1,333 research outputs found

    Challenges and opportunities for digital marketing within contemporary art book publishing

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    This dissertation examines a number of challenges and opportunities in digital marketing within contemporary art book publishing. As products of a uniquely cross-pollinated strain of culture and publishing, their tactility and physicality are amongst their most appealing qualities, standing out in a world where so much takes place in a virtual space. The appeal of art books today is thought to be getting stronger and stronger as many other kinds of books dematerialise in the digital space, standing out more than ever as objects. However, art books still have to contend with a marketing landscape where digital grows increasingly more dominant and influential each year. The differences that make art books stand out may well give rise to difficulties and challenges when it comes to marketing and selling them in a digital environment. But conversely, there could be a greater amount and broader spread of opportunities for effectively marketing art books online that would not be available to different kinds of books. This dissertation seeks to investigate how a number of art book publishers are currently using the digital marketing tools that are available to them, the effectiveness of their strategies, what challenges are being faced and which opportunities are being under-utilised

    Analytical study of non Gaussian fluctuations in a stochastic scheme of autocatalytic reactions

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    A stochastic model of autocatalytic chemical reactions is studied both numerically and analytically. The van Kampen perturbative scheme is implemented, beyond the second order approximation, so to capture the non Gaussianity traits as displayed by the simulations. The method is targeted to the characterization of the third moments of the distribution of fluctuations, originating from a system of four populations in mutual interaction. The theory predictions agree well with the simulations, pointing to the validity of the van Kampen expansion beyond the conventional Gaussian solution.Comment: 15 pages, 8 figures, submitted to Phys. Rev.

    PDB29 HEALTH ECONOMIC EVALUATION OF INSULIN GLARGINE FOR THE TREATMENT OF TYPE-1 AND TYPE-2 DIABETES

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    Steady-state fluctuations of a genetic feedback loop:an exact solution

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    Genetic feedback loops in cells break detailed balance and involve bimolecular reactions; hence exact solutions revealing the nature of the stochastic fluctuations in these loops are lacking. We here consider the master equation for a gene regulatory feedback loop: a gene produces protein which then binds to the promoter of the same gene and regulates its expression. The protein degrades in its free and bound forms. This network breaks detailed balance and involves a single bimolecular reaction step. We provide an exact solution of the steady-state master equation for arbitrary values of the parameters, and present simplified solutions for a number of special cases. The full parametric dependence of the analytical non-equilibrium steady-state probability distribution is verified by direct numerical solution of the master equations. For the case where the degradation rate of bound and free protein is the same, our solution is at variance with a previous claim of an exact solution (Hornos et al, Phys. Rev. E {\bf 72}, 051907 (2005) and subsequent studies). We show explicitly that this is due to an unphysical formulation of the underlying master equation in those studies.Comment: 31 pages, 3 figures. Accepted for publication in the Journal of Chemical Physics (2012

    Sampling bias in systems with structural heterogeneity and limited internal diffusion

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    Complex systems research is becomingly increasingly data-driven, particularly in the social and biological domains. Many of the systems from which sample data are collected feature structural heterogeneity at the mesoscopic scale (i.e. communities) and limited inter-community diffusion. Here we show that the interplay between these two features can yield a significant bias in the global characteristics inferred from the data. We present a general framework to quantify this bias, and derive an explicit corrective factor for a wide class of systems. Applying our analysis to a recent high-profile survey of conflict mortality in Iraq suggests a significant overestimate of deaths

    The 5'-3' exoribonuclease Pacman (Xrn1) regulates expression of the heat shock protein Hsp67Bc and the microRNA miR-277-3p in Drosophila wing imaginal discs

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    Pacman/Xrn1 is a highly conserved exoribonuclease known to play a critical role in gene regulatory events such as control of mRNA stability, RNA interference and regulation via miRNAs. Although Pacman has been well studied in Drosophila tissue culture cells, the biologically relevant cellular pathways controlled by Pacman in natural tissues are unknown. This study shows that a hypomorphic mutation in pacman (pcm5) results in smaller wing imaginal discs. These tissues, found in the larva, are known to grow and differentiate to form wing and thorax structures in the adult fly. Using microarray analysis, followed by quantitative RT-PCR, we show that eight mRNAs were increased in level by >2 fold in the pcm5 mutant wing discs compared to the control. The levels of pre mRNAs were tested for five of these mRNAs; four did not increase in the pcm5 mutant, showing that they are regulated at the post-transcriptional level and therefore could be directly affected by Pacman. These transcripts include one that encodes the heat-shock protein Hsp67Bc, which is upregulated 11.9-fold at the post-transcriptional level and 2.3-fold at the protein level. One miRNA, miR-277-3p, is 5.6-fold downregulated at the post-transcriptional level in mutant discs, suggesting that Pacman affects its processing in this tissue. Together, these data show that a relatively small number of mRNAs and miRNAs substantially change in abundance in pacman mutant wing imaginal discs. Since Hsp67Bc is known to regulate autophagy and protein synthesis, it is possible that Pacman may control the growth of wing imaginal discs by regulating these processes

    Accurate discretization of advection-diffusion equations

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    We present an exact mathematical transformation which converts a wide class of advection-diffusion equations into a form allowing simple and direct spatial discretization in all dimensions, and thus the construction of accurate and more efficient numerical algorithms. These discretized forms can also be viewed as master equations which provides an alternative mesoscopic interpretation of advection-diffusion processes in terms of diffusion with spatially varying hopping rates

    Low serum phosphate levels are related to increased cardiovascular risk in HIV-1 infected patients

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    Purpose of the study Hypophosphatemia may contribute directly to the devel- opment of obesity, hypertension and dyslipidemia. Hyperglycemia, insulin resistance, hyperlipidemia and hypertension, which are components of metabolic syn- drome, are also recognized as strong risk factors for car- diovascular disease [1]. This study was performed to determine whether serum phosphate levels are asso- ciated with increased risk for cardiovascular events. Methods We enrolled 125 consecutive HIV-1-infected patients in a cross-sectional study. All patients were receiving highly active antiretroviral therapy (HAART) for more than six months. Fasting phosphate, lipids (cholesterol, HDL, triglycerides), Homeostasis Model Assessment (HOMA), blood pressure were evaluated. Framingham 10 years risk of general cardiovascular disease was used to assess three cardiovascular risk (CVR) categories (low CVR 20%). Summary of results We observed a statistically significant decrease in serum phosphate levels in the three different CVR groups (low risk: 3.5 mg/dl; medium risk: 3.3 mg/dl; high risk: 2.9 mg/dl; p=0.001). There was a strong negative correlation between Framingham score and phosphate levels (r:- 0.37, p<0.0001). Figure 1 Multiple regression analysis, including age, months of HAART, CD4 cells count, cholesterol, HDL, HOMA, systolic pressure, months of Tenofovir use, showed that only HOMA (r:-0.30, p<0.01) and age (r:-0.3, p<0.01) were the most important determinants of serum phos- phate values. Conclusions We found that lower phosphate level is correlated with cardiovascular risk and insulin resistance. Therefore, when serum phosphate levels are too low the patients is at risk for cardiovascular events and/or metabolic syndrome

    Mathematical Model of the Impact of a Nonantibiotic Treatment for Clostridium difficile on the Endemic Prevalence of Vancomycin-Resistant Enterococci in a Hospital Setting

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    Introduction. Clostridium difficile-associated disease (CDAD) is treated using antibiotics, which often leads to the emergence of antibiotic-resistant bacteria such as vancomycin-resistant enterococci (VRE). This study estimated the impact of a non antibiotic treatment for CDAD on VRE prevalence. Methods. A previously published model describing the impact of in-hospital antibiotic use on VRE prevalence was adapted to include CDAD treatment. Simulations compared the prevalence of VRE when nonantibiotic versus antibiotic therapy was used. Results. Nonantibiotic treatment in 50% of CDAD patients resulted in an 18% relative reduction in the prevalence of VRE colonization compared with antibiotic use only. Sensitivity analysis found the model to be most sensitive to rates of antibiotic initiation and discontinuation, prevalence of VRE in admitted patients, length of stay of colonized patients, probability of CDAD acquisition, and hand-washing compliance. Conclusion. Nonantibiotic treatment of patients hospitalized with CDAD may significantly reduce the incidence of VRE colonization

    Optimisation of abiraterone based non-steroidal lead molecules

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    Management of castration resistant prostate cancer is limited by androgen receptor reactivation resulting in loss of remission. A recent study indicated that abiraterone exhibits antagonist activity towards the androgen receptor in addition to CYP17A1 inhibition.Metribolone has demonstrable in vitro and in vivo high affinity for the AR thus it was established as a benchmark against which the affinity of abiraterone and de novo designed non-steroidal molecules could be compared. Binding affinities of abiraterone manually superimposed onto the steroid scaffold of metribolone (pKd 7.16) and abiraterone that was allowed limited rotation (pKd 7.23)were comparable to metribolone (pKd 7.44).The de novo study generated an 8 analogue molecular series with affinities ranging between 5.26 and 7.23. This study yielded sufficient analogues that may be proposed for further molecular optimisation to yield innovative non-steroidal high affinity molecules with superior side-effect profiles for the management of prostate cancer.peer-reviewe
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