9,073 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
Recruitment of AP-1 clathrin adaptors to liposomal membranes
No full textProtein and membrane traffic between organelles within the endocytic and exocytic pathway is mediated most prominently by coated vesicles. These vesicles are formed by the assembly of cytosolic coat proteins onto the donor membrane, which deform it into a bud so that vesicles can pinch off. Clathrin with its associated adaptors, COPI and COPII are the three major coats. Various in vitro studies allowed insight into the mechanism of coat formation. COPI and COPII vesicle budding from chemically defined liposomes has been reconstituted in vitro, using pure coat compounds. Further, it has been demonstrated that cargo is sorted into these vesicles. The mechanism of clathrin-coated vesicle formation appears to be more complicated. The AP-1 clathrin adaptor is involved in vesicle formation at the transGolgi network and endosomes. This work presents an in vitro assay where AP-1 is recruited to peptidoliposomes, presenting covalently linked peptides corresponding to sorting signals. In this system, AP-1 recruitment depends on myristyolated ADP-ribosylation factor(ARF1), GTP or GMP-PNP, tyrosine signals and a small amount of phosphoinositides, most prominently phosphatidyl inositol 4,5bisphosphate. In such a minimal system AP-1 is recruited as a highmolecular weight complex indicating the formation of a precoat in the absence of clathrin. GTP hydrolysis, induced by ARF GTPase-activating protein(ARFGAP1), disassembled this complex. Further, AP-1 is able to enhance the GAP activity of ARFGAP1 on myristoylated ARF1, suggesting a regulatory function of GTP hydrolysis in early steps of coat recruitment. This work provides insights into the mechanism of AP-1 clathrin coat formation which might also be used to investigate the recruitment of other coats
Approaches to Broadening Participation with AP Computer Science Principles
No full textThe Advanced Placement Computer Science Principles (AP CSP) course framework was created with the intention of broadening participation in computing. Research has produced mixed results on whether or not the framework succeeds in that goal. Given that teachers have significant freedom in how they choose to teach the AP CSP content, students can have a variety of experiences that may or may not impact their continued participation in CS. In this paper, I compare four different approaches to the AP CSP framework by examining their impact on AP exam scores, self-efficacy and confidence, belongingness and identity, and persistence and interest, to examine how these approaches might impact those traditionally underrepresented in CS. I also discuss how social and curricular interventions may differ in outcomes
About some Théories de la nécropole antique : Colloque Théories de la nécropole antique : les nécropoles et l'idéologie du pouvoir dans le monde des cités (VIIle s. av. J.-C. - IIe s. ap. J.-C), Maison de l'Orient Méditerranéen, Université Lumière Lyon 2, 22-25 janvier 1995
No full textMorris Ian. About some Théories de la nécropole antique : Colloque Théories de la nécropole antique : les nécropoles et l'idéologie du pouvoir dans le monde des cités (VIIle s. av. J.-C. - IIe s. ap. J.-C), Maison de l'Orient Méditerranéen, Université Lumière Lyon 2, 22-25 janvier 1995. In: Topoi, volume 5/1, 1995. pp. 295-302
About some Théories de la nécropole antique : Colloque Théories de la nécropole antique : les nécropoles et l'idéologie du pouvoir dans le monde des cités (VIIle s. av. J.-C. - IIe s. ap. J.-C), Maison de l'Orient Méditerranéen, Université Lumière Lyon 2, 22-25 janvier 1995
No full textMorris Ian. About some Théories de la nécropole antique : Colloque Théories de la nécropole antique : les nécropoles et l'idéologie du pouvoir dans le monde des cités (VIIle s. av. J.-C. - IIe s. ap. J.-C), Maison de l'Orient Méditerranéen, Université Lumière Lyon 2, 22-25 janvier 1995. In: Topoi, volume 5/1, 1995. pp. 295-302
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
Two mechanisms regulate keratin K15 expression in keratinocytes:role of PKC/AP-1 and FOXM1 mediated signalling
No full textBackground: Keratin 15 (K15) is a type I keratin that is used as a marker of stem cells. Its expression is restricted to the basal layer of stratified epithelia, and the bulge in hair follicles. However, in certain clinical situations including oral lichen planus, K15 is induced in suprabasal layers, which is inconsistent with the role of a stem cell marker. This study provides insights into the mechanisms of K15 expression in the basal and differentiating keratinocytes. Methodology/Principal Findings: Human keratinocytes were differentiated by three different methods; suspension in methylcellulose, high cell density and treatment with phorbol ester. The expression of mRNA was determined by quantitative PCR and protein by western blotting and immunostaining. Keratinocytes in suspension suppressed ß1-integrin expression, induced differentiation-specific markers and K15, whereas FOXM1 (a cell cycle regulated protein) and K14 were downregulated. Rescuing ß1-integrin by either fibronectin or the arginine-glycine-aspartate peptide suppressed K15 but induced K14 and FOXM1 expression. Specific inhibition of PKCd, by siRNA, and AP-1 transcription factor, by TAM67 (dominant negative c-Jun), suppressed K15 expression, suggesting that PKC/AP-1 pathway plays a role in the differentiation-specific expression of K15. The basal cell-specific K15 expression may involve FOXM1 because ectopic expression of the latter is known to induce K15. Using chromatin immunoprecipitation, we have identified a single FOXM1 binding motif in the K15 promoter. Conclusions/Significance: The data suggests that K15 is induced during terminal differentiation mediated by the down regulation of ß1-integrin. However, this cannot be the mechanism of basal/stem cell-specific K15 expression in stratified epithelia, because basal keratinocytes do not undergo terminal differentiation. We propose that there are two mechanisms regulating K15 expression in stratified epithelia; differentiation-specific involving PKC/AP-1 pathway, and basal-specific mediated by FOXM1, and therefore the use of K15 expression as a marker of stem cells must be viewed with caution
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
Epidemiology and clinical impact of Pseudomonas aeruginosa infection in cystic fibrosis using AP-PCR fingerprinting
No full textArbitrarily primed PCR (AP-PCR) was utilized to genetically fingerprint 252 Pseudomonas aeruginosa strains isolated from the sputa of 50 cystic fibrosis (CF) patients attending the Cork CF clinic over a period of 3 years. Ten distinct P. aeruginosa strains were identified and the distribution, temporal trends and clinical impact of colonization with these individual P. aeruginosa clones was studied. A number of random isolates from each AP-PCR group were analysed using pulsed field gel electrophoresis (PFGE) in order to confirm the discriminatory power of the AP-PCR technique. The majority of patients were colonized with a single strain over the time period of the study, but it was also possible to harbour two or more strains transiently or simultaneously. Four main strains were relatively evenly distributed throughout the CF population, and it was noted that patients from the same family or attending the same school tended to harbour the same P. aeruginosa clone. Disease severity was significantly associated with the age of the patient (P<0.001), clearly indicating an increase in severity with increase in age. The general clinical status of the CF patients was not significantly associated with the P. aeruginosa variant isolated from their sputa. Lung status was defined by FEV1 measurement and chest X-ray score (CXR). The non parametric Kruskal-Wallis significance test of FEV1, CXR and age by colonizing P. aeruginosa clone indicated that FEV1 (P=0.017), but not CXR (P=0.19) or age (P=0.842), differed significantly across the clones of P. aeruginosa isolated. Patients harbouring P. aeruginosa strains B, F or G clearly had lower FEV1 scores while those harbouring clones A, C, D or H generally had higher FEV1 scores. Thus, the sub-species variant of P. aeruginosa colonizing CF patients may be associated with the severity of progressive lung disease
The training and development of Assistant Practitioners(AP): An action research project to develop a tool to evaluate the impact of the AP role in practice and inform service development within NHS and Non -NHS organisations
No full textThis research study looks at how resources can be produced to assist managers making decisions about developing the role of the Assistant Practitioner(AP). It investigates evaluations of the AP role to date and considers how an impact evaluation tool can be produced to inform practice. The tool looks at how a mixed methods approach can be utilised to create evidence that is both qualitative and quantitative in nature. The aims of the study are to provide managers with evidence based resources that can inform their decision making when contemplating the training and development of non-registered staff into the role of AP and develop a tool that will evaluate the impact of the AP role within a service area. The study examines the stages taken to develop a tool that can be applied to the AP role but is also generic in nature and can be utilised in any area considering role development within their team
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