881 resultados para The Cagan Model
Resumo:
This paper presents ongoing work toward constructing efficient completely non-malleable public-key encryption scheme based on lattices in the standard (common reference string) model. An encryption scheme is completely non-malleable if it requires attackers to have negligible advantage, even if they are allowed to transform the public key under which the related message is encrypted. Ventre and Visconti proposed two inefficient constructions of completely non-malleable schemes, one in the common reference string model using non-interactive zero-knowledge proofs, and another using interactive encryption schemes. Recently, two efficient public-key encryption schemes have been proposed, both of them are based on pairing identity-based encryption.
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Epithelial-mesenchymal transition (EMT) is a feature of migratory cellular processes in all stages of life, including embryonic development and wound healing. Importantly, EMT features cluster with disease states such as chronic fibrosis and cancer. The dissolution of the E-cadherin-mediated adherens junction (AJ) is a key preliminary step in EMT and may occur early or late in the growing epithelial tumour. This is a first step for tumour cells towards stromal invasion, intravasation, extravasation and distant metastasis. The AJ may be inactivated in EMT by directed E-cadherin cleavage; however, it is increasingly evident that the majority of AJ changes are transcriptional and mediated by an expanding group of transcription factors acting directly or indirectly to repress E-cadherin expression. A review of the current literature has revealed that these factors may regulate each other in a hierarchical pattern where Snail1 (formerly Snail) and Snail2 (formerly Slug) are initially induced, leading to the activation of Zeb family members, TCF3, TCF4, Twist, Goosecoid and FOXC2. Within this general pathway, many inter-regulatory relationships have been defined which may be important in maintaining the EMT phenotype. This may be important given the short half-life of Snail1 protein. We have investigated these inter-regulatory relationships in the mesenchymal breast carcinoma cell line PMC42 (also known as PMC42ET) and its epithelial derivative, PMC42LA. This review also discusses several newly described regulators of E-cadherin repressors including oestrogen receptor-α and new discoveries in hypoxia- and growth factor-induced EMT. Finally, we evaluated how these findings may influence approaches to current cancer treatment.
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Reflective thinking is an important skill in psychology, both as a tool in the therapeutic process and in professional development. The adapted 4Rs Model provides reflective writing structure and highlights the importance of Reporting & Responding, Relating, Reasoning and Reconstructing to students who are new to writing reflections. This chapter presents a case in which the 4Rs model (modified from the 5Rs model in Chap. 2 of this edition) was adopted to support reflective writing skills of undergraduate psychology students in a first year unit and in a final year unit. Although all students reflected on their learning within the units, the support activities leading up to the reflective tasks were adjusted to account for differences in the abilities of the cohorts and the focus of the units. In an evaluation survey, both groups of students endorsed statements about the importance of reflections and the utility of using the model. First year students also reported some difficulties understanding the 4Rs. This chapter will explore how first and final year students can be supported to develop reflection skills through scaffolding and modification of the same approaches and model.
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In the analysis of tagging data, it has been found that the least-squares method, based on the increment function known as the Fabens method, produces biased estimates because individual variability in growth is not allowed for. This paper modifies the Fabens method to account for individual variability in the length asymptote. Significance tests using t-statistics or log-likelihood ratio statistics may be applied to show the level of individual variability. Simulation results indicate that the modified method reduces the biases in the estimates to negligible proportions. Tagging data from tiger prawns (Penaeus esculentus and Penaeus semisulcatus) and rock lobster (Panulirus ornatus) are analysed as an illustration.
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The effect of pressure on the conductivity of fast ion conducting AgI-Ag2O-MoO3 glasses has been investigated down to 150 K. The observed variation of conductivities appears to support the application of cluster model to the ionic glasses.
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The rule of law is understood to be a core aspect in achieving a stable economy and an ordered society. Without the elements that are inherent in this principle the possibilities of anarchy, unfairness and uncertainty are amplified, which in turn can result in an economy with dramatic fluctuations. In this regard, commentators do not always agree that the rule of law is strictly adhered to in the international legal context. Therefore, this paper will explore one aspect of international regulation and consider whether the UNCITRAL Model Law on Cross-border Insolvency (1997) (‘Model Law’) and its associated Guide to Enactment and Interpretation (2013) contribute to the promotion of the key elements of the rule of law.
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Self-tuning is applied to the control of nonlinear systems represented by the Hammerstein model wherein the nonlinearity is any odd-order polynomial. But control costing is not feasible in general. Initial relay control is employed to contain the deviations.
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Maize grown in eastern and southern Africa experiences random occurrences of drought. This uncertainty creates difficulty in developing superior varieties and their agronomy. Characterisation of drought types and their frequencies could help in better defining selection environments for improving resistance to drought. We used the well tested APSIM maize model to characterise major drought stress patterns and their frequencies across six countries of the region including Ethiopia, Kenya, Tanzania, Malawi, Mozambique and Zimbabwe. The database thus generated covered 35 sites, 17 to 86 years of daily climate records, 3 varieties and 3 planting densities from a total of 11,174 simulations. The analysis identified four major drought environment types including those characterised by low-stress which occurred in 42% of the years, mid-season drought occurring in 15% of the years, late-terminal stress which occurred in 22% of the years and early-terminal drought occurring in 21% of the years. These frequencies varied in relation to sites, genotypes and management. The simulations showed that early terminal stress could result in a yield reduction of 70% compared with low-stress environmental types. The study presents the importance of environmental characterization in contributing to maize improvement in eastern and southern Africa.
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A high temperature source has been developed and coupled to a high resolution Fourier transform spectrometer to record emission spectra of acetylene around 3 mu m up to 1455 K under Doppler limited resolution (0.015 cm(-1)). The nu(3)-ground state (GS) and nu(2)+nu(4)+nu(5)(Sigma(+)(u) and Delta(u))-GS bands and 76 related hot bands, counting e and f parities separately, are assigned using semiautomatic methods based on a global model to reproduce all related vibration-rotation states. Significantly higher J-values than previously reported are observed for 40 known substates while 37 new e or f vibrational substates, up to about 6000 cm(-1), are identified and characterized by vibration-rotation parameters. The 3 811 new or improved data resulting from the analysis are merged into the database presented by Robert et al. [Mol. Phys. 106, 2581 (2008)], now including 15 562 lines accessing vibrational states up to 8600 cm(-1). A global model, updated as compared to the one in the previous paper, allows all lines in the database to be simultaneously fitted, successfully. The updates are discussed taking into account, in particular, the systematic inclusion of Coriolis interaction.
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This thesis clarifies important molecular pathways that are activated during the cell death observed in Huntington’s disease. Huntington’s disease is one of the most common inherited neurodegenerative diseases, which is primarily inherited in an autosomal dominant manner. HD is caused by an expansion of CAG repeats in the first exon of the IT15 gene. IT15 encodes the production of a Huntington’s disease protein huntingtin. Mutation of the IT15 gene results in a long stretch of polyQ residues close to the amino-terminal region of huntingtin. Huntington’s disease is a fatal autosomal neurodegenerative disorder. Despite the current knowledge of HD, the precise mechanism behind the selective neuronal death, and how the disease propagates, still remains an enigma. The studies mainly focused on the control of endoplasmic reticulum (ER) stress triggered by the mutant huntingtin proteins. The ER is a delicate organelle having essential roles in protein folding and calcium regulation. Even the slightest perturbations on ER homeostasis are effective enough to trigger ER stress and its adaptation pathways, called unfolded protein response (UPR). UPR is essential for cellular homeostasis and it adapts ER to the changing environment and decreases ER stress. If adaptation processes fail and stress is excessive and prolonged; irreversible cell death pathways are engaged. The results showed that inhibition of ER stress with chemical agents are able to decrease cell death and formation of toxic cell aggregates caused by mutant huntingtin proteins. The study concentrated also to the NF-κB (nuclear factor-kappaB) pathway, which is activated during ER stress. NF-κB pathway is capable to regulate the levels of important cellular antioxidants. Cellular antioxidants provide a first line of defence against excess reactive oxygen species. Excess accumulation of reactive oxygen species and subsequent activation of oxidative stress damages motley of vital cellular processes and induce cell degeneration. Data showed that mutant huntingtin proteins downregulate the expression levels of NF-κB and vital antioxidants, which was followed by increased oxidative stress and cell death. Treatment with antioxidants and inhibition of oxidative stress were able to counteract these adverse effects. In addition, thesis connects ER stress caused by mutant huntingtin to the cytoprotective autophagy. Autophagy sustains cellular balance by degrading potentially toxic cell proteins and components observed in Huntington’s disease. The results revealed that cytoprotective autophagy is active at the early points (24h) of ER stress after expression of mutant huntingtin proteins. GADD34 (growth arrest and DNA damage-inducible gene 34), which is previously connected to the regulation of translation during cell stress, was shown to control the stimulation of autophagy. However, GADD34 and autophagy were downregulated at later time points (48h) during mutant huntingtin proteins induced ER stress, and subsequently cell survival decreased. Overexpression GADD34 enhanced autophagy and decreased cell death, indicating that GADD34 plays a critical role in cell protection. The thesis reveales new interesting data about the neuronal cell death pathways seen in Huntington’s disease, and how cell degeneration is partly counteracted by various therapeutic agents. Expression of mutant huntingtin proteins is shown to alter signaling events that control ER stress, oxidative stress and autophagy. Despite that Huntington’s disease is mainly an untreatable disorder; these findings offer potential targets and neuroprotective strategies in designing novel therapies for Huntington’s disease.
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A number of analogues of diaryl dihydropyrazole-3-carboxamides have been synthesized. Their activities were evaluated for appetite suppression and body weight reduction in animal models. Depending on the chemical modification of the selected dihydropyrazole scaffold, the lead compoundsthe bisulfate salt of (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 26 and the bisulfate salt of (−)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 30showed significant body weight reduction in vivo, which is attributed to their CB1 antagonistic activity and exhibited a favorable pharmacokinetic profile. The molecular modeling studies also showed interactions of two isomers of (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 9 with CB1 receptor in the homology model similar to those of N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (rimonabant) 1 and 4S-(−)-3-(4-chlorophenyl)-N-methyl-N‘-[(4-chlorophenyl)-sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamidine (SLV-319) 2.
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The leucine zipper region of activator protein-1 (AP-1) comprises the c-Jun and c-Fos proteins and constitutes a well-known coiled coil protein−protein interaction motif. We have used molecular dynamics (MD) simulations in conjunction with the molecular mechanics/Poisson−Boltzmann generalized-Born surface area [MM/PB(GB)SA] methods to predict the free energy of interaction of these proteins. In particular, the influence of the choice of solvation model, protein force field, and water potential on the stability and dynamic properties of the c-Fos−c-Jun complex were investigated. Use of the AMBER polarizable force field ff02 in combination with the polarizable POL3 water potential was found to result in increased stability of the c-Fos−c-Jun complex. MM/PB(GB)SA calculations revealed that MD simulations using the POL3 water potential give the lowest predicted free energies of interaction compared to other nonpolarizable water potentials. In addition, the calculated absolute free energy of binding was predicted to be closest to the experimental value using the MM/GBSA method with independent MD simulation trajectories using the POL3 water potential and the polarizable ff02 force field, while all other binding affinities were overestimated.
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We evaluate the mixed partition function for dyonic BPS black holes using the recently proposed degeneracy formula for the STU model. The result factorizes into the OSV mixed partition function times a proportionality factor. The latter is in agreement with the measure factor that was recently conjectured for a class of N = 2 black holes that contains the STU model.