magnitude of electromagnetic interference remained constant. Electromagnetic interference occurring on CIEDs resulting from monopolar instruments is minimized by decreasing generator power, using cut mode, using desiccation technique, orienting the active electrode cord from the feet, avoiding the current vector for crossing the CIED system, and increasing the distance between the active electrode and the CIED. Surgeons and operating room staff can minimize electromagnetic interference on CIEDs during monopolar instrument use by accounting for these modifiable clinical factors. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

A Luciferase Functional Quantitative Assay for Measuring NF-ĸB Promoter Transactivation Mediated by HTLV-1 and HTLV-2 Tax Proteins.

PubMed

Bergamo, Elisa; Diani, Erica; Bertazzoni, Umberto; Romanelli, Maria Grazia

2017-01-01

HTLV-1 and HTLV-2 viruses express Tax transactivator proteins required for viral genome transcription and capable of transforming cells in vivo and in vitro. Although Tax oncogenic potential needs to be further elucidated, it is well established that Tax proteins activate, among others, transcription factors of the NF-ĸB family, which are involved in immune and inflammatory responses, cell growth, apoptosis, stress responses and oncogenesis. Here, we describe a reporter gene assay applied for quantitative analysis of Tax-dependent NF-ĸB activation. The procedure is based on co-transfection of two individual vectors containing the cDNA for firefly and Renilla luciferase enzymes and vectors expressing Tax proteins. The luciferase expression is driven by cis-NF-ĸB promoter regulatory elements responsive to Tax transactivating factor. This assay is particularly useful to investigate Tax influence on NF-ĸB activation mediated by viral or host factors.

SALIVARY GLAND EXTRACTS OF CULICOIDES SONORENSIS INHIBIT MURINE LYMPHOCYTE PROLIFERATION AND NO PRODUCTION BY MACROPHAGES

PubMed Central

BISHOP, JEANETTE V.; MEJIA, J. SANTIAGO; PÉREZ DE LEÓN, ADALBERTO A.; TABACHNICK, WALTER J.; TITUS, RICHARD G.

2006-01-01

Culicoides biting midges serve as vectors of pathogens affecting humans and domestic animals. Culicoides sonorensis is a vector of several arboviruses in North American that cause substantial economic losses to the US livestock industry. Previous studies showed that C. sonorensis saliva, like the saliva of many hematophagous arthropods, contains numerous pharmacological agents that affect hemostasis and early events in the inflammatory response, which may enhance the infectivity of Culicoides-borne pathogens. This paper reports on the immunomodulatory properties of C. sonorensis salivary gland extracts on murine immune cells and discusses the possible immunomodulatory role of C. sonorensis saliva in vesicular stomatitis virus infection of vertebrate hosts. Splenocytes treated with C. sonorensis mitogens were significantly affected in their proliferative response, and peritoneal macrophages secreted significantly less NO. A 66-kDa glycoprotein was purified from C. sonorensis salivary gland extract, which may be in part responsible for these observations and may be considered as a vaccine candidate. PMID:16968936

Salivary gland extracts of Culicoides sonorensis inhibit murine lymphocyte proliferation and no production by macrophages.

PubMed

Bishop, Jeanette V; Mejia, J Santiago; Pérez de León, Adalberto A; Tabachnick, Walter J; Titus, Richard G

2006-09-01

Culicoides biting midges serve as vectors of pathogens affecting humans and domestic animals. Culicoides sonorensis is a vector of several arboviruses in North American that cause substantial economic losses to the US livestock industry. Previous studies showed that C. sonorensis saliva, like the saliva of many hematophagous arthropods, contains numerous pharmacological agents that affect hemostasis and early events in the inflammatory response, which may enhance the infectivity of Culicoides-borne pathogens. This paper reports on the immunomodulatory properties of C. sonorensis salivary gland extracts on murine immune cells and discusses the possible immunomodulatory role of C. sonorensis saliva in vesicular stomatitis virus infection of vertebrate hosts. Splenocytes treated with C. sonorensis mitogens were significantly affected in their proliferative response, and peritoneal macrophages secreted significantly less NO. A 66-kDa glycoprotein was purified from C. sonorensis salivary gland extract, which may be in part responsible for these observations and may be considered as a vaccine candidate.

Management of dry eye disease.

PubMed

Lemp, Michael A

2008-04-01

The management of dry eye disease (DED) encompasses both pharmacologic and nonpharmacologic approaches, including avoidance of exacerbating factors, eyelid hygiene, tear supplementation, tear retention, tear stimulation, and anti-inflammatory agents. Artificial tears are the mainstay of DED therapy but, although they improve symptoms and objective findings, there is no evidence that they can resolve the underlying inflammation in DED. Topical corticosteroids are effective anti-inflammatory agents, but are not recommended for long-term use because of their adverse-effect profiles. Topical cyclosporine--currently the only pharmacologic treatment approved by the US Food and Drug Administration specifically for DED--is safe for long-term use and is disease-modifying rather than merely palliative. Treatment selection is guided primarily by DED severity. Recently published guidelines propose a severity classification based on clinical signs and symptoms, with treatment recommendations according to severity level.

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

PubMed Central

Hanson, Daniel R; Gottesman, Irving I

2005-01-01

Background Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. Discussion A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. Summary A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons. PMID:15707482

Laboratory Diagnosis of Sepsis? No SIRS, Not Just Yet.

PubMed

Dunne, W Michael

2015-08-01

In order to maximize the benefit of prompt antimicrobial therapy and avoid the risk associated with inappropriate use of antimicrobial agents, patients with suspected sepsis must be rapidly differentiated from patients with systemic inflammatory response syndrome (SIRS). In combination with standard microbiological testing, a number of biomarkers have been recently evaluated for this purpose, and the performance characteristics of the most promising of these are reviewed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Nickel-free stainless steel avoids neointima formation following coronary stent implantation

PubMed Central

Fujiu, Katsuhito; Manabe, Ichiro; Sasaki, Makoto; Inoue, Motoki; Iwata, Hiroshi; Hasumi, Eriko; Komuro, Issei; Katada, Yasuyuki; Taguchi, Tetsushi; Nagai, Ryozo

2012-01-01

SUS316L stainless steel and cobalt–chromium and platinum–chromium alloys are widely used platforms for coronary stents. These alloys also contain nickel (Ni), which reportedly induces allergic reactions in some subjects and is known to have various cellular effects. The effects of Ni on neointima formation after stent implantation remain unknown, however. We developed coronary stents made of Ni-free high-nitrogen austenitic stainless steel prepared using a N2-gas pressurized electroslag remelting (P-ESR) process. Neointima formation and inflammatory responses following stent implantation in porcine coronary arteries were then compared between the Ni-free and SUS316L stainless steel stents. We found significantly less neointima formation and inflammation in arteries implanted with Ni-free stents, as compared to SUS316L stents. Notably, Ni2+ was eluted into the medium from SUS316L but not from Ni-free stainless steel. Mechanistically, Ni2+ increased levels of hypoxia inducible factor protein-1α (HIF-1α) and its target genes in cultured smooth muscle cells. HIF-1α and their target gene levels were also increased in the vascular wall at SUS316L stent sites but not at Ni-free stent sites. The Ni-free stainless steel coronary stent reduces neointima formation, in part by avoiding activation of inflammatory processes via the Ni-HIF pathway. The Ni-free-stainless steel stent is a promising new coronary stent platform. PMID:27877545

Nickel-free stainless steel avoids neointima formation following coronary stent implantation.

PubMed

Fujiu, Katsuhito; Manabe, Ichiro; Sasaki, Makoto; Inoue, Motoki; Iwata, Hiroshi; Hasumi, Eriko; Komuro, Issei; Katada, Yasuyuki; Taguchi, Tetsushi; Nagai, Ryozo

2012-12-01

SUS316L stainless steel and cobalt-chromium and platinum-chromium alloys are widely used platforms for coronary stents. These alloys also contain nickel (Ni), which reportedly induces allergic reactions in some subjects and is known to have various cellular effects. The effects of Ni on neointima formation after stent implantation remain unknown, however. We developed coronary stents made of Ni-free high-nitrogen austenitic stainless steel prepared using a N 2 -gas pressurized electroslag remelting (P-ESR) process. Neointima formation and inflammatory responses following stent implantation in porcine coronary arteries were then compared between the Ni-free and SUS316L stainless steel stents. We found significantly less neointima formation and inflammation in arteries implanted with Ni-free stents, as compared to SUS316L stents. Notably, Ni 2+ was eluted into the medium from SUS316L but not from Ni-free stainless steel. Mechanistically, Ni 2+ increased levels of hypoxia inducible factor protein-1 α (HIF-1 α ) and its target genes in cultured smooth muscle cells. HIF-1 α and their target gene levels were also increased in the vascular wall at SUS316L stent sites but not at Ni-free stent sites. The Ni-free stainless steel coronary stent reduces neointima formation, in part by avoiding activation of inflammatory processes via the Ni-HIF pathway. The Ni-free-stainless steel stent is a promising new coronary stent platform.

Postoperative ileus following major colorectal surgery.

PubMed

Chapman, S J; Pericleous, A; Downey, C; Jayne, D G

2018-06-01

Postoperative ileus (POI) is characterized by delayed gastrointestinal recovery following surgery. Current knowledge of pathophysiology, clinical interventions and methodological challenges was reviewed to inform modern practice and future research. A systematic search of MEDLINE and Embase databases was performed using search terms related to ileus and colorectal surgery. All RCTs involving an intervention to prevent or reduce POI published between 1990 and 2016 were identified. Grey literature, non-full-text manuscripts, and reanalyses of previous RCTs were excluded. Eligible articles were assessed using the Cochrane tool for assessing risk of bias. Of 5614 studies screened, 86 eligible articles describing 88 RCTs were identified. Current knowledge of pathophysiology acknowledges neurogenic, inflammatory and pharmacological mechanisms, but much of the evidence arises from animal studies. The most common interventions tested were chewing gum (11 trials) and early enteral feeding (11), which are safe but of unclear benefit for actively reducing POI. Others, including thoracic epidural analgesia (8), systemic lidocaine (8) and peripheral μ antagonists (5), show benefit but require further investigation for safety and cost-effectiveness. POI is a common condition with no established definition, aetiology or treatment. According to current literature, minimally invasive surgery, protocol-driven recovery (including early feeding and opioid avoidance strategies) and measures to avoid major inflammatory events (such as anastomotic leak) offer the best chances of reducing POI. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

The first detected airline introductions of yellow fever mosquitoes (Aedes aegypti) to Europe, at Schiphol International airport, the Netherlands.

PubMed

Ibañez-Justicia, A; Gloria-Soria, A; den Hartog, W; Dik, M; Jacobs, F; Stroo, A

2017-12-08

Air-borne introduction of exotic mosquitoes to Schiphol airport in the Netherlands has been considered plausible based upon findings of mosquitoes in aircraft cabins during 2008, 2010 and 2011. Beginning in 2013, surveillance efforts at Schiphol had focused on promptly detecting accidental introductions at the airport facilities in order to quickly react and avoid temporary proliferation or establishment of mosquito populations, identify the origin of the introductions, and avoid potential transmission of vector-borne diseases. BG-Mosquitaire mosquito traps were set at the most likely locations for arrival of the invasive Aedes mosquitoes as part of the mosquito monitoring program at Schiphol airport. Samples were collected bi-weekly. Upon detection of exotic specimens, information about the origin of the flights arriving to the particular location at the airport where specimens were captured was requested from airport authorities. The GIS tool Intersect was then used to identify airports of origin common to positive trapping locations during the specific trapping period. Captured Aedes aegypti mosquitoes were subsequently genotyped at 12 highly polymorphic microsatellite markers and compared to a reference database of 79 populations around the world to further narrow down their location of origin. In 2016, six adult yellow fever mosquitoes were captured indoors and outdoors at the airport of Schiphol in the Netherlands confirming, for the first time, air-borne transport of this mosquito vector species into Europe. Mosquitoes were captured during three time periods: June, September and October. Containers carried by aircrafts are considered the most likely pathway for this introduction. GIS analysis and genetic assignment tests on these mosquitoes point to North America or the Middle East as possible origins, but the small sample size prevents us from reliably identifying the geographic origin of this introduction. The arrival of Ae. aegypti mosquitoes to Schiphol airport from flights arriving from overseas, demonstrates the potential risk of international flights to public health as carriers of arthropod vectors of disease. The results strongly suggest that disinsection of containers and their storage compartments inside the aircrafts could contribute to preventing future introductions of mosquito vectors. Invasive mosquito species introduced by aircrafts from overseas could become seasonally established during the warmer months in Europe, or permanently in certain climatically suitable areas for the species, with major consequences for human health.

Tissue-engineered cartilage with inducible and tunable immunomodulatory properties

PubMed Central

Glass, Katherine A.; Link, Jarrett M.; Brunger, Jonathan M.; Moutos, Franklin T.; Gersbach, Charles A.; Guilak, Farshid

2014-01-01

The pathogenesis of osteoarthritis is mediated in part by inflammatory cytokines including interleukin-1 (IL-1), which promote degradation of articular cartilage and prevent human mesenchymal stem cell (MSC) chondrogenesis. In this study, we combined gene therapy and functional tissue engineering to develop engineered cartilage with immunomodulatory properties that allow chondrogenesis in the presence of pathologic levels of IL-1 by inducing overexpression of IL-1 receptor antagonist (IL-1Ra) in MSCs via scaffold-mediated lentiviral gene delivery. A doxycycline-inducible vector was used to transduce MSCs in monolayer or within 3D woven PCL scaffolds to enable tunable IL-1Ra production. In the presence of IL-1, IL-1Ra-expressing engineered cartilage produced cartilage-specific extracellular matrix, while resisting IL-1-induced upregulation of matrix metalloproteinases and maintaining mechanical properties similar to native articular cartilage. The ability of functional engineered cartilage to deliver tunable anti-inflammatory cytokines to the joint may enhance the long-term success of therapies for cartilage injuries or osteoarthritis. PMID:24767790

Lysophosphatidylcholine: A Novel Modulator of Trypanosoma cruzi Transmission

PubMed Central

Silva-Neto, Mário A. C.; Carneiro, Alan B.; Silva-Cardoso, Livia; Atella, Georgia C.

2012-01-01

Lysophosphatidylcholine is a bioactive lipid that regulates a large number of cellular processes and is especially present during the deposition and infiltration of inflammatory cells and deposition of atheromatous plaque. Such molecule is also present in saliva and feces of the hematophagous organism Rhodnius prolixus, a triatominae bug vector of Chagas disease. We have recently demonstrated that LPC is a modulator of Trypanosoma cruzi transmission. It acts as a powerful chemoattractant for inflammatory cells at the site of the insect bite, which will provide a concentrated population of cells available for parasite infection. Also, LPC increases macrophage intracellular calcium concentrations that ultimately enhance parasite invasion. Finally, LPC inhibits NO production by macrophages stimulated by live T. cruzi, and thus interferes with the immune system of the vertebrate host. In the present paper, we discuss the main signaling mechanisms that are likely used by such molecule and their eventual use as targets to block parasite transmission and the pathogenesis of Chagas disease. PMID:22132309

Interleukin 35 and Hepatocyte Growth Factor; as a novel combined immune gene therapy for Multiple Sclerosis disease.

PubMed

Moghadam, Samira; Erfanmanesh, Maryam; Esmaeilzadeh, Abdolreza

2017-11-01

An autoimmune demyelination disease of the Central Nervous System, Multiple Sclerosis, is a chronic inflammation which mostly involves young adults. Suffering people face functional loss with a severe pain. Most current MS treatments are focused on the immune response suppression. Approved drugs suppress the inflammatory process, but factually, there is no definite cure for Multiple Sclerosis. Recently developed knowledge has demonstrated that gene and cell therapy as a hopeful approach in tissue regeneration. The authors propose a novel combined immune gene therapy for Multiple Sclerosis treatment using anti-inflammatory and remyelination of Interleukine-35 and Hepatocyte Growth Factor properties, respectively. In this hypothesis Interleukine-35 and Hepatocyte Growth Factor introduce to Mesenchymal Stem Cells of EAE mouse model via an adenovirus based vector. It is expected that Interleukine-35 and Hepatocyte Growth Factor genes expressed from MSCs could effectively perform in immunotherapy of Multiple Sclerosis. Copyright © 2017. Published by Elsevier Ltd.

A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis.

PubMed

Bi, Lianxiang; Wacker, Bradley K; Bueren, Emma; Ham, Ervin; Dronadula, Nagadhara; Dichek, David A

2017-12-15

Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate-yet significant-pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

ENHANCED GENE DELIVERY IN PORCINE VASCULATURE TISSUE FOLLOWING INCORPORATION OF ADENO-ASSOCIATED VIRUS NANOPARTICLES INTO POROUS SILICON MICROPARTICLES

PubMed Central

McConnell, Kellie I.; Rhudy, Jessica; Yokoi, Kenji; Gu, Jianhua; Mack, Aaron; Suh, Junghae; La Francesca, Saverio; Sakamoto, Jason; Serda, Rita E.

2014-01-01

There is an unmet clinical need to increase lung transplant successes, patient satisfaction and to improve mortality rates. We offer the development of a nanovector-based solution that will reduce the incidence of lung ischemic reperfusion injury (IRI) leading to graft organ failure through the successful ex vivo treatment of the lung prior to transplantation. The innovation is in the integrated application of our novel porous silicon (pSi) microparticles carrying adeno-associated virus (AAV) nanoparticles, and the use of our ex vivo lung perfusion/ventilation system for the modulation of pro-inflammatory cytokines initiated by ischemic pulmonary conditions prior to organ transplant that often lead to complications. Gene delivery of anti-inflammatory agents to combat the inflammatory cascade may be a promising approach to prevent IRI following lung transplantation. The rationale for the device is that the microparticle will deliver a large payload of virus to cells and serve to protect the AAV from immune recognition. The microparticle-nanoparticle hybrid device was tested both in vitro on cell monolayers and ex vivo using either porcine venous tissue or a pig lung transplantation model, which recapitulates pulmonary IRI that occurs clinically post-transplantation. Remarkably, loading AAV vectors into pSi microparticles increases gene delivery to otherwise non-permissive endothelial cells. PMID:25180449

Polarized object detection in crabs: a two-channel system.

PubMed

Basnak, Melanie Ailín; Pérez-Schuster, Verónica; Hermitte, Gabriela; Berón de Astrada, Martín

2018-05-25

Many animal species take advantage of polarization vision for vital tasks such as orientation, communication and contrast enhancement. Previous studies have suggested that decapod crustaceans use a two-channel polarization system for contrast enhancement. Here, we characterize the polarization contrast sensitivity in a grapsid crab . We estimated the polarization contrast sensitivity of the animals by quantifying both their escape response and changes in heart rate when presented with polarized motion stimuli. The motion stimulus consisted of an expanding disk with an 82 deg polarization difference between the object and the background. More than 90% of animals responded by freezing or trying to avoid the polarized stimulus. In addition, we co-rotated the electric vector (e-vector) orientation of the light from the object and background by increments of 30 deg and found that the animals' escape response varied periodically with a 90 deg period. Maximum escape responses were obtained for object and background e-vectors near the vertical and horizontal orientations. Changes in cardiac response showed parallel results but also a minimum response when e-vectors of object and background were shifted by 45 deg with respect to the maxima. These results are consistent with an orthogonal receptor arrangement for the detection of polarized light, in which two channels are aligned with the vertical and horizontal orientations. It has been hypothesized that animals with object-based polarization vision rely on a two-channel detection system analogous to that of color processing in dichromats. Our results, obtained by systematically varying the e-vectors of object and background, provide strong empirical support for this theoretical model of polarized object detection. © 2018. Published by The Company of Biologists Ltd.

Cost-effectiveness of environmental management for vector control in resource development projects.

PubMed

Bos, R

1991-01-01

Vector control methods are traditionally divided in chemical, biological and environmental management approaches, and this distinction also reflected in certain financial and economic aspects. This is particularly true for environmental modification, usually engineering or other structural works. It is highly capital intensive, as opposed to chemical and biological control which require recurrent expenditures, and discount rates are therefore a prominent consideration in deciding for one or the other approach. Environmental manipulation requires recurrent action, but can often be carried out with the community participation, which raises the issue of opportunity costs. The incorporation of environmental management in resource projects is generally impeded by economic considerations. The Internal Rate of Return continues to be a crucial criterion for funding agencies and development banks to support new projects; at the same time Governments of debt-riden countries in the Third World will do their best to avoid additional loans on such frills as environmental and health safeguards. Two approaches can be recommended to nevertheless ensure the incorporation of environmental management measures in resource projects in an affordable way. First, there are several examples of cases where environmental management measures either have a dual benefit (increasing both agricultural production and reducing vector-borne disease transmission) or can be implemented at zero costs. Second, the additional costs involved in structural modifications can be separated from the project development costs considered in the calculations of the Internal Rate of Return, and financial support can be sought from bilateral technical cooperation agencies particularly interested in environmental and health issues. There is a dearth of information in the cost-effectiveness of alternative vector control strategies in the developing country context. The process of integrating vector control in the general health services will make it even more difficult to gain a clear insight in the matter.

Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans

PubMed Central

Borggren, Marie; Nielsen, Jens; Bragstad, Karoline; Karlsson, Ingrid; Krog, Jesper S; Williams, James A; Fomsgaard, Anders

2015-01-01

The threat posed by the 2009 pandemic H1N1 virus emphasized the need for new influenza A virus vaccines inducing a broad cross-protective immune response for use in both humans and pigs. An effective and broad influenza vaccine for pigs would greatly benefit the pork industry and contribute to public health by diminishing the risk of emerging highly pathogenic reassortants. Current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against heterologous strains. DNA vaccines are a potential alternative with advantages such as the induction of cellular and humoral immunity, inherent safety and rapid production time. We have previously developed a DNA vaccine encoding selected influenza proteins of pandemic origin and demonstrated broad protective immune responses in ferrets and pigs. In this study, we evaluated our DNA vaccine expressed by next-generation vectors. These new vectors can improve gene expression, but they are also efficiently produced on large scales and comply with regulatory guidelines by avoiding antibiotic resistance genes. In addition, a new needle-free delivery of the vaccine, convenient for mass vaccinations, was compared with intradermal needle injection followed by electroporation. We report that when our DNA vaccine is expressed by the new vectors and delivered to the skin with the needle-free device in the rabbit model, it can elicit an antibody response with the same titers as a conventional vector with intradermal electroporation. The needle-free delivery is already in use for traditional protein vaccines in pigs but should be considered as a practical alternative for the mass administration of broadly protective influenza DNA vaccines. PMID:25746201

Vector delivery technique affects gene transfer in the cornea in vivo.

PubMed

Mohan, Rajiv R; Sharma, Ajay; Cebulko, Tyler C; Tandon, Ashish

2010-11-27

This study tested whether controlled drying of the cornea increases vector absorption in mouse and rabbit corneas in vivo and human cornea ex vivo, and studied the effects of corneal drying on gene transfer, structure and inflammatory reaction in the mouse cornea in vivo. Female C57 black mice and New Zealand White rabbits were used for in vivo studies. Donor human corneas were used for ex vivo experiments. A hair dryer was used for drying the corneas after removing corneal epithelium by gentle scraping. The corneas received no, once, twice, thrice, or five times warm air for 10 s with a 5 s interval after each 10 s hair dryer application. Thereafter, balanced salt solution (BSS) was topically applied immediately on the cornea for 2 min using a custom-cloning cylinder. The absorbed BSS was quantified using Hamilton microsyringes. The adeno-associated virus 8 (AAV8) vector (1.1×10(8) genomic copies/µl) expressing marker gene was used to study the effect of corneal drying on gene transfer. Animals were sacrificed on day 14 and gene expression was analyzed using commercial staining kit. Morphological changes and infiltration of inflammatory cells were examined with H & E staining and immunocytochemistry. Mice, rabbit or human corneas subjected to no or 10 s drying showed 6%-8% BSS absorption whereas 20, 30, or 50 s corneal drying showed significantly high 14%-19% (p<0.001), 21%-22% (p<0.001), and 25%-27% (p<0.001) BSS absorption, respectively. The AAV8 application on mouse cornea after 50 s drying showed significantly higher transgene delivery (p<0.05) in vivo with mild-to-moderate changes in corneal morphology. The 30 s of drying also showed significantly (p<0.05) high transgene delivery in mouse stroma in vivo without jeopardizing corneal morphology whereas 10 or 20 s drying showed moderate degree of gene transfer with no altered corneal morphology. Corneas that underwent 50 s drying showed high CD11b-positive cells (p<0.01) compared to control corneas whereas 20 or 30 s air-dried corneas showed insignificant CD11b-positive cells compared to control corneas. Controlled corneal drying with hair dryer increases vector absorption significantly. The dispensing of efficacious AAV serotype into cornea with optimized minimally invasive topical application technique could provide high and targeted expression of therapeutic genes in the stroma in vivo without causing significant side effects.

Apyrase activity and adenosine diphosphate induced platelet aggregation inhibition by the salivary gland proteins of Culicoides variipennis, the North American vector of bluetongue viruses.

PubMed

Pérez de León, A A; Tabachnick, W J

1996-02-01

Salivary gland homogenates of Culicoides variipennis, the primary vector of bluetongue (BLU) viruses in North America, were analyzed for apyrase activity. Apyrase (ATP diphosphohydrolase, EC 3.6.1.5) is an anti-hemostatic and anti-inflammatory salivary enzyme of most hematophagous arthropods. The enzyme activity was measured by the release of orthophosphate using ATP, ADP, and AMP as substrates with Ca2+ as the divalent cation. ATPase (11.5 +/- 1 mU/pair of glands), ADPase (7.3 +/- 0.7 mU/pair of glands), and insignificant (P < 0.05) AMPase (0.07 mU/pair of glands) activities were detected in female salivary glands. Male salivary glands contained lower amounts of ATPase and ADPase activity (P < 0.05). The ATPase and ADPase activities were greatest at pH 8.5, and were similarly activated by Mg2+. Molecular sieving HPLC of salivary gland homogenates generated a single peak which coincided with ATPase and ADPase, but no AMPase, activity; the protein has an estimated molecular mass of 35,000 Da. ATPase and ADPase activity, and total protein concentration, were reduced (P < 0.05) in the salivary glands of females after taking a blood meal from a sheep. Salivary gland homogenates also inhibited ADP-induced platelet aggregation in vitro. It is concluded that the salivary ATPase and ADPase activities of C. variipennis reside in one enzyme, and that this enzyme is likely an apyrase. The apyrase activity is thought to be responsible for the inhibition of ADP-induced platelet aggregation, as indicated by the apparent discharge of apyrase from salivary glands into the host during blood feeding. This suggests that apyrase is one of the salivary proteins present in C. variipennis acting as antigens in the development of Culicoides hypersensitivity in ruminants and horses. Apyrase may inhibit an inflammatory response at the feeding site through the subsequent degradation of its end-product, AMP, to adenosine, a potent anti-inflammatory substance, by the ecto-5' nucleotidase activity of neutrophils.

Increased lung inflammation with oxygen supplementation in tracheotomized spontaneously breathing rabbits: an experimental prospective randomized study.

PubMed

Machado, Humberto S; Nunes, Catarina S; Sá, Paula; Couceiro, Antonio; da Silva, Álvaro Moreira; Águas, Artur

2014-01-01

Mechanical ventilation is a well-known trigger for lung inflammation. Research focuses on tidal volume reduction to prevent ventilator-induced lung injury. Mechanical ventilation is usually applied with higher than physiological oxygen fractions. The purpose of this study was to investigate the after effect of oxygen supplementation during a spontaneous ventilation set up, in order to avoid the inflammatory response linked to mechanical ventilation. A prospective randomised study using New Zealand rabbits in a university research laboratory was carried out. Rabbits (n = 20) were randomly assigned to 4 groups (n = 5 each group). Groups 1 and 2 were submitted to 0.5 L/min oxygen supplementation, for 20 or 75 minutes, respectively; groups 3 and 4 were left at room air for 20 or 75 minutes. Ketamine/xylazine was administered for induction and maintenance of anaesthesia. Lungs were obtained for histological examination in light microscopy. All animals survived the complete experiment. Procedure duration did not influence the degree of inflammatory response. The hyperoxic environment was confirmed by blood gas analyses in animals that were subjected to oxygen supplementation, and was accompanied with lower mean respiratory rates. The non-oxygen supplemented group had lower mean oxygen arterial partial pressures and higher mean respiratory rates during the procedure. All animals showed some inflammatory lung response. However, rabbits submitted to oxygen supplementation showed significant more lung inflammation (Odds ratio = 16), characterized by more infiltrates and with higher cell counts; the acute inflammatory response cells was mainly constituted by eosinophils and neutrophils, with a relative proportion of 80 to 20% respectively. This cellular observation in lung tissue did not correlate with a similar increase in peripheral blood analysis. Oxygen supplementation in spontaneous breathing is associated with an increased inflammatory response when compared to breathing normal room air. This inflammatory response was mainly constituted with polymorphonuclear cells (eosinophils and neutrophils). As confirmed in all animals by peripheral blood analyses, the eosinophilic inflammatory response was a local organ event.

Inflammatory status in human hepatic cirrhosis

PubMed Central

Martínez-Esparza, María; Tristán-Manzano, María; Ruiz-Alcaraz, Antonio J; García-Peñarrubia, Pilar

2015-01-01

This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gut-mesenteric lymph nodes-peritoneal-systemic axis. PMID:26556984

Treating inflammatory bowel disease by adsorptive leucocytapheresis: a desire to treat without drugs.

PubMed

Saniabadi, Abbi R; Tanaka, Tomotaka; Ohmori, Toshihide; Sawada, Koji; Yamamoto, Takayuki; Hanai, Hiroyuki

2014-08-07

Ulcerative colitis and Crohn's disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients' own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients' disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.

Treating inflammatory bowel disease by adsorptive leucocytapheresis: A desire to treat without drugs

PubMed Central

Saniabadi, Abbi R; Tanaka, Tomotaka; Ohmori, Toshihide; Sawada, Koji; Yamamoto, Takayuki; Hanai, Hiroyuki

2014-01-01

Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs. PMID:25110409

Structure of weakly 2-dependent siphons

NASA Astrophysics Data System (ADS)

Chao, Daniel Yuh; Chen, Jiun-Ting

2013-09-01

Deadlocks arising from insufficiently marked siphons in flexible manufacturing systems can be controlled by adding monitors to each siphon - too many for large systems. Li and Zhou add monitors to elementary siphons only while controlling the rest of (called dependent) siphons by adjusting control depth variables of elementary siphons. Only a linear number of monitors are required. The control of weakly dependent siphons (WDSs) is rather conservative since only positive terms were considered. The structure for strongly dependent siphons (SDSs) has been studied earlier. Based on this structure, the optimal sequence of adding monitors has been discovered earlier. Better controllability has been discovered to achieve faster and more permissive control. The results have been extended earlier to S3PGR2 (systems of simple sequential processes with general resource requirements). This paper explores the structures for WDSs, which, as found in this paper, involve elementary resource circuits interconnecting at more than (for SDSs, exactly) one resource place. This saves the time to compute compound siphons, their complementary sets and T-characteristic vectors. Also it allows us (1) to improve the controllability of WDSs and control siphons and (2) to avoid the time to find independent vectors for elementary siphons. We propose a sufficient and necessary test for adjusting control depth variables in S3PR (systems of simple sequential processes with resources) to avoid the sufficient-only time-consuming linear integer programming test (LIP) (Nondeterministic Polynomial (NP) time complete problem) required previously for some cases.

Hybrid lentivirus-phiC31-int-NLS vector allows site-specific recombination in murine and human cells but induces DNA damage.

PubMed

Grandchamp, Nicolas; Altémir, Dorothée; Philippe, Stéphanie; Ursulet, Suzanna; Pilet, Héloïse; Serre, Marie-Claude; Lenain, Aude; Serguera, Che; Mallet, Jacques; Sarkis, Chamsy

2014-01-01

Gene transfer allows transient or permanent genetic modifications of cells for experimental or therapeutic purposes. Gene delivery by HIV-derived lentiviral vector (LV) is highly effective but the risk of insertional mutagenesis is important and the random/uncontrollable integration of the DNA vector can deregulate the cell transcriptional activity. Non Integrative Lentiviral Vectors (NILVs) solve this issue in non-dividing cells, but they do not allow long term expression in dividing cells. In this context, obtaining stable expression while avoiding the problems inherent to unpredictable DNA vector integration requires the ability to control the integration site. One possibility is to use the integrase of phage phiC31 (phiC31-int) which catalyzes efficient site-specific recombination between the attP site in the phage genome and the chromosomal attB site of its Streptomyces host. Previous studies showed that phiC31-int is active in many eukaryotic cells, such as murine or human cells, and directs the integration of a DNA substrate into pseudo attP sites (pattP) which are homologous to the native attP site. In this study, we combined the efficiency of NILV for gene delivery and the specificity of phiC31-int for DNA substrate integration to engineer a hybrid tool for gene transfer with the aim of allowing long term expression in dividing and non-dividing cells preventing genotoxicity. We demonstrated the feasibility to target NILV integration in human and murine pattP sites with a dual NILV vectors system: one which delivers phiC31-int, the other which constitute the substrate containing an attB site in its DNA sequence. These promising results are however alleviated by the occurrence of significant DNA damages. Further improvements are thus required to prevent chromosomal rearrangements for a therapeutic use of the system. However, its use as a tool for experimental applications such as transgenesis is already applicable.

Evolutionary and dispersal history of Triatoma infestans, main vector of Chagas disease, by chromosomal markers.

PubMed

Panzera, Francisco; Ferreiro, María J; Pita, Sebastián; Calleros, Lucía; Pérez, Ruben; Basmadjián, Yester; Guevara, Yenny; Brenière, Simone Frédérique; Panzera, Yanina

2014-10-01

Chagas disease, one of the most important vector-borne diseases in the Americas, is caused by Trypanosoma cruzi and transmitted to humans by insects of the subfamily Triatominae. An effective control of this disease depends on elimination of vectors through spraying with insecticides. Genetic research can help insect control programs by identifying and characterizing vector populations. In southern Latin America, Triatoma infestans is the main vector and presents two distinct lineages, known as Andean and non-Andean chromosomal groups, that are highly differentiated by the amount of heterochromatin and genome size. Analyses with nuclear and mitochondrial sequences are not conclusive about resolving the origin and spread of T. infestans. The present paper includes the analyses of karyotypes, heterochromatin distribution and chromosomal mapping of the major ribosomal cluster (45S rDNA) to specimens throughout the distribution range of this species, including pyrethroid-resistant populations. A total of 417 specimens from seven different countries were analyzed. We show an unusual wide rDNA variability related to number and chromosomal position of the ribosomal genes, never before reported in species with holocentric chromosomes. Considering the chromosomal groups previously described, the ribosomal patterns are associated with a particular geographic distribution. Our results reveal that the differentiation process between both T. infestans chromosomal groups has involved significant genomic reorganization of essential coding sequences, besides the changes in heterochromatin and genomic size previously reported. The chromosomal markers also allowed us to detect the existence of a hybrid zone occupied by individuals derived from crosses between both chromosomal groups. Our genetic studies support the hypothesis of an Andean origin for T. infestans, and suggest that pyrethroid-resistant populations from the Argentinean-Bolivian border are most likely the result of recent secondary contact between both lineages. We suggest that vector control programs should make a greater effort in the entomological surveillance of those regions with both chromosomal groups to avoid rapid emergence of resistant individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

Macroscopic theory of dark sector

NASA Astrophysics Data System (ADS)

Meierovich, Boris

A simple Lagrangian with squared covariant divergence of a vector field as a kinetic term turned out an adequate tool for macroscopic description of the dark sector. The zero-mass field acts as the dark energy. Its energy-momentum tensor is a simple additive to the cosmological constant [1]. Space-like and time-like massive vector fields describe two different forms of dark matter. The space-like massive vector field is attractive. It is responsible for the observed plateau in galaxy rotation curves [2]. The time-like massive field displays repulsive elasticity. In balance with dark energy and ordinary matter it provides a four parametric diversity of regular solutions of the Einstein equations describing different possible cosmological and oscillating non-singular scenarios of evolution of the universe [3]. In particular, the singular big bang turns into a regular inflation-like transition from contraction to expansion with the accelerate expansion at late times. The fine-tuned Friedman-Robertson-Walker singular solution corresponds to the particular limiting case at the boundary of existence of regular oscillating solutions in the absence of vector fields. The simplicity of the general covariant expression for the energy-momentum tensor allows to analyse the main properties of the dark sector analytically and avoid unnecessary model assumptions. It opens a possibility to trace how the additional attraction of the space-like dark matter, dominating in the galaxy scale, transforms into the elastic repulsion of the time-like dark matter, dominating in the scale of the Universe. 1. B. E. Meierovich. "Vector fields in multidimensional cosmology". Phys. Rev. D 84, 064037 (2011). 2. B. E. Meierovich. "Galaxy rotation curves driven by massive vector fields: Key to the theory of the dark sector". Phys. Rev. D 87, 103510, (2013). 3. B. E. Meierovich. "Towards the theory of the evolution of the Universe". Phys. Rev. D 85, 123544 (2012).

Improvements on ν-Twin Support Vector Machine.

PubMed

Khemchandani, Reshma; Saigal, Pooja; Chandra, Suresh

2016-07-01

In this paper, we propose two novel binary classifiers termed as "Improvements on ν-Twin Support Vector Machine: Iν-TWSVM and Iν-TWSVM (Fast)" that are motivated by ν-Twin Support Vector Machine (ν-TWSVM). Similar to ν-TWSVM, Iν-TWSVM determines two nonparallel hyperplanes such that they are closer to their respective classes and are at least ρ distance away from the other class. The significant advantage of Iν-TWSVM over ν-TWSVM is that Iν-TWSVM solves one smaller-sized Quadratic Programming Problem (QPP) and one Unconstrained Minimization Problem (UMP); as compared to solving two related QPPs in ν-TWSVM. Further, Iν-TWSVM (Fast) avoids solving a smaller sized QPP and transforms it as a unimodal function, which can be solved using line search methods and similar to Iν-TWSVM, the other problem is solved as a UMP. Due to their novel formulation, the proposed classifiers are faster than ν-TWSVM and have comparable generalization ability. Iν-TWSVM also implements structural risk minimization (SRM) principle by introducing a regularization term, along with minimizing the empirical risk. The other properties of Iν-TWSVM, related to support vectors (SVs), are similar to that of ν-TWSVM. To test the efficacy of the proposed method, experiments have been conducted on a wide range of UCI and a skewed variation of NDC datasets. We have also given the application of Iν-TWSVM as a binary classifier for pixel classification of color images. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reproducibility Issues: Avoiding Pitfalls in Animal Inflammation Models.

PubMed

Laman, Jon D; Kooistra, Susanne M; Clausen, Björn E

2017-01-01

In light of an enhanced awareness of ethical questions and ever increasing costs when working with animals in biomedical research, there is a dedicated and sometimes fierce debate concerning the (lack of) reproducibility of animal models and their relevance for human inflammatory diseases. Despite evident advancements in searching for alternatives, that is, replacing, reducing, and refining animal experiments-the three R's of Russel and Burch (1959)-understanding the complex interactions of the cells of the immune system, the nervous system and the affected tissue/organ during inflammation critically relies on in vivo models. Consequently, scientific advancement and ultimately novel therapeutic interventions depend on improving the reproducibility of animal inflammation models. As a prelude to the remaining hands-on protocols described in this volume, here, we summarize potential pitfalls of preclinical animal research and provide resources and background reading on how to avoid them.

Role of primary and secondary prevention in atopic dermatitis

PubMed Central

Michalak, Iwonna; Gutfreund, Katarzyna; Bienias, Wojciech; Matych, Marta; Szewczyk, Anna; Kaszuba, Andrzej

2015-01-01

Atopic dermatitis (AD) is a serious epidemiological problem in industrialized countries. The incidence of AD has increased considerably over the last 30 years. Atopic dermatitis is a chronic, recurrent, inflammatory skin disease accompanied by strong itching. It is characterized by typical features depending on age. The parents of children suffering from AD must be prepared to change their lifestyle. They should avoid factors which can promote skin lesions and apply appropriate, regular skin care. The article describes primary prevention of AD as well as prophylactic measures to avoid skin eczema. It presents the role of infections, vaccinations, breastfeeding and the influence of domestic animals, house renovation and moulds on development of AD. The article also describes the significance of the epidermal barrier, skin colonization by microbial agents, pruritus, stress, food and inhalant allergy among people who suffer from AD. PMID:26755903

Co-immunization with DNA and protein mixture: a safe and efficacious immunotherapeutic strategy for Alzheimer's disease in PDAPP mice.

PubMed

Liu, Si; Shi, DanYang; Wang, Hai-Chao; Yu, Yun-Zhou; Xu, Qing; Sun, Zhi-Wei

2015-01-14

Active immunotherapy targeting β-amyloid (Aβ) is the most promising strategy to prevent or treat Alzheimer's disease (AD). Based on pre-clinical studies and clinical trials, a safe and effective AD vaccine requires a delicate balance between providing therapeutically adequate anti-Aβ antibodies and eliminating or suppressing unwanted adverse T cell-mediated inflammatory reactions. We describe here the immunological characterization and protective efficacy of co-immunization with a 6Aβ15-T DNA and protein mixture without adjuvant as an AD immunotherapeutic strategy. Impressively, this co-immunization induced robust Th2-polarized Aβ-specific antibodies while simultaneously suppressed unwanted inflammatory T cell reactions and avoiding Aβ42-specific T cell-mediated autoimmune responses in immunized mice. Co-immunization with the DNA + protein vaccine could overcome Aβ42-associated hypo-responsiveness and elicit long-term Aβ-specific antibody responses, which helped to maintain antibody-mediated clearance of amyloid and accordingly alleviated AD symptoms in co-immunized PDAPP mice. Our DNA and protein combined vaccine, which could induce an anti-inflammatory Th2 immune response with high level Aβ-specific antibodies and low level IFN-γ production, also demonstrated the capacity to inhibit amyloid accumulation and prevent cognitive dysfunction. Hence, co-immunization with antigen-matched DNA and protein may represent a novel and efficacious strategy for AD immunotherapy to eliminate T cell inflammatory reactions while retaining high level antibody responses.

[Aseptic cutaneous breast abscesses associated with ulcerative colitis].

PubMed

Sallé de Chou, C; Ortonne, N; Hivelin, M; Wolkenstein, P; Chosidow, O; Valeyrie-Allanore, L

2016-02-01

Inflammatory bowel diseases are associated with a broad range of cutaneous lesions. Herein we report the first case of aseptic skin abscesses associated with ulcerative colitis. Since March 2008, a 40-year-old woman presented with bilateral mammary abscesses, relapsing despite repeated antibiotic treatment. She was followed for ulcerative colitis diagnosed in 2011 by means of a rectal biopsy. Despite four surgical procedures, there was no improvement in her mammary abscesses and bilateral mastectomy was then proposed because of the persistent symptoms. Her general state of health remained stable. Clinically, there were bilateral inflammatory nodes with fistulae and pus. These lesions were extremely painful. Mild inflammatory syndrome was noted, but the immunological tests revealed nothing of note. Bacteriological, parasitological and mycological tests on biopsy specimens were negative. Histological examination of a surgical biopsy revealed lymphoplasmacytic infiltration of the dermis and subcutis with altered polymorphonuclear cells and epithelioid granuloma. The CT-scan showed no other remote lesions. The final diagnosis was cutaneous aseptic abscess syndrome associated with ulcerative colitis. Colchicine 1mg/day was initiated and resulted in regression of the skin lesions, with complete remission at one year of follow-up. Aseptic abscess syndrome must be considered in the event of recurrent aseptic cutaneous abscesses which may be associated with inflammatory bowel disease. Surgery should be avoided and treatment should be based on suitable drug therapy. Copyright © 2016. Published by Elsevier Masson SAS.

Effects of LPS-induced immune activation prior to trauma exposure on PTSD-like symptoms in mice.

PubMed

Deslauriers, Jessica; van Wijngaarde, Myrthe; Geyer, Mark A; Powell, Susan; Risbrough, Victoria B

2017-04-14

The prevalence of posttraumatic stress disorder (PTSD) is high in the armed services, with a rate up to 20%. Multiple studies have associated markers of inflammatory signaling prior to trauma with increased risk of PTSD, suggesting a potential role of the immune system in the development of this psychiatric disorder. One question that arises is if "priming" the immune system before acute trauma alters the stress response and increases enduring effects of trauma. We investigated the time course of inflammatory response to predator stress, a robust stressor that induces enduring PTSD-like behaviors, and the modulation of these effects via prior immune activation with the bacterial endotoxin, lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist. Mice exposed to predator stress exhibited decreased pro-/anti-inflammatory balance in the brain 6h after stress, suggesting that predator exposure acutely suppressed the immune system by increasing anti-inflammatory cytokines levels. Acute immune activation with LPS before a single predator stress did not alter the enduring avoidance behavior in stressed mice. Our findings suggest that acute inflammation, at least via TLR4 activation, is not sufficient to increase susceptibility for PTSD-like behaviors in this model. Future studies will examine if chronic inflammation is required to induce similar immune changes to those observed in PTSD patients in this model. Published by Elsevier B.V.

Luteinized unruptured follicle syndrome increased by inactive disease and selective cyclooxygenase 2 inhibitors in women with inflammatory arthropathies.

PubMed

Micu, Mihaela C; Micu, Romeo; Ostensen, Monika

2011-09-01

Administration of nonsteroidal antiinflammatory drugs (NSAIDs) may impair fertility. The occurrence of the luteinized unruptured follicle (LUF) syndrome was assessed in women with inflammatory arthropathies exposed to NSAIDs and compared to that in nonexposed women. Fourteen patients with inflammatory rheumatic disease, 29 women with noninflammatory musculoskeletal conditions, and 449 women not exposed to NSAIDs were studied by intravaginal ultrasound monitoring for follicular development and ovulation in 1 or more menstrual cycles. Disease activity was assessed in inflammatory rheumatic disease. In 59 monitored cycles of patients with continuous NSAID exposure, 35.6% of LUF syndromes occurred compared to 3.4% of LUF syndromes in untreated women (P < 0.001). Etoricoxib was responsible for 75% of LUF syndromes in patients exposed continuously, whereas diclofenac generated 15% of LUF syndromes. An ibuprofen dosage of 1,600 mg/day did not induce LUF syndrome either at continuous periovulatory or discontinuous exposure. Interestingly, the frequency of LUF syndrome was 46.2% in patients with inactive inflammatory disease compared to 15% in patients with active disease (P = 0.023). Etoricoxib generated LUF syndrome in 94.2% of the cases with inactive disease versus 28.6% in patients with active disease (P = 0.003). NSAIDs increased the risk of the LUF syndrome, particularly in patients with inactive disease. The selective cyclooxygenase 2 (COX-2) inhibitor etoricoxib was a more potent inductor of LUF syndrome than nonselective COX inhibitors. Continuous periovulatory exposure to NSAIDs should be avoided when planning a pregnancy in patients with rheumatic diseases. Copyright © 2011 by the American College of Rheumatology.

Targeted knockout of TNF-α by injection of lentivirus-mediated siRNA into the subacromial bursa for the treatment of subacromial bursitis in rats.

PubMed

Wang, Yi; Li, Quan; Wei, Xianzhao; Xu, Jie; Chen, Qi; Song, Shuang; Lu, Zhe; Wang, Zimin

2015-09-01

Subacromial bursitis (SAB) is the major source of pain in rotator cuff disease. Although multiple investigations have provided support for the role of inflammatory cytokines in SAB, few have focussed on the use these cytokines in the treatment of SAB. The aim of the present study was to observe the therapeutic efficacy of lentivirus‑mediated RNA interference (RNAi) on carrageenan‑induced SAB by injecting lentivirus‑tumor necrosis factor (TNF)‑α‑RNAi expressing TNF‑α small interfering (si)RNA. Using screened siRNA segments, an siRNA was designed. A lentivirus vector expressing siRNA was established and packed as lentivirus particles. A lentivirus that expressed the negative sequence was used as a lentivirus‑negative control (NC). The carrageenan‑induced SAB model was established in 32 male Sprague‑Dawley rats. The modeled rats were randomly assigned to four groups: Lentivirus‑RNAi treatment group, lentivirus‑NC group, SAB group and phosphate‑buffered saline (PBS) blank control group. The lentivirus was injected (1x10(7) transducing units) into the subacromial bursa of the rats in the lentivirus‑RNAi group and lentivirus‑NC group, whereas 100 µl PBS was injected at the same site in the SAB group and the PBS blank control group. At 5 weeks following injection, the animals were sacrificed and venous blood was obtained. The effect of TNF‑α interference and the expression of inflammatory cytokines were determined by reverse transcription‑quantitative polymerase chain reaction, western blotting, hematoxylin and eosin staining, Van Gieson's staining and immunofluorescence. The expression of TNF‑α was decreased in the lentivirus‑TNF‑α‑RNAi group compared with that in the SAB group. Morphological observations revealed that the number of inflammatory cells were reduced and damage to tendon fibers was attenuated in this group, suggesting that the downregulation of the protein expression levels of TNF‑α‑associated nuclear factor‑κB, matrix metalloproteinase (MMP)1, MMP9, cyclooxygenase (COX)‑1 and COX‑2 may exert a therapeutic effect on inflammation of the SAB caused by rheumatoid arthritis. It was also found that the expression of stromal cell‑derived growth factor‑1 was downregulated in the lentivirus‑TNF‑α‑RNAi group. Therefore, the present study demonstrated that lentivirus‑mediated TNF‑α RNAi effectively inhibited the inflammatory response in SAB, and that injection of a lentivirus vector into the affected region is an effective way of achieving RNAi in vivo.

How I Manage Athlete's Foot.

PubMed

Hoffmann, Thomas J; Schelkun, Patrice Heinz

1995-04-01

Athlete's foot, or tinea pedis, is a fungal infection that commonly affects active individuals. Intense itching is the primary symptom. Rash distribution, degree of redness, type of scaling, and presence of vesicles can distinguish athlete's foot from inflammatory conditions, but there is much overlap in presentation. Antifungal creams, used consistently for a period of weeks, are generally effective; in certain cases, keratolytics or oral antifungals are necessary. Educating patients about medication use, appropriate footwear, and avoiding excessive heat and moisture can help keep the condition in tow.

Current management of atopic dermatitis and interruption of the atopic march.

PubMed

Boguniewicz, Mark; Eichenfield, Lawrence F; Hultsch, Thomas

2003-12-01

Treatment of atopic dermatitis requires a comprehensive approach that includes evaluation of potential triggers and education of the patient and family regarding proper avoidance measures. Hydration of the skin and maintenance of an intact skin barrier remain integral to proper management. Although topical corticosteroids have been a mainstay of anti-inflammatory therapy, the newer topical calcineurin inhibitors offer advantages for treatment of this chronic, relapsing disease. Studies aimed at defining optimal combination therapy and early intervention might change the treatment paradigm for atopic dermatitis.

Perioperative management of a child with glutaric aciduria type I undergoing cardiac surgery.

PubMed

Kölker, Stefan; Eichhorn, Joachim; Sebening, Christian; Klein, Berthold; Springer, Wolfgang; Bopp, Christian; Rauch, Helmut

2013-10-01

Patients with glutaric aciduria type I are at risk for acute striatal injury precipitated by catabolic stress. Here, we report the successful interdisciplinary anesthetic and perioperative management of a child with glutaric aciduria type I undergoing cardiac surgery with extracorporeal circulation. Given the central focus on prevention of acute striatal injury, our anesthetic strategy emphasized avoiding a high protein load, high-dose inotropics, especially epinephrine (associated with impaired glucose utilization), deliberate hyperventilation, and other interventions associated with systemic inflammatory response.

Necrotizing sialometaplasia of tongue

PubMed Central

Randhawa, Tanu; Varghese, Ipe; Shameena, PM; Sudha, S; Nair, Resmi G

2009-01-01

Necrotizing sialometaplasia, is a benign inflammatory lesion primarily involving the minor salivary glands of the hard palate. The lesion often presents itself as a deep-seated palatal ulcer with clinical and histological features similar to those of a malignant neoplasm. Here we report a case of necrotizing sialometaplasia in a 40-year-old female, present on the lateral border of the tongue, mimicking squamous cell carcinoma, clinically. A correct diagnosis to avoid mutilant surgical treatments is essential, considering that it is a self-limiting disease. PMID:21886996

Spontaneous thrombosis of congenital extrahepatic portosystemic shunt (Abernethy malformation) simulating inguinal hernia incarceration.

PubMed

Afzal, Samara; Nair, Amit; Grainger, Jennie; Latif, Sherif; Rehman, Atiq-ur

2010-08-01

Tender lumps in the inguinal region are often explored emergently to treat suspected hernial strangulation. We discuss the case of an adult male who presented acutely with a tender inguinal swelling and raised inflammatory markers and was therefore deemed as requiring surgical exploration. However preoperative abdominal computerized tomography (CT) revealed an extensive thrombosing congenital venous malformation of portosystemic origin with extension into the symptomatic inguinal canal. A potentially lethal exsanguination from surgery was thus avoided.

Oral pulse granuloma associated with keratocystic odontogenic tumor: Report of a case and review on etiopathogenesis

PubMed Central

Kotrashetti, Vijayalakshmi S.; Angadi, Punnya V.; Mane, Deepa R.; Hallikerimath, Seema R.

2011-01-01

Pulse granuloma is a distinct oral entity characterized as a foreign body reaction occurring either centrally or peripherally. It is usually seen in the periapical or in the sulcus area. Occasionally the lesions occur in the wall of the cyst, commonest being the inflammatory odontogenic cyst. Histologically, they present as eosinophilic hyaline mass with giant cell inclusions and inflammatory cells. They may show different histological characteristics, possibly related to the length of time in the tissue. Adequate recognition is important to avoid misdiagnosis. Many authors suggest that pulse granuloma results due to implantation of food particles of plant or vegetable origin into the tissue following tooth extraction. This paper aims to report a case of pulse granuloma associated with keratocystic odontogenic tumor with its histochemical and polarizing microscopic features and discuss on etiopathogenesis of pulse granuloma. PMID:23482677

Vitamin D-Regulated MicroRNAs: Are They Protective Factors against Dengue Virus Infection?

PubMed Central

Arboleda, John F.; Urcuqui-Inchima, Silvio

2016-01-01

Over the last few years, an increasing body of evidence has highlighted the critical participation of vitamin D in the regulation of proinflammatory responses and protection against many infectious pathogens, including viruses. The activity of vitamin D is associated with microRNAs, which are fine tuners of immune activation pathways and provide novel mechanisms to avoid the damage that arises from excessive inflammatory responses. Severe symptoms of an ongoing dengue virus infection and disease are strongly related to highly altered production of proinflammatory mediators, suggesting impairment in homeostatic mechanisms that control the host's immune response. Here, we discuss the possible implications of emerging studies anticipating the biological effects of vitamin D and microRNAs during the inflammatory response, and we attempt to extrapolate these findings to dengue virus infection and to their potential use for disease management strategies. PMID:27293435

Acute urinary retention due to benign inflammatory nervous diseases.

PubMed

Sakakibara, Ryuji; Yamanishi, Tomonori; Uchiyama, Tomoyuki; Hattori, Takamichi

2006-08-01

Both neurologists and urologists might encounter patients with acute urinary retention due to benign inflammatory nervous diseases. Based on the mechanism of urinary retention, these disorders can be divided into two subgroups: disorders of the peripheral nervous system (e.g., sacral herpes) or the central nervous system (e.g., meningitis-retention syndrome [MRS]). Laboratory abnormalities include increased herpes virus titers in sacral herpes, and increased myelin basic protein in the cerebrospinal fluid (CSF) in some cases with MRS. Urodynamic abnormality in both conditions is detrusor areflexia; the putative mechanism of it is direct involvement of the pelvic nerves in sacral herpes; and acute spinal shock in MRS. There are few cases with CSF abnormality alone. Although these cases have a benign course, management of the acute urinary retention is necessary to avoid bladder injury due to overdistension. Clinical features of sacral herpes or MRS differ markedly from those of the original "Elsberg syndrome" cases.

Simultaneous Overexpression of Functional Human HO-1, E5NT and ENTPD1 Protects Murine Fibroblasts against TNF-α-Induced Injury In Vitro

PubMed Central

Cinti, Alessandro; De Giorgi, Marco; Chisci, Elisa; Arena, Claudia; Galimberti, Gloria; Farina, Laura; Bugarin, Cristina; Rivolta, Ilaria; Gaipa, Giuseppe; Smolenski, Ryszard Tom; Cerrito, Maria Grazia; Lavitrano, Marialuisa; Giovannoni, Roberto

2015-01-01

Several biomedical applications, such as xenotransplantation, require multiple genes simultaneously expressed in eukaryotic cells. Advances in genetic engineering technologies have led to the development of efficient polycistronic vectors based on the use of the 2A self-processing oligopeptide. The aim of this work was to evaluate the protective effects of the simultaneous expression of a novel combination of anti-inflammatory human genes, ENTPD1, E5NT and HO-1, in eukaryotic cells. We produced an F2A system-based multicistronic construct to express three human proteins in NIH3T3 cells exposed to an inflammatory stimulus represented by tumor necrosis factor alpha (TNF-α), a pro-inflammatory cytokine which plays an important role during inflammation, cell proliferation, differentiation and apoptosis and in the inflammatory response during ischemia/reperfusion injury in several organ transplantation settings. The protective effects against TNF-α-induced cytotoxicity and cell death, mediated by HO-1, ENTPD1 and E5NT genes were better observed in cells expressing the combination of genes as compared to cells expressing each single gene and the effect was further improved by administrating enzymatic substrates of the human genes to the cells. Moreover, a gene expression analyses demonstrated that the expression of the three genes has a role in modulating key regulators of TNF-α signalling pathway, namely Nemo and Tnfaip3, that promoted pro-survival phenotype in TNF-α injured cells. These results could provide new insights in the research of protective mechanisms in transplantation settings. PMID:26513260

Characterization and anti-inflammation role of swine IFITM3 gene

PubMed Central

Li, He-Ping; Chen, Pei-Ge; Liu, Fu-Tao; Zhu, He-Shui; Jiao, Xian-Qin; Zhong, Kai; Guo, Yu-Jie; Zha, Guang-Ming; Han, Li-Qiang; Lu, Wei-Fei; Wang, Yue-Ying; Yang, Guo-Yu

2017-01-01

IFITM3 is involved in cell adhesion, apoptosis, immune, and antivirus activity. Furthermore, IFITM3 gene has been considered as a preferential marker for inflammatory diseases, and positive correlation to pathological grades. Therefore, we assumed that IFITM3 was regulated by different signal pathways. To better understand IFITM3 function in inflammatory response, we cloned swine IFITM3 gene, and detected IFITM3 distribution in tissues, as well as characterized this gene. Results indicated that the length of swine IFITM3 gene was 438 bp, encoding 145 amino acids. IFITM3 gene expression abundance was higher in spleen and lungs. Moreover, we next constructed the eukaryotic expression vector PBIFM3 and transfected into PK15 cells, finally obtained swine IFITM3 gene stable expression cell line. Meanwhile, we explored the effects of LPS on swine IFITM3 expression. Results showed that LPS increased IFITM3 mRNA abundance and exhibited time-dependent effect for LPS treatment. To further demonstrate the mechanism that IFITM3 regulated type I IFNs production, we also detected the important molecules expression of TLR4 signaling pathway. In transfected and non-transfected IFITM3 PK15 cells, LPS exacerbated the relative expression of TLR4-NFκB signaling molecules. However, the IFITM3 overexpression suppressed the inflammatory development of PK15 cells. In conclusion, these data indicated that the overexpression of swine IFITM3 could decrease the inflammatory response through TLR4 signaling pathway, and participate in type I interferon production. These findings may lead to an improved understanding of the biological function of IFITM3 in inflammation. PMID:29088728

Transgene Expression and Host Cell Responses to Replication-Defective, Single-Cycle, and Replication-Competent Adenovirus Vectors.

PubMed

Crosby, Catherine M; Barry, Michael A

2017-02-18

Most adenovirus (Ad) vectors are E1 gene deleted replication defective (RD-Ad) vectors that deliver one transgene to the cell and all expression is based on that one gene. In contrast, E1-intact replication-competent Ad (RC-Ad) vectors replicate their DNA and their transgenes up to 10,000-fold, amplifying transgene expression markedly higher than RD-Ad vectors. While RC-Ad are more potent, they run the real risk of causing adenovirus infections in vector recipients and those that administer them. To gain the benefits of transgene amplification, but avoid the risk of Ad infections, we developed "single cycle" Ad (SC-Ad) vectors. SC-Ads amplify transgene expression and generated markedly stronger and more persistent immune responses than RD-Ad as expected. However, they also unexpectedly generated stronger immune responses than RC-Ad vectors. To explore the basis of this potency here, we compared gene expression and the cellular responses to infection to these vectors in vitro and in vivo. In vitro, in primary human lung epithelial cells, SC- and RC-Ad amplified their genomes more than 400-fold relative to RD-Ad with higher replication by SC-Ad. This replication translated into higher green fluorescent protein (GFP) expression for 48 h by SC- and RC-Ad than by RD-Ad. In vitro, in the absence of an immune system, RD-Ad expression became higher by 72 h coincident with cell death mediated by SC- and RC-Ad and release of transgene product from the dying cells. When the vectors were compared in human THP-1 Lucia- interferon-stimulated gene (ISG) cells, which are a human monocyte cell line that have been modified to quantify ISG activity, RC-Ad6 provoked significantly stronger ISG responses than RD- or SC-Ad. In mice, intravenous or intranasal injection produced up to 100-fold genome replication. Under these in vivo conditions in the presence of the immune system, luciferase expression by RC and SC-Ad was markedly higher than that by RD-Ad. In immunodeficient mice, SC-Ad drove stronger luciferase expression than RC- or RD-Ad. These data demonstrate better transgene expression by SC- and RC-Ad in vitro and in vivo than RD-Ad. This higher expression by the replicating vectors results in a peak of expression within 1 to 2 days followed by cell death of infected cells and release of transgene products. While SC- and RC-Ad expression were similar in mice and in Syrian hamsters, RC-Ad provoked much stronger ISG induction which may explain in part SC-Ad's ability to generate stronger and more persistent immune responses than RC-Ad in Ad permissive hamsters.

Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases.

PubMed

Ciechomska, Marzena; O'Reilly, Steven

2016-01-01

Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient's functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases.

Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and Their Extracellular Vesicles: Are We Still Learning?

PubMed Central

Lohan, Paul; Treacy, Oliver; Griffin, Matthew D.; Ritter, Thomas; Ryan, Aideen E.

2017-01-01

Mesenchymal stromal cells (MSC) have been used to treat a broad range of disease indications such as acute and chronic inflammatory disorders, autoimmune diseases, and transplant rejection due to their potent immunosuppressive/anti-inflammatory properties. The breadth of their usage is due in no small part to the vast quantity of published studies showing their ability to modulate multiple immune cell types of both the innate and adaptive immune response. While patient-derived (autologous) MSC may be the safer choice in terms of avoiding unwanted immune responses, factors including donor comorbidities may preclude these cells from use. In these situations, allogeneic MSC derived from genetically unrelated individuals must be used. While allogeneic MSC were initially believed to be immune-privileged, substantial evidence now exists to prove otherwise with multiple studies documenting specific cellular and humoral immune responses against donor antigens following administration of these cells. In this article, we will review recent published studies using non-manipulated, inflammatory molecule-activated (licensed) and differentiated allogeneic MSC, as well as MSC extracellular vesicles focusing on the immune responses to these cells and whether or not such responses have an impact on allogeneic MSC-mediated safety and efficacy. PMID:29225601

Optimal management of collagenous colitis: a review

PubMed Central

O’Toole, Aoibhlinn

2016-01-01

Collagenous colitis (CC) is an increasingly recognized cause of chronic inflammatory bowel disease characterized by watery non-bloody diarrhea. As a lesser studied inflammatory bowel disease, many aspects of the CC’s natural history are poorly understood. This review discusses strategies to optimally manage CC. The goal of therapy is to induce clinical remission, <3 stools a day or <1 watery stool a day with subsequent improved quality of life (QOL). Antidiarrheal can be used as monotherapy or with other medications to control diarrhea. Budesonide therapy has revolutionized treatment and is superior to prednisone, however, the treatment is associated with high-relapse rates and the management of refractory disease is challenging. Ongoing trials will address the safety and efficacy of low-dose maintenance therapy. For those with refractory disease, case reports and case series support the role of biologic agents. Diversion of the fecal stream normalizes colonic mucosal changes and ileostomy may be considered where anti-tumor necrosis factor (TNF)-α agents are contraindicated. Underlying celiac disease, bile salt diarrhea, and associated thyroid dysfunction should be ruled out. The author recommends smoking cessation as well as avoidance of nonsteroidal anti-inflammatories as well as other associated medications. PMID:26929656

Diversion colitis: histological features in the colon and rectum after defunctioning colostomy.

PubMed Central

Geraghty, J M; Talbot, I C

1991-01-01

Diversion of the faecal stream by ileostomy or colostomy leads to inflammation in the defunctioned segment, known as diversion colitis. The affected bowel is rapidly restored to normality by reanastomosis. Diversion colitis should not be mistaken for inflammatory bowel disease, for which reanastomosis would be inappropriate. Studies of biopsy material from patients with diversion colitis have shown a variety of histological features, but no consistent pattern. The histology in resection specimens of defunctioned large bowel from 15 patients with no pre-existing inflammatory bowel disease was studied. Nine patients had symptoms of abdominal pain or rectal discharge of blood or mucus that developed between 9 months and 17 years after diversion procedure. The histology was abnormal in all. Findings were similar in 14 patients, regardless of the duration of faecal diversion, and comprised diffuse mild chronic inflammation with or without mild crypt architectural abnormalities, crypt abscesses, or follicular lymphoid hyperplasia. One patient had more severe changes, resembling active ulcerative colitis. These features in biopsy specimens are unlikely to be diagnostic but should provide useful information in avoiding a mistaken diagnosis of inflammatory bowel disease in these patients. Images Figure 1 Figure 2 Figure 3 PMID:1916483

[Protective role of high density lipoproteins in sepsis: basic issues and clinical implications].

PubMed

Contreras-Duarte, Susana; Varas, Pablo; Awad, Fernanda; Busso, Dolores; Rigotti, Attilio

2014-02-01

High density lipoproteins (HDL) are responsible of reverse cholesterol transport and play an important antiatherogenic role. In recent years, several studies suggest that HDL have additional functions, including a possible anti-inflammatory activity in infectious conditions. Furthermore, available evidence indicates that the presence of lipopolysaccharide (LPS) within the circulation during infectious states induced by gram-negative bacteria may be involved in the decrease in HDL cholesterol levels and changes in lipoprotein composition, which have been associated with a higher mortality due to sepsis in animal models and in humans. In this article, we review this subject and also discuss possible mechanisms that explain the positive impact achieved by native HDL, reconstituted HDL, or HDL apolipoprotein peptides on the inflammatory response and mortality in models of endotoxemia. In this regard, it has been proposed that one of the mechanisms by which HDL protect against sepsis may be mediated by its binding ability and/or neutralizing capacity on LPS, avoiding an excessive response of the immune system. Thus, increasing blood levels of HDL and/or parenteral HDL administration may represent a new anti-inflammatory tool for managing septic states in humans.

Histological dermal changes caused by preparation and application procedures in percutaneous dose toxicity studies in dogs, rabbits and rats

PubMed Central

Mitsuishi, Mikio; Oshikata, Takafumi; Kumabe, Shino; Kobayashi, Azusa; Katoku, Koshiro; Kanno, Takeshi; Hamamura, Masao; Tsuchitani, Minoru

2014-01-01

We reevaluated histological slides of dorsal skin in control animals from past percutaneous dose toxicity studies using dogs, rabbits and rats to provide background data concerning histological changes related to preparation and application procedures and vehicles or embrocations of every variety. Acanthosis, dermal or perifollicular inflammatory cell infiltration in dogs; hyperkeratosis, acanthosis, dermal inflammatory cell infiltration or hemorrhage in rabbits; and acanthosis, dermal inflammatory cell infiltration, crust or foreign body granuloma in rats were present as procedure-related underlying histological changes in the control animals. Four mechanical acts, (1) rubbing with gauze to remove an administered substance for reapplication, (2) use of a taut bandage to avoid slipping from the application site, (3) peeling a patch off as a preparation procedure for reapplication, and (4) clipping or shaving, were considered to cause injury to the skin. The degree of influence of the various application procedures was found to be as follows: sham, lotion < cream < ointment and tape in dogs; untreated control, sham < lotion < tape and poultice in rabbits; and sham, sodium carboxymethylcellulose < olive oil and lotion < ointment and tape in rats. The degree of ointment influence on rabbits is equivocal. PMID:26023255

Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization.

PubMed

Braun, Molly; Khan, Zenab T; Khan, Mohammad B; Kumar, Manish; Ward, Ayobami; Achyut, Bhagelu R; Arbab, Ali S; Hess, David C; Hoda, Md Nasrul; Baban, Babak; Dhandapani, Krishnan M; Vaibhav, Kumar

2018-02-01

Inflammation is an important mediator of secondary neurological injury after traumatic brain injury (TBI). Endocannabinoids, endogenously produced arachidonate based lipids, have recently emerged as powerful anti-inflammatory compounds, yet the molecular and cellular mechanisms underlying these effects are poorly defined. Endocannabinoids are physiological ligands for two known cannabinoid receptors, CB1R and CB2R. In the present study, we hypothesized that selective activation of CB2R attenuates neuroinflammation and reduces neurovascular injury after TBI. Using a murine controlled cortical impact (CCI) model of TBI, we observed a dramatic upregulation of CB2R within infiltrating myeloid cells beginning at 72 h. Administration of the selective CB2R agonist, GP1a (1-5 mg/kg), attenuated pro-inflammatory M1 macrophage polarization, increased anti-inflammatory M2 polarization, reduced edema development, enhanced cerebral blood flow, and improved neurobehavioral outcomes after TBI. In contrast, the CB2R antagonist, AM630, worsened outcomes. Taken together, our findings support the development of selective CB2R agonists as a therapeutic strategy to improve TBI outcomes while avoiding the psychoactive effects of CB1R activation. Published by Elsevier Inc.

Management of health care expenditure by soft computing methodology

NASA Astrophysics Data System (ADS)

Maksimović, Goran; Jović, Srđan; Jovanović, Radomir; Aničić, Obrad

2017-01-01

In this study was managed the health care expenditure by soft computing methodology. The main goal was to predict the gross domestic product (GDP) according to several factors of health care expenditure. Soft computing methodologies were applied since GDP prediction is very complex task. The performances of the proposed predictors were confirmed with the simulation results. According to the results, support vector regression (SVR) has better prediction accuracy compared to other soft computing methodologies. The soft computing methods benefit from the soft computing capabilities of global optimization in order to avoid local minimum issues.

Protein Degradation in a TX-TL Cell-free Expression System Using ClpXP Protease

DTIC Science & Technology

2014-07-14

function in TX-TL, as well as bacteriophage assembly [2, 6]. Circuits can also be prototyped from basic parts within 8 hours, avoiding cloning and...mRFP, and Venus and variants eGFP-ssrA, mRFP-ssrA, and Venus-ssrA, coding sequences were cloned into a T7-lacO inducible vector containing a N...12672L12677.! 6.! Shin,!J.,!P.!Jardine,!and!V.!Noireaux,!Genome(Replication,(Synthesis,(and( Assembly(of(the( Bacteriophage (T7(in(a(Single(Cell9Free

Performance Analysis of the Enhanced Bio-Inspired Planning Algorithm for Rapid Situation Awareness Response

DTIC Science & Technology

2013-10-18

low cost robot testbed. 15. SUBJECT TERMS Bio-inspired trajectory generation, in-situ obstacle avoidance, low-cost LEGO robots, vision- based...will not affect the solution optimality and thus will be regarded as zero. Following the LP motion strategy Eq. (1), the position vector of the Lego ...Lobatto (LGL) method [14], the position of Lego robot can be further represented as ’ 1 ,( )j p jD   ζ ζ (6) in which ,0 ,,..., T j j j

Application of Improved APO Algorithm in Vulnerability Assessment and Reconstruction of Microgrid

NASA Astrophysics Data System (ADS)

Xie, Jili; Ma, Hailing

2018-01-01

Artificial Physics Optimization (APO) has good global search ability and can avoid the premature convergence phenomenon in PSO algorithm, which has good stability of fast convergence and robustness. On the basis of APO of the vector model, a reactive power optimization algorithm based on improved APO algorithm is proposed for the static structure and dynamic operation characteristics of microgrid. The simulation test is carried out through the IEEE 30-bus system and the result shows that the algorithm has better efficiency and accuracy compared with other optimization algorithms.

Viral vector vaccines protect cockatiels from inflammatory lesions after heterologous parrot bornavirus 2 challenge infection.

PubMed

Runge, Solveig; Olbert, Marita; Herden, Christiane; Malberg, Sara; Römer-Oberdörfer, Angela; Staeheli, Peter; Rubbenstroth, Dennis

2017-01-23

Avian bornaviruses are causative agents of proventricular dilatation disease (PDD), a chronic neurologic and often fatal disorder of psittacines including endangered species. To date no causative therapy or immunoprophylaxis is available. Our previous work has shown that viral vector vaccines can delay the course of homologous bornavirus challenge infections but failed to protect against PDD when persistent infection was not prevented. The goal of this study was to refine our avian bornavirus vaccination and infection model to better represent natural bornavirus infections in order to achieve full protection against a heterologous challenge infection. We observed that parrot bornavirus 2 (PaBV-2) readily infected cockatiels (Nymphicus hollandicus) by combined intramuscular and subcutaneous injection with as little as 10 2.7 foci-forming units (ffu) per bird, whereas a 500-fold higher dose of the same virus administered via peroral and oculonasal route did not result in persistent infection. These results indicated that experimental bornavirus challenge infections with this virus should be performed via the parenteral route. Prime-boost vaccination of cockatiels with Newcastle disease virus (NDV) and modified vaccinia virus Ankara (MVA) vectors expressing the nucleoprotein and phosphoprotein genes of PaBV-4 substantially blocked bornavirus replication following parenteral challenge infection with 10 3.5 ffu of heterologous PaBV-2. Only two out of six vaccinated birds had very low viral levels detectable in a few organs. As a consequence, only one vaccinated bird developed mild PDD-associated microscopic lesions, while mock-vaccinated controls were not protected against PaBV-2 infection and inflammation. Our results demonstrate that NDV and MVA vector vaccines can protect against invasive heterologous bornavirus challenge infections and subsequent PDD. These vector vaccines represent a promising tool to combat avian bornaviruses in psittacine populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Viral vector mediated continuous expression of interleukin-10 in DRG alleviates pain in type 1 diabetic animals.

PubMed

Thakur, Vikram; Gonzalez, Mayra; Pennington, Kristen; Chattopadhyay, Munmun

2016-04-01

Painful diabetic neuropathy is a common and difficult to treat complication of diabetes. A growing body of evidence implicates the role of inflammatory mediators in the damage to the peripheral axons and in the pathogenesis of neuropathic pain. Increased expression of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the peripheral nervous system suggests the possibility of change in pain perception in diabetes. In this study we investigated that continuous delivery of IL10 in the nerve fibers achieved by HSV vector mediated transduction of dorsal root ganglion (DRG) in animals with Type 1 diabetes, blocks the nociceptive and stress responses in the DRG neurons by reducing IL1β expression along with inhibition of phosphorylation of p38 MAPK (mitogen-activated protein kinase) and protein kinase C (PKC). The continuous expression of IL10 also alters Toll like receptor (TLR)-4 expression in the DRG with increased expression of heat shock protein (HSP)-70 in conjunction with the reduction of pain. Taken together, this study suggests that macrophage activation in the peripheral nervous system may be involved in the pathogenesis of pain in Type 1 diabetes and therapeutic benefits of HSV mediated local expression of IL10 in the DRG with the reduction of a number of proinflammatory cytokines, subsequently inhibits the development of painful neuropathy along with a decrease in stress associated markers in the DRG. This basic and preclinical study provides an important evidence for a novel treatment strategy that could lead to a clinical trial for what is currently a treatment resistant complication of diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Systemic Upregulation of IL-10 (Interleukin-10) Using a Nonimmunogenic Vector Reduces Growth and Rate of Dissecting Abdominal Aortic Aneurysm.

PubMed

Adam, Matti; Kooreman, Nigel; Jagger, Ann; Wagenhaeuser, Markus U; Mehrkens, Dennis; Wang, Yongming; Kayama, Yosuke; Toyama, Kensuke; Raaz, Uwe; Schellinger, Isabel N; Maegdefessel, Lars; Spin, Joshua M; Hamming, Jaap F; Quax, Paul H A; Baldus, Stephan; Wu, Joseph C; Tsao, Philip S

2018-06-07

Recruitment of immunologic competent cells to the vessel wall is a crucial step in formation of abdominal aortic aneurysms (AAA). Innate immunity effectors (eg, macrophages), as well as mediators of adaptive immunity (eg, T cells), orchestrate a local vascular inflammatory response. IL-10 (interleukin-10) is an immune-regulatory cytokine with a crucial role in suppression of inflammatory processes. We hypothesized that an increase in systemic IL-10-levels would mitigate AAA progression. Using a single intravenous injection protocol, we transfected an IL-10 transcribing nonimmunogenic minicircle vector into the Ang II (angiotensin II)-ApoE -/- infusion mouse model of AAA. IL-10 minicircle transfection significantly reduced average aortic diameter measured via ultrasound at day 28 from 166.1±10.8% (control) to 131.0±5.8% (IL-10 transfected). Rates of dissecting AAA were reduced by IL-10 treatment, with an increase in freedom from dissecting AAA from 21.5% to 62.3%. Using flow cytometry of aortic tissue from minicircle IL-10-treated animals, we found a significantly higher percentage of CD4 + /CD25 + /Foxp3 (forkhead box P3) + regulatory T cells, with fewer CD8 + /Granzyme B + cytotoxic T cells. Furthermore, isolated aortic macrophages produced less TNF-α (tumor necrosis factor-α), more IL-10, and were more likely to be MRC1 (mannose receptor, C type 1)-positive alternatively activated macrophages. These results concurred with gene expression analysis of LPS-stimulated and Ang II-primed human peripheral blood mononuclear cells. Taken together, we provide an effective gene therapy approach to AAA in mice by enhancing antiinflammatory and dampening proinflammatory pathways through minicircle-induced augmentation of systemic IL-10 expression. © 2018 American Heart Association, Inc.

Virally delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness

PubMed Central

Doroudchi, M Mehdi; Greenberg, Kenneth P; Liu, Jianwen; Silka, Kimberly A; Boyden, Edward S; Lockridge, Jennifer A; Arman, A Cyrus; Janani, Ramesh; Boye, Shannon E; Boye, Sanford L; Gordon, Gabriel M; Matteo, Benjamin C; Sampath, Alapakkam P; Hauswirth, William W; Horsager, Alan

2011-01-01

Previous work established retinal expression of channelrhodopsin-2 (ChR2), an algal cation channel gated by light, restored physiological and behavioral visual responses in otherwise blind rd1 mice. However, a viable ChR2-based human therapy must meet several key criteria: (i) ChR2 expression must be targeted, robust, and long-term, (ii) ChR2 must provide long-term and continuous therapeutic efficacy, and (iii) both viral vector delivery and ChR2 expression must be safe. Here, we demonstrate the development of a clinically relevant therapy for late stage retinal degeneration using ChR2. We achieved specific and stable expression of ChR2 in ON bipolar cells using a recombinant adeno-associated viral vector (rAAV) packaged in a tyrosine-mutated capsid. Targeted expression led to ChR2-driven electrophysiological ON responses in postsynaptic retinal ganglion cells and significant improvement in visually guided behavior for multiple models of blindness up to 10 months postinjection. Light levels to elicit visually guided behavioral responses were within the physiological range of cone photoreceptors. Finally, chronic ChR2 expression was nontoxic, with transgene biodistribution limited to the eye. No measurable immune or inflammatory response was observed following intraocular vector administration. Together, these data indicate that virally delivered ChR2 can provide a viable and efficacious clinical therapy for photoreceptor disease-related blindness. PMID:21505421

Combined dispersive/interference spectroscopy for producing a vector spectrum

DOEpatents

Erskine, David J.

2002-01-01

A method of measuring the spectral properties of broadband waves that combines interferometry with a wavelength disperser having many spectral channels to produce a fringing spectrum. Spectral mapping, Doppler shifts, metrology of angles, distances and secondary effects such as temperature, pressure, and acceleration which change an interferometer cavity length can be measured accurately by a compact instrument using broadband illumination. Broadband illumination avoids the fringe skip ambiguities of monochromatic waves. The interferometer provides arbitrarily high spectral resolution, simple instrument response, compactness, low cost, high field of view and high efficiency. The inclusion of a disperser increases fringe visibility and signal to noise ratio over an interferometer used alone for broadband waves. The fringing spectrum is represented as a wavelength dependent 2-d vector, which describes the fringe amplitude and phase. Vector mathematics such as generalized dot products rapidly computes average broadband phase shifts to high accuracy. A Moire effect between the interferometer's sinusoidal transmission and the illumination heterodynes high resolution spectral detail to low spectral detail, allowing the use of a low resolution disperser. Multiple parallel interferometer cavities of fixed delay allow the instantaneous mapping of a spectrum, with an instrument more compact for the same spectral resolution than a conventional dispersive spectrometer, and not requiring a scanning delay.

Pattern Classification Using an Olfactory Model with PCA Feature Selection in Electronic Noses: Study and Application

PubMed Central

Fu, Jun; Huang, Canqin; Xing, Jianguo; Zheng, Junbao

2012-01-01

Biologically-inspired models and algorithms are considered as promising sensor array signal processing methods for electronic noses. Feature selection is one of the most important issues for developing robust pattern recognition models in machine learning. This paper describes an investigation into the classification performance of a bionic olfactory model with the increase of the dimensions of input feature vector (outer factor) as well as its parallel channels (inner factor). The principal component analysis technique was applied for feature selection and dimension reduction. Two data sets of three classes of wine derived from different cultivars and five classes of green tea derived from five different provinces of China were used for experiments. In the former case the results showed that the average correct classification rate increased as more principal components were put in to feature vector. In the latter case the results showed that sufficient parallel channels should be reserved in the model to avoid pattern space crowding. We concluded that 6∼8 channels of the model with principal component feature vector values of at least 90% cumulative variance is adequate for a classification task of 3∼5 pattern classes considering the trade-off between time consumption and classification rate. PMID:22736979

Design and application of cationic amphiphilic β-cyclodextrin derivatives as gene delivery vectors

NASA Astrophysics Data System (ADS)

Wan, Ning; Huan, Meng-Lei; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

2017-11-01

The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

ESPRIT-Like Two-Dimensional DOA Estimation for Monostatic MIMO Radar with Electromagnetic Vector Received Sensors under the Condition of Gain and Phase Uncertainties and Mutual Coupling

PubMed Central

Zhang, Yongshun; Zheng, Guimei; Feng, Cunqian; Tang, Jun

2017-01-01

In this paper, we focus on the problem of two-dimensional direction of arrival (2D-DOA) estimation for monostatic MIMO Radar with electromagnetic vector received sensors (MIMO-EMVSs) under the condition of gain and phase uncertainties (GPU) and mutual coupling (MC). GPU would spoil the invariance property of the EMVSs in MIMO-EMVSs, thus the effective ESPRIT algorithm unable to be used directly. Then we put forward a C-SPD ESPRIT-like algorithm. It estimates the 2D-DOA and polarization station angle (PSA) based on the instrumental sensors method (ISM). The C-SPD ESPRIT-like algorithm can obtain good angle estimation accuracy without knowing the GPU. Furthermore, it can be applied to arbitrary array configuration and has low complexity for avoiding the angle searching procedure. When MC and GPU exist together between the elements of EMVSs, in order to make our algorithm feasible, we derive a class of separated electromagnetic vector receiver and give the S-SPD ESPRIT-like algorithm. It can solve the problem of GPU and MC efficiently. And the array configuration can be arbitrary. The effectiveness of our proposed algorithms is verified by the simulation result. PMID:29072588

ESPRIT-Like Two-Dimensional DOA Estimation for Monostatic MIMO Radar with Electromagnetic Vector Received Sensors under the Condition of Gain and Phase Uncertainties and Mutual Coupling.

PubMed

Zhang, Dong; Zhang, Yongshun; Zheng, Guimei; Feng, Cunqian; Tang, Jun

2017-10-26

In this paper, we focus on the problem of two-dimensional direction of arrival (2D-DOA) estimation for monostatic MIMO Radar with electromagnetic vector received sensors (MIMO-EMVSs) under the condition of gain and phase uncertainties (GPU) and mutual coupling (MC). GPU would spoil the invariance property of the EMVSs in MIMO-EMVSs, thus the effective ESPRIT algorithm unable to be used directly. Then we put forward a C-SPD ESPRIT-like algorithm. It estimates the 2D-DOA and polarization station angle (PSA) based on the instrumental sensors method (ISM). The C-SPD ESPRIT-like algorithm can obtain good angle estimation accuracy without knowing the GPU. Furthermore, it can be applied to arbitrary array configuration and has low complexity for avoiding the angle searching procedure. When MC and GPU exist together between the elements of EMVSs, in order to make our algorithm feasible, we derive a class of separated electromagnetic vector receiver and give the S-SPD ESPRIT-like algorithm. It can solve the problem of GPU and MC efficiently. And the array configuration can be arbitrary. The effectiveness of our proposed algorithms is verified by the simulation result.

The effect of global warming on infectious diseases.

PubMed

Kurane, Ichiro

2010-12-01

Global warming has various effects on human health. The main indirect effects are on infectious diseases. Although the effects on infectious diseases will be detected worldwide, the degree and types of the effect are different, depending on the location of the respective countries and socioeconomical situations. Among infectious diseases, water- and foodborne infectious diseases and vector-borne infectious diseases are two main categories that are forecasted to be most affected. The effect on vector-borne infectious diseases such as malaria and dengue fever is mainly because of the expansion of the infested areas of vector mosquitoes and increase in the number and feeding activity of infected mosquitoes. There will be increase in the number of cases with water- and foodborne diarrhoeal diseases. Even with the strongest mitigation procedures, global warming cannot be avoided for decades. Therefore, implementation of adaptation measures to the effect of global warming is the most practical action we can take. It is generally accepted that the impacts of global warming on infectious diseases have not been apparent at this point yet in East Asia. However, these impacts will appear in one form or another if global warming continues to progress in future. Further research on the impacts of global warming on infectious diseases and on future prospects should be conducted.

A conservative scheme for electromagnetic simulation of magnetized plasmas with kinetic electrons

NASA Astrophysics Data System (ADS)

Bao, J.; Lin, Z.; Lu, Z. X.

2018-02-01

A conservative scheme has been formulated and verified for gyrokinetic particle simulations of electromagnetic waves and instabilities in magnetized plasmas. An electron continuity equation derived from the drift kinetic equation is used to time advance the electron density perturbation by using the perturbed mechanical flow calculated from the parallel vector potential, and the parallel vector potential is solved by using the perturbed canonical flow from the perturbed distribution function. In gyrokinetic particle simulations using this new scheme, the shear Alfvén wave dispersion relation in the shearless slab and continuum damping in the sheared cylinder have been recovered. The new scheme overcomes the stringent requirement in the conventional perturbative simulation method that perpendicular grid size needs to be as small as electron collisionless skin depth even for the long wavelength Alfvén waves. The new scheme also avoids the problem in the conventional method that an unphysically large parallel electric field arises due to the inconsistency between electrostatic potential calculated from the perturbed density and vector potential calculated from the perturbed canonical flow. Finally, the gyrokinetic particle simulations of the Alfvén waves in sheared cylinder have superior numerical properties compared with the fluid simulations, which suffer from numerical difficulties associated with singular mode structures.

Detection of Hard Exudates in Colour Fundus Images Using Fuzzy Support Vector Machine-Based Expert System.

PubMed

Jaya, T; Dheeba, J; Singh, N Albert

2015-12-01

Diabetic retinopathy is a major cause of vision loss in diabetic patients. Currently, there is a need for making decisions using intelligent computer algorithms when screening a large volume of data. This paper presents an expert decision-making system designed using a fuzzy support vector machine (FSVM) classifier to detect hard exudates in fundus images. The optic discs in the colour fundus images are segmented to avoid false alarms using morphological operations and based on circular Hough transform. To discriminate between the exudates and the non-exudates pixels, colour and texture features are extracted from the images. These features are given as input to the FSVM classifier. The classifier analysed 200 retinal images collected from diabetic retinopathy screening programmes. The tests made on the retinal images show that the proposed detection system has better discriminating power than the conventional support vector machine. With the best combination of FSVM and features sets, the area under the receiver operating characteristic curve reached 0.9606, which corresponds to a sensitivity of 94.1% with a specificity of 90.0%. The results suggest that detecting hard exudates using FSVM contribute to computer-assisted detection of diabetic retinopathy and as a decision support system for ophthalmologists.

Design and application of cationic amphiphilic β-cyclodextrin derivatives as gene delivery vectors.

PubMed

Wan, Ning; Huan, Meng-Lei; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

2017-11-17

The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

The vomeronasal system mediates sick conspecific avoidance.

PubMed

Boillat, Madlaina; Challet, Ludivine; Rossier, Daniel; Kan, Chenda; Carleton, Alan; Rodriguez, Ivan

2015-01-19

Although sociability offers many advantages, a major drawback is the increased risk of exposure to contagious pathogens, like parasites, viruses, or bacteria. Social species have evolved various behavioral strategies reducing the probability of pathogen exposure. In rodents, sick conspecific avoidance can be induced by olfactory cues emitted by parasitized or infected conspecifics. The neural circuits involved in this behavior remain largely unknown. We observed that olfactory cues present in bodily products of mice in an acute inflammatory state or infected with a viral pathogen are aversive to conspecifics. We found that these chemical signals trigger neural activity in the vomeronasal system, an olfactory subsystem controlling various innate behaviors. Supporting the functional relevance of these observations, we show that preference toward healthy individuals is abolished in mice with impaired vomeronasal function. These findings reveal a novel function played by the vomeronasal system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diagnosis, treatment, and prevention of gout.

PubMed

Hainer, Barry L; Matheson, Eric; Wilkes, R Travis

2014-12-15

Gout is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint, resulting from precipitation of monosodium urate crystals in a joint space. Gout is typically diagnosed using clinical criteria from the American College of Rheumatology. Diagnosis may be confirmed by identification of monosodium urate crystals in synovial fluid of the affected joint. Acute gout may be treated with nonsteroidal anti-inflammatory drugs, corticosteroids, or colchicine. To reduce the likelihood of recurrent flares, patients should limit their consumption of certain purine-rich foods (e.g., organ meats, shellfish) and avoid alcoholic drinks (especially beer) and beverages sweetened with high-fructose corn syrup. Consumption of vegetables and low-fat or nonfat dairy products should be encouraged. The use of loop and thiazide diuretics can increase uric acid levels, whereas the use of the angiotensin receptor blocker losartan increases urinary excretion of uric acid. Reduction of uric acid levels is key to avoiding gout flares. Allopurinol and febuxostat are first-line medications for the prevention of recurrent gout, and colchicine and/or probenecid are reserved for patients who cannot tolerate first-line agents or in whom first-line agents are ineffective. Patients receiving urate-lowering medications should be treated concurrently with nonsteroidal anti-inflammatory drugs, colchicine, or low-dose corticosteroids to prevent flares. Treatment should continue for at least three months after uric acid levels fall below the target goal in those without tophi, and for six months in those with a history of tophi.

Intracellular TLR22 acts as an inflammation equalizer via suppression of NF-κB and selective activation of MAPK pathway in fish.

PubMed

Ding, Xu; Liang, Yaosi; Peng, Wan; Li, Ruozhu; Lin, Haoran; Zhang, Yong; Lu, Danqi

2018-01-01

TLR22, a typical member of the fish-specific TLRs, is a crucial sensor in virally triggered innate immune signalling retained from natural selection. To elucidate the role of the TLR22-specific signalling cascade mechanism, we provide evidence that the double-stranded (ds) RNA-sensor TLR22 positively regulates the ERK pathway and negatively regulates the JNK, p38 MAP kinase and NF-κB pathway. Here, we show that TLR22 restrains NF-κB activation and IFN (interferon) β and AP-1 (activator protein-1) promoter binding (impairing "primary response" genes (TNF and IL-1)), induces "secondary response" genes (IL-12 and IL-6) and mediates the irregular expression of inflammatory genes. Therefore, TLR22 promotes ERK phosphorylation but impairs the JNK and p38 MAP kinases and IκB phosphorylation. Additionally, TLR22 controls the excessive generation of reactive oxygen species (ROS) to avoid damaging the organism. The specific kinetics of TLR22 depends on its distinct cellular localization. We demonstrate that TLR22 is an intracellular receptor localized in the endosome, and the TLR22-TIR domain is the functional structure inducing the signalling cascade post-viral replication in the body. As mentioned above, our data reveal a novel mechanism whereby TLR22-induced positive adjustment and negative regulation evolved independently to avoid harmful and inappropriate inflammatory responses. Copyright © 2017. Published by Elsevier Ltd.

Cost-effective accurate coarse-grid method for highly convective multidimensional unsteady flows

NASA Technical Reports Server (NTRS)

Leonard, B. P.; Niknafs, H. S.

1991-01-01

A fundamentally multidimensional convection scheme is described based on vector transient interpolation modeling rewritten in conservative control-volume form. Vector third-order upwinding is used as the basis of the algorithm; this automatically introduces important cross-difference terms that are absent from schemes using component-wise one-dimensional formulas. Third-order phase accuracy is good; this is important for coarse-grid large-eddy or full simulation. Potential overshoots or undershoots are avoided by using a recently developed universal limiter. Higher order accuracy is obtained locally, where needed, by the cost-effective strategy of adaptive stencil expansion in a direction normal to each control-volume face; this is controlled by monitoring the absolute normal gradient and curvature across the face. Higher (than third) order cross-terms do not appear to be needed. Since the wider stencil is used only in isolated narrow regions (near discontinuities), extremely high (in this case, seventh) order accuracy can be achieved for little more than the cost of a globally third-order scheme.

SME filter approach to multiple target tracking with false and missing measurements

NASA Astrophysics Data System (ADS)

Lee, Yong J.; Kamen, Edward W.

1993-10-01

The symmetric measurement equation (SME) filter for track maintenance in multiple target tracking is extended to the general case when there are an arbitrary unknown number of false and missing position measurements in the measurement set at any time point. It is assumed that the number N of targets is known a priori and that the target motions consist of random perturbations of constant-velocity trajectories. The key idea in the paper is to generate a new measurement vector from sums-of-products of the elements of 'feasible' N-element data vectors that pass a thresholding operation in the sums-of-products framework. Via this construction, the data association problem is completely avoided, and in addition, there is no need to identify which target measurements may correspond to false returns or which target measurements may be missing. A computer simulation of SME filter performance is given, including a comparison with the associated filter (a benchmark) and the joint probabilistic data association (JPDA) filter.

Empirical evidence of the effect of school gathering on the dynamics of dengue epidemics.

PubMed

Hernández-Suárez, Carlos M; Mendoza-Cano, Oliver

2016-01-01

Dengue fever is an important vector-transmitted disease that affects more than 100 countries worldwide. Locations where individuals tend to gather may play an important role in disease transmission in the presence of the vector. By controlling mosquitoes' breeding places, this study aims to analyze the effect of reducing transmission in elementary schools (grades 1-9) on the dynamics of the epidemic at a regional level. In 2007, we implemented a massive campaign in a region of México (Colima state, 5,191 km(2), population 568,000) focused on training janitors to locate and avoid mosquitoes' breeding places, the objective being to maintain elementary schools free of mosquitoes. We observed 45% reduction in dengue incidence compared to the previous year. In contrast, the rest of Mexico observed an 81% increase in incidence on average. Costs associated with campaigns focusing on cleaning schools are very low and results seem to be promising. Nevertheless, more controlled studies are needed.

A hybrid sales forecasting scheme by combining independent component analysis with K-means clustering and support vector regression.

PubMed

Lu, Chi-Jie; Chang, Chi-Chang

2014-01-01

Sales forecasting plays an important role in operating a business since it can be used to determine the required inventory level to meet consumer demand and avoid the problem of under/overstocking. Improving the accuracy of sales forecasting has become an important issue of operating a business. This study proposes a hybrid sales forecasting scheme by combining independent component analysis (ICA) with K-means clustering and support vector regression (SVR). The proposed scheme first uses the ICA to extract hidden information from the observed sales data. The extracted features are then applied to K-means algorithm for clustering the sales data into several disjoined clusters. Finally, the SVR forecasting models are applied to each group to generate final forecasting results. Experimental results from information technology (IT) product agent sales data reveal that the proposed sales forecasting scheme outperforms the three comparison models and hence provides an efficient alternative for sales forecasting.

Algorithms for Computing the Magnetic Field, Vector Potential, and Field Derivatives for Circular Current Loops in Cylindrical Coordinates

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

Walstrom, Peter Lowell

A numerical algorithm for computing the field components B r and B z and their r and z derivatives with open boundaries in cylindrical coordinates for circular current loops is described. An algorithm for computing the vector potential is also described. For the convenience of the reader, derivations of the final expressions from their defining integrals are given in detail, since their derivations (especially for the field derivatives) are not all easily found in textbooks. Numerical calculations are based on evaluation of complete elliptic integrals using the Bulirsch algorithm cel. Since cel can evaluate complete elliptic integrals of a fairlymore » general type, in some cases the elliptic integrals can be evaluated without first reducing them to forms containing standard Legendre forms. The algorithms avoid the numerical difficulties that many of the textbook solutions have for points near the axis because of explicit factors of 1=r or 1=r 2 in the some of the expressions.« less

Decontaminate feature for tracking: adaptive tracking via evolutionary feature subset

NASA Astrophysics Data System (ADS)

Liu, Qiaoyuan; Wang, Yuru; Yin, Minghao; Ren, Jinchang; Li, Ruizhi

2017-11-01

Although various visual tracking algorithms have been proposed in the last 2-3 decades, it remains a challenging problem for effective tracking with fast motion, deformation, occlusion, etc. Under complex tracking conditions, most tracking models are not discriminative and adaptive enough. When the combined feature vectors are inputted to the visual models, this may lead to redundancy causing low efficiency and ambiguity causing poor performance. An effective tracking algorithm is proposed to decontaminate features for each video sequence adaptively, where the visual modeling is treated as an optimization problem from the perspective of evolution. Every feature vector is compared to a biological individual and then decontaminated via classical evolutionary algorithms. With the optimized subsets of features, the "curse of dimensionality" has been avoided while the accuracy of the visual model has been improved. The proposed algorithm has been tested on several publicly available datasets with various tracking challenges and benchmarked with a number of state-of-the-art approaches. The comprehensive experiments have demonstrated the efficacy of the proposed methodology.

A global multilevel atmospheric model using a vector semi-Lagrangian finite-difference scheme. I - Adiabatic formulation

NASA Technical Reports Server (NTRS)

Bates, J. R.; Moorthi, S.; Higgins, R. W.

1993-01-01

An adiabatic global multilevel primitive equation model using a two time-level, semi-Lagrangian semi-implicit finite-difference integration scheme is presented. A Lorenz grid is used for vertical discretization and a C grid for the horizontal discretization. The momentum equation is discretized in vector form, thus avoiding problems near the poles. The 3D model equations are reduced by a linear transformation to a set of 2D elliptic equations, whose solution is found by means of an efficient direct solver. The model (with minimal physics) is integrated for 10 days starting from an initialized state derived from real data. A resolution of 16 levels in the vertical is used, with various horizontal resolutions. The model is found to be stable and efficient, and to give realistic output fields. Integrations with time steps of 10 min, 30 min, and 1 h are compared, and the differences are found to be acceptable.

Meson effective mass in the isospin medium in hard-wall AdS/QCD model

NASA Astrophysics Data System (ADS)

Mamedov, Shahin

2016-02-01

We study a mass splitting of the light vector, axial-vector, and pseudoscalar mesons in the isospin medium in the framework of the hard-wall model. We write an effective mass definition for the interacting gauge fields and scalar field introduced in gauge field theory in the bulk of AdS space-time. Relying on holographic duality we obtain a formula for the effective mass of a boundary meson in terms of derivative operator over the extra bulk coordinate. The effective mass found in this way coincides with the one obtained from finding of poles of the two-point correlation function. In order to avoid introducing distinguished infrared boundaries in the quantization formula for the different mesons from the same isotriplet we introduce extra action terms at this boundary, which reduces distinguished values of this boundary to the same value. Profile function solutions and effective mass expressions were found for the in-medium ρ , a_1, and π mesons.

Impact of spatio-temporal scale of adjustment on variational assimilation of hydrologic and hydrometeorological data in operational distributed hydrologic models

NASA Astrophysics Data System (ADS)

Lee, H.; Seo, D.; McKee, P.; Corby, R.

2009-12-01

One of the large challenges in data assimilation (DA) into distributed hydrologic models is to reduce the large degrees of freedom involved in the inverse problem to avoid overfitting. To assess the sensitivity of the performance of DA to the dimensionality of the inverse problem, we design and carry out real-world experiments in which the control vector in variational DA (VAR) is solved at different scales in space and time, e.g., lumped, semi-distributed, and fully-distributed in space, and hourly, 6 hourly, etc., in time. The size of the control vector is related to the degrees of freedom in the inverse problem. For the assessment, we use the prototype 4-dimenational variational data assimilator (4DVAR) that assimilates streamflow, precipitation and potential evaporation data into the NWS Hydrology Laboratory’s Research Distributed Hydrologic Model (HL-RDHM). In this talk, we present the initial results for a number of basins in Oklahoma and Texas.

Empirical evidence of the effect of school gathering on the dynamics of dengue epidemics

PubMed Central

Hernández-Suárez, Carlos M.; Mendoza-Cano, Oliver

2016-01-01

Introduction Dengue fever is an important vector-transmitted disease that affects more than 100 countries worldwide. Locations where individuals tend to gather may play an important role in disease transmission in the presence of the vector. By controlling mosquitoes’ breeding places, this study aims to analyze the effect of reducing transmission in elementary schools (grades 1–9) on the dynamics of the epidemic at a regional level. Materials and methods In 2007, we implemented a massive campaign in a region of México (Colima state, 5,191 km2, population 568,000) focused on training janitors to locate and avoid mosquitoes’ breeding places, the objective being to maintain elementary schools free of mosquitoes. Results We observed 45% reduction in dengue incidence compared to the previous year. In contrast, the rest of Mexico observed an 81% increase in incidence on average. Discussion Costs associated with campaigns focusing on cleaning schools are very low and results seem to be promising. Nevertheless, more controlled studies are needed. PMID:26743450

The Jovian rings as observed from Jupiter.

NASA Astrophysics Data System (ADS)

Malinnikova Bang, A.; Joergensen, J. L.; Joergensen, P. S.; Denver, T.; Connerney, J. E. P.; Bolton, S. J.; Levin, S.

2017-12-01

Juno entered a highly eliptic orbit around Jupiter on the 4. July 2016. Since then, it has completed 8 perijove passages. The Magnetometer experiment consists of two measurement platforms mounted 10m and 12m from the spacecraft spin axis, on one of three large solar panels. Each magnetometer platform is equipped with two star trackers to provide accurate attitude information to the vector magnetometers. The star trackers are pointed 13deg from the (anti) spin vector, and clocked 180deg to avoid simultaneous blinding effects from bright Jupiter only 6000km away, during perijove. This brings Juno well inside the innermost known satellite, Metis. The star trackers pointing close to, and above the Jovian horizon for most of each rotation of Juno, has an excellent view of the Jovian ring systems with a beta-angle close to 180deg. We report on the ring imaging performed during the first 8 orbits, discuss the structure, optical depth and moon sheparding of the inner rings as measured so far.

Automated Text Analysis Based on Skip-Gram Model for Food Evaluation in Predicting Consumer Acceptance

PubMed Central

Kim, Augustine Yongwhi; Choi, Hoduk

2018-01-01

The purpose of this paper is to evaluate food taste, smell, and characteristics from consumers' online reviews. Several studies in food sensory evaluation have been presented for consumer acceptance. However, these studies need taste descriptive word lexicon, and they are not suitable for analyzing large number of evaluators to predict consumer acceptance. In this paper, an automated text analysis method for food evaluation is presented to analyze and compare recently introduced two jjampong ramen types (mixed seafood noodles). To avoid building a sensory word lexicon, consumers' reviews are collected from SNS. Then, by training word embedding model with acquired reviews, words in the large amount of review text are converted into vectors. Based on these words represented as vectors, inference is performed to evaluate taste and smell of two jjampong ramen types. Finally, the reliability and merits of the proposed food evaluation method are confirmed by a comparison with the results from an actual consumer preference taste evaluation. PMID:29606960

Automated Text Analysis Based on Skip-Gram Model for Food Evaluation in Predicting Consumer Acceptance.

PubMed

Kim, Augustine Yongwhi; Ha, Jin Gwan; Choi, Hoduk; Moon, Hyeonjoon

2018-01-01

The purpose of this paper is to evaluate food taste, smell, and characteristics from consumers' online reviews. Several studies in food sensory evaluation have been presented for consumer acceptance. However, these studies need taste descriptive word lexicon, and they are not suitable for analyzing large number of evaluators to predict consumer acceptance. In this paper, an automated text analysis method for food evaluation is presented to analyze and compare recently introduced two jjampong ramen types (mixed seafood noodles). To avoid building a sensory word lexicon, consumers' reviews are collected from SNS. Then, by training word embedding model with acquired reviews, words in the large amount of review text are converted into vectors. Based on these words represented as vectors, inference is performed to evaluate taste and smell of two jjampong ramen types. Finally, the reliability and merits of the proposed food evaluation method are confirmed by a comparison with the results from an actual consumer preference taste evaluation.

Cloning of Bordetella pertussis putative outer protein D (BopD) and Leucin/Isoleucine/Valin binding protein (LivJ)

NASA Astrophysics Data System (ADS)

Öztürk, Burcu Emine Tefon

2017-04-01

Whooping cough also known as pertussis is a contagious acute upper respiratory disease primarily caused by Bordetella pertussis. It is known that this disease may be fatal especially in infants and recently, the number of pertussis cases has been increased. Despite the fact that there are numbers of acellular vaccines on the market, the current acellular vaccine compositions are inadequate for providing sustainable immunity and avoiding subclinical disease cases. Hence, exploring novel proteins with high immune protective capacities is essential to enhance the clinical efficacy of current vaccines. In this study, genes of selected immunogenic proteins via -omics studies, namely Putative outer protein D (BopD) and Leucin/Isoleucine/Valin Binding Protein (LivJ) were first cloned into pGEM-T Easy vector and transformed to into E. coli DH5α cells and then cloned into the expression vector pET-28a(+) and transformed into E. coli BL21 (DE3) cells to express the proteins.

Performance evaluation for epileptic electroencephalogram (EEG) detection by using Neyman-Pearson criteria and a support vector machine

NASA Astrophysics Data System (ADS)

Wang, Chun-mei; Zhang, Chong-ming; Zou, Jun-zhong; Zhang, Jian

2012-02-01

The diagnosis of several neurological disorders is based on the detection of typical pathological patterns in electroencephalograms (EEGs). This is a time-consuming task requiring significant training and experience. A lot of effort has been devoted to developing automatic detection techniques which might help not only in accelerating this process but also in avoiding the disagreement among readers of the same record. In this work, Neyman-Pearson criteria and a support vector machine (SVM) are applied for detecting an epileptic EEG. Decision making is performed in two stages: feature extraction by computing the wavelet coefficients and the approximate entropy (ApEn) and detection by using Neyman-Pearson criteria and an SVM. Then the detection performance of the proposed method is evaluated. Simulation results demonstrate that the wavelet coefficients and the ApEn are features that represent the EEG signals well. By comparison with Neyman-Pearson criteria, an SVM applied on these features achieved higher detection accuracies.

A Hybrid Sales Forecasting Scheme by Combining Independent Component Analysis with K-Means Clustering and Support Vector Regression

PubMed Central

2014-01-01

Sales forecasting plays an important role in operating a business since it can be used to determine the required inventory level to meet consumer demand and avoid the problem of under/overstocking. Improving the accuracy of sales forecasting has become an important issue of operating a business. This study proposes a hybrid sales forecasting scheme by combining independent component analysis (ICA) with K-means clustering and support vector regression (SVR). The proposed scheme first uses the ICA to extract hidden information from the observed sales data. The extracted features are then applied to K-means algorithm for clustering the sales data into several disjoined clusters. Finally, the SVR forecasting models are applied to each group to generate final forecasting results. Experimental results from information technology (IT) product agent sales data reveal that the proposed sales forecasting scheme outperforms the three comparison models and hence provides an efficient alternative for sales forecasting. PMID:25045738

Ag85A-specific CD4+ T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties.

PubMed

Metcalfe, Hannah J; Biffar, Lucia; Steinbach, Sabine; Guzman, Efrain; Connelley, Tim; Morrison, Ivan; Vordermeier, H Martin; Villarreal-Ramos, Bernardo

2018-05-11

There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4 + T cells post-boosting. Here, the capacity of Ag85A-specific CD4 + T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4 + T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β, IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4 + T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology. Copyright © 2018 Department for Environment Food and Rural Affairs. Published by Elsevier Ltd.. All rights reserved.

Altered Functional Connectivity Following an Inflammatory White Matter Injury in the Newborn Rat: A High Spatial and Temporal Resolution Intrinsic Optical Imaging Study

PubMed Central

Guevara, Edgar; Pierre, Wyston C.; Tessier, Camille; Akakpo, Luis; Londono, Irène; Lesage, Frédéric; Lodygensky, Gregory A.

2017-01-01

Very preterm newborns have an increased risk of developing an inflammatory cerebral white matter injury that may lead to severe neuro-cognitive impairment. In this study we performed functional connectivity (fc) analysis using resting-state optical imaging of intrinsic signals (rs-OIS) to assess the impact of inflammation on resting-state networks (RSN) in a pre-clinical model of perinatal inflammatory brain injury. Lipopolysaccharide (LPS) or saline injections were administered in postnatal day (P3) rat pups and optical imaging of intrinsic signals were obtained 3 weeks later. (rs-OIS) fc seed-based analysis including spatial extent were performed. A support vector machine (SVM) was then used to classify rat pups in two categories using fc measures and an artificial neural network (ANN) was implemented to predict lesion size from those same fc measures. A significant decrease in the spatial extent of fc statistical maps was observed in the injured group, across contrasts and seeds (*p = 0.0452 for HbO2 and **p = 0.0036 for HbR). Both machine learning techniques were applied successfully, yielding 92% accuracy in group classification and a significant correlation r = 0.9431 in fractional lesion volume prediction (**p = 0.0020). Our results suggest that fc is altered in the injured newborn brain, showing the long-standing effect of inflammation. PMID:28725174

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

Xu, Xueqing; Chang, Bianca W.; Mans, Ben J.

Biogenic amine-binding proteins mediate the anti-inflammatory and antihemostatic activities of blood-feeding insect saliva. The structure of the amine-binding protein from R. prolixus reveals the interaction of biogenic amine ligands with the protein. Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus,more » a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the β-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity.« less

Vineyard Colonization by Hyalesthes obsoletus (Hemiptera: Cixiidae) Induced by Stinging Nettle Cut Along Surrounding Ditches.

PubMed

Mori, N; Pozzebon, A; Duso, C; Reggiani, N; Pavan, F

2016-02-01

Stinging nettle (Urtica dioica L.) is the most important host plant for both phytoplasma associated with Bois noir disease of the grapevine and its vector Hyalesthes obsoletus Signoret (Hemiptera: Cixiidae). Vector abundance in vineyards is favored by stinging nettle growing in surrounding areas. Nettle control by herbicides or cutting can reduce vector population in vineyards. However, chemical weeding can cause environmental problems. Many authors suggest that stinging nettle control applied during H. obsoletus flight could force adults to migrate into vineyards. We evaluate if cutting of nettle growing along ditches during adult flight favors vineyard colonization by H. obsoletus. Three different weed management regimes ("no cuts," "one cut" just before the beginning of adult flight, and "frequent cuts" over the whole vegetative season) were applied to the herbaceous vegetation in ditches bordering two vineyards. The flight dynamics of H. obsoletus were recorded by placing yellow sticky traps on the vegetation along the ditches and at different positions in the vineyards. Frequent stinging nettle cuts (compared with a single cut) in surrounding areas favored the dispersion of vectors inside the vineyards. Stinging nettle control should be based on an integration of a single herbicide application before H. obsoletus emergence followed by frequent cuts to minimize negative side effects of chemical weeding. In organic viticulture, a frequent-cuts strategy should avoid cuts during H. obsoletus flight period, at least in the first year of adoption. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Emerging Vector-Borne Diseases.

PubMed

Huntington, Mark K; Allison, Jay; Nair, Dilip

2016-10-01

Several mosquito-borne viral infections have recently emerged in North America; West Nile virus is the most common in the United States. Although West Nile virus generally causes a self-limited, flulike febrile illness, a serious neuroinvasive form may occur. Dengue is the most common vector-borne viral disease worldwide, and it has been a significant public health threat in the United States since 2009. Known as breakbone fever for its severe myalgias and arthralgias, dengue may cause a hemorrhagic syndrome. Chikungunya also causes flulike febrile illness and disabling arthralgias. Although meningoencephalitis may occur with chikungunya, bleeding is uncommon. Symptoms of Zika virus infection are similar to those of dengue, but milder. Zika virus increases the risk of fetal brain abnormalities, including microcephaly, if a pregnant woman is infected. Zika virus is spread through Aedes albopictus mosquito bites, is transmitted sexually, and may rarely spread nonsexually from person to person. Diagnosis of these vectorborne infections is clinical and serologic, and treatment is supportive. Other, well-established vector-borne diseases are also important. Ehrlichiosis is a tick-borne bacterial disease that presents as a nonspecific syndrome of fever, headache, malaise, and myalgias. It is diagnosed via blood smear testing, with confirmatory serology. Ehrlichiosis is treated with doxycycline. Rickettsial infections are transmitted by fleas, mites, and ticks, and severity ranges from mild to life threatening. Rocky Mountain spotted fever, the most significant rickettsial infection, is primarily a clinical diagnosis that presents as fever, headache, myalgias, petechial rash, and tick exposure. Doxycycline is effective for rickettsial infections if administered promptly. Vector avoidance strategies are critical to the prevention of all of these infections.

Template protection and its implementation in 3D face recognition systems

NASA Astrophysics Data System (ADS)

Zhou, Xuebing

2007-04-01

As biometric recognition systems are widely applied in various application areas, security and privacy risks have recently attracted the attention of the biometric community. Template protection techniques prevent stored reference data from revealing private biometric information and enhance the security of biometrics systems against attacks such as identity theft and cross matching. This paper concentrates on a template protection algorithm that merges methods from cryptography, error correction coding and biometrics. The key component of the algorithm is to convert biometric templates into binary vectors. It is shown that the binary vectors should be robust, uniformly distributed, statistically independent and collision-free so that authentication performance can be optimized and information leakage can be avoided. Depending on statistical character of the biometric template, different approaches for transforming biometric templates into compact binary vectors are presented. The proposed methods are integrated into a 3D face recognition system and tested on the 3D facial images of the FRGC database. It is shown that the resulting binary vectors provide an authentication performance that is similar to the original 3D face templates. A high security level is achieved with reasonable false acceptance and false rejection rates of the system, based on an efficient statistical analysis. The algorithm estimates the statistical character of biometric templates from a number of biometric samples in the enrollment database. For the FRGC 3D face database, the small distinction of robustness and discriminative power between the classification results under the assumption of uniquely distributed templates and the ones under the assumption of Gaussian distributed templates is shown in our tests.

An alternative approach in regulation of expression of a transgene by endogenous miR-145 in carcinoma and normal breast cell lines.

PubMed

Ghanbari Safari, Maryam; Baesi, Kazem; Hosseinkhani, Saman

2017-03-01

MicroRNAs are small noncoding RNAs that regulate gene expression by repressing translation of target cellular transcripts. Increasing evidences indicate that miRNAs have different expression profiles and play crucial roles in numerous cellular processes. Delivery and expression of transgenes for cancer therapy must be specific for tumors to avoid killing of healthy tissues. Many investigators have shown that transgene expression can be suppressed in normal cells using vectors that are responsive to microRNA regulation. To overcome this problem, miR-145 that exhibits downregulation in many types of cancer cells was chosen for posttranscriptional regulatory systems mediated by microRNAs. In this study, a psiCHECK-145T vector carrying four tandem copies of target sequences of miR-145 into 3'-UTR of the Renilla luciferase gene was constructed. Renilla luciferase activity from the psiCHECK-145T vector was 57% lower in MCF10A cells with high miR-145 expression as compared to a control condition. Additionally, overexpression of miR-145 in MCF-7 cells with low expression level of miR-145 showed more than 76% reduction in the Renilla luciferase activity from the psiCHECK-145T vector. Inclusion of miR-145 target sequences into the 3'-UTR of the Renilla luciferase gene is a feasible strategy for restricting transgene expression in a breast cancer cell line while sparing a breast normal cell line. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.

PubMed

Volz, A; Sutter, G

2017-01-01

Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology. © 2017 Elsevier Inc. All rights reserved.

Condition Assessment of Foundation Piles and Utility Poles Based on Guided Wave Propagation Using a Network of Tactile Transducers and Support Vector Machines

PubMed Central

Yu, Yang; Niederleithinger, Ernst; Li, Jianchun; Wiggenhauser, Herbert

2017-01-01

This paper presents a novel non-destructive testing and health monitoring system using a network of tactile transducers and accelerometers for the condition assessment and damage classification of foundation piles and utility poles. While in traditional pile integrity testing an impact hammer with broadband frequency excitation is typically used, the proposed testing system utilizes an innovative excitation system based on a network of tactile transducers to induce controlled narrow-band frequency stress waves. Thereby, the simultaneous excitation of multiple stress wave types and modes is avoided (or at least reduced), and targeted wave forms can be generated. The new testing system enables the testing and monitoring of foundation piles and utility poles where the top is inaccessible, making the new testing system suitable, for example, for the condition assessment of pile structures with obstructed heads and of poles with live wires. For system validation, the new system was experimentally tested on nine timber and concrete poles that were inflicted with several types of damage. The tactile transducers were excited with continuous sine wave signals of 1 kHz frequency. Support vector machines were employed together with advanced signal processing algorithms to distinguish recorded stress wave signals from pole structures with different types of damage. The results show that using fast Fourier transform signals, combined with principal component analysis as the input feature vector for support vector machine (SVM) classifiers with different kernel functions, can achieve damage classification with accuracies of 92.5% ± 7.5%. PMID:29258274

Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

PubMed

Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

2017-03-15

It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

A study of chemokines, chemokine receptors and interleukin-6 in patients with panic disorder, personality disorders and their co-morbidity.

PubMed

Ogłodek, Ewa A; Szota, Anna M; Just, Marek J; Szromek, Adam R; Araszkiewicz, Aleksander

2016-08-01

Stress may induce inflammatory changes in the immune system and activate pro-inflammatory cytokines and their receptors by activating the hypothalamic-pituitary-adrenal axis. 460 hospitalized patients with panic disorders (PD) and/or personality disorders (P) were studied. The study group comprised subjects with PD, avoidant personality disorder (APD), borderline personality disorder (BPD), obsessive-compulsive personality disorder (OCPD), and concomitant (PD+APD; PD+BPD; PD+OCPD). Each study group consisted of 60 subjects (30 females and 30 males). The control group included 20 females and 20 males without any history of mental disorder. ELISA was used to assess the levels of chemokines: CCL-5/RANTES (regulated on activation, normal T-cell expressed and secreted), CXCL-12/SDF-1 (stromal derived factor), their receptors CXCR-5 (C-C chemokine receptor type-5), CXCR-4 (chemokine C-X-C motif receptor-4), and IL-6. Statistically significant differences in the levels of CCL-5 and CCR-5 were revealed between all study groups. The greatest differences were found between the groups with PD+OCPD and PD+APD. Moreover, concomitance of PD with P significantly increased the level of chemokines and their receptors in all study groups versus the subjects with P alone. The results of the study show differences between the groups. To be specific, inflammatory markers were more elevated in the study groups than the controls. Therefore, chemokines and chemokine receptors may be used as inflammatory markers in patients with PD co-existent with P to indicate disease severity. PD was found to be a factor in maintaining inflammatory activity in the immune system in patients with P. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Diarctigenin, a lignan constituent from Arctium lappa, down-regulated zymosan-induced transcription of inflammatory genes through suppression of DNA binding ability of nuclear factor-kappaB in macrophages.

PubMed

Kim, Byung Hak; Hong, Seong Su; Kwon, Soon Woo; Lee, Hwa Young; Sung, Hyeran; Lee, In-Jeong; Hwang, Bang Yeon; Song, Sukgil; Lee, Chong-Kil; Chung, Daehyun; Ahn, Byeongwoo; Nam, Sang-Yoon; Han, Sang-Bae; Kim, Youngsoo

2008-11-01

Diarctigenin was previously isolated as an inhibitor of nitric oxide (NO) production in macrophages from the seeds of Arctium lappa used as an alternative medicine for the treatment of inflammatory disorders. However, little is known about the molecular basis of these effects. Here, we demonstrated that diarctigenin inhibited the production of NO, prostaglandin E(2), tumor necrosis factor-alpha, and interleukin (IL)-1beta and IL-6 with IC(50) values of 6 to 12 miciroM in zymosan- or lipopolysaccharide-(LPS) activated macrophages. Diarctigenin attenuated zymosan-induced mRNA synthesis of inducible NO synthase (iNOS) and also inhibited promoter activities of iNOS and cytokine genes in the cells. Because nuclear factor (NF)-kappaB plays a pivotal role in inflammatory gene transcription, we next investigated the effect of diarctigenin on NF-kappaB activation. Diarctigenin inhibited the transcriptional activity and DNA binding ability of NF-kappaB in zymosan-activated macrophages but did not affect the degradation and phosphorylation of inhibitory kappaB (IkappaB) proteins. Moreover, diarctigenin suppressed expression vector NF-kappaB p65-elicited NF-kappaB activation and also iNOS promoter activity, indicating that the compound could directly target an NF-kappa-activating signal cascade downstream of IkappaB degradation and inhibit NF-kappaB-regulated iNOS expression. Diarctigenin also inhibited the in vitro DNA binding ability of NF-kappaB but did not affect the nuclear import of NF-kappaB p65 in the cells. Taken together, diarctigenin down-regulated zymosan- or LPS-induced inflammatory gene transcription in macrophages, which was due to direct inhibition of the DNA binding ability of NF-kappaB. Finally, this study provides a pharmacological potential of diarctigenin in the NF-kappaB-associated inflammatory disorders.

In Sickness and in Health: The Co-Regulation of Inflammation and Social Behavior

PubMed Central

Eisenberger, Naomi I; Moieni, Mona; Inagaki, Tristen K; Muscatell, Keely A; Irwin, Michael R

2017-01-01

Although it has commonly been assumed that the immune system and the processes that govern social behavior are separate, non-communicating entities, research over the past several decades suggests otherwise. Considerable evidence now shows that inflammatory processes and social behavior are actually powerful regulators of one another. This review first summarizes evidence that inflammatory processes regulate social behavior, leading to characteristic changes that may help an individual navigate the social environment during times of sickness. Specifically, this review shows that inflammation: (1) increases threat-related neural sensitivity to negative social experiences (eg, rejection, negative social feedback), presumably to enhance sensitivity to threats to well-being or safety in order to avoid them and (2) enhances reward-related neural sensitivity to positive social experiences (eg, viewing close others and receiving positive social feedback), presumably to increase approach-related motivation towards others who might provide support and care during sickness. Next, this review summarizes evidence showing that social behavior also regulates aspects of inflammatory activity, preparing the body for situations in which wounding and infection may be more likely (social isolation). Here, we review research showing: (1) that exposure to social stressors increases proinflammatory activity, (2) that individuals who are more socially isolated (ie, lonely) show increased proinflammatory activity, and (3) that individuals who are more socially isolated show increased proinflammatory activity in response to an inflammatory challenge or social stressor. The implications of the co-regulation of inflammation and social behavior are discussed. PMID:27480575

Non-inflammatory causes of emergency consultation in patients with multiple sclerosis.

PubMed

Rodríguez de Antonio, L A; García Castañón, I; Aguilar-Amat Prior, M J; Puertas, I; González Suárez, I; Oreja Guevara, C

2018-05-26

To describe non-relapse-related emergency consultations of patients with multiple sclerosis (MS): causes, difficulties in the diagnosis, clinical characteristics, and treatments administered. We performed a retrospective study of patients who attended a multiple sclerosis day hospital due to suspected relapse and received an alternative diagnosis, over a 2-year period. Demographic data, clinical characteristics, final diagnosis, and treatments administered were evaluated. Patients who were initially diagnosed with pseudo-relapse and ultimately diagnosed with true relapse were evaluated specifically. As an exploratory analysis, patients who consulted with non-inflammatory causes were compared with a randomly selected cohort of patients with true relapses who attended the centre in the same period. The study included 50 patients (33 were women; mean age 41.4±11.7years). Four patients (8%) were initially diagnosed with pseudo-relapse and later diagnosed as having a true relapse. Fever and vertigo were the main confounding factors. The non-inflammatory causes of emergency consultation were: neurological, 43.5% (20 patients); infectious, 15.2% (7); psychiatric, 10.9% (5); vertigo, 8.6% (4); trauma, 10.9% (5); and miscellaneous, 10.9% (5). MS-related symptoms constituted the most frequent cause of non-inflammatory emergency consultations. Close follow-up of relapse and pseudo-relapse is necessary to detect incorrect initial diagnoses, avoid unnecessary treatments, and relieve patients' symptoms. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Sickle cell anemia induces changes in peripheral lymphocytes E-NTPDase/E-ADA activities and cytokines secretion in patients under treatment.

PubMed

Castilhos, Lívia G; Doleski, Pedro H; Bertoldo, Tatiana M D; Passos, Daniela F; Bertoncheli, Claudia de M; Rezer, João F P; Schlemmer, Josiane B; Leal, Daniela B R

2015-07-01

Sickle cell anemia (SCA) is characterized by hemoglobin polymerization that results in sickle-shaped red blood cells. The vascular obstruction by sickle erythrocytes is often inflammatory, and purinergic system ecto-enzymes play an important role in modulating the inflammatory and immune response. This study aimed to evaluate the E-NTPDase and E-ADA activities in lymphocytes of SCA treated patients, as well as verify the cytokine profile in this population. Fifteen SCA treated patients and 30 health subjects (control group) were selected. The peripheral lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated from clot formation for the cytokines quantification. E-NTPDase (ATP and ADP as substrate) and E-ADA (adenosine as substrate) activities were increased in lymphocytes from SCA patients (P<0.001). The TNF-α and IL-6 serum cytokines showed decreased on SCA patients comparing to control (P<0.001). The regulation of extracellular nucleotides released in response to hypoxia and inflammation through E-NTPDase and E-ADA enzymes represent an important control of purine-mediated in the SCA disease, avoiding elevated adenosine levels in the extracellular medium and consequent organ injuries in these patients. The pro-inflammatory cytokines decreased levels by use of hydroxyurea occur in attempt to reduce the pro-inflammatory response and prevent vaso-oclusive crisis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Stance Postural Strategies in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy

PubMed Central

Missori, Paolo; Trompetto, Carlo; Fattapposta, Francesco

2016-01-01

Introduction Polyneuropathy leads to postural instability and an increased risk of falling. We investigated how impaired motor impairment and proprioceptive input due to neuropathy influences postural strategies. Methods Platformless bisegmental posturography data were recorded in healthy subjects and patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Each subject stood on the floor, wore a head and a hip electromagnetic tracker. Sway amplitude and velocity were recorded and the mean direction difference (MDD) in the velocity vector between trackers was calculated as a flexibility index. Results Head and hip postural sway increased more in patients with CIDP than in healthy controls. MDD values reflecting hip strategies also increased more in patients than in controls. In the eyes closed condition MDD values in healthy subjects decreased but in patients remained unchanged. Discussion Sensori-motor impairment changes the balance between postural strategies that patients adopt to maintain upright quiet stance. Motor impairment leads to hip postural strategy overweight (eyes open), and prevents strategy re-balancing when the sensory context predominantly relies on proprioceptive input (eyes closed). PMID:26977594

Arginase-I enhances vascular endothelial inflammation and senescence through eNOS-uncoupling.

PubMed

Zhu, Cuicui; Yu, Yi; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

2017-02-02

Augmented arginase-II (Arg-II) is implicated in endothelial senescence and inflammation through a mutual positive regulatory circuit with S6K1. This study was conducted to investigate whether Arg-I, another isoform of arginase that has been also reported to play a role in vascular endothelial dysfunction, promotes endothelial senescence through similar mechanisms. The non-senescent human endothelial cells from umbilical veins (passage 2 to 4) were transduced with empty recombinant adenovirus vector (rAd/CMV) as control or rAd/CMV-Arg-I to overexpress Arg-I. Overexpressing Arg-I promoted eNOS-uncoupling, enhanced senescence markers including p53-S15, p21 and senescence-associated β-galactosidase (SA-β-gal) staining, and increased inflammatory vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) as well as monocyte adhesion to endothelial cells without activating S6K1. All the effects of Arg-I were inhibited by the anti-oxidant N-acetylcysteine (NAC). Our study demonstrates that Arg-I promotes endothelial senescence and inflammatory responses through eNOS-uncoupling unrelated to activation of the S6K1 pathway.

Tissue-engineered cartilage with inducible and tunable immunomodulatory properties.

PubMed

Glass, Katherine A; Link, Jarrett M; Brunger, Jonathan M; Moutos, Franklin T; Gersbach, Charles A; Guilak, Farshid

2014-07-01

The pathogenesis of osteoarthritis is mediated in part by inflammatory cytokines including interleukin-1 (IL-1), which promote degradation of articular cartilage and prevent human mesenchymal stem cell (MSC) chondrogenesis. In this study, we combined gene therapy and functional tissue engineering to develop engineered cartilage with immunomodulatory properties that allow chondrogenesis in the presence of pathologic levels of IL-1 by inducing overexpression of IL-1 receptor antagonist (IL-1Ra) in MSCs via scaffold-mediated lentiviral gene delivery. A doxycycline-inducible vector was used to transduce MSCs in monolayer or within 3D woven PCL scaffolds to enable tunable IL-1Ra production. In the presence of IL-1, IL-1Ra-expressing engineered cartilage produced cartilage-specific extracellular matrix, while resisting IL-1-induced upregulation of matrix metalloproteinases and maintaining mechanical properties similar to native articular cartilage. The ability of functional engineered cartilage to deliver tunable anti-inflammatory cytokines to the joint may enhance the long-term success of therapies for cartilage injuries or osteoarthritis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Imported Zika Virus in a European City: How to Prevent Local Transmission?

PubMed

Millet, Joan-Pau; Montalvo, Tomàs; Bueno-Marí, Ruben; Romero-Tamarit, Arancha; Prats-Uribe, Albert; Fernández, Lidia; Camprubí, Esteve; Del Baño, Lucía; Peracho, Victor; Figuerola, Jordi; Sulleiro, Elena; Martínez, Miguel J; Caylà, Joan A

2017-01-01

Background: On February 1st 2016 the WHO declared the Zika Virus (ZIKV) infection a worldwide public health emergency because of its rapid expansion and severe complications, such as Guillain-Barré Syndrome or microcephaly in newborn. The huge amount of people traveling to endemic areas and the presence of Aedes albopictus in Barcelona increase the risk of autochtonous transmission. The objective of this study was to describe the first ZIKV cases diagnosed in our city and to analyze the surveillance, prevention, and control measures implemented to avoid autochthonous transmission. Methods: An observational cross-sectional population-based study in Barcelona, Spain was performed.An analysis of the socio-demographic, epidemiological, clinical characteristics, and mosquito control activities of the ZIKV cases detected between January 1st and December 2016 was carried out using a specific ZIKV epidemiological survey of the Barcelona Public Health Agency. Results: A total of 118 notifications of possible ZIKV infections were received, and 44 corresponded to confirmed cases in Barcelona residents.Amongst these, the median age was 35 years and 57% were women. All cases were imported, 48% were Spanish-born and 52% foreign-born. Dominican Republic was the most visited country amongst foreign-born patients and Nicaragua amongst Spanish-born. The most frequent symptoms were exanthema, fever, and arthralgia. Among the 24 diagnosed women, 6 (25%) were pregnant. There was one case of microcephaly outside Barcelona city. Entomological inspections were done at the homes of 19 cases (43.2% of the total) and in 34 (77.3%) public spaces. Vector activity was found in one case of the 44 confirmed cases, and 134 surveillance and vector control were carried out associated to imported ZIKV cases. In all cases prevention measures were recommended to avoid mosquito bites on infected cases. Conclusion: Epidemiological and entomological surveillance are essential for the prevention of autochthonous transmission of arbovirosis that may have a great impact on Public Health.The good coordination between epidemiologists, entomologists, microbiologists, and clinicians is a priority in a touristic city with an intense relationship with endemic countries to minimize the risk of local transmission by competent vectors.

Imported Zika Virus in a European City: How to Prevent Local Transmission?

PubMed Central

Millet, Joan-Pau; Montalvo, Tomàs; Bueno-Marí, Ruben; Romero-Tamarit, Arancha; Prats-Uribe, Albert; Fernández, Lidia; Camprubí, Esteve; del Baño, Lucía; Peracho, Victor; Figuerola, Jordi; Sulleiro, Elena; Martínez, Miguel J.; Caylà, Joan A.; Álamo-Junquera, Dolores

2017-01-01

Background: On February 1st 2016 the WHO declared the Zika Virus (ZIKV) infection a worldwide public health emergency because of its rapid expansion and severe complications, such as Guillain-Barré Syndrome or microcephaly in newborn. The huge amount of people traveling to endemic areas and the presence of Aedes albopictus in Barcelona increase the risk of autochtonous transmission. The objective of this study was to describe the first ZIKV cases diagnosed in our city and to analyze the surveillance, prevention, and control measures implemented to avoid autochthonous transmission. Methods: An observational cross-sectional population-based study in Barcelona, Spain was performed.An analysis of the socio-demographic, epidemiological, clinical characteristics, and mosquito control activities of the ZIKV cases detected between January 1st and December 2016 was carried out using a specific ZIKV epidemiological survey of the Barcelona Public Health Agency. Results: A total of 118 notifications of possible ZIKV infections were received, and 44 corresponded to confirmed cases in Barcelona residents.Amongst these, the median age was 35 years and 57% were women. All cases were imported, 48% were Spanish-born and 52% foreign-born. Dominican Republic was the most visited country amongst foreign-born patients and Nicaragua amongst Spanish-born. The most frequent symptoms were exanthema, fever, and arthralgia. Among the 24 diagnosed women, 6 (25%) were pregnant. There was one case of microcephaly outside Barcelona city. Entomological inspections were done at the homes of 19 cases (43.2% of the total) and in 34 (77.3%) public spaces. Vector activity was found in one case of the 44 confirmed cases, and 134 surveillance and vector control were carried out associated to imported ZIKV cases. In all cases prevention measures were recommended to avoid mosquito bites on infected cases. Conclusion: Epidemiological and entomological surveillance are essential for the prevention of autochthonous transmission of arbovirosis that may have a great impact on Public Health.The good coordination between epidemiologists, entomologists, microbiologists, and clinicians is a priority in a touristic city with an intense relationship with endemic countries to minimize the risk of local transmission by competent vectors. PMID:28769893

A Chimeric HS4-SAR Insulator (IS2) That Prevents Silencing and Enhances Expression of Lentiviral Vectors in Pluripotent Stem Cells

PubMed Central

Gutierrez-Guerrero, Alejandra; Cobo, Marién; Muñoz, Pilar

2014-01-01

Chromatin insulators, such as the chicken β-globin locus control region hypersensitive site 4 (HS4), and scaffold/matrix attachment regions (SARs/MARs) have been incorporated separately or in combination into retroviral vectors (RVs) in order to increase transgene expression levels, avoid silencing and reduce expression variability. However, their incorporation into RVs either produces a reduction on titer and/or expression levels or do not have sufficient effect on stem cells. In order to develop an improved insulator we decided to combine SAR elements with HS4 insulators. We designed several synthetic shorter SAR elements containing 4 or 5 MAR/SARs recognition signatures (MRS) and studied their effects on a lentiviral vector (LV) expressing eGFP through the SFFV promoter (SE). A 388 bp SAR element containing 5 MRS, named SAR2, was as efficient or superior to the other SARs analyzed. SAR2 enhanced transgene expression and reduced silencing and variability on human embryonic stem cells (hESCs). We next compared the effect of different HS4-based insulators, the HS4-Core (250 bp), the HS4-Ext (400 bp) and the HS4-650 (650 bp). All HS4 elements reduced silencing and expression variability but they also had a negative effect on transgene expression levels and titer. In general, the HS4-650 element had a better overall effect. Based on these data we developed a chimeric insulator, IS2, combining the SAR2 and the HS4-650. When incorporated into the 3′ LTR of the SE LV, the IS2 element was able to enhance expression, avoid silencing and reduce variability of expression on hESCs. Importantly, these effects were maintained after differentiation of the transduced hESCs toward the hematopoietic linage. Neither the HS4-650 nor the SAR2 elements had these effects. The IS2 element is therefore a novel insulator that confers expression stability and enhances expression of LVs on stem cells. PMID:24400083

Simplified bionic solutions: a simple bio-inspired vehicle collision detection system.

PubMed

Hartbauer, Manfred

2017-02-15

Modern cars are equipped with both active and passive sensor systems that can detect potential collisions. In contrast, locusts avoid collisions solely by responding to certain visual cues that are associated with object looming. In neurophysiological experiments, I investigated the possibility that the 'collision-detector neurons' of locusts respond to impending collisions in films recorded with dashboard cameras of fast driving cars. In a complementary modelling approach, I developed a simple algorithm to reproduce the neuronal response that was recorded during object approach. Instead of applying elaborate algorithms that factored in object recognition and optic flow discrimination, I tested the hypothesis that motion detection restricted to a 'danger zone', in which frontal collisions on the motorways are most likely, is sufficient to estimate the risk of a collision. Furthermore, I investigated whether local motion vectors, obtained from the differential excitation of simulated direction-selective networks, could be used to predict evasive steering maneuvers and prevent undesired responses to motion artifacts. The results of the study demonstrate that the risk of impending collisions in real traffic scenes is mirrored in the excitation of the collision-detecting neuron (DCMD) of locusts. The modelling approach was able to reproduce this neuronal response even when the vehicle was driving at high speeds and image resolution was low (about 200  ×  100 pixels). Furthermore, evasive maneuvers that involved changing the steering direction and steering force could be planned by comparing the differences in the overall excitation levels of the simulated right and left direction-selective networks. Additionally, it was possible to suppress undesired responses of the algorithm to translatory movements, camera shake and ground shadows by evaluating local motion vectors. These estimated collision risk values and evasive steering vectors could be used as input for a driving assistant, converting the first into braking force and the latter into steering responses to avoid collisions. Since many processing steps were computed on the level of pixels and involved elements of direction-selective networks, this algorithm can be implemented in hardware so that parallel computations enhance the processing speed significantly.

Simplified bionic solutions: a simple bio-inspired vehicle collision detection system

PubMed Central

Hartbauer, Manfred

2018-01-01

Modern cars are equipped with both active and passive sensor systems that can detect potential collisions. In contrast, locusts avoid collisions solely by responding to certain visual cues that are associated with object looming. In neurophysiological experiments, I investigated the possibility that the ‘collision-detector neurons’ of locusts respond to impending collisions in films recorded with dashboard cameras of fast driving cars. In a complementary modelling approach, I developed a simple algorithm to reproduce the neuronal response that was recorded during object approach. Instead of applying elaborate algorithms that factored in object recognition and optic flow discrimination, I tested the hypothesis that motion detection restricted to a ‘danger zone’, in which frontal collisions on the motorways are most likely, is sufficient to estimate the risk of a collision. Furthermore, I investigated whether local motion vectors, obtained from the differential excitation of simulated direction-selective networks, could be used to predict evasive steering maneuvers and prevent undesired responses to motion artifacts. The results of the study demonstrate that the risk of impending collisions in real traffic scenes is mirrored in the excitation of the collision-detecting neuron (DCMD) of locusts. The modelling approach was able to reproduce this neuronal response even when the vehicle was driving at high speeds and image resolution was low (about 200 × 100 pixels). Furthermore, evasive maneuvers that involved changing the steering direction and steering force could be planned by comparing the differences in the overall excitation levels of the simulated right and left direction-selective networks. Additionally, it was possible to suppress undesired responses of the algorithm to translatory movements, camera shake and ground shadows by evaluating local motion vectors. These estimated collision risk values and evasive steering vectors could be used as input for a driving assistant, converting the first into braking force and the latter into steering responses to avoid collisions. Since many processing steps were computed on the level of pixels and involved elements of direction-selective networks, this algorithm can be implemented in hardware so that parallel computations enhance the processing speed significantly. PMID:28091394

Anti-inflammatory activity of an ethanolic Caesalpinia sappan extract in human chondrocytes and macrophages.

PubMed

Wu, Shengqian Q; Otero, Miguel; Unger, Frank M; Goldring, Mary B; Phrutivorapongkul, Ampai; Chiari, Catharina; Kolb, Alexander; Viernstein, Helmut; Toegel, Stefan

2011-11-18

Caesalpinia sappan is a common remedy in Traditional Chinese Medicine and possesses diverse biological activities including anti-inflammatory properties. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. In order to provide a scientific basis for the applicability of Caesalpinia sappan in arthritic diseases, the present study aimed to assess the effects of an ethanolic Caesalpinia sappan extract (CSE) on human chondrocytes and macrophages. Primary human chondrocytes were isolated from cartilage specimens of OA patients. Primary cells, SW1353 chondrocytes and THP-1 macrophages were serum-starved and pretreated with different concentrations of CSE prior to stimulation with 10 ng/ml of interleukin-1beta (IL-1β) or lipopolysaccharide (LPS). Following viability tests, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were evaluated by Griess assay and ELISA, respectively. Using validated real-time PCR assays, mRNA levels of IL-1β, TNF-α, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were quantified. SW1353 cells were cotransfected with a COX-2 luciferase reporter plasmid and nuclear factor-kappa-B (NF-κB) p50 and p65 expression vectors in the presence or absence of CSE. CSE dose-dependently inhibited the expression of pro-inflammatory cytokines IL-1β and TNF-α in IL-1β-stimulated chondrocytes and LPS-stimulated THP-1 macrophages. CSE further suppressed the synthesis of NO in primary OA chondrocytes by blocking iNOS mRNA expression. The inhibition of COX-2 transcription was found to be related with the CSE inhibition of the p65/p50-driven transactivation of the COX-2 promoter. The present report is first to demonstrate the anti-inflammatory activity of CSE in an in vitro cell model of joint inflammation. CSE can effectively abrogate the IL-1β-induced over-expression of inflammatory mediators at the transcriptional level in human chondrocytes and macrophages, most likely by inhibiting NF-κB (p65/p50) signaling. Blockade of IL-1β-induced NF-κB signaling and its downstream pro-inflammatory targets by CSE may be beneficial for reducing cartilage breakdown in arthritis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

SAPHO: What radiologists should know.

PubMed

Depasquale, R; Kumar, N; Lalam, R K; Tins, B J; Tyrrell, P N M; Singh, J; Cassar-Pullicino, V N

2012-03-01

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) is an umbrella acronym for inflammatory clinical conditions whose common denominator is aseptic osteoarticular involvement with characteristic skin lesions. It involves all ages, can involve any skeletal site, and has variable imaging appearances depending on the stage/age of the lesion and imaging method. It mimics important differentials including infection and neoplasia. Awareness of the imaging features, especially in the spine, facilitates early diagnosis, prevents repeated biopsies, and avoids unnecessary surgery, while initiating appropriate treatment. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

[Cyclosporine A in the treatment of autoimmune hepatitis in the child: a case report].

PubMed

Ben Halima, Nabil; Chaabouni, Melek; Karray, Abderrahmen; Krichen, Anas; Masmoudi, Hatem; Jlidi, Rachid; Triki, Ali

2002-09-01

The current immunosuppressive treatment of patients with autoimmune hepatitis consists of prednisone and azathioprine. High doses of prednisone used to obtain the remission of the disease are associated with serious adverse effects. To avoid harmful consequences of prednisone, we proposed to treat patients with oral cyclosporine to obtain the remission of the inflammatory process. This case and review of the cases in the literature show that cyclosporine can induce remission of liver disease in children with autoimmune hepatitis, with few and well tolerated adverse effects.

Recurrent haematomas of the thigh: a case of von Willebrand's disease presenting to a sports clinic

PubMed Central

Owens, S.; Baglin, T.

2000-01-01

Von Willebrand's disease is a relatively common mild form of haemophilia. It should be suspected in assessing sports injuries when excessive bleeding occurs in response to relatively mild trauma. Those with the disease should remain active but avoid contact sports. They should not take aspirin or non-steroidal anti-inflammatory drugs, which may exacerbate bleeding, and should be given supportive treatment to cover dental extraction, surgery, or significant bleeding episodes. Key Words: von Willebrand's disease; haemophilia; haematoma; sports clinic PMID:10786868

[Suprapubic urinary diversion using Cystofix--an alternative to the urethral indwelling catheter].

PubMed

Müller, J; Sulmoni, M

1992-01-01

Suprapubic Cystofix-cystostomy is a valuable alternative to the Foley-catheter. The advantages of suprapubic cystostomy are mainly a reduction of urinary tract infections, inflammatory reactions in the lower urinary tract and avoidance of late urethral strictures after transurethral catheterism. There are a few contraindications to be considered, mainly an empty bladder and coagulation disorders. The complication rate of suprapubic Cystofix-cystostomy, usually gross haematuria, is very low. Cystofix-cystostomy is as useful for short term urinary drainage as for long term drainage in the case of chronic voiding disorders.

Technique of retinal gene therapy: delivery of viral vector into the subretinal space

PubMed Central

Xue, K; Groppe, M; Salvetti, A P; MacLaren, R E

2017-01-01

Purpose Safe and reproducible delivery of gene therapy vector into the subretinal space is essential for successful targeting of the retinal pigment epithelium (RPE) and photoreceptors. The success of surgery is critical for the clinical efficacy of retinal gene therapy. Iatrogenic detachment of the degenerate (often adherent) retina in patients with hereditary retinal degenerations and small volume (eg, 0.1 ml) subretinal injections pose new surgical challenges. Methods Our subretinal gene therapy technique involved pre-operative planning with optical coherence tomography (OCT) and autofluorescence (AF) imaging, 23 G pars plana vitrectomy, internal limiting membrane staining with Membrane Blue Dual (DORC BV, Zuidland, Netherlands), a two-step subretinal injection using a 41 G Teflon tipped cannula (DORC) first with normal saline to create a parafoveal bleb followed by slow infusion of viral vector via the same self-sealing retinotomy. Surgical precision was further enhanced by intraoperative OCT (Zeiss Rescan 7000, Carl Zeiss Meditec AG, Jena, Germany). Foveal functional and structural recovery was evaluated using best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, microperimetry and OCT. Results Two patients with choroideremia aged 29 (P1) and 27 (P2) years, who had normal and symmetrical levels of best-corrected visual acuity (BCVA) in both eyes, underwent unilateral gene therapy with the fellow eye acting as internal control. The surgeries were uncomplicated in both cases with successful detachment of the macula by subretinal vector injection. Both treated eyes showed recovery of BCVA (P1: 76–77 letters; P2: 84–88 letters) and mean threshold sensitivity of the central macula (P1: 10.7–10.7 dB; P2: 14.2–14.1 dB) to baseline within a month. This was accompanied by normalisation of central retinal thickness on OCT. Conclusions Herein we describe a reliable technique for subretinal gene therapy, which is currently used in clinical trials to treat choroideremia using an adeno-associated viral (AAV) vector encoding the CHM gene. Strategies to minimise potential complications, such as avoidance of excessive retinal stretch, air bubbles within the injection system, reflux of viral vector and post-operative vitritis are discussed. PMID:28820183

Determining areas that require indoor insecticide spraying using Multi Criteria Evaluation, a decision-support tool for malaria vector control programmes in the Central Highlands of Madagascar

PubMed Central

Rakotomanana, Fanjasoa; Randremanana, Rindra V; Rabarijaona, Léon P; Duchemin, Jean Bernard; Ratovonjato, Jocelyn; Ariey, Frédéric; Rudant, Jean Paul; Jeanne, Isabelle

2007-01-01

Background The highlands of Madagascar present an unstable transmission pattern of malaria. The population has no immunity, and the central highlands have been the sites of epidemics with particularly high fatality. The most recent epidemic occurred in the 1980s, and caused about 30,000 deaths. The fight against malaria epidemics in the highlands has been based on indoor insecticide spraying to control malaria vectors. Any preventive programme involving generalised cover in the highlands will require very substantial logistical support. We used multicriteria evaluation, by the method of weighted linear combination, as basis for improved targeting of actions by determining priority zones for intervention. Results Image analysis and field validation showed the accuracy of mapping rice fields to be between 82.3% and 100%, and the Kappa coefficient was 0.86 to 0.99. A significant positive correlation was observed between the abundance of the vector Anopheles funestus and temperature; the correlation coefficient was 0.599 (p < 0.001). A significant negative correlation was observed between vector abundance and human population density: the correlation coefficient was -0.551 (p < 0.003). Factor weights were determined by pair-wise comparison and the consistency ratio was 0.04. Risk maps of the six study zones were obtained according to a gradient of risk. Nine of thirteen results of alert confirmed by the Epidemiological Surveillance Post were in concordance with the risk map. Conclusion This study is particularly valuable for the management of vector control programmes, and particularly the reduction of the vector population with a view to preventing disease. The risk map obtained can be used to identify priority zones for the management of resources, and also help avoid systematic and generalised spraying throughout the highlands: such spraying is particularly difficult and expensive. The accuracy of the mapping, both as concerns time and space, is dependent on the availability of data. Continuous monitoring of malaria transmission factors must be undertaken to detect any changes. A regular case notification allows risk map to be verified. These actions should therefore be implemented so that risk maps can be satisfactorily assessed. PMID:17261177

Lentiviral Protein Transfer Vectors Are an Efficient Vaccine Platform and Induce a Strong Antigen-Specific Cytotoxic T Cell Response

PubMed Central

Uhlig, Katharina M.; Schülke, Stefan; Scheuplein, Vivian A. M.; Malczyk, Anna H.; Reusch, Johannes; Kugelmann, Stefanie; Muth, Anke; Koch, Vivian; Hutzler, Stefan; Bodmer, Bianca S.; Schambach, Axel; Buchholz, Christian J.; Waibler, Zoe; Scheurer, Stephan

2015-01-01

ABSTRACT To induce and trigger innate and adaptive immune responses, antigen-presenting cells (APCs) take up and process antigens. Retroviral particles are capable of transferring not only genetic information but also foreign cargo proteins when they are genetically fused to viral structural proteins. Here, we demonstrate the capacity of lentiviral protein transfer vectors (PTVs) for targeted antigen transfer directly into APCs and thereby induction of cytotoxic T cell responses. Targeting of lentiviral PTVs to APCs can be achieved analogously to gene transfer vectors by pseudotyping the particles with truncated wild-type measles virus (MV) glycoproteins (GPs), which use human SLAM (signaling lymphocyte activation molecule) as a main entry receptor. SLAM is expressed on stimulated lymphocytes and APCs, including dendritic cells. SLAM-targeted PTVs transferred the reporter protein green fluorescent protein (GFP) or Cre recombinase with strict receptor specificity into SLAM-expressing CHO and B cell lines, in contrast to broadly transducing vesicular stomatitis virus G protein (VSV-G) pseudotyped PTVs. Primary myeloid dendritic cells (mDCs) incubated with targeted or nontargeted ovalbumin (Ova)-transferring PTVs stimulated Ova-specific T lymphocytes, especially CD8+ T cells. Administration of Ova-PTVs into SLAM-transgenic and control mice confirmed the observed predominant induction of antigen-specific CD8+ T cells and demonstrated the capacity of protein transfer vectors as suitable vaccines for the induction of antigen-specific immune responses. IMPORTANCE This study demonstrates the specificity and efficacy of antigen transfer by SLAM-targeted and nontargeted lentiviral protein transfer vectors into antigen-presenting cells to trigger antigen-specific immune responses in vitro and in vivo. The observed predominant activation of antigen-specific CD8+ T cells indicates the suitability of SLAM-targeted and also nontargeted PTVs as a vaccine for the induction of cytotoxic immune responses. Since cytotoxic CD8+ T lymphocytes are a mainstay of antitumoral immune responses, PTVs could be engineered for the transfer of specific tumor antigens provoking tailored antitumoral immunity. Therefore, PTVs can be used as safe and efficient alternatives to gene transfer vectors or live attenuated replicating vector platforms, avoiding genotoxicity or general toxicity in highly immunocompromised patients, respectively. Thereby, the potential for easy envelope exchange allows the circumventing of neutralizing antibodies, e.g., during repeated boost immunizations. PMID:26085166

A comparison of linear approaches to filter out environmental effects in structural health monitoring

NASA Astrophysics Data System (ADS)

Deraemaeker, A.; Worden, K.

2018-05-01

This paper discusses the possibility of using the Mahalanobis squared-distance to perform robust novelty detection in the presence of important environmental variability in a multivariate feature vector. By performing an eigenvalue decomposition of the covariance matrix used to compute that distance, it is shown that the Mahalanobis squared-distance can be written as the sum of independent terms which result from a transformation from the feature vector space to a space of independent variables. In general, especially when the size of the features vector is large, there are dominant eigenvalues and eigenvectors associated with the covariance matrix, so that a set of principal components can be defined. Because the associated eigenvalues are high, their contribution to the Mahalanobis squared-distance is low, while the contribution of the other components is high due to the low value of the associated eigenvalues. This analysis shows that the Mahalanobis distance naturally filters out the variability in the training data. This property can be used to remove the effect of the environment in damage detection, in much the same way as two other established techniques, principal component analysis and factor analysis. The three techniques are compared here using real experimental data from a wooden bridge for which the feature vector consists in eigenfrequencies and modeshapes collected under changing environmental conditions, as well as damaged conditions simulated with an added mass. The results confirm the similarity between the three techniques and the ability to filter out environmental effects, while keeping a high sensitivity to structural changes. The results also show that even after filtering out the environmental effects, the normality assumption cannot be made for the residual feature vector. An alternative is demonstrated here based on extreme value statistics which results in a much better threshold which avoids false positives in the training data, while allowing detection of all damaged cases.

The flagellar protein FLAG1/SMP1 is a candidate for Leishmania-sand fly interaction.

PubMed

Di-Blasi, Tatiana; Lobo, Amanda R; Nascimento, Luanda M; Córdova-Rojas, Jose L; Pestana, Karen; Marín-Villa, Marcel; Tempone, Antonio J; Telleria, Erich L; Ramalho-Ortigão, Marcelo; McMahon-Pratt, Diane; Traub-Csekö, Yara M

2015-03-01

Leishmaniasis is a serious problem that affects mostly poor countries. Various species of Leishmania are the agents of the disease, which take different clinical manifestations. The parasite is transmitted by sandflies, predominantly from the Phlebotomus genus in the Old World and Lutzomyia in the New World. During development in the gut, Leishmania must survive various challenges, which include avoiding being expelled with blood remnants after digestion. It is believed that attachment to the gut epithelium is a necessary step for vector infection, and molecules from parasites and sand flies have been implicated in this attachment. In previous work, monoclonal antibodies were produced against Leishmania. Among these an antibody was obtained against Leishmania braziliensis flagella, which blocked the attachment of Leishmania panamensis flagella to Phlebotomus papatasi guts. The protein recognized by this antibody was identified and named FLAG1, and the complete FLAG1 gene sequence was obtained. This protein was later independently identified as a small, myristoylated protein and called SMP1, so from now on it will be denominated FLAG1/SMP1. The FLAG1/SMP1 gene is expressed in all developmental stages of the parasite, but has higher expression in promastigotes. The anti-FLAG1/SMP1 antibody recognized the flagellum of all Leishmania species tested and generated the expected band by western blots. This antibody was used in attachment and infection blocking experiments. Using the New World vector Lutzomyia longipalpis and Leishmania infantum chagasi, no inhibition of attachment ex vivo or infection in vivo was seen. On the other hand, when the Old World vectors P. papatasi and Leishmania major were used, a significant decrease of both attachment and infection were seen in the presence of the antibody. We propose that FLAG1/SMP1 is involved in the attachment/infection of Leishmania in the strict vector P. papatasi and not the permissive vector L. longipalpis.

Differentiation of Enhancing Glioma and Primary Central Nervous System Lymphoma by Texture-Based Machine Learning.

PubMed

Alcaide-Leon, P; Dufort, P; Geraldo, A F; Alshafai, L; Maralani, P J; Spears, J; Bharatha, A

2017-06-01

Accurate preoperative differentiation of primary central nervous system lymphoma and enhancing glioma is essential to avoid unnecessary neurosurgical resection in patients with primary central nervous system lymphoma. The purpose of the study was to evaluate the diagnostic performance of a machine-learning algorithm by using texture analysis of contrast-enhanced T1-weighted images for differentiation of primary central nervous system lymphoma and enhancing glioma. Seventy-one adult patients with enhancing gliomas and 35 adult patients with primary central nervous system lymphomas were included. The tumors were manually contoured on contrast-enhanced T1WI, and the resulting volumes of interest were mined for textural features and subjected to a support vector machine-based machine-learning protocol. Three readers classified the tumors independently on contrast-enhanced T1WI. Areas under the receiver operating characteristic curves were estimated for each reader and for the support vector machine classifier. A noninferiority test for diagnostic accuracy based on paired areas under the receiver operating characteristic curve was performed with a noninferiority margin of 0.15. The mean areas under the receiver operating characteristic curve were 0.877 (95% CI, 0.798-0.955) for the support vector machine classifier; 0.878 (95% CI, 0.807-0.949) for reader 1; 0.899 (95% CI, 0.833-0.966) for reader 2; and 0.845 (95% CI, 0.757-0.933) for reader 3. The mean area under the receiver operating characteristic curve of the support vector machine classifier was significantly noninferior to the mean area under the curve of reader 1 ( P = .021), reader 2 ( P = .035), and reader 3 ( P = .007). Support vector machine classification based on textural features of contrast-enhanced T1WI is noninferior to expert human evaluation in the differentiation of primary central nervous system lymphoma and enhancing glioma. © 2017 by American Journal of Neuroradiology.

Presence of a predator image in potential breeding sites and oviposition responses of a dengue vector.

PubMed

Dieng, Hamady; Satho, Tomomitsu; Suradi, Nur Farrahana Binti; Hakim, Hafijah; Abang, Fatimah; Aliasan, Nur Ezzati; Miake, Fumio; Zuharah, Wan Fatma; Kassim, Nur Faeza A; Majid, Abdul Hafiz A; Fadzly, Nik; Vargas, Ronald E Morales; Morales, Noppawan P; Noweg, Gabriel Tonga

2017-12-01

In dengue vector control, attempts to minimize or replace the use of pesticides have mostly involved use of predators, but success has been severely impeded by difficulties associated with financial and environmental costs, predator mass production, and persistence in target habitats. Visual deterrents have been used successfully to control animal pests, in some cases in an effort to replace pesticide use. Despite evidence that visual signals are crucial in site choice for egg deposition by dengue vectors, and that female mosquitoes respond to artificial predation, the role of predator intimidation as it affects the oviposition behavior of dengue vectors remains largely unexplored. Here, we examined the oviposition responses of Aedes aegypti exposed to various mosquito predator pictures. Gravid females were presented with equal opportunities to oviposit in two cups with predator images [Toxorhynchites splendens-TXI, Goldfish (Carassius auratus)-small (SFI) and large (LFI) and Tx. splendens+Goldfish-TXFI] and two others without pictures. Differences in egg deposition were examined between sites with and without these images. When given a chance to oviposit in cups with and without TXI, Ae. aegypti females were similarly attracted to both sites. When provided an opportunity to oviposit in cups displaying pictures of fish (SFI or LFI) and blank cups, egg deposition rates were much lower in the fish picture sites. Females showed a preference for blank cups over TXFI for egg deposition. They also equally avoided cups with pictures of fish, regardless of the size of the picture. Our results indicate that the presence of images of goldfish and their association with Tx. larvae significantly reduced egg deposition by Ae. aegypti, and this was not the case with the predatory larvae alone. The observations that the images of natural predators can repel gravid females of a dengue vector provide novel possibilities to develop effective and inexpensive alternative tools to harmful insecticides. Copyright © 2017 Elsevier B.V. All rights reserved.

Q-vector measurements: physical examination versus magnetic resonance imaging measurements and their relationship with tibial tubercle-trochlear groove distance.

PubMed

Graf, Kristin H; Tompkins, Marc A; Agel, Julie; Arendt, Elizabeth A

2018-03-01

An increased lateral quadriceps vector has been associated with lateral patellar dislocation. Surgical correction of this increased vector through tibial tubercle medialization is often recommended when the quadriceps vector is "excessive". This can be evaluated by physical examination measurements of Q-angle and/or tubercle sulcus angle (TSA), as well as the magnetic resonance imaging (MRI) measurement of tibial tubercle-trochlear groove (TT-TG) distance. This study examined the relationship between three objective measurements of lateral quadriceps vector (TT-TG, Q-angle, TSA). A secondary goal was to relate lateral patellar tilt to these measurements. Consecutive patients undergoing patellofemoral stabilization surgery from 9/2010 to 6/2011 were included. The Q-angle and TSA were measured on intra-operative physical examination. The TT-TG and patellar tilt were measured on MRI. TSA, Q-angle, and patellar tilt were compared to TT-TG using Pearson correlation coefficient. The study cohort included 49 patients, ages 12-37 (mean 23.2); 62% female. The Pearson correlation coefficients showed (+) significance (p < 0.01) between the TT-TG and both TSA and Q-angle. Tilt and TT-TG were (+) non-significantly correlated. Despite positive correlations of each measurement with TT-TG, there is not uniform intra-patient correlation. In other words, if TT-TG is elevated for a patient, it does not guarantee that all other measurements, including tilt, are elevated in that individual patient. The TT-TG distance has significant positive correlation with the measurements of TSA and Q-angle in patients undergoing surgery for patellofemoral instability. The clinical relevance is that the variability within individual patients demonstrates the need for considering both TSA and TT-TG before and during surgical intervention to avoid overcorrection with a medial tibial tubercle osteotomy. Diagnostic study, Level III.

Air Traffic Control/Active Beacon Collision Avoidance System Knoxville Simulation.

DTIC Science & Technology

1980-05-01

I’s & AIRCRAFT 2’s POSITION VECTOR. ENTER (X1l,Y,Zl,,ZI,2) & (X2,Y2,Z2,X2,Y2,i2) As x = XI-X2 Y= Yl-Y2 VRX =Xi-X2 VRY = YI-Y2 MD2 -(4X*\\’RY - AY*vHJ...2 VRX 2 + vRy 2 M SQRT(MD2) YES MD> MDCM FILTER + OR - COMAND IF FITER VAVE TITRj-SITnLD PERFORMANCE LEATl. VALIE 3 o . U mi 5 3.0 1in t ;u~i:F-2

Intoxications from the seas: ciguatera, scombroid, and paralytic shellfish poisoning.

PubMed

Sanders, W E

1987-09-01

Sporadic cases and outbreaks of intoxications borne by fish and shellfish have increased in frequency during recent years. Ciguatera, scombroid, and paralytic shellfish poisoning account for nearly 16 per cent of all reported foodborne outbreaks of disease in the United States. Fishborne ciguatera and paralytic shellfish poisoning are characterized by gastrointestinal and neuromuscular manifestations attributable to toxins of dinoflagellates. These toxins impair sodium transport in cell membranes. Treatment is primarily supportive. Scombroid fish intoxication resembles histamine poisoning and may be treated effectively with antihistamines or cimetidine. Prevention of these intoxications at present depends upon avoidance of potential vectors.

Kernel canonical-correlation Granger causality for multiple time series

NASA Astrophysics Data System (ADS)

Wu, Guorong; Duan, Xujun; Liao, Wei; Gao, Qing; Chen, Huafu

2011-04-01

Canonical-correlation analysis as a multivariate statistical technique has been applied to multivariate Granger causality analysis to infer information flow in complex systems. It shows unique appeal and great superiority over the traditional vector autoregressive method, due to the simplified procedure that detects causal interaction between multiple time series, and the avoidance of potential model estimation problems. However, it is limited to the linear case. Here, we extend the framework of canonical correlation to include the estimation of multivariate nonlinear Granger causality for drawing inference about directed interaction. Its feasibility and effectiveness are verified on simulated data.

Inception of self-interacting dark matter with dark charge conjugation symmetry

DOE PAGES

Ma, Ernest

2017-07-04

A new understanding of the stability of self-interacting dark matter is pointed out, based on the simplest spontaneously broken Abelian gauge model with one complex scalar and one Dirac fermion. The key is the imposition of dark charge conjugation symmetry. It allows the possible existence of two stable particles: the Dirac fermion and the vector gauge boson which acts as a light mediator for the former's self-interaction. Since this light mediator does not decay, it avoids the strong cosmological constraints recently obtained for all such models where the light mediator decays into standard-model particles.

Biodegradable polymers as non-viral carriers for plasmid DNA delivery.

PubMed

Luten, Jordy; van Nostrum, Cornelus F; De Smedt, Stefaan C; Hennink, Wim E

2008-03-03

Gene therapy holds a great promise for the treatment of acquired and inherited diseases with a genetic origin that are currently incurable. Non-viral gene delivery systems are gaining recognition as an alternative to viral gene vectors for their potential in avoiding immunogenicity and toxicity problems inherently associated with the use of viral systems. Many cationic polymers have been studied both in vitro and in vivo for gene delivery purposes. However, in recent years there has been a focus on biodegradable carrier systems. The potential advantage of biodegradable carriers as compared to their non-degradable counterparts is their reduced toxicity and the avoidance of accumulation of the polymer in the cells after repeated administration. Also, the degradation of the polymer can be used as a tool to release the plasmid DNA into the cytosol. In this article the recent results obtained with two classes of degradable gene delivery systems, namely those based on water-soluble cationic polymers and on micro- and nanoparticles will be summarized and discussed.

Cost-effective bidirectional digitized radio-over-fiber systems employing sigma delta modulation

NASA Astrophysics Data System (ADS)

Lee, Kyung Woon; Jung, HyunDo; Park, Jung Ho

2016-11-01

We propose a cost effective digitized radio-over-fiber (D-RoF) system employing a sigma delta modulation (SDM) and a bidirectional transmission technique using phase modulated downlink and intensity modulated uplink. SDM is transparent to different radio access technologies and modulation formats, and more suitable for a downlink of wireless system because a digital to analog converter (DAC) can be avoided at the base station (BS). Also, Central station and BS share the same light source by using a phase modulation for the downlink and an intensity modulation for the uplink transmission. Avoiding DACs and light sources have advantages in terms of cost reduction, power consumption, and compatibility with conventional wireless network structure. We have designed a cost effective bidirectional D-RoF system using a low pass SDM and measured the downlink and uplink transmission performance in terms of error vector magnitude, signal spectra, and constellations, which are based on the 10MHz LTE 64-QAM standard.

Localized Sympathectomy Reduces Mechanical Hypersensitivity by Restoring Normal Immune Homeostasis in Rat Models of Inflammatory Pain

PubMed Central

Xie, Wenrui; Chen, Sisi; Strong, Judith A.; Li, Ai-Ling; Lewkowich, Ian P.

2016-01-01

Some forms of chronic pain are maintained or enhanced by activity in the sympathetic nervous system (SNS), but attempts to model this have yielded conflicting findings. The SNS has both pro- and anti-inflammatory effects on immunity, confounding the interpretation of experiments using global sympathectomy methods. We performed a “microsympathectomy” by cutting the ipsilateral gray rami where they entered the spinal nerves near the L4 and L5 DRG. This led to profound sustained reductions in pain behaviors induced by local DRG inflammation (a rat model of low back pain) and by a peripheral paw inflammation model. Effects of microsympathectomy were evident within one day, making it unlikely that blocking sympathetic sprouting in the local DRGs or hindpaw was the sole mechanism. Prior microsympathectomy greatly reduced hyperexcitability of sensory neurons induced by local DRG inflammation observed 4 d later. Microsympathectomy reduced local inflammation and macrophage density in the affected tissues (as indicated by paw swelling and histochemical staining). Cytokine profiling in locally inflamed DRG showed increases in pro-inflammatory Type 1 cytokines and decreases in the Type 2 cytokines present at baseline, changes that were mitigated by microsympathectomy. Microsympathectomy was also effective in reducing established pain behaviors in the local DRG inflammation model. We conclude that the effect of sympathetic fibers in the L4/L5 gray rami in these models is pro-inflammatory. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some chronic inflammatory pain conditions. SIGNIFICANCE STATEMENT Sympathetic blockade is used for many pain conditions, but preclinical studies show both pro- and anti-nociceptive effects. The sympathetic nervous system also has both pro- and anti-inflammatory effects on immune tissues and cells. We examined effects of a very localized sympathectomy. By cutting the gray rami to the spinal nerves near the lumbar sensory ganglia, we avoided widespread sympathetic denervation. This procedure profoundly reduced mechanical pain behaviors induced by a back pain model and a model of peripheral inflammatory pain. One possible mechanism was reduction of inflammation in the sympathetically denervated regions. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some inflammatory conditions. PMID:27535916

Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation.

PubMed

Kostyuk, Vladimir A; Potapovich, Alla I; Suhan, Tatyana O; de Luca, Chiara; Korkina, Liudmila G

2011-05-11

Oxidized low-density lipoproteins (oxLDL) play a critical role in the initiation of atherosclerosis through activation of inflammatory signaling. In the present work we investigated the role of antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation. Significant decrease in intracellular NO level and superoxide overproduction was found in human umbilical vein endothelial cells (HUVEC) treated with oxLDL, but not with LDL. The redox imbalance was prevented by the addition of quercetin or resveratrol. Expression analysis of 14 genes associated with oxidative stress and inflammation revealed oxLDL-mediated up-regulation of genes specifically involved in leukocyte recruitment and adhesion. This up-regulation could be partially avoided by the addition of verbascoside or resveratrol, while treatment with quercetin resulted in a further increase in the expression of these genes. Lipopolysaccharide (LPS)-treated HUVEC were also used for the evaluation of anti-inflammatory potency of plant polyphenols. Significant differences between HUVEC treaded with oxLDL and LPS were found in both the expression pattern of inflammation-related genes and the effects of plant polyphenols on cellular responses. The present data indicate that plant polyphenols may affect vascular inflammation not only as antioxidants but also as modulators of inflammatory redox signaling pathways. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

The dormant blood microbiome in chronic, inflammatory diseases.

PubMed

Potgieter, Marnie; Bester, Janette; Kell, Douglas B; Pretorius, Etheresia

2015-07-01

Blood in healthy organisms is seen as a 'sterile' environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. 'Non-culturability', reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as 'dysbiosis'). Another source is microbes translocated from the oral cavity. 'Dysbiosis' is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term 'atopobiosis' for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines. © FEMS 2015.

Immunomodulatory/inflammatory effects of geopropolis produced by Melipona fasciculata Smith in combination with doxorubicin on THP-1 cells.

PubMed

Oliveira, Lucas Pires Garcia; Conte, Fernanda Lopes; Cardoso, Eliza de Oliveira; Conti, Bruno José; Santiago, Karina Basso; Golim, Marjorie de Assis; Cruz, Maria Teresa; Sforcin, José Maurício

2016-12-01

Geopropolis (GEO) in combination with doxorubicin (DOX) reduced HEp-2 cells viability compared to GEO and DOX alone. A possible effect of this combination on the innate immunity could take place, and its effects were analysed on THP-1 cell - a human leukaemia monocytic cell line used as a model to study monocyte activity and macrophage activity, assessing cell viability, expression of cell markers and cytokine production. THP-1 cells were incubated with GEO, DOX and their combination. Cell viability was assessed by MTT assay, cell markers expression by flow cytometry and cytokine production by ELISA. GEO + DOX did not affect cell viability. GEO alone or in combination increased TLR-4 and CD80 but not HLA-DR and TLR-2 expression. GEO stimulated TNF-α production while DOX alone or in combination did not affect it. GEO alone or in combination inhibited IL-6 production. GEO exerted a pro-inflammatory profile by increasing TLR-4 and CD80 expression and TNF-α production, favouring the activation of the immune/inflammatory response. GEO + DOX did not affect cell viability and presented an immunomodulatory action. Lower concentrations of DOX combined to GEO could be used in cancer patients, avoiding side effects and benefiting from the biological properties of GEO. © 2016 Royal Pharmaceutical Society.

The dormant blood microbiome in chronic, inflammatory diseases

PubMed Central

Potgieter, Marnie; Bester, Janette; Kell, Douglas B.; Pretorius, Etheresia

2015-01-01

Blood in healthy organisms is seen as a ‘sterile’ environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. ‘Non-culturability’, reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as ‘dysbiosis’). Another source is microbes translocated from the oral cavity. ‘Dysbiosis’ is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term ‘atopobiosis’ for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines. PMID:25940667

Aztec user`s guide. Version 1

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

Hutchinson, S.A.; Shadid, J.N.; Tuminaro, R.S.

1995-10-01

Aztec is an iterative library that greatly simplifies the parallelization process when solving the linear systems of equations Ax = b where A is a user supplied n x n sparse matrix, b is a user supplied vector of length n and x is a vector of length n to be computed. Aztec is intended as a software tool for users who want to avoid cumbersome parallel programming details but who have large sparse linear systems which require an efficiently utilized parallel processing system. A collection of data transformation tools are provided that allow for easy creation of distributed sparsemore » unstructured matrices for parallel solution. Once the distributed matrix is created, computation can be performed on any of the parallel machines running Aztec: nCUBE 2, IBM SP2 and Intel Paragon, MPI platforms as well as standard serial and vector platforms. Aztec includes a number of Krylov iterative methods such as conjugate gradient (CG), generalized minimum residual (GMRES) and stabilized biconjugate gradient (BICGSTAB) to solve systems of equations. These Krylov methods are used in conjunction with various preconditioners such as polynomial or domain decomposition methods using LU or incomplete LU factorizations within subdomains. Although the matrix A can be general, the package has been designed for matrices arising from the approximation of partial differential equations (PDEs). In particular, the Aztec package is oriented toward systems arising from PDE applications.« less

The role of model dynamics in ensemble Kalman filter performance for chaotic systems

USGS Publications Warehouse

Ng, G.-H.C.; McLaughlin, D.; Entekhabi, D.; Ahanin, A.

2011-01-01

The ensemble Kalman filter (EnKF) is susceptible to losing track of observations, or 'diverging', when applied to large chaotic systems such as atmospheric and ocean models. Past studies have demonstrated the adverse impact of sampling error during the filter's update step. We examine how system dynamics affect EnKF performance, and whether the absence of certain dynamic features in the ensemble may lead to divergence. The EnKF is applied to a simple chaotic model, and ensembles are checked against singular vectors of the tangent linear model, corresponding to short-term growth and Lyapunov vectors, corresponding to long-term growth. Results show that the ensemble strongly aligns itself with the subspace spanned by unstable Lyapunov vectors. Furthermore, the filter avoids divergence only if the full linearized long-term unstable subspace is spanned. However, short-term dynamics also become important as non-linearity in the system increases. Non-linear movement prevents errors in the long-term stable subspace from decaying indefinitely. If these errors then undergo linear intermittent growth, a small ensemble may fail to properly represent all important modes, causing filter divergence. A combination of long and short-term growth dynamics are thus critical to EnKF performance. These findings can help in developing practical robust filters based on model dynamics. ?? 2011 The Authors Tellus A ?? 2011 John Wiley & Sons A/S.

Modeling the spatial distribution of Chagas disease vectors using environmental variables and people´s knowledge.

PubMed

Hernández, Jaime; Núñez, Ignacia; Bacigalupo, Antonella; Cattan, Pedro E

2013-05-31

Chagas disease is caused by the protozoan Trypanosoma cruzi, which is transmitted to mammal hosts by triatomine insect vectors. The goal of this study was to model the spatial distribution of triatomine species in an endemic area. Vector's locations were obtained with a rural householders' survey. This information was combined with environmental data obtained from remote sensors, land use maps and topographic SRTM data, using the machine learning algorithm Random Forests to model species distribution. We analysed the combination of variables on three scales: 10 km, 5 km and 2.5 km cell size grids. The best estimation, explaining 46.2% of the triatomines spatial distribution, was obtained for 5 km of spatial resolution. Presence probability distribution increases from central Chile towards the north, tending to cover the central-coastal region and avoiding areas of the Andes range. The methodology presented here was useful to model the distribution of triatomines in an endemic area; it is best explained using 5 km of spatial resolution, and their presence increases in the northern part of the study area. This study's methodology can be replicated in other countries with Chagas disease or other vectorial transmitted diseases, and be used to locate high risk areas and to optimize resource allocation, for prevention and control of vectorial diseases.

Review of methods to prevent and reduce the risk of Lyme disease.

PubMed

Lindsay, L R; Ogden, N H; Schofield, S W

2015-06-04

Cases of Lyme disease and areas with self-sustaining populations of vector ticks are increasing in Canada. This trend is expected to continue. Preventing Lyme disease will therefore become relevant to an increasing number of Canadians. To summarize methods for reducing the risk of tick bites and preventing transmission once a tick is feeding. A literature search was conducted to identify methods to reduce the risk of tick bites and the abundance of vector ticks, as well as the risk of becoming infected with the Lyme disease pathogen, Borrelia burgdorferi (BB), if bitten by a vector tick. Current approaches to reducing the risk of tick bites or preventing infection with BB once bitten are largely reliant on the individual. They include use of topical repellents, use of protective clothing, avoidance of risk areas and removing ticks soon (ideally within a day) after they attach. These methods are efficacious, but constrained by user adherence. Other approaches such as landscape modification or the use of acaricides to control ticks, have shown promise in other countries, but have not been widely adopted in Canada. Lyme disease will continue to present a threat in Canada. In additional to the existing interventions for prevention of tick bites and Lyme disease, there is a need for new tools to help reduce the risk of Lyme disease to Canadians.

Cosmology in beyond-generalized Proca theories

NASA Astrophysics Data System (ADS)

Nakamura, Shintaro; Kase, Ryotaro; Tsujikawa, Shinji

2017-05-01

The beyond-generalized Proca theories are the extension of second-order massive vector-tensor theories (dubbed generalized Proca theories) with two transverse vector modes and one longitudinal scalar besides two tensor polarizations. Even with this extension, the propagating degrees of freedom remain unchanged on the isotropic cosmological background without an Ostrogradski instability. We study the cosmology in beyond-generalized Proca theories by paying particular attention to the dynamics of late-time cosmic acceleration and resulting observational consequences. We derive conditions for avoiding ghosts and instabilities of tensor, vector, and scalar perturbations and discuss viable parameter spaces in concrete models allowing the dark energy equation of state smaller than -1 . The propagation speeds of those perturbations are subject to modifications beyond the domain of generalized Proca theories. There is a mixing between scalar and matter sound speeds, but such a mixing is suppressed during most of the cosmic expansion history without causing a new instability. On the other hand, we find that derivative interactions arising in beyond-generalized Proca theories give rise to important modifications to the cosmic growth history. The growth rate of matter perturbations can be compatible with the redshift-space distortion data due to the realization of gravitational interaction weaker than that in generalized Proca theories. Thus, it is possible to distinguish the dark energy model in beyond-generalized Proca theories from the counterpart in generalized Proca theories as well as from the Λ CDM model.

Positive and negative tropic curvature induced by microbeam irradiation of protonemal tip cells of the moss Ceratodon purpureus.

PubMed

Lamparter, T; Kagawa, T; Brücker, G; Wada, M

2004-01-01

The photoreceptor phytochrome mediates tropic responses in protonemata of the moss Ceratodon purpureus. Under standard conditions the tip cells grow towards unilateral red light, or perpendicular to the electrical vector of polarized light. In this study the response of tip cells to partial irradiation of the apical region was analysed using a microbeam apparatus. The fluence response curve gave an unexpected pattern: whereas a 15-min microbeam with light intensities around 3 micro mol m (-2) s (-1) induced a growth curvature towards the irradiated side, higher light intensities around 100 micro mol m (-2) s (-1) caused a negative response, the cells grew away from the irradiated side. This avoidance response is explained by two effects: the light intensity is high enough to induce photoconversion into the active Pfr form of phytochrome, not only on the irradiated but also on the non-irradiated side by stray light. At the same time, the strong light on the irradiated side acts antagonistically to Pfr. As a result of this inhibition, the growth direction is moved to the light-avoiding side. Such a Pfr-independent mechanism might be important for the phototropic response to distinguish between the light-directed and light-avoiding side under unilateral light.

In vivo imaging of leukocyte recruitment to glomeruli in mice using intravital microscopy.

PubMed

Kitching, A Richard; Kuligowski, Michael P; Hickey, Michael J

2009-01-01

Leukocytes mediate some forms of glomerulonephritis, particularly severe proliferative and crescentic forms. The renal glomerulus is one of the few sites within the microvasculature in which leukocyte recruitment occurs in capillaries. However, due to the difficulty of directly visualising the glomerulus, the mechanisms of leukocyte recruitment to glomerular capillaries are poorly understood. To overcome this, a murine kidney can be rendered hydronephrotic, by ligating one ureter, and allowing the mouse to rest for 12 weeks. This allows the visualisation of the glomerular microvasculature during inflammatory responses. In inflammation, in this example induced by anti-glomerular basement membrane (GBM) antibody, leukocytes can be observed undergoing adhesion in glomerular capillaries using intravital microscopy. Leukocyte adhesion can be quantitated using this approach. An observation protocol involving few, limited periods of epifluorescence avoids phototoxicity-induced leukocyte recruitment. The process of hydronephrosis does not alter the ability of anti-GBM-antibody to induce a glomerular inflammatory response. This approach allows detailed investigation of the mechanisms of leukocyte recruitment within glomeruli.

UNDERSTANDING THE CAUTIONS AND CONTRAINDICATIONS OF IMMUNOMODULATOR AND BIOLOGIC THERAPIES FOR USE IN INFLAMMATORY BOWEL DISEASE

PubMed Central

Cohn, H. Matthew; Dave, Maneesh; Loftus, Edward V.

2017-01-01

Ulcerative colitis and Crohn’s disease are chronic inflammatory bowel diseases for which there are no cures. These diseases are immunopathogenic, and medical treatment is centered on the temperance of a dysregulated immune response to allow mucosal healing and prevent the sequelae of fistulation and stenosis. Accordingly, the armamentarium of medications, which has expanded immensely in recent history, is not without significant infectious and neoplastic risks. Many of these untoward effects can be mitigated by screening and avoidance of contraindicated medications. This review seeks to highlight the cautions for use of immunomodulators, anticytokine and α4-integrin antagonists. The potential adverse events are further complicated by substantial heterogeneity in disease phenotype in the IBD population. Large patient registries and databases provide considerable experience and knowledge to calculate the incidence of safety outcomes. To identify rarer outcomes after prolonged therapy, more prospective studies and continued adverse event reporting will aid safe application and minimize potential harms. PMID:28708806

Nutritional evaluation and management of AKI patients.

PubMed

Fiaccadori, Enrico; Maggiore, Umberto; Cabassi, Aderville; Morabito, Santo; Castellano, Giuseppe; Regolisti, Giuseppe

2013-05-01

Protein-energy wasting is common in patients with acute kidney injury (AKI) and represents a major negative prognostic factor. Nutritional support as parenteral and/or enteral nutrition is frequently needed because the early phases of this are often a highly catabolic state, although the optimal nutritional requirements and nutrient intake composition remain a partially unresolved issue. Nutrient needs of patients with AKI are highly heterogeneous, depending on different pathogenetic mechanisms, catabolic rate, acute and chronic comorbidities, and renal replacement therapy (RRT) modalities. Thus, quantitative and qualitative aspects of nutrient intake should be frequently evaluated in this clinical setting to achieve better individualization of nutritional support, to integrate nutritional support with RRT, and to avoid under- and overfeeding. Moreover, AKI is now considered a kidney-centered inflammatory syndrome; indeed, recent experimental data indicate that specific nutrients with anti-inflammatory effects could play an important role in the prevention of renal function loss after an episode of AKI. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

L-selectin mechanochemistry restricts neutrophil priming in vivo.

PubMed

Liu, Zhenghui; Yago, Tadayuki; Zhang, Nan; Panicker, Sumith R; Wang, Ying; Yao, Longbiao; Mehta-D'souza, Padmaja; Xia, Lijun; Zhu, Cheng; McEver, Rodger P

2017-05-12

Circulating neutrophils must avoid premature activation to prevent tissue injury. The leukocyte adhesion receptor L-selectin forms bonds with P-selectin glycoprotein ligand-1 (PSGL-1) on other leukocytes and with peripheral node addressin (PNAd) on high endothelial venules. Mechanical forces can strengthen (catch) or weaken (slip) bonds between biological molecules. How these mechanochemical processes influence function in vivo is unexplored. Here we show that mice expressing an L-selectin mutant (N138G) have altered catch bonds and prolonged bond lifetimes at low forces. Basal lymphocyte homing and neutrophil recruitment to inflamed sites are normal. However, circulating neutrophils form unstable aggregates and are unexpectedly primed to respond robustly to inflammatory mediators. Priming requires signals transduced through L-selectin N138G after it engages PSGL-1 or PNAd. Priming enhances bacterial clearance but increases inflammatory injury and enlarges venous thrombi. Thus, L-selectin mechanochemistry limits premature activation of neutrophils. Our results highlight the importance of probing how mechanochemistry functions in vivo.

L-selectin mechanochemistry restricts neutrophil priming in vivo

PubMed Central

Liu, Zhenghui; Yago, Tadayuki; Zhang, Nan; Panicker, Sumith R.; Wang, Ying; Yao, Longbiao; Mehta-D'souza, Padmaja; Xia, Lijun; Zhu, Cheng; McEver, Rodger P.

2017-01-01

Circulating neutrophils must avoid premature activation to prevent tissue injury. The leukocyte adhesion receptor L-selectin forms bonds with P-selectin glycoprotein ligand-1 (PSGL-1) on other leukocytes and with peripheral node addressin (PNAd) on high endothelial venules. Mechanical forces can strengthen (catch) or weaken (slip) bonds between biological molecules. How these mechanochemical processes influence function in vivo is unexplored. Here we show that mice expressing an L-selectin mutant (N138G) have altered catch bonds and prolonged bond lifetimes at low forces. Basal lymphocyte homing and neutrophil recruitment to inflamed sites are normal. However, circulating neutrophils form unstable aggregates and are unexpectedly primed to respond robustly to inflammatory mediators. Priming requires signals transduced through L-selectin N138G after it engages PSGL-1 or PNAd. Priming enhances bacterial clearance but increases inflammatory injury and enlarges venous thrombi. Thus, L-selectin mechanochemistry limits premature activation of neutrophils. Our results highlight the importance of probing how mechanochemistry functions in vivo. PMID:28497779

Emerging approaches for histone deacetylase inhibitor drug discovery.

PubMed

Zwergel, Clemens; Valente, Sergio; Jacob, Claus; Mai, Antonello

2015-06-01

Histone deacetylases (HDACs) are key players in the mediation of gene expression for both cancerous and noncancerous malignancies. Overexpression of these enzymes has been demonstrated in numerous types of cancer with some enzyme isoforms also involved in neurological, inflammatory and viral pathologies. Hence, the development of HDAC inhibitors (HDACis) represents a promising approach for their treatment. Numerous chemical entities have been studied in the recent years and some of them have reached clinical trials. This review summarizes the recent efforts in the drug development of HDACis and their potential application as therapeutic agents in cancerous, neurological, inflammatory and viral diseases. The development of novel potent and selective HDACis is ongoing. However, increased scientific effort is needed to aid the fight of specific types of cancerous or noncancerous disease with more selective agents required to avoid side effects during therapy. An interesting therapeutic approach is the use of HDACis in combination with other epigenetic target modulators to combine their therapeutic potential for a synergistic effect.

Lasers for treatment of melasma and post-inflammatory hyperpigmentation.

PubMed

Arora, Pooja; Sarkar, Rashmi; Garg, Vijay K; Arya, Latika

2012-04-01

Hyperpigmentary disorders, especially melasma and post-inflammatory hyperpigmentation (PIH), cause significant social and emotional stress to the patients. Although many treatment modalities have been developed for melasma and PIH, its management still remains a challenge due to its recurrent and refractory nature. With the advent of laser technology, the treatment options have increased especially for dermal or mixed melasma. To review the literature on the use of cutaneous lasers for melasma and PIH. We carried out a PubMed search using following terms "lasers, IPL, melasma, PIH". We cited the use of various lasers to treat melasma and PIH, including Q-switched Nd:YAG, Q-switched alexandrite, pulsed dye laser, and various fractional lasers. We describe the efficacy and safety of these lasers for the treatment of hyperpigmentation. Choosing the appropriate laser and the correct settings is vital in the treatment of melasma. The use of latter should be restricted to cases unresponsive to topical therapy or chemical peels. Appropriate maintenance therapy should be selected to avoid relapse of melasma.

Natural (Mineral, Vegetable, Coconut, Essential) Oils and Contact Dermatitis.

PubMed

Verallo-Rowell, Vermén M; Katalbas, Stephanie S; Pangasinan, Julia P

2016-07-01

Natural oils include mineral oil with emollient, occlusive, and humectant properties and the plant-derived essential, coconut, and other vegetable oils, composed of triglycerides that microbiota lipases hydrolyze into glycerin, a potent humectant, and fatty acids (FAs) with varying physico-chemical properties. Unsaturated FAs have high linoleic acid used for synthesis of ceramide-I linoleate, a barrier lipid, but more pro-inflammatory omega-6:-3 ratios above 10:1, and their double bonds form less occlusive palisades. VCO FAs have a low linoleic acid content but shorter and saturated FAs that form a more compact palisade, more anti-inflammatory omega-6:-3 ratio of 2:1, close to 7:1 of olive oil, which disrupts the skin barrier, otherwise useful as a penetration enhancer. Updates on the stratum corneum illustrate how this review on the contrasting actions of NOs provide information on which to avoid and which to select for barrier repair and to lower inflammation in contact dermatitis genesis.

Lasers for Treatment of Melasma and Post-Inflammatory Hyperpigmentation

PubMed Central

Arora, Pooja; Sarkar, Rashmi; Garg, Vijay K; Arya, Latika

2012-01-01

Hyperpigmentary disorders, especially melasma and post-inflammatory hyperpigmentation (PIH), cause significant social and emotional stress to the patients. Although many treatment modalities have been developed for melasma and PIH, its management still remains a challenge due to its recurrent and refractory nature. With the advent of laser technology, the treatment options have increased especially for dermal or mixed melasma. To review the literature on the use of cutaneous lasers for melasma and PIH. We carried out a PubMed search using following terms “lasers, IPL, melasma, PIH”. We cited the use of various lasers to treat melasma and PIH, including Q-switched Nd:YAG, Q-switched alexandrite, pulsed dye laser, and various fractional lasers. We describe the efficacy and safety of these lasers for the treatment of hyperpigmentation. Choosing the appropriate laser and the correct settings is vital in the treatment of melasma. The use of latter should be restricted to cases unresponsive to topical therapy or chemical peels. Appropriate maintenance therapy should be selected to avoid relapse of melasma. PMID:23060704

Effect of Systemically Used Anti-Tumor Necrosis Factor-α Medication on the Corneal Epithelium and Stroma of Patients with Ankylosing Spondylitis.

PubMed

Arikan, Sedat; Gokmen, Ferhat; Ersan, Ismail; Akbal, Ayla; Resorlu, Hatice; Gencer, Baran; Ali Tufan, Hasan; Kara, Selcuk

2017-04-01

To evaluate the effect of systemically used anti-tumor necrosis factor alpha (TNF-α) medication on the thickness of corneal epithelium and stroma in patients with ankylosing spondylitis (AS). A total of 125 eyes of 69 participants were included in this retrospective study of three groups: healthy participants (Group 1), AS patients receiving anti-TNF-α medication (Group 2), and AS patients receiving a nonsteroidal anti-inflammatory medication (Group 3). According to anterior segment optical coherence tomography, the mean thickness of the corneal epithelium was significantly thicker in Group 2 than in Group 3 (51.6 ± 3.2 µm versus 50.4 ± 3 µm, p = 0.01), as was that of the stroma (475 ± 33 µm versus 443 ± 29 µm, p = 0.002). Anti-TNF-α medication and/or avoidance of nonsteroidal anti-inflammatory drugs could improve the thickness of both the corneal epithelium and stroma in AS patients.

Corneal Nerves in Health and Disease

PubMed Central

Shaheen, Brittany; Bakir, May; Jain, Sandeep

2013-01-01

Corneal nerves are responsible for the sensations of touch, pain, and temperature and play an important role in the blink reflex, wound healing, and tear production and secretion. Corneal nerve dysfunction is a frequent feature of diseases that cause opacities and result in corneal blindness. Corneal opacities rank as the second most frequent cause of blindness. Technological advances in in vivo corneal nerve imaging, such as optical coherence tomography and confocal scanning, have generated new knowledge regarding the phenomenological events that occur during reinnervation of the cornea following disease, injury, or surgery. The recent availability of transgenic neurofluorescent murine models has stimulated the search for molecular modulators of corneal nerve regeneration. New evidence suggests that neuro-regenerative and inflammatory pathways in the cornea are intertwined. Evidence-based treatment of neurotrophic corneal diseases includes using neuro-regenerative (blood component-based and neurotrophic factors), neuroprotective, and ensconcing (bandage contact lens and amniotic membrane) strategies and avoiding anti-inflammatory therapies, such as cyclosporine and corticosteroids. PMID:24461367

Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis

PubMed Central

Pountos, Ippokratis; Georgouli, Theodora; Calori, Giorgio M.; Giannoudis, Peter V.

2012-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients. PMID:22272177

A case of vemurafenib-induced polyarhritis in a patient with melanoma: how to manage it?

PubMed

Babacan, Taner; Türkbeyler, Ibrahim Halil; Balakan, Ozan; Pehlivan, Yavuz; Suner, Ali; Kısacık, Bunyamin

2017-03-01

Vemurafenib is an inhibitor of the BRAF V600E mutation which is associated with tumor responses in patients with metastatic melanoma. Although it is generally well tolerated, common side effects of vemurafenib have been reported. Arthralgia is one of the more common adverse event associated with vemurafenib. We herein report a 49-year-old woman diagnosed with metastatic melanoma harboring the BRAF V600E mutation with severe polyarthritis associated with vemurafenib after 7 days of treatment. Sonographic examination of affected joints revealed synovitis and the patient's articular symptoms were improved by analgesic and anti-inflammatory treatment, including corticosteroids. During therapy with selective BRAF inhibitors, arthritis represents a new adverse event that can require dose reduction. In case of this adverse event, treatment with anti-inflammatory drugs, such as ibuprofen and prednisone, should be initiated early to keep patients on treatment and to avoid drug discontinuation and tumor progression. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Modelling affective pain in mice: Effects of inflammatory hypersensitivity on place escape/avoidance behaviour, anxiety and hedonic state.

PubMed

Refsgaard, L K; Hoffmann-Petersen, J; Sahlholt, M; Pickering, D S; Andreasen, J T

2016-03-15

The place escape/avoidance paradigm (PEAP) has been used to assess the affective component of pain in rats. Using the Complete Freund's Adjuvant (CFA) model of inflammatory pain, the current study aimed at developing a mouse version of PEAP and investigating the relation between PEAP and other behavioural responses, namely anxiety-like behaviour, locomotor activity, and hedonic state. A novel paradigm assessing the affective component of pain in mice was developed by modifying the setup known from rat studies: Animals were forced to stay 2 × 5 min in the light and the dark area of a box while being stimulated with a suprathreshold filament on the untreated or treated paw, respectively. This was followed by a 30-min test with unrestricted movement. Anxiety-like behaviour, locomotor activity, and hedonic state were assessed with the elevated zero maze (EZM), an open field setup, and a saccharin preference test, respectively, and correlated with the PEAP behaviour to examine potentially confounding parameters of the novel paradigm. In the PEAP, CFA-treated animals spent more time in the light area. CFA also increased anxiety-like behaviour significantly, whereas locomotor activity was unaffected. A significant, albeit modest, reduction in saccharin preference was observed. PEAP responses showed no significant correlations with any other behavioural measure. The PEAP results suggest that this paradigm might be successfully applied in mice to study affective pain. CFA treatment was associated with increased anxiety-like behaviour and anhedonia; however, this appeared unrelated to the PEAP responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Genistein improves 3-NPA-induced memory impairment in ovariectomized rats: impact of its antioxidant, anti-inflammatory and acetylcholinesterase modulatory properties.

PubMed

Menze, Esther T; Esmat, Ahmed; Tadros, Mariane G; Abdel-Naim, Ashraf B; Khalifa, Amani E

2015-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder. The pre-motor symptomatic stages of the disease are commonly characterized by cognitive problems including memory loss. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar to that of HD and was proven to cause memory impairment in rodents. Phytoestrogens have well-established neuroprotective and memory enhancing effects with fewer side effects in comparison to estrogens. This study investigated the potential neuroprotective and memory enhancing effect of genistein (5, 10 and 20 mg/kg), a phytoestrogen, in ovariectomized rats challenged with 3-NPA (20 mg/kg). These potential effects were compared to those of 17β-estradiol (2.5 mg/kg). Systemic administration of 3-NPA for 4 consecutive days impaired locomotor activity, decreased retention latencies in the passive avoidance task, decreased striatal, cortical and hippocampal ATP levels, increased oxidative stress, acetylcholinesterase (AChE) activity, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Pretreatment with genistein and 17β-estradiol attenuated locomotor hypoactivity, increased retention latencies in the passive avoidance task, increased ATP levels, improved the oxidative stress profile, attenuated the increase in AChE activity and decreased the expression of COX-2 and iNOS. Overall, the higher genistein dose (20 mg/kg) was the most effective. In conclusion, this study suggests neuroprotective and memory enhancing effects for genistein in a rat model of HD. These effects might be attributed to its antioxidant, anti-inflammatory and cholinesterase inhibitory activities.

Bayesian statistics and Monte Carlo methods

NASA Astrophysics Data System (ADS)

Koch, K. R.

2018-03-01

The Bayesian approach allows an intuitive way to derive the methods of statistics. Probability is defined as a measure of the plausibility of statements or propositions. Three rules are sufficient to obtain the laws of probability. If the statements refer to the numerical values of variables, the so-called random variables, univariate and multivariate distributions follow. They lead to the point estimation by which unknown quantities, i.e. unknown parameters, are computed from measurements. The unknown parameters are random variables, they are fixed quantities in traditional statistics which is not founded on Bayes' theorem. Bayesian statistics therefore recommends itself for Monte Carlo methods, which generate random variates from given distributions. Monte Carlo methods, of course, can also be applied in traditional statistics. The unknown parameters, are introduced as functions of the measurements, and the Monte Carlo methods give the covariance matrix and the expectation of these functions. A confidence region is derived where the unknown parameters are situated with a given probability. Following a method of traditional statistics, hypotheses are tested by determining whether a value for an unknown parameter lies inside or outside the confidence region. The error propagation of a random vector by the Monte Carlo methods is presented as an application. If the random vector results from a nonlinearly transformed vector, its covariance matrix and its expectation follow from the Monte Carlo estimate. This saves a considerable amount of derivatives to be computed, and errors of the linearization are avoided. The Monte Carlo method is therefore efficient. If the functions of the measurements are given by a sum of two or more random vectors with different multivariate distributions, the resulting distribution is generally not known. TheMonte Carlo methods are then needed to obtain the covariance matrix and the expectation of the sum.

Copolymers of poly-L-lysine with serine and tryptophan form stable DNA vectors: implications for receptor-mediated gene transfer.

PubMed

Gómez-Valadés, A G; Molas, M; Vidal-Alabró, A; Bermúdez, J; Bartrons, R; Perales, J C

2005-01-20

Inefficient gene transfer and poor stability in physiological medium are important shortcomings for receptor-mediated gene transfer vectors. Here, we evaluate vectors formulated with random copolymers of L-lysine/L-serine (3:1) and L-lysine/L-tryptophan (4:1), focusing on both their biophysical and functional characterization. By means of dynamic light scattering (DLS) and transmission electron microscopy (TEM), we demonstrate that poly-L-lysine (pK), poly-L-lysine-L-tryptophan (pKW) and poly-L-lysine-L-serine (pKS) are able to form compacted, small particles when mixed with plasmid DNA in the absence of salt. Upon dilution in physiological medium, copolymers of both lys/ser and lys/trp do not aggregate, in contrast with poly-L-lysine DNA complexes as determined by scattering, DLS and TEM measurements. Tight packing, as demonstrated by resistance to heparin, SDS and trypsin treatments, is also featured in tryptophan-containing complexes. Successful receptor-mediated endocytosis gene transfer using galactosylated copolymers into cells expressing the asiagloglycoprotein receptor correlated with lack of aggregation. Particles obtained using galactosylated poly-L-lysine-L-tryptophan (Gal-pKW) copolymer demonstrated specific receptor-mediated gene transfer since reporter gene activity dropped in the presence of an excess ligand in the culture medium during transfection. Although copolymers of galactosylated poly-L-lysine-L-serine (Gal-pKS) do not aggregate in the presence of salt, they are not able to internalize in a specific receptor-mediated endocytosis fashion. The introduction of bulky aromatic/hydrophobic (tryptophan) or hydrophillic (serine) moieties into the positively charged vectors allows the compacted particles to disperse into salt-containing medium avoiding salt-induced aggregation. Moreover, tryptophan-containing particles are able to mediate specific gene transfer via receptor-mediated endocytosis.

Errors induced by the neglect of polarization in radiance calculations for Rayleigh-scattering atmospheres

NASA Technical Reports Server (NTRS)

Mishchenko, M. I.; Lacis, A. A.; Travis, L. D.

1994-01-01

Although neglecting polarization and replacing the rigorous vector radiative transfer equation by its approximate scalar counterpart has no physical background, it is a widely used simplification when the incident light is unpolarized and only the intensity of the reflected light is to be computed. We employ accurate vector and scalar multiple-scattering calculations to perform a systematic study of the errors induced by the neglect of polarization in radiance calculations for a homogeneous, plane-parallel Rayleigh-scattering atmosphere (with and without depolarization) above a Lambertian surface. Specifically, we calculate percent errors in the reflected intensity for various directions of light incidence and reflection, optical thicknesses of the atmosphere, single-scattering albedos, depolarization factors, and surface albedos. The numerical data displayed can be used to decide whether or not the scalar approximation may be employed depending on the parameters of the problem. We show that the errors decrease with increasing depolarization factor and/or increasing surface albedo. For conservative or nearly conservative scattering and small surface albedos, the errors are maximum at optical thicknesses of about 1. The calculated errors may be too large for some practical applications, and, therefore, rigorous vector calculations should be employed whenever possible. However, if approximate scalar calculations are used, we recommend to avoid geometries involving phase angles equal or close to 0 deg and 90 deg, where the errors are especially significant. We propose a theoretical explanation of the large vector/scalar differences in the case of Rayleigh scattering. According to this explanation, the differences are caused by the particular structure of the Rayleigh scattering matrix and come from lower-order (except first-order) light scattering paths involving right scattering angles and right-angle rotations of the scattering plane.

Anisotropic cosmological solutions in massive vector theories

NASA Astrophysics Data System (ADS)

Heisenberg, Lavinia; Kase, Ryotaro; Tsujikawa, Shinji

2016-11-01

In beyond-generalized Proca theories including the extension to theories higher than second order, we study the role of a spatial component v of a massive vector field on the anisotropic cosmological background. We show that, as in the case of the isotropic cosmological background, there is no additional ghostly degrees of freedom associated with the Ostrogradski instability. In second-order generalized Proca theories we find the existence of anisotropic solutions on which the ratio between the anisotropic expansion rate Σ and the isotropic expansion rate H remains nearly constant in the radiation-dominated epoch. In the regime where Σ/H is constant, the spatial vector component v works as a dark radiation with the equation of state close to 1/3. During the matter era, the ratio Σ/H decreases with the decrease of v. As long as the conditions |Σ| ll H and v2 ll phi2 are satisfied around the onset of late-time cosmic acceleration, where phi is the temporal vector component, we find that the solutions approach the isotropic de Sitter fixed point (Σ = 0 = v) in accordance with the cosmic no-hair conjecture. In the presence of v and Σ the early evolution of the dark energy equation of state wDE in the radiation era is different from that in the isotropic case, but the approach to the isotropic value wDE(iso) typically occurs at redshifts z much larger than 1. Thus, apart from the existence of dark radiation, the anisotropic cosmological dynamics at low redshifts is similar to that in isotropic generalized Proca theories. In beyond-generalized Proca theories the only consistent solution to avoid the divergence of a determinant of the dynamical system corresponds to v = 0, so Σ always decreases in time.

Virus vector-mediated genetic modification of brain tumor stromal cells after intravenous delivery.

PubMed

Volak, Adrienn; LeRoy, Stanley G; Natasan, Jeya Shree; Park, David J; Cheah, Pike See; Maus, Andreas; Fitzpatrick, Zachary; Hudry, Eloise; Pinkham, Kelsey; Gandhi, Sheetal; Hyman, Bradley T; Mu, Dakai; GuhaSarkar, Dwijit; Stemmer-Rachamimov, Anat O; Sena-Esteves, Miguel; Badr, Christian E; Maguire, Casey A

2018-05-16

The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively. Delivery of transgenes encoding secreted, anti-tumor proteins to tumor stromal cells may provide a more stable and localized reservoir of therapy as they are more differentiated than fast-dividing tumor cells. Reactive astrocytes and tumor-associated macrophage/microglia (TAMs) are stromal cells that comprise a large portion of the tumor mass and are associated with tumorigenesis. In mouse models of GBM, we used IV delivery of exosome-associated AAV vectors driving green fluorescent protein expression by specific promoters (NF-κB-responsive promoter and a truncated glial fibrillary acidic protein promoter), to obtain targeted transduction of TAMs and reactive astrocytes, respectively, while avoiding transgene expression in the periphery. We used our approach to express the potent, yet toxic anti-tumor cytokine, interferon beta, in tumor stroma of a mouse model of GBM, and achieved a modest, yet significant enhancement in survival compared to controls. Noninvasive genetic modification of tumor microenvironment represents a promising approach for therapy against cancers. Additionally, the vectors described here may facilitate basic research in the study of tumor stromal cells in situ.

Anisotropic cosmological solutions in massive vector theories

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

Heisenberg, Lavinia; Kase, Ryotaro; Tsujikawa, Shinji, E-mail: Lavinia.heisenberg@googlemail.com, E-mail: r.kase@rs.tus.ac.jp, E-mail: shinji@rs.kagu.tus.ac.jp

In beyond-generalized Proca theories including the extension to theories higher than second order, we study the role of a spatial component v of a massive vector field on the anisotropic cosmological background. We show that, as in the case of the isotropic cosmological background, there is no additional ghostly degrees of freedom associated with the Ostrogradski instability. In second-order generalized Proca theories we find the existence of anisotropic solutions on which the ratio between the anisotropic expansion rate Σ and the isotropic expansion rate H remains nearly constant in the radiation-dominated epoch. In the regime where Σ/ H is constant,more » the spatial vector component v works as a dark radiation with the equation of state close to 1/3. During the matter era, the ratio Σ/ H decreases with the decrease of v . As long as the conditions |Σ| || H and v {sup 2} || φ{sup 2} are satisfied around the onset of late-time cosmic acceleration, where φ is the temporal vector component, we find that the solutions approach the isotropic de Sitter fixed point (Σ = 0 = v ) in accordance with the cosmic no-hair conjecture. In the presence of v and Σ the early evolution of the dark energy equation of state w {sub DE} in the radiation era is different from that in the isotropic case, but the approach to the isotropic value w {sub DE}{sup (iso)} typically occurs at redshifts z much larger than 1. Thus, apart from the existence of dark radiation, the anisotropic cosmological dynamics at low redshifts is similar to that in isotropic generalized Proca theories. In beyond-generalized Proca theories the only consistent solution to avoid the divergence of a determinant of the dynamical system corresponds to v = 0, so Σ always decreases in time.« less

Simple Method for Markerless Gene Deletion in Multidrug-Resistant Acinetobacter baumannii

PubMed Central

Oh, Man Hwan; Lee, Je Chul; Kim, Jungmin

2015-01-01

The traditional markerless gene deletion technique based on overlap extension PCR has been used for generating gene deletions in multidrug-resistant Acinetobacter baumannii. However, the method is time-consuming because it requires restriction digestion of the PCR products in DNA cloning and the construction of new vectors containing a suitable antibiotic resistance cassette for the selection of A. baumannii merodiploids. Moreover, the availability of restriction sites and the selection of recombinant bacteria harboring the desired chimeric plasmid are limited, making the construction of a chimeric plasmid more difficult. We describe a rapid and easy cloning method for markerless gene deletion in A. baumannii, which has no limitation in the availability of restriction sites and allows for easy selection of the clones carrying the desired chimeric plasmid. Notably, it is not necessary to construct new vectors in our method. This method utilizes direct cloning of blunt-end DNA fragments, in which upstream and downstream regions of the target gene are fused with an antibiotic resistance cassette via overlap extension PCR and are inserted into a blunt-end suicide vector developed for blunt-end cloning. Importantly, the antibiotic resistance cassette is placed outside the downstream region in order to enable easy selection of the recombinants carrying the desired plasmid, to eliminate the antibiotic resistance cassette via homologous recombination, and to avoid the necessity of constructing new vectors. This strategy was successfully applied to functional analysis of the genes associated with iron acquisition by A. baumannii ATCC 19606 and to ompA gene deletion in other A. baumannii strains. Consequently, the proposed method is invaluable for markerless gene deletion in multidrug-resistant A. baumannii. PMID:25746991

Overexpression of heart-type fatty acid binding protein enhances fatty acid-induced podocyte injury.

PubMed

Gao, Qing; Sarkar, Alhossain; Chen, Yizhi; Xu, Bo; Zhu, Xiaojuan; Yuan, Yang; Guan, Tianjun

2018-02-01

Deregulated lipid metabolism is a characteristic of metabolic diseases including type 2 diabetes and obesity, and likely contributes to podocyte injury and end-stage kidney disease. Heart-type fatty acid binding protein (H-FABP) was reported to be associated with lipid metabolism. The present study investigated whether H-FABP contributes to podocyte homeostasis. Podocytes were transfected by lentiviral vector to construct a cell line which stably overexpressed H-FABP. Small interfering RNA capable of effectively silencing H-FABP was introduced into podocytes to construct a cell line with H-FABP knockdown. Certain groups were treated with palmitic acid (PA) and the fat metabolism, as well as inflammatory and oxidative stress markers were measured. PA accelerated lipid metabolism derangement, inflammatory reaction and oxidative stress in podocytes. Overexpression of H-FABP enhanced the PA-induced disequilibrium in podocytes. The mRNA and protein expression levels of acyl-coenzyme A oxidase 3 and monocyte chemotactic protein 1, and the protein expression levels of 8-hydroxy-2'-deoxyguanosine and 4-hydroxynonenal were upregulated in the H-FABP overexpression group, while the mRNA and protein expression of peroxisome proliferator activated receptor α was downregulated. Knockdown of H-FABP inhibited the PA-induced injury and lipid metabolism derangement, as well as the inflammatory reaction and oxidative stress in podocytes. These results indicated that overexpression of H-FABP enhances fatty acid-induced podocyte injury, while H-FABP inhibition may represent a potential therapeutic strategy for the prevention of lipid metabolism-associated podocyte injury.

Nocardia infections among immunomodulated inflammatory bowel disease patients: A review

PubMed Central

Abreu, Cândida; Rocha-Pereira, Nuno; Sarmento, António; Magro, Fernando

2015-01-01

Human nocardiosis, caused by Nocardia spp., an ubiquitous soil-borne bacteria, is a rare granulomatous disease close related to immune dysfunctions. Clinically can occur as an acute life-threatening disease, with lung, brain and skin being commonly affected. The infection was classically diagnosed in HIV infected persons, organ transplanted recipients and long term corticosteroid treated patients. Currently the widespread use of immunomodulators and immunossupressors in the treatment of inflammatory diseases changed this scenario. Our purpose is to review all published cases of nocardiosis in immunomodulated patients due to inflammatory diseases and describe clinical and laboratory findings. We reviewed the literature concerning human cases of nocardiosis published between 1980 and 2014 in peer reviewed journals. Eleven cases of nocardiosis associated with anti-tumor necrosis factor (TNF) prescription (9 related with infliximab and 2 with adalimumab) were identified; 7 patients had inflammatory bowel disease (IBD), 4 had rheumatological conditions; nocardia infection presented as cutaneous involvement in 3 patients, lung disease in 4 patients, hepatic in one and disseminated disease in 3 patients. From the 10 cases described in IBD patients 7 were associated with anti-TNF and 3 with steroids and azathioprine. In conclusion, nocardiosis requires high levels of clinical suspicion and experience of laboratory staff, in order to establish a timely diagnosis and by doing so avoid worst outcomes. Treatment for long periods tailored by the susceptibility of the isolated species whenever possible is essential. The safety of restarting immunomodulators or anti-TNF after the disease or the value of prophylaxis with cotrimoxazole is still debated. PMID:26074688

Economic evaluation of the restriction in the use piroxicam in Spain.

PubMed

Maciá Martínez, Miguel-Ángel

2015-01-01

A retrospective economic evaluation was performed on the restriction of the use of piroxicam in Spain, a non-steroidal anti-inflammatory drug, with a proven higher risk of serious gastrointestinal complications compared to other non-steroidal anti-inflammatory drugs with the objective of putting the relevance of these activities into context. A retrospective cost-effectiveness analysis and a budget impact analysis were performed. Costs and cases of serious gastrointestinal complications were compared in the non-intervention (use of piroxicam) and the intervention scenarios (use of other non-steroidal anti-inflammatory drugs). The cost of serious gastrointestinal complications was obtained from the Diagnosis Related Groups and the cost of non-steroidal anti-inflammatory drugs from usage data in the Spanish national health system. The risk of serious gastrointestinal complications was obtained from epidemiological studies. The regulatory intervention was the dominant option. In that sense, 0.81 euros per treated patient were saved, 2.75 cases of serious gastrointestinal complications were avoided per 10,000 patients and 578,608 euros were saved in total in Spain in the first year following the intervention. It is possible to perform complete economical evaluations on pharmacovigilance actions. The intervention performed by the Spanish Agency for Medicines and Medical Devices, AEMPS on piroxicam not only achieved the objective of preventing adverse drug reactions but also resulted in significant economical savings even under conservative assumptions. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Smuggling across the border: how arthropod-borne pathogens evade and exploit the host defense system of the skin.

PubMed

Bernard, Quentin; Jaulhac, Benoit; Boulanger, Nathalie

2014-05-01

The skin is a critical barrier between hosts and pathogens in arthropod-borne diseases. It harbors many resident cells and specific immune cells to arrest or limit infections by secreting inflammatory molecules or by directly killing pathogens. However, some pathogens are able to use specific skin cells and arthropod saliva for their initial development, to hide from the host immune system, and to establish persistent infection in the vertebrate host. A better understanding of the initial mechanisms taking place in the skin should allow the development of new strategies to fight these vector-borne pathogens that are spread worldwide and are of major medical importance.

SCIENCE PARAMETRICS FOR MISSIONS TO SEARCH FOR EARTH-LIKE EXOPLANETS BY DIRECT IMAGING

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

Brown, Robert A., E-mail: rbrown@stsci.edu

2015-01-20

We use N{sub t} , the number of exoplanets observed in time t, as a science metric to study direct-search missions like Terrestrial Planet Finder. In our model, N has 27 parameters, divided into three categories: 2 astronomical, 7 instrumental, and 18 science-operational. For various ''27-vectors'' of those parameters chosen to explore parameter space, we compute design reference missions to estimate N{sub t} . Our treatment includes the recovery of completeness c after a search observation, for revisits, solar and antisolar avoidance, observational overhead, and follow-on spectroscopy. Our baseline 27-vector has aperture D = 16 m, inner working angle IWAmore » = 0.039'', mission time t = 0-5 yr, occurrence probability for Earth-like exoplanets η = 0.2, and typical values for the remaining 23 parameters. For the baseline case, a typical five-year design reference mission has an input catalog of ∼4700 stars with nonzero completeness, ∼1300 unique stars observed in ∼2600 observations, of which ∼1300 are revisits, and it produces N {sub 1} ∼ 50 exoplanets after one year and N {sub 5} ∼ 130 after five years. We explore offsets from the baseline for 10 parameters. We find that N depends strongly on IWA and only weakly on D. It also depends only weakly on zodiacal light for Z < 50 zodis, end-to-end efficiency for h > 0.2, and scattered starlight for ζ < 10{sup –10}. We find that observational overheads, completeness recovery and revisits, solar and antisolar avoidance, and follow-on spectroscopy are all important factors in estimating N.« less

Flight Mechanics and Control Requirements for a Modular Solar Electric Tug Operating in Earth-Moon Space

NASA Astrophysics Data System (ADS)

Woodcock, Gordon; Wingo, Dennis

2006-01-01

A modular design for a solar-electric tug was analyzed to establish flight control requirements and methods. Thrusters are distributed around the periphery of the solar array. This design enables modules to be berthed together to create a larger system from smaller modules. It requires a different flight mode than traditional design and a different thrust direction scheme, to achieve net thrust in the desired direction, observe thruster pointing constraints that avoid plume impingement on the tug, and balance moments. The array is perpendicular to the Sun vector for maximum electric power. The tug may maintain a constant inertial attitude or rotate around the Sun vector once per orbit. Either non-rotating or constant angular velocity rotation offers advantages over the conventional flight mode, which has highly variable roll rates. The baseline single module has 12 thrusters: two 2-axis gimbaling main thrusters, one at each ``end'', and two back-to-back Z axis thrusters at each corner of the array. Thruster pointing and throttling were optimized to maximize net thrust effectiveness while observing constraints. Control design used a spread sheet with Excel Solver to calculate nominal thruster pointing and throttling. These results are used to create lookup tables. A conventional control system generates a thruster pointing and throttling overlay on the nominals to maintain active attitude control. Gravity gradients can cause major attitude perturbations during occultation periods if thrust is off during these periods. Thrust required to maintain attitude is about 4% of system rated power. This amount of power can be delivered by a battery system, avoiding the performance penalty if chemical propulsion thrusters were used to maintain attitude.

Geodesic synchrotron radiation in the Kerr geometry by the method of asymptotically factorized Green's functions

NASA Technical Reports Server (NTRS)

Chrzanowski, P. L.; Misner, C. W.

1974-01-01

The scalar, electromagnetic, and gravitational geodesic-synchrotron-radiation (GSR) spectra are determined for the case of a test particle moving on a highly relativistic circular orbit about a rotating (Kerr) black hole. It is found that the spectral shape depends only weakly on the value of the angular-momentum parameter (a/M) of the black hole, but the total radiated power drops unexpectedly for a value of at least 0.95 and vanishes as the value approaches unity. A spin-dependent factor (involving the inner product of the polarization of a radiated quantum with the source) is isolated to explain the dependence of the spectral shape on the spin of the radiated field. Although the scalar wave equation is solved by separation of variables, this procedure is avoided for the vector and tensor cases by postulating a sum-over-states expansion for the Green's function similar to that found to hold in the scalar case. The terms in this sum, significant for GSR, can then be evaluated in the geometric-optics approximation without requiring the use of vector or tensor spherical harmonics.

A versatile and efficient high-throughput cloning tool for structural biology.

PubMed

Geertsma, Eric R; Dutzler, Raimund

2011-04-19

Methods for the cloning of large numbers of open reading frames into expression vectors are of critical importance for challenging structural biology projects. Here we describe a system termed fragment exchange (FX) cloning that facilitates the high-throughput generation of expression constructs. The method is based on a class IIS restriction enzyme and negative selection markers. FX cloning combines attractive features of established recombination- and ligation-independent cloning methods: It allows the straightforward transfer of an open reading frame into a variety of expression vectors and is highly efficient and very economic in its use. In addition, FX cloning avoids the common but undesirable feature of significantly extending target open reading frames with cloning related sequences, as it leaves a minimal seam of only a single extra amino acid to either side of the protein. The method has proven to be very robust and suitable for all common pro- and eukaryotic expression systems. It considerably speeds up the generation of expression constructs compared to traditional methods and thus facilitates a broader expression screening.

Polyethylenimine functionalized magnetic nanoparticles as a potential non-viral vector for gene delivery.

PubMed

Zhou, Yangbo; Tang, Zhaomin; Shi, Chunli; Shi, Shuai; Qian, Zhiyong; Zhou, Shaobing

2012-11-01

Polyethylenimine (PEI) functionalized magnetic nanoparticles were synthesized as a potential non-viral vector for gene delivery. The nanoparticles could provide the magnetic-targeting, and the cationic polymer PEI could condense DNA and avoid in vitro barriers. The magnetic nanoparticles were characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, dynamic light scattering measurements, transmission electron microscopy, vibrating sample magnetometer and atomic force microscopy. Agarose gel electrophoresis was used to asses DNA binding and perform a DNase I protection assay. The Alamar blue assay was used to evaluate negative effects on the metabolic activity of cells incubated with PEI modified magnetic nanoparticles and their complexes with DNA both in the presence or absence of an external magnetic field. Flow cytometry and fluorescent microscopy were also performed to investigate the transfection efficiency of the DNA-loaded magnetic nanoparticles in A549 and B16-F10 tumor cells with (+M) or without (-M) the magnetic field. The in vitro transfection efficiency of magnetic nanoparticles was improved obviously in a permanent magnetic field. Therefore, the magnetic nanoparticles show considerable potential as nanocarriers for gene delivery.

Automated detection of pulmonary nodules in CT images with support vector machines

NASA Astrophysics Data System (ADS)

Liu, Lu; Liu, Wanyu; Sun, Xiaoming

2008-10-01

Many methods have been proposed to avoid radiologists fail to diagnose small pulmonary nodules. Recently, support vector machines (SVMs) had received an increasing attention for pattern recognition. In this paper, we present a computerized system aimed at pulmonary nodules detection; it identifies the lung field, extracts a set of candidate regions with a high sensitivity ratio and then classifies candidates by the use of SVMs. The Computer Aided Diagnosis (CAD) system presented in this paper supports the diagnosis of pulmonary nodules from Computed Tomography (CT) images as inflammation, tuberculoma, granuloma..sclerosing hemangioma, and malignant tumor. Five texture feature sets were extracted for each lesion, while a genetic algorithm based feature selection method was applied to identify the most robust features. The selected feature set was fed into an ensemble of SVMs classifiers. The achieved classification performance was 100%, 92.75% and 90.23% in the training, validation and testing set, respectively. It is concluded that computerized analysis of medical images in combination with artificial intelligence can be used in clinical practice and may contribute to more efficient diagnosis.

Trochoidal X-ray Vector Radiography: Directional dark-field without grating stepping

NASA Astrophysics Data System (ADS)

Sharma, Y.; Bachche, S.; Kageyama, M.; Kuribayashi, M.; Pfeiffer, F.; Lasser, T.; Momose, A.

2018-03-01

X-ray Vector Radiography (XVR) is an imaging technique that reveals the orientations of sub-pixel sized structures within a sample. Several dark-field radiographs are acquired by rotating the sample around the beam propagation direction and stepping one of the gratings to several positions for every pose of the sample in an X-ray grating interferometry setup. In this letter, we present a method of performing XVR of a continuously moving sample without the need of any grating motion. We reconstruct the orientations within a sample by analyzing the change in the background moire fringes caused by the sample moving and simultaneously rotating in plane (trochoidal trajectory) across the detector field-of-view. Avoiding the motion of gratings provides significant advantages in terms of stability and repeatability, while the continuous motion of the sample makes this kind of system adaptable for industrial applications such as the scanning of samples on a conveyor belt. Being the first step in the direction of utilizing advanced sample trajectories to replace grating motion, this work also lays the foundations for a full three dimensional reconstruction of scattering function without grating motion.

Multivariate statistical analysis strategy for multiple misfire detection in internal combustion engines

NASA Astrophysics Data System (ADS)

Hu, Chongqing; Li, Aihua; Zhao, Xingyang

2011-02-01

This paper proposes a multivariate statistical analysis approach to processing the instantaneous engine speed signal for the purpose of locating multiple misfire events in internal combustion engines. The state of each cylinder is described with a characteristic vector extracted from the instantaneous engine speed signal following a three-step procedure. These characteristic vectors are considered as the values of various procedure parameters of an engine cycle. Therefore, determination of occurrence of misfire events and identification of misfiring cylinders can be accomplished by a principal component analysis (PCA) based pattern recognition methodology. The proposed algorithm can be implemented easily in practice because the threshold can be defined adaptively without the information of operating conditions. Besides, the effect of torsional vibration on the engine speed waveform is interpreted as the presence of super powerful cylinder, which is also isolated by the algorithm. The misfiring cylinder and the super powerful cylinder are often adjacent in the firing sequence, thus missing detections and false alarms can be avoided effectively by checking the relationship between the cylinders.

Stem cell gene therapy for fanconi anemia: report from the 1st international Fanconi anemia gene therapy working group meeting.

PubMed

Tolar, Jakub; Adair, Jennifer E; Antoniou, Michael; Bartholomae, Cynthia C; Becker, Pamela S; Blazar, Bruce R; Bueren, Juan; Carroll, Thomas; Cavazzana-Calvo, Marina; Clapp, D Wade; Dalgleish, Robert; Galy, Anne; Gaspar, H Bobby; Hanenberg, Helmut; Von Kalle, Christof; Kiem, Hans-Peter; Lindeman, Dirk; Naldini, Luigi; Navarro, Susana; Renella, Raffaele; Rio, Paula; Sevilla, Julián; Schmidt, Manfred; Verhoeyen, Els; Wagner, John E; Williams, David A; Thrasher, Adrian J

2011-07-01

Survival rates after allogeneic hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) have increased dramatically since 2000. However, the use of autologous stem cell gene therapy, whereby the patient's own blood stem cells are modified to express the wild-type gene product, could potentially avoid the early and late complications of allogeneic HCT. Over the last decades, gene therapy has experienced a high degree of optimism interrupted by periods of diminished expectation. Optimism stems from recent examples of successful gene correction in several congenital immunodeficiencies, whereas diminished expectations come from the realization that gene therapy will not be free of side effects. The goal of the 1st International Fanconi Anemia Gene Therapy Working Group Meeting was to determine the optimal strategy for moving stem cell gene therapy into clinical trials for individuals with FA. To this end, key investigators examined vector design, transduction method, criteria for large-scale clinical-grade vector manufacture, hematopoietic cell preparation, and eligibility criteria for FA patients most likely to benefit. The report summarizes the roadmap for the development of gene therapy for FA.

Offline handwritten word recognition using MQDF-HMMs

NASA Astrophysics Data System (ADS)

Ramachandrula, Sitaram; Hambarde, Mangesh; Patial, Ajay; Sahoo, Dushyant; Kochar, Shaivi

2015-01-01

We propose an improved HMM formulation for offline handwriting recognition (HWR). The main contribution of this work is using modified quadratic discriminant function (MQDF) [1] within HMM framework. In an MQDF-HMM the state observation likelihood is calculated by a weighted combination of MQDF likelihoods of individual Gaussians of GMM (Gaussian Mixture Model). The quadratic discriminant function (QDF) of a multivariate Gaussian can be rewritten by avoiding the inverse of covariance matrix by using the Eigen values and Eigen vectors of it. The MQDF is derived from QDF by substituting few of badly estimated lower-most Eigen values by an appropriate constant. The estimation errors of non-dominant Eigen vectors and Eigen values of covariance matrix for which the training data is insufficient can be controlled by this approach. MQDF has been successfully shown to improve the character recognition performance [1]. The usage of MQDF in HMM improves the computation, storage and modeling power of HMM when there is limited training data. We have got encouraging results on offline handwritten character (NIST database) and word recognition in English using MQDF HMMs.

Embedded 3D shape measurement system based on a novel spatio-temporal coding method

NASA Astrophysics Data System (ADS)

Xu, Bin; Tian, Jindong; Tian, Yong; Li, Dong

2016-11-01

Structured light measurement has been wildly used since 1970s in industrial component detection, reverse engineering, 3D molding, robot navigation, medical and many other fields. In order to satisfy the demand for high speed, high precision and high resolution 3-D measurement for embedded system, a new patterns combining binary and gray coding principle in space are designed and projected onto the object surface orderly. Each pixel corresponds to the designed sequence of gray values in time - domain, which is treated as a feature vector. The unique gray vector is then dimensionally reduced to a scalar which could be used as characteristic information for binocular matching. In this method, the number of projected structured light patterns is reduced, and the time-consuming phase unwrapping in traditional phase shift methods is avoided. This algorithm is eventually implemented on DM3730 embedded system for 3-D measuring, which consists of an ARM and a DSP core and has a strong capability of digital signal processing. Experimental results demonstrated the feasibility of the proposed method.

Maiden outbreaks of dengue virus 1 genotype III in rural central India.

PubMed

Barde, P V; Kori, B K; Shukla, M K; Bharti, P K; Chand, G; Kumar, G; Ukey, M J; Ali, N A; Singh, N

2015-01-01

Dengue is regarded as the most important arboviral disease. Although sporadic cases have been reported, serotypes responsible for outbreaks have not been identified from central India over the last 20 years. We investigated two outbreaks of febrile illness, in August and November 2012, from Korea district (Chhattisgarh) and Narsinghpur district (Madhya Pradesh), respectively. Fever and entomological surveys were conducted in the affected regions. Molecular and serological tests were conducted on collected serum samples. Dengue-specific amplicons were sequenced and phylogenetic analyses were performed. In Korea and Narsinghpur districts 37·3% and 59% of cases were positive, respectively, for dengue infection, with adults being the worst affected. RT-PCR confirmed dengue virus serotype 1 genotype III as the aetiology. Ninety-six percent of infections were primary. This is the first time that dengue virus 1 outbreaks have been documented from central India. Introduction of the virus into the population and a conducive mosquitogenic environment favouring increased vector density caused the outbreak. Timely diagnosis and strengthening vector control measures are essential to avoid future outbreaks.

Ranking Support Vector Machine with Kernel Approximation

PubMed Central

Dou, Yong

2017-01-01

Learning to rank algorithm has become important in recent years due to its successful application in information retrieval, recommender system, and computational biology, and so forth. Ranking support vector machine (RankSVM) is one of the state-of-art ranking models and has been favorably used. Nonlinear RankSVM (RankSVM with nonlinear kernels) can give higher accuracy than linear RankSVM (RankSVM with a linear kernel) for complex nonlinear ranking problem. However, the learning methods for nonlinear RankSVM are still time-consuming because of the calculation of kernel matrix. In this paper, we propose a fast ranking algorithm based on kernel approximation to avoid computing the kernel matrix. We explore two types of kernel approximation methods, namely, the Nyström method and random Fourier features. Primal truncated Newton method is used to optimize the pairwise L2-loss (squared Hinge-loss) objective function of the ranking model after the nonlinear kernel approximation. Experimental results demonstrate that our proposed method gets a much faster training speed than kernel RankSVM and achieves comparable or better performance over state-of-the-art ranking algorithms. PMID:28293256

Ranking Support Vector Machine with Kernel Approximation.

PubMed

Chen, Kai; Li, Rongchun; Dou, Yong; Liang, Zhengfa; Lv, Qi

2017-01-01

Learning to rank algorithm has become important in recent years due to its successful application in information retrieval, recommender system, and computational biology, and so forth. Ranking support vector machine (RankSVM) is one of the state-of-art ranking models and has been favorably used. Nonlinear RankSVM (RankSVM with nonlinear kernels) can give higher accuracy than linear RankSVM (RankSVM with a linear kernel) for complex nonlinear ranking problem. However, the learning methods for nonlinear RankSVM are still time-consuming because of the calculation of kernel matrix. In this paper, we propose a fast ranking algorithm based on kernel approximation to avoid computing the kernel matrix. We explore two types of kernel approximation methods, namely, the Nyström method and random Fourier features. Primal truncated Newton method is used to optimize the pairwise L2-loss (squared Hinge-loss) objective function of the ranking model after the nonlinear kernel approximation. Experimental results demonstrate that our proposed method gets a much faster training speed than kernel RankSVM and achieves comparable or better performance over state-of-the-art ranking algorithms.