976 resultados para EXPERIMENTAL CONCURRENT INFECTION


Relevância:

30.00% 30.00%

Publicador:

Resumo:

Thesis (Ph.D.)--University of Washington, 2016-04

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Targeted inhibition of oncogenes in tumor cells is a rational approach toward the development of cancer therapies based on RNA interference (RNAi). Tumors caused by human papillomavirus (HPV) infection are an ideal model system for RNAi-based cancer therapies because the oncogenes that cause cervical cancer, E6 and E7, are expressed only in cancerous cells. We investigated whether targeting HPV E6 and E7 oncogenes yields cancer cells more sensitive to chemotherapy by cisplatin, the chemotherapeutic agent currently used for the treatment of advanced cervical cancer. We have designed siRNAs directed against the HPV E6 oncogene that simultaneously targets both E6 and E7, which results in an 80% reduction in E7 protein and reactivation of the p53 pathway. The loss of E6 and E7 resulted in a reduction in cellular viability concurrent with the induction of cellular senescence. Interference was specific in that no effect on HPV-negative cells was observed. We demonstrate that RNAi against E6 and E7 oncogenes enhances the chemotherapeutic effect of cisplatin in HeLa cells. The IC50 for HeLa cells treated with cisplatin was 9.4 mu M, but after the addition of a lentivirus-delivered shRNA against E6, the IC50 was reduced almost 4-fold to 2.4 mu M. We also observed a decrease in E7 expression with a concurrent increase in p53 protein levels upon cotreatment with shRNA and cisplatin over that seen with individual treatment alone. Our results provide strong evidence that loss of E6 and E7 results in increased sensitivity to cisplatin, probably because of increased p53 levels.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

We have investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting group A streptococcal (GAS) vaccine delivery approach. LCP constructs were synthesised incorporating peptides from the M protein conserved carboxy terminal C-repeat region, the amino terminal type-specific region and from both of these regions. Immunisation with the constructs without adjuvant led to the induction of peptide-specific serum IgG antibody responses, heterologous opsonic antibodies, and complete protection from GAS infection. These data indicate that protective immunity to GAS infection can be evoked using the self-adjuvanting LCP system, and point to the potential application of this system in human mucosal GAS vaccine development. (c) 2005 Elsevier Ltd. All rights reserved.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Changes in heart rate (f(H)) and cloacal ventilation frequency (f(C)) were investigated in the Fitzroy turtle, Rheodytes leukops, under normoxic (17.85 kPa) and hypoxic (3.79 kPa) conditions at 25 degrees C. Given R. leukops' high reliance on aquatic respiration via the cloacal bursae, the objective Of this Study was to examine the effect of varying aquatic PO2 levels upon the expression of a bradycardia in a freely diving, bimodally respiring turtle. In normoxia, mean diving f(H) and f(C) for R. leukops remained constant with increasing submergence length, indicating that a bradycardia failed to develop during extended dives of up to 3 days. Alternatively, exposure to aquatic hypoxia resulted in the expression of a bradycardia as recorded by a decreasing mean diving f(H) with increasing dive duration. The observed bradycardia is attributed to a hypoxic-induced metabolic depression, possibly facilitated by a concurrent decrease in f(C). Results suggest that R. leukops alters its strategy from aquatic O-2 extraction via cloacal respiration in normoxia to O-2 conservation when exposed to aquatic hypoxia for the purpose of extending dive duration. Upon surfacing, a significant tachycardia was observed for R. leukops regardless of aquatic PO2, presumably functioning to rapidly equilibrate blood and tissue gas tensions with alveolar gas to reduce surfacing duration.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Recent literature has argued that whereas remembering the past and imagining the future make use of shared cognitive substrates, simulating future events places heavier demands on executive resources. These propositions were explored in 3 experiments comparing the impact of imagery and concurrent task demands on speed and accuracy of past event retrieval and future event simulation. Results provide support for the suggestion that both past and future episodes can be constructed through 2 mechanisms: a noneffortful "direct" pathway and a controlled, effortful "generative" pathway. However, limited evidence emerged for the suggestion that simulating of future, compared with retrieving past, episodes places heavier demands on executive resources; only under certain conditions did it emerge as a more error prone and lengthier process. The findings are discussed in terms of how retrieval and simulation make use of the same cognitive substrates in subtly different ways. © 2011 American Psychological Association.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

This series of 5 single-subject studies used the operant conditioning paradigm to investigate, within the two-way influence process, how (a) contingent infant attention can reinforce maternal verbal behaviors during a period of mother-infant interaction and under subsequent experimental manipulation. Differential reinforcement was used to determine if it is possible that an infant attending to the mother (denoted by head-turns towards the image of the mother plus eye contact) increases (reinforces) the mother's verbal response (to a cue from the infant) upon which the infant behavior is contingent. There was also (b) an evaluation during the contrived parent-infant interaction for concurrent operant learning of infant vocal behavior via contingent verbal responding (reinforcement) implemented by the mother. Further, it was noted (c) whether or not the mother reported being aware that her responses were influenced by the infant's behavior. Findings showed: the operant conditioning of the maternal verbal behaviors were reinforced by contingent infant attention; and the operant conditioning of infant vocalizations was reinforced by contingent maternal verbal behaviors. No parent reported (1) being aware of the increase in their verbal response reinforced during operant conditioning of parental behavior nor a decrease in those responses during the DRA reversal phase, or (2) noticing a contingency between infant's and mother's response. By binomial 1-tail tests, the verbal-behavior patterns of the 5 mothers were conditioned by infant reinforcement (p < 0.02) and, concurrently, the vocal-response patterns of the 5 infants were conditioned by maternal reinforcement (p < 0.02). A program of systematic empirical research on the determinants of concurrent conditioning within mother-child interaction may provide a way to evaluate the differential effectiveness of interventions aimed at improving parent-child interactions. The work conducted in the present study is one step in this direction. ^

Relevância:

30.00% 30.00%

Publicador:

Resumo:

A large series of laboratory ice crushing experiments was performed to investigate the effects of external boundary condition and indenter contact geometry on ice load magnitude under crushing conditions. Four boundary conditions were considered: dry cases, submerged cases, and cases with the presence of snow and granular ice material on the indenter surface. Indenter geometries were a flat plate, wedge shaped indenter, (reverse) conical indenter, and spherical indenter. These were impacted with artificially produced ice specimens of conical shape with 20° and 30° cone angles. All indenter – ice combinations were tested in dry and submerged environments at 1 mm/s and 100 mm/s indentation rates. Additional tests with the flat indentation plate were conducted at 10 mm/s impact velocity and a subset of scenarios with snow and granular ice material was evaluated. The tests were performed using a material testing system (MTS) machine located inside a cold room at an ambient temperature of - 7°C. Data acquisition comprised time, vertical force, and displacement. In several tests with the flat plate and wedge shaped indenter, supplementary information on local pressure patterns and contact area were obtained using tactile pressure sensors. All tests were recorded with a high speed video camera and still photos were taken before and after each test. Thin sections were taken of some specimens as well. Ice loads were found to strongly depend on contact condition, interrelated with pre-existing confinement and indentation rate. Submergence yielded higher forces, especially at the high indentation rate. This was very evident for the flat indentation plate and spherical indenter, and with restrictions for the wedge shaped indenter. No indication was found for the conical indenter. For the conical indenter it was concluded that the structural restriction due to the indenter geometry was dominating. The working surface for the water to act was not sufficient to influence the failure processes and associated ice loads. The presence of snow and granular ice significantly increased the forces at the low indentation rate (with the flat indentation plate) that were higher compared to submerged cases and far above the dry contact condition. Contact area measurements revealed a correlation of higher forces with a concurrent increase in actual contact area that depended on the respective boundary condition. In submergence, ice debris constitution was changed; ice extrusion, as well as crack development and propagation were impeded. Snow and granular ice seemed to provide additional material sources for establishing larger contact areas. The dry contact condition generally had the smallest real contact area, as well as the lowest forces. The comparison of nominal and measured contact areas revealed distinct deviations. The incorporation of those differences in contact process pressures-area relationships indicated that the overall process pressure was not substantially affected by the increased loads.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Trypanosma cruzi is the causative agent of Chagas disease. This trypanosomiasis has become a global public health problem due to migration of Latin Americans to non-endemic countries. In Latin America with the succesful implementation of control domiciliated vector infestation and blood transfusion, the importance of congenital transmission has recently increased. Considering the tight regulation of immune system during gestation, we aimed to investigate the changes in the immune system caused by T.cruzi infection in the gestation outcome. T cruzi G and Y strain were used to infect female BALB/c mice before or after mating with non-infected male mice. The presence of vaginal plug was used as indicative of mating. Females were euthanized 8 days after confirmation of vaginal plug. We used three female control groups, only infected, only infected and non-infected and non-pregnant females. Two groups were infected before mating and other two were infected 4 days after confirmation of vaginal plug. The uterus and spleen were collected to immunochemistry, qPCR, immunofluorescence and cytokine analysis. Our results showed that despite the MMP’s identification being similarly among groups, T.cruzi higher virulent strain can impaire gestation outcome prior mating; the infection also increased cytokines like IFN-γ, IL-1β and IL-4; and leucocytes in uterine environment was altered, responding locally to systemic changes caused by T.cruzi infection. In conclusion this work suggests that T.cruzi infection can impaire gestation outcome and local response to sistemic infection was able to control the infection allowing pregnancy development in some conditions.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Current interest in measuring quality of life is generating interest in the construction of computerized adaptive tests (CATs) with Likert-type items. Calibration of an item bank for use in CAT requires collecting responses to a large number of candidate items. However, the number is usually too large to administer to each subject in the calibration sample. The concurrent anchor-item design solves this problem by splitting the items into separate subtests, with some common items across subtests; then administering each subtest to a different sample; and finally running estimation algorithms once on the aggregated data array, from which a substantial number of responses are then missing. Although the use of anchor-item designs is widespread, the consequences of several configuration decisions on the accuracy of parameter estimates have never been studied in the polytomous case. The present study addresses this question by simulation, comparing the outcomes of several alternatives on the configuration of the anchor-item design. The factors defining variants of the anchor-item design are (a) subtest size, (b) balance of common and unique items per subtest, (c) characteristics of the common items, and (d) criteria for the distribution of unique items across subtests. The results of this study indicate that maximizing accuracy in item parameter recovery requires subtests of the largest possible number of items and the smallest possible number of common items; the characteristics of the common items and the criterion for distribution of unique items do not affect accuracy.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. Though usually self-limited, it can be severe and debilitating. Little is known about the host transcriptional response to infection. We report the first gene expression analysis of the human host response to experimental challenge with ETEC. METHODS: We challenged 30 healthy adults with an unattenuated ETEC strain, and collected serial blood samples shortly after inoculation and daily for 8 days. We performed gene expression analysis on whole peripheral blood RNA samples from subjects in whom severe symptoms developed (n = 6) and a subset of those who remained asymptomatic (n = 6) despite shedding. RESULTS: Compared with baseline, symptomatic subjects demonstrated significantly different expression of 406 genes highlighting increased immune response and decreased protein synthesis. Compared with asymptomatic subjects, symptomatic subjects differentially expressed 254 genes primarily associated with immune response. This comparison also revealed 29 genes differentially expressed between groups at baseline, suggesting innate resilience to infection. Drug repositioning analysis identified several drug classes with potential utility in augmenting immune response or mitigating symptoms. CONCLUSIONS: There are statistically significant and biologically plausible differences in host gene expression induced by ETEC infection. Differential baseline expression of some genes may indicate resilience to infection.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Simultaneous Localization and Mapping (SLAM) is a procedure used to determine the location of a mobile vehicle in an unknown environment, while constructing a map of the unknown environment at the same time. Mobile platforms, which make use of SLAM algorithms, have industrial applications in autonomous maintenance, such as the inspection of flaws and defects in oil pipelines and storage tanks. A typical SLAM consists of four main components, namely, experimental setup (data gathering), vehicle pose estimation, feature extraction, and filtering. Feature extraction is the process of realizing significant features from the unknown environment such as corners, edges, walls, and interior features. In this work, an original feature extraction algorithm specific to distance measurements obtained through SONAR sensor data is presented. This algorithm has been constructed by combining the SONAR Salient Feature Extraction Algorithm and the Triangulation Hough Based Fusion with point-in-polygon detection. The reconstructed maps obtained through simulations and experimental data with the fusion algorithm are compared to the maps obtained with existing feature extraction algorithms. Based on the results obtained, it is suggested that the proposed algorithm can be employed as an option for data obtained from SONAR sensors in environment, where other forms of sensing are not viable. The algorithm fusion for feature extraction requires the vehicle pose estimation as an input, which is obtained from a vehicle pose estimation model. For the vehicle pose estimation, the author uses sensor integration to estimate the pose of the mobile vehicle. Different combinations of these sensors are studied (e.g., encoder, gyroscope, or encoder and gyroscope). The different sensor fusion techniques for the pose estimation are experimentally studied and compared. The vehicle pose estimation model, which produces the least amount of error, is used to generate inputs for the feature extraction algorithm fusion. In the experimental studies, two different environmental configurations are used, one without interior features and another one with two interior features. Numerical and experimental findings are discussed. Finally, the SLAM algorithm is implemented along with the algorithms for feature extraction and vehicle pose estimation. Three different cases are experimentally studied, with the floor of the environment intentionally altered to induce slipping. Results obtained for implementations with and without SLAM are compared and discussed. The present work represents a step towards the realization of autonomous inspection platforms for performing concurrent localization and mapping in harsh environments.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, which shares many similarities with its human counterpart, human immunodeficiency virus (HIV). FIV infects its main target cell, the CD4+ T lymphocyte, via interactions with its primary receptor CD134 (an activation marker expressed on activated CD4+ T lymphocytes), and, the chemokine receptor CXCR4. According to the different ways in which FIV isolates interact with CD134, FIV may be categorised into two groups. The first group contains strains that tend to dominate during the earlier phase of infection, such as GL8 and CPG41. These strains are characterized by their requirement for an additional interaction with the second cysteine rich domain (CRD2) of the CD134 molecule and are classified as “CRD2-dependent” strains. The second group, on the other hand, contains either laboratory-adapted isolates or isolates that emerge after several years of infection, such as PPR or the GL8 variants that emerged in cats 6 years post experimental infection and were studied in this thesis. These isolates are designated “CRD2-independent” as they can infect target cells without interacting with CRD2 of the CD134 molecule. This study provides the first evidence that FIV compartmentalisation is related to FIV-CD134 usage and the tissue availability of CD134+ target cells. In tissue compartments containing high levels of CD134+ cells such as peripheral blood and lymph nodes, CRD2-dependent viruses predominated, whereas CRD2-independent viruses predominated in compartments with fewer CD134+ cells, such as the thymus. The dynamics of CD4+CD134+ T lymphocytes at different stages of FIV infection were also described. The levels of CD4+CD134+ T lymphocytes, which were very high in the early phase, gradually decreased in the later phase of infection. The dynamics of CD4+CD134+ T lymphocyte numbers appeared to correlate with FIV tropism switching, as more CRD2-independent viruses were isolated from cats in the late phase of infection. Moreover, it was observed that pseudotypes bearing Envs of CRD2-dependent variants infected CD134+ target cells more efficiently than pseudotypes bearing Envs of CRD2-independent variants, confirming the selective advantage of CRD2-dependent variants in environments with high levels of CD134+ target cells. In conclusion, this study demonstrated that target cell types and numbers, as well as their dynamics, play important roles in the selection and expansion of FIV variants within the viral quasispecies. Improved understanding of the roles of target cells in FIV transmission and pathogenesis will provide important information required for the development of an improved, more successful protective FIV vaccine and will provide insight into the development of effective vaccines against other lentiviral infections such as HIV.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The pathogenecity of white spot syndrome virus (WSV) was studied experimentally with challenge exposure of two hundred shrimp with average weight 10 to 12 grams of Litopenaeus vannamei. The shrimp L. vannamei before introducing examined with IQ 2000 detection Kit for WSV. The Fenneropenaeus indicus that showed the clinical sign and PCR positive of white spot disease (WSD) was used the source of WSV. The challenge exposures were accomplished by feeding minced tissue of F. indicus for 24 hours. The result showed L. vannamei after three days revealed the clinical sign of WSV, the PCR examined was positive and all shrimp died after ten days. The shrimp that showed sign of disease were collected for histpathology in Davidson fixator and a part of samples preserved in Ethyl alcohol %75to %90 for PCR. The histopathology showed the effect of virus and cowdly type A inclusion body can see in all tissue except hepatopancreas. The PCR also indicate the virus infected the shrimp Litpeneaus vannamei after 3 days. The SOI and ROI determined the severity of infection and rate of infection in different tissue.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

In this study, the effect of phospholipase A2 (PLA2) derived from Crotalus durissus collilineatus was evaluated in vitro and in vivo on experimental cutaneous leishmaniasis. The promastigote and amastigote forms treated with PLA2 presented increased growth rate. In vivo studies showed that PLA2-treated Leishmania (Leishmania) amazonensis promastigotes increased the size of lesions in BALB/c mice, and histopathological analysis showed numerous necrotic regions presenting a higher density of polymorphonuclear, mononuclear, and amastigote cells. Additionally, infected macrophages treated with PLA2 were able to generate prostaglandin E2 (PGE2). Cytokine quantification showed that the supernatant from infected macrophages presented moderate and high amounts of IL-2 and IL-10, respectively. However, in PLA2-treated infected macrophages, suppression of IL-2 levels occurred, but not of IL-10 levels. Observation also revealed that both the supernatant and lysate of L. (L.) amazonensis promastigotes exhibited PLA2 activity, which, in the presence of dexamethasone, showed no reduction in their activities; while glucocorticoid maintained the ability of promastigote forms to infect macrophages, which presented values similar to controls. In conclusion, the results indicate that PLA2 may be a progression factor for cutaneous leishmaniasis, since the PLA2 effect suppressed IL-2 levels and generated PGE2, an inflammatory lipid mediator.