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Search Results: 1 - 10 of 53357 matches for " David Fitzgerald "
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Rese a de "Que se queden allá: El gobierno de México y la repatriación de mexicanos en Estados Unidos (1934-1940)" de Fernando Saúl Alanís Enciso
David Fitzgerald
Migraciones internacionales , 2009,
Immunotoxins: The Role of the Toxin
Antonella Antignani,David FitzGerald
Toxins , 2013, DOI: 10.3390/toxins5081486
Abstract: Immunotoxins are antibody-toxin bifunctional molecules that rely on intracellular toxin action to kill target cells. Target specificity is determined via the binding attributes of the chosen antibody. Mostly, but not exclusively, immunotoxins are purpose-built to kill cancer cells as part of novel treatment approaches. Other applications for immunotoxins include immune regulation and the treatment of viral or parasitic diseases. Here we discuss the utility of protein toxins, of both bacterial and plant origin, joined to antibodies for targeting cancer cells. Finally, while clinical goals are focused on the development of novel cancer treatments, much has been learned about toxin action and intracellular pathways. Thus toxins are considered both medicines for treating human disease and probes of cellular function.
Higher Diet Quality Does Not Predict Lower Medicare Costs but Does Predict Number of Claims in Mid-Aged Australian Women
Clare E. Collins,Amanda Patterson,David Fitzgerald
Nutrients , 2011, DOI: 10.3390/nu3010040
Abstract: Optimal dietary quality, indicated by higher diet quality index scores, reflects greater adherence to National dietary recommendations and is also associated with lower morbidity and mortality from chronic disease. Whether this is reflected in lower health care cost over time has rarely been examined. The aim of this study was to examine whether higher diet quality, as measured by the Australian Recommended Food Score (ARFS), was associated with lower health care costs within the mid-aged cohort of the Australian Longitudinal Study on Women’s Health. We found that there was a statistically significant association between five year cumulative costs and ARFS, but in the opposite direction to that predicted, with those in the highest quintiles of ARFS having higher health care costs. However the number of Medicare claims over the six year period (2002–2007) was lower for those in the highest compared with the lowest quintile, p = 0.002. There is a need to monitor both costs and claims over time to examine health care usage in the longer term in order to determine whether savings are eventually obtained for those with the dietary patterns that adhere more closely to National recommendations.
Combination Treatments with the PKC Inhibitor, Enzastaurin, Enhance the Cytotoxicity of the Anti-Mesothelin Immunotoxin, SS1P
Abid R. Mattoo, Ira Pastan, David FitzGerald
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075576
Abstract: Activated protein kinase C (PKC) contributes to tumor survival and proliferation, provoking the development of inhibitory agents as potential cancer therapeutics. Immunotoxins are antibody-based recombinant proteins that employ antibody fragments for cancer targeting and bacterial toxins as the cytotoxic agent. Pseudomonas exotoxin-based immunotoxins act via the ADP-ribosylation of EF2 leading to the enzymatic inhibition of protein synthesis. Combining PKC inhibitors with the immunotoxin SS1P, targeted to surface mesothelin, was undertaken to explore possible therapeutic strategies. Enzastaurin but not two other PKC inhibitors combined with SS1P to produce synergistic cell death via apoptosis. Mechanistic insights of the synergistic killing centered on the complete loss of the prosurvival Bcl2 protein, Mcl-1, the loss of AKT and the activation of caspase 3/7. Synergy was most evident when cells exhibited resistance to the immunotoxin alone. Further, because PKC inhibition by itself was not sufficient to enhance SS1P action, enzastaurin must target other kinases that are involved in the immunotoxin pathway.
A Presentation for the Dual Symmetric Inverse Monoid
David Easdown,James East,D. G. FitzGerald
Mathematics , 2007,
Abstract: The dual symmetric inverse monoid $\mathscr{I}_n^*$ is the inverse monoid of all isomorphisms between quotients of an $n$-set. We give a monoid presentation of $\mathscr{I}_n^*$ and, along the way, establish criteria for a monoid to be inverse when it is generated by completely regular elements.
The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury
David Vega-Avelaira, Rebecca McKelvey, Gareth Hathway, Maria Fitzgerald
Molecular Pain , 2012, DOI: 10.1186/1744-8069-8-30
Abstract: Spared nerve injury (SNI) or sham surgery was performed on 10 day old (P10) rat pups and mechanical nociceptive reflex thresholds were analysed 3, 7, 14, 21, 28, 38 and 44 days post surgery. While mechanical thresholds on the ipsilateral side are not significantly different from controls for the first 2–3 weeks post P10 surgery, after that time period, beginning at 21 days post surgery (P31), the SNI group developed following early life nerve injury significant hypersensitivity compared to the other groups. Ipsilateral mechanical nociceptive threshold was 2-fold below that of the contralateral and sham thresholds at 21 days post surgery (SNI-ipsilateral 28 (±5) g control groups 69 (±9) g, p < 0.001, 3-way ANOVA, n = 6 per group). Importantly, no effect was observed on thermal thresholds. This hypersensivity was accompanied by macrophage, microglial and astrocyte activation in the DRG and dorsal horn, but no significant change in dorsal horn p38 or JNK expression. Preemptive minocycline (daily 40 mg/kg, s.c) did not prevent the effect. Ketamine (20 mg/kg, s.c), on the other hand, produced a dose-dependent reversal of mechanical nociceptive thresholds ipsilateral to the nerve injury such that thresholds return to control levels at the highest doses of 20 mg/Kg.We report a novel consequence of early life nerve injury whereby mechanical hypersensitivity only emerges later in life. This delayed adolescent onset in mechanical pain thresholds is accompanied by neuroimmune activation and NMDA dependent central sensitization of spinal nociceptive circuits. This delayed onset in mechanical pain sensitivity may provide clues to understand the long term effects of early injury such as late onset phantom pain and the emergence of complex adolescent chronic pain syndromes.
Differential regulation of immune responses and macrophage/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury
David Vega-Avelaira, Sandrine M Géranton, Maria Fitzgerald
Molecular Pain , 2009, DOI: 10.1186/1744-8069-5-70
Abstract: We have performed a microarray analysis of the rat L4/L5 dorsal root ganglia (DRG), 7 days post spared nerve injury, a model of neuropathic pain. Genes that are regulated in adult rats displaying neuropathic behaviour were compared to those regulated in young rats (10 days old) that did not show the same neuropathic behaviour. The results show a set of genes, differentially regulated in the adult DRG, that are principally involved in immune system modulation. A functional consequence of this different immune response to injury is that resident macrophages cluster around the large A sensory neuron bodies in the adult DRG seven days post injury, whereas the macrophages in young DRG remain scattered evenly throughout the ganglion, as in controls.The results show, for the first time, a major difference in the neuroimmune response to nerve injury in the dorsal root ganglion of young and adult rats. Differential analysis reveals a new set of immune related genes in the ganglia, that are differentially regulated in adult neuropathic pain, and that are consistent with the selective activation of macrophages around adult, but not young large A sensory neurons post injury. These differences may contribute to the reduced incidence of neuropathic pain in infants.Physiological pain is an acute experience that results from the activation of peripheral nociceptors in injured and inflamed tissues and which normally passes when the stimulus ceases. In contrast, neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia and as it is poorly relieved by conventional analgesics, it is a significant clinical problem [1]. Neuropathic pain is less common in children than in adults. Although it has been reported in very young paediatric patients [2], there i
Exploring the Association between Adult Attachment Styles in Romantic Relationships, Perceptions of Parents from Childhood and Relationship Satisfaction  [PDF]
Gwen Gleeson, Amanda Fitzgerald
Health (Health) , 2014, DOI: 10.4236/health.2014.613196
Abstract: Little research has examined how attachment styles in childhood are related to current romantic relationship experiences. The aim of this study was to explore the association between perceptions of childhood experiences with parents, attachment styles in romantic relationships, and relationship satisfaction in a sample of young adults. The sample consisted of 227 participants, 153 of which were university students and the remaining 69 were members of the general population. Of these, 177 (78%) were female and 50 (22%) were male, with an age range of 18 - 39. Participants completed a battery of self-report measures assessing their attachment style in romantic relationships, satisfaction in their current romantic relationship, and an adjective checklist describing their parents and their parent’s relationship with each other. The majority of males had an avoidant-fearful style, while females tended to have an avoidant-fearful or secure style. Findings were that participants’ descriptions of their mother, father, and parental relationship were associated with their attachment style. In terms of a current romantic relationship, those with a secure attachment style were much more likely to be in a relationship whereas those with an avoidant-fearful style were not. Secure participants were more satisfied in their relationships than the insecure styles of attachment. Finally, chi-square tests revealed that there was no association between gender and attachment style. Results were discussed in terms of methodological limitations such as the use of self-report measures; theoretical weaknesses for example the variability in the approaches used in attachment research; and future research, which included the use of longitudinal studies which may offer insight into how early parenting behaviours act as predictors of later relationship functioning.
Increasing Road Traffic Throughput through Dynamic Traffic Accident Risk Mitigation  [PDF]
Emma Fitzgerald, Bjorn Landfeldt
Journal of Transportation Technologies (JTTs) , 2015, DOI: 10.4236/jtts.2015.54021
Abstract: The introduction of vehicular ad-hoc networks (VANETs) leads to the possibility to re-evaluate many traditional functions and views of road traffic networks. The ability for vehicles and infrastructure to communicate and collaborate will enable many novel solutions for problems as diverse as collision avoidance and traffic management with the view of reducing traffic congestion, increasing the effectiveness of logistics systems etc. In this paper we introduce a novel framework that utilises VANET information to share information about risk factors among road occupants and infrastructure. We introduce the concept of risk limits as a means of traffic accident risk mitigation, whereby vehicles need to adjust their behaviour to maintain a given level of risk. We discuss determination of risk values and detail this process using the NSW traffic accident database. We show how the effects on risk of particular vehicular behaviours such as speed and headway can be calculated and use these results to modify vehicle behaviour in real time to maintain a predefined risk limit. Experiments are carried out using the Paramics Microsimulator. Our results show that it is possible to reduce the accident rate among vehicles while at the same time increasing road network throughput by exploiting the variation in risk between vehicles.
Efficiency of Immunotoxin Cytotoxicity Is Modulated by the Intracellular Itinerary
Lori L. Tortorella, Nina H. Pipalia, Sushmita Mukherjee, Ira Pastan, David Fitzgerald, Frederick R. Maxfield
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047320
Abstract: Pseudomonas exotoxin-based immunotoxins, including LMB-2 (antiTac(Fv)-PE38), are proposed to traffic to the trans-Golgi network (TGN) and move by a retrograde pathway to the endoplasmic reticulum, where they undergo translocation to the cytoplasm, a step that is essential for cytotoxicity. The retrograde transport pathways used by LMB-2 are not completely understood, so it is unclear if transit through specific organelles is critical for maximal cytotoxic activity. In this study, we used Chinese hamster ovary (CHO) cell lines that express chimeric constructs of CD25, the Tac antigen, attached to the cytoplasmic domain of the TGN-targeted transmembrane proteins, TGN38 and furin. These chimeras are both targeted to the TGN, but the itineraries they follow are quite different. LMB-2 was incubated with the two cell lines, and the efficiency of cell killing was determined using cell viability and cytotoxicity assays. LMB-2 that is targeted through the endocytic recycling compartment to the TGN via Tac-TGN38 kills the cells more efficiently than immunotoxins delivered through the late endosomes by Tac-furin. Although the processing to the 37 kDa active fragment was more efficient in Tac-furin cells than in Tac-TGN38 cells, this was not associated with enhanced cytotoxicity – presumably because the toxin was also degraded more rapidly in these cells. These data indicate that trafficking through specific organelles is an important factor modulating toxicity by LMB-2.
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