Joint optimization of customer segmentation and marketing policy to maximize long-term profitability

With the advent of one-to-one marketing media, e.g. targeted direct mail or internet marketing, the opportunities to develop targeted marketing campaigns are enhanced in such a way that it is now both organizationally and economically feasible to profitably support a substantially larger number of marketing segments. However, the problem of what segments to distinguish, and what actions to take towards the different segments increases substantially in such an environment. A systematic analytic procedure optimizing both steps would be very welcome.In this study, we present a joint optimization approach addressing two issues: (1) the segmentation of customers into homogeneous groups of customers, (2) determining the optimal policy (i.e., what action to take from a set of available actions) towards each segment. We implement this joint optimization framework in a direct-mail setting for a charitable organization. Many previous studies in this area highlighted the importance of the following variables: R(ecency), F(requency), and M(onetary value). We use these variables to segment customers. In a second step, we determine which marketing policy is optimal using markov decision processes, following similar previous applications. The attractiveness of this stochastic dynamic programming procedure is based on the long-run maximization of expected average profit. Our contribution lies in the combination of both steps into one optimization framework to obtain an optimal allocation of marketing expenditures. Moreover, we control segment stability and policy performance by a bootstrap procedure. Our framework is illustrated by a real-life application. The results show that the proposed model outperforms a CHAID segmentation

DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches

In ostriches, the population densities resulting from intensive rearing increases susceptibility to pathogens such as mycoplasmas. In addition to good management practices, vaccination offers an attractive alternative for controlling mycoplasma infections in food animals, instead of using antibiotics, which often leave unacceptable residues. The use of live attenuated vaccines, however, carry the concern of reversion to virulence or genetic recombination with field strains. Currently there are no commercially available vaccines against ostrich-infecting mycoplasmas and this study therefore set out to develop and evaluate the use of a DNA vaccine against mycoplasma infections in ostriches using an OppA protein as antigen. To this end, the oppA gene of “Mycoplasma nasistruthionis sp. nov.” str. Ms03 was cloned into two DNA vaccine expression vectors after codon correction by site-directed mutagenesis. Three-months-old ostriches were then vaccinated intramuscularly at different doses followed by a booster vaccination after 6 weeks. The ability of the DNA vaccines to elicit an anti-OppA antibody response was evaluated by ELISA using the recombinant OppA protein of Ms03 as coating antigen. A statistically significant anti-OppA antibody response could be detected after administration of a booster vaccination indicating that the OppA protein was successfully immunogenic. The responses were also both dose and vector dependent. In conclusion, the DNA vaccines were able to elicit an immune response in ostriches and can therefore be viewed as an option for the development of vaccines against mycoplasma infections

From Differential DNA Methylation in COPD to Mitochondria:Regulation of AHRR Expression Affects Airway Epithelial Response to Cigarette Smoke

Cigarette smoking causes hypomethylation of the gene Aryl Hydrocarbon Receptor Repressor (AHRR), which regulates detoxification and oxidative stress-responses. We investigated whether AHRR DNA methylation is related to chronic obstructive pulmonary disease (COPD) and studied its function in airway epithelial cells (AECs). The association with COPD was assessed in blood from never and current smokers with/without COPD, and in AECs from ex-smoking non-COPD controls and GOLD stage II-IV COPD patients cultured with/without cigarette smoke extract (CSE). The effect of CRISPR/Cas9-induced AHRR knockout on proliferation, CSE-induced mitochondrial membrane potential and apoptosis/necrosis in human bronchial epithelial 16HBE cells was studied. In blood, DNA methylation of AHRR at cg05575921 and cg21161138 was lower in smoking COPD subjects than smoking controls. In vitro, AHRR DNA methylation at these CpG-sites was lower in COPD-derived than control-derived AECs only upon CSE exposure. Upon AHRR knockout, we found a lower proliferation rate at baseline, stronger CSE-induced decrease in mitochondrial membrane potential, and higher CSE-induced late apoptosis/necroptosis. Together, our results show lower DNA methylation of AHRR upon smoking in COPD patients compared to non-COPD controls. Our data suggest that higher airway epithelial AHRR expression may lead to impaired cigarette smoke-induced mitochondrial dysfunction and apoptosis/necroptosis, potentially promoting unprogrammed/immunogenic cell death

Reflecting back, looking forward: the challenges for location-based learning

This final section of the report has been reproduced from “D3.1 The STELLAR Rendez-Vous I report and white papers”, published in 2009 by the STELLAR Network of Excellence. It is included here for completeness; we, as co-authors, felt that it was important to look back at the main contributions to theworkshop and also where the challenges lie for the future. This chapter addresses two critical questions: - What has been learned from this workshop, especially in respect to the STELLAR Grand Challenges (“Connecting learners”, “Orchestration” and “Contextualisation”)? - What are the new research questions and issues for location-based learning, with respect to the Grand Challenges (“Connecting learners”, “Orchestration”and “Contextualisation”)

Alternative nano-lithographic tools for shell-isolated nanoparticle enhanced Raman spectroscopy substrates

Chemically synthesized metal nanoparticles (MNPs) have been widely used as surface-enhanced Raman spectroscopy (SERS) substrates for monitoring catalytic reactions. In some applications, however, the SERS MNPs, besides being plasmonically active, can also be catalytically active and result in Raman signals from undesired side products. The MNPs are typically insulated with a thin (∼3 nm), in principle pin-hole-free shell to prevent this. This approach, which is known as shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), offers many advantages, such as better thermal and chemical stability of the plasmonic nanoparticle. However, having both a high enhancement factor and ensuring that the shell is pin-hole-free is challenging because there is a trade-off between the two when considering the shell thickness. So far in the literature, shell insulation has been successfully applied only to chemically synthesized MNPs. In this work, we alternatively study different combinations of chemical synthesis (bottom-up) and lithographic (top-down) routes to obtain shell-isolated plasmonic nanostructures that offer chemical sensing capabilities. The three approaches we study in this work include (1) chemically synthesized MNPs + chemical shell, (2) lithographic substrate + chemical shell, and (3) lithographic substrate + atomic layer deposition (ALD) shell. We find that ALD allows us to fabricate controllable and reproducible pin-hole-free shells. We showcase the ability to fabricate lithographic SHINER substrates which report an enhancement factor of 7.5 × 103 ± 17% for our gold nanodot substrates coated with a 2.8 nm aluminium oxide shell. Lastly, by introducing a gold etchant solution to our fabricated SHINER substrate, we verified that the shells fabricated with ALD are truly pin-hole-free.</p

Microglial activation in Alzheimer's disease: an (R)-[11C]PK11195 positron emission tomography study

AbstractInflammatory mechanisms, like microglial activation, could be involved in the pathogenesis of Alzheimer's disease (AD). (R)-[11C]PK11195 (1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3-isoquinolinecarboxamide), a positron emission tomography (PET) ligand, can be used to quantify microglial activation in vivo. The purpose of this study was to assess whether increased (R)-[11C]PK11195 binding is present in AD and mild cognitive impairment (MCI), currently also known as “prodromal AD.”MethodsNineteen patients with probable AD, 10 patients with prodromal AD (MCI), and 21 healthy control subjects were analyzed. Parametric images of binding potential (BPND) of (R)-[11C]PK11195 scans were generated using receptor parametric mapping (RPM) with supervised cluster analysis. Differences between subject groups were tested using mixed model analysis, and associations between BPND and cognition were evaluated using Pearson correlation coefficients.ResultsVoxel-wise statistical parametric mapping (SPM) analysis showed small clusters of significantly increased (R)-[11C]PK11195 BPND in occipital lobe in AD dementia patients compared with healthy control subjects. Regions of interest (ROI)-based analyses showed no differences, with large overlap between groups. There were no differences in (R)-[11C]PK11195 BPND between clinically stable prodromal AD patients and those who progressed to dementia, and BPND did not correlate with cognitive function.ConclusionMicroglial activation is a subtle phenomenon occurring in AD

Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload

Abstract Background The skeletal muscle plays a central role in glucose homeostasis through the uptake of glucose from the extracellular medium in response to insulin. A number of factors are known to disrupt the normal response to insulin leading to the emergence of insulin resistance (IR). Advanced age and a high-fat diet are factors that increase the susceptibility to IR, with lipid accumulation in the skeletal muscle being a key driver of this phenomenon. It is debated, however, whether lipid accumulation arises due to dietary lipid overload or from a decline of mitochondrial function. To gain insights into the interplay of diet and age in the flexibility of muscle lipid and glucose handling, we combined lipidomics, proteomics, mitochondrial function analysis and computational modelling to investigate young and aged mice on a low- or high-fat diet (HFD). Results As expected, aged mice were more susceptible to IR when given a HFD than young mice. The HFD induced intramuscular lipid accumulation specifically in aged mice, including C18:0-containing ceramides and diacylglycerols. This was reflected by the mitochondrial β-oxidation capacity, which was upregulated by the HFD in young, but not in old mice. Conspicuously, most β-oxidation proteins were upregulated by the HFD in both groups, but carnitine palmitoyltransferase 1B (CPT1B) declined in aged animals. Computational modelling traced the flux control mostly to CPT1B, suggesting a CPT1B-driven loss of flexibility to the HFD with age. Finally, in old animals, glycolytic protein levels were reduced and less flexible to the diet. Conclusion We conclude that intramuscular lipid accumulation and decreased insulin sensitivity are not due to age-related mitochondrial dysfunction or nutritional overload alone, but rather to their combined effects. Moreover, we identify CPT1B as a potential target to counteract age-dependent intramuscular lipid accumulation and thereby IR

Estado nutricional vinculado a ingesta alimentaria y actividad física que realizan estudiantes de séptimo grado de tres colegios privados. Managua-Nicaragua. Abril-Agosto 2015.

Estudio descriptivo de corte transversal en 150 estudiantes de séptimo grado de los colegios: Mi Redentor, Bautista y Jesús Divino Obrero del departamento de Managua. Se concluye que más de la mitad de estudiantes, presentaron estado nutricional normal. Coexiste malnutrición por déficit, y por exceso, asociado al riesgo cardiovascular y antecedentes patológicos familiares de hipertensión y diabetes. El desayuno es la comida que se saltaron con mayor frecuencia. El patrón alimentario lo conforman trece alimentos. La práctica de actividades físicas que realizan: caminar, correr, montar en bicicleta, jugar futbol, voleibol y baloncesto. En la clase de educación física los alumnos están siempre y algunas veces activos