6,914 research outputs found
Transcription Factor AP-2 Regulatory Signatures in Breast Cancer
No full textPhDAP-2 transcription factors are highly conserved basic helix-span-helix proteins whose
members ((x, ß, y, S and c) are crucial regulators of bryonic development. They also
play an important role in human neoplasia. uohis ochemical studies have detected
high levels of AP-2y expression in primary tumo of breast cancer patients. This high
expression has been correlated with reduced survival in all patients and reduced survival
in an ERa positive subset treated with hormone therapy. In breast cancer cell lines, AP-
2 factors have been implicated in the regulation of the ERBB2 proto-oncogene and ERa.
In an effort to further understand the role of AP-2y in breast carcinoma, this study has
sought to identify additional AP-2 activated cellular pathways and ultimately novel
transcriptional targets for AP-2 through the use of gene expression profiling.
RNAi using three independent AP-2y targeting sequences, has been used to deplete AP-
2y levels in the ERa positive MCF-7 breast carcinoma cell line, chosen as it exclusively
expresses the AP-2y family member. Microarrays were then utilised to create an AP-2y
dependent transcription profile. Statistical comparisons between non-silencing control
siRNA and AP-2y targeting siRNA groups identified a total of 162 gene expression
changes (p<0.01). These changes implicate AP-2y in the control of cell cycle
progression and developmental signalling. Indeed a role for AP-2y in the control of cell
cycle, in particular at the GUS transition, has been verified using flow cytometry.
Several of these gene expression changes, including IGFBP3, Transgelin and
KIAA1324, have been confirmed using qPCR and immunoblotting.
Finally, elevated levels of p21 mRNA and protein have been observed following AP-2y
silencing in MCF-7 cells. Additionally, the activity of a p21 promoter reporter is
repressed following transfection with an AP-2y expression construct in HepG2 cells.
These results coupled with ChIP experiments showing AP-2y occupancy at the proximal
promoter region of p21 in cycling MCF-7 cells, implicate AP-2y in the repression of
p21 transcription and suggest a role for AP2y in- the, control of cell cycle in breast
carcinoma in part through the transcriptional repression of p21
AP-4-mediated axonal transport controls endocannabinoid production in neurons
No full textDavies et al. identify a putative mechanism underlying the childhood neurological disorder AP-4 deficiency syndrome. In the absence of AP-4, an enzyme that makes 2-AG is not transported to the axon, leading to axonal growth defects, which can be rescued by inhibition of 2-AG breakdown. The adaptor protein complex AP-4 mediates anterograde axonal transport and is essential for axon health. AP-4-deficient patients suffer from a severe neurodevelopmental and neurodegenerative disorder. Here we identify DAGLB (diacylglycerol lipase-beta), a key enzyme for generation of the endocannabinoid 2-AG (2-arachidonoylglycerol), as a cargo of AP-4 vesicles. During normal development, DAGLB is targeted to the axon, where 2-AG signalling drives axonal growth. We show that DAGLB accumulates at the trans-Golgi network of AP-4-deficient cells, that axonal DAGLB levels are reduced in neurons from a patient with AP-4 deficiency, and that 2-AG levels are reduced in the brains of AP-4 knockout mice. Importantly, we demonstrate that neurite growth defects of AP-4-deficient neurons are rescued by inhibition of MGLL (monoacylglycerol lipase), the enzyme responsible for 2-AG hydrolysis. Our study supports a new model for AP-4 deficiency syndrome in which axon growth defects arise through spatial dysregulation of endocannabinoid signalling.Special thanks to the MPIB Imaging Facility for outstanding technical support, in particular to Giovanni Cardone for his advice and assistance with the implementation of image analysis pipelines, as well as feedback on the manuscript, and to Martin Spitaler for his expert technical advice for imaging experiments
The Treatment of Ties in AP Correlation
No full textThe Kendall tau and AP correlation coefficients are very commonly use to compare two rankings over the same set of items. Even though Kendall tau was originally defined assuming that there are no ties in the rankings, two alternative versions were soon developed to account for ties in two different scenarios: measure the accuracy of an observer with respect to a true and objective ranking, and measure the agreement between two observers in the absence of a true ranking. These two variants prove useful in cases where ties are possible in either ranking, and may indeed result in very different scores. AP correlation was devised to incorporate a top-heaviness component into Kendall tau, penalizing more heavily if differences occur between items at the top of the rankings, making it a very compelling coefficient in Information Retrieval settings. However, the treatment of ties in AP correlation remains an open problem. In this paper we fill this gap, providing closed analytical formulations of AP correlation under the two scenarios of ties contemplated in Kendall tau. In addition,we developed an R package that implements these coefficients.Best Short Paper Accepted author manuscriptMultimedia ComputingWeb Information System
Green crime and victimization: Tensions between social and environmental justice
No full textIn 2011, Rio-Tinto Alcan, one of the world’s largest producers of aluminium, announced the closure of the smelter at Lynemouth, Northumberland, North East England. The plant, a major local employer, finally closed in March, 2013. This article examines global concerns about environmental emission standards and the costs of compliance. This plants closure is a success in green terms. However, where closure is officially considered a compliance option, costs to deprived communities are high. From a (green) victimological perspective, the article contemplates the hidden costs of closure on already deprived local and regional communities. The discussion focuses on how green crime and green compliance creates victimisation and reflects on the moral and ethical challenges this presents for a green criminology
2024 guidelines for the vaccination of dogs and cats – compiled by the Vaccination Guidelines Group (VGG) of the World Small Animal Veterinary Association (WSAVA)
No full textFormerly Discipline of Veterinary Science James Cook UniversityCollege of Veterinary Medicine University of Florida, 2015 SW 16th AvenueDepartment of Clinical Medicine Surgery and Animal Reproduction São Paulo State University, Rua Sergipe 575, ap. 32, SPInternal Medicine Davies Veterinary Specialists, Manor Farm Business Park, Higham GobionDepartment of Clinical Medicine Surgery and Animal Reproduction São Paulo State University, Rua Sergipe 575, ap. 32, S
Delamination Analysis of A Class of AP-PLY Composite Laminates
No full textA recently developed fiber placement architecture, AP-PLY, has been shown to give significantly improved damage tolerance characteristics of composite structures. The behavior of delaminations resulting from low speed impact damage is of particular concern. Major attention has been paid to expand current knowledge on the delamination response of simple AP-PLY composite structure and move towards in-depth understanding of the failure mechanisms behind the damage tolerance. This thesis presents the approaches to predict delamination onset and analyze delamination growth, in support of the search of the optimum woven pattern for AP-PLY composite laminates. The recovered interlaminar stress between layers combined with the maximum stress criterion determined the delamination onset of simple AP-PLY composite laminate under out-of-plane loads. 2D finite element models with cohesive elements inserted in the interfaces of woven layers have been built to evaluate the delamination initiation and propagation in the different woven patterns of simple AP-PLY composite beams. The parameters of the woven pattern, such as the woven angle, the number of woven plies, the number of straight filled plies, and the location of the woven patterns in through the thickness direction, were investigated and shown to have a significant effect on delamination creation and growth. An energy method based on beam theory was proposed to analyze the strain energy release rate (SERR) of an existing crack in an AP-PLY beam structure. The developed analytical method was implemented in isotropic materials and the obtained SERR of a crack was validated by reference results and finite element solutions. The general behavior of crack growth on the left or right crack tip was evaluated and basic trends leading to crack propagation on one side of the crack were established. A correction factor was introduced to improve the accuracy of the SERR of a small crack through the numerical calculation. The singularity of crack tip caused by dissimilar materials was investigated and was found that the inclusion of the singularity effect could increase the accuracy for small cracks. It has been shown that the neutral axis needs to be relocated to decouple the bending and membrane behavior of unsymmetrical composite laminates, thus to meet the requirement of minimizing the strain energy of the delaminated beam to calculate the SERR of a delaminated composite beam. The calculated SERR of a crack in a composite beam has been verified by comparing with a finite element model. The woven plies in AP-PLY composite laminate altered the layup and two conventional laminates with different stacking sequences were identified in an AP-PLY composite laminate based on the assumption that the resin areas were ignored. A step by step approach was developed to obtain the SERR of a crack that goes across different materials. The analytical SERR determined when two materials are used in sequence, sets the stage for optimization of AP-PLY composite laminates without taking account of the effect of the resin area. The procedure of optimization of simple AP-PLY pattern was proposed and industry may benefit for many applications. An equivalent stiffness approach was used to model regions containing resin pockets and straight or inclined composite layers. A series of three point bending tests was carried out where the failure process and loading capacity were evaluated. The methodology, procedure of optimization, philosophy outlined in this thesis might also be applied to the more complicated fully woven AP-PLY composite laminates. The work in this thesis contributes to the understanding of the behavior of AP-PLY composite laminates with delaminations
Cultural constructions of infancy : an anthropological study of infant care in Cardiff.
No full textThis thesis is about infancy, independence, and how
medicalisation shapes mothers' perceptions of their
infants. It draws on ethnographic research in Cardiff,
undertaken during a period of heightened concern about the
Sudden Infant Death Syndrome (SIDS), and funded by the
Foundation for the Study of Infant Deaths.
Three "cultural constructions" of infancy are juxtaposed:
the vulnerable and constantly accompanied Bangladeshi
infant, the Welsh or English infant encouraged towards
independence, and the autonomous infant of epidemiological
analysis.
The thesis shows how the processes of medicalisation
brought contrasting perceptions of infancy to light,
suggesting that Bangladeshi women taking part in an
"English for Pregnancy" project were not only learning
language, but also learning about medicalised infant care.
It argues too that health professionals shape the way in
which mothers perceive their infants through the
introduction of the language of "risk factors".
The infant body itself emerged at the boundary of powerful
systems of meaning. If the boundaries of the Bangladeshi
infant body were blurred through constant contact, those of
the Welsh or English infant were marked intermittently
through alternating periods of solitude with "attention".
Some Welsh and English mothers spoke of infants and their
care in terms of the care of domestic animals, and the
mothers' own ambivalence about their own animality, while
some Bangladeshi mothers spoke of the spiritual power and
vulnerability of infants, and in doing so articulated their
links with Bangladesh. For health professionals the
infant body was a site for demonstrating expertise through
both research (which constructed ethnic minorities as
'natural') and recommendations for action.
The thesis discusses the location of contemporary
anthropology at cultural boundaries. Juxtaposing
contrasting beliefs about infancy revealed very different
perceptions of independence, marked in particular by
contrasting perceptions of time, space, and the infant body
itself
Kerrith Davies, Winning the West : the creation of lower Normandy, c.889-c.1087
No full textKerrith Davies, Winning the West : the creation of lower Normandy, c.889-c.1087, Thèse de doctorat soutenue en 2016 (Université d’Oxford) Résumé/abstract : This thesis re-evaluates the chronology of Lower Normandyâs integration into the duchy growing around Rouen from the tenth century onwards. The introduction argues that modern accounts of Normandyâs development remain dependent on the works of Dudo of Saint-Quentin and Flodoard of Rheims. Difficulties with these authors and alternative ap..
Llywelyn ab Iorwerth : the making of a Welsh prince
No full textLlywelyn ab Iorwerth (1173-1140) has long been considered one of the leading heroes of Wales. The life and rule of Llywelyn, known as Llywelyn the Great, is explored in detail in this thesis. The grandson of Owain Gwynedd, ruler of North Wales from 1137-1170, Llywelyn grew up during the period of turmoil following Owain’s death. After wresting control of Gwynedd from his rival family members in the latter decade of the 12th century, he proceeded to gain recognition as the foremost representative of Wales on the political stage.
Although viewed as a legendary hero in Welsh history, poetry and culture, Llywelyn's route to power is more complex than that. The thesis explores the development of the man from rebel and warlord, to leader and spokesman, to statesman, traces the expansion of his hegemony throughout Wales, and discusses the methods he used to gain and maintain power. Particular attention is paid to his use of family, marriage, allies, rivals and the church to achieve his goals. These insights can be derived from the surviving charters, letters, and other acta of Llywelyn and the Royal Chancery of England, the titles accorded therein, Welsh and English chronicles, as well as, occasionally, Venedotian Poetry. Finally, this thesis seeks to address the limitations on Llywelyn’s successes, in light of succeeding events and concludes with a discussion of Llywelyn’s legendary status in the modern world
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