Promotion of purine nucleotide binding to thymidylate synthase by a potent folate analogue inhibitor, 1843U89.

A folate analogue, 1843U89 (U89), with potential as a chemotherapeutic agent due to its potent and specific inhibition of thymidylate synthase (TS; EC 2.1.1.45), greatly enhances not only the binding of 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and dUMP to Escherichia coli TS but also that of dGMP, GMP, dIMP, and IMP. Guanine nucleotide binding was first detected by CD analysis, which revealed a unique spectrum for the TS-dGMP-U89 ternary complex. The quantitative binding of dGMP relative to GMP, FdUMP, and dUMP was determined in the presence and absence of U89 by ultrafiltration analysis, which revealed that although the binding of GMP and dGMP could not be detected in the absence of U89 both were bound in its presence. The Kd for dGMP was about the same as that for dUMP and FdUMP, with binding of the latter two nucleotides being increased by two orders of magnitude by U89. An explanation for the binding of dGMP was provided by x-ray diffraction studies that revealed an extensive stacking interaction between the guanine of dGMP and the benzoquinazoline ring of U89 and hydrogen bonds similar to those involved in dUMP binding. In addition, binding energy was provided through a water molecule that formed hydrogen bonds to both N7 of dGMP and the hydroxyl of Tyr-94. Accommodation of the larger dGMP molecule was accomplished through a distortion of the active site and a shift of the deoxyribose moiety to a new position. These rearrangements also enabled the binding of GMP to occur by creating a pocket for the ribose 2' hydroxyl group, overcoming the normal TS discrimination against nucleotides containing the 2' hydroxyl.

Customer response to media in marketing promotion: print versus online

Il lavoro di tesi, che si compone di tre articoli di ricerca, analizza, nel contesto della marketing promotion, la risposta del consumatore ai media in termini di ricordo, intenzione di acquisto, comportamento di acquisto e preferenza per il medium. Il lavoro, in particolare, mette a confronto due tipologie di media, carta e online, nell’ambito della price e loyalty promotion, utilizzando due disegni di ricerca sperimentali ed uno correlazionale. I risultati del lavoro mostrano che la risposta del consumatore alla comunicazione promozionale e ai media è eterogenea: segmenti di clienti diversi rispondono in maniera differente sia alla comunicazione promozionale che a carta e digitale. Online e carta hanno in media la stessa efficacia sui comportamenti di acquisto dei clienti, ma differiscono rispetto all’effetto su ricordo e atteggiamento e rispetto alla preferenza per il medium espressa dalla clientela. Lo spostamento delle risorse di marketing dalla carta al digitale permetterebbe quindi di ridurre i costi mantenendo lo stesso livello di efficacia. Inoltre, il presente lavoro mostra come sia possibile aumentare la risposta dei consumatori ai media attraverso un approccio di segmentazione della clientela.

Assessment and Promotion of Partner Support: A Prevention-Focused Intervention for Perinatal Depression in Primary Care

Perinatal depression significantly impacts the mother, her partner, the unborn fetus, and the infant/child after delivery. A review of the literature supports the need for preventive intervention methods as research has shown that even with successful treatment, disruptions in attachment, temperament, and cognitive development often remain. Primary care settings are ideal targets for prevention given that they can reach a number of people at low-cost without the stigma associated with seeking help in a mental health facility. This paper purposes a preventive intervention method for perinatal depression that can be implemented in primary care settings in both Western and non-Western countries. The intervention targets two of the primary risk factors for perinatal depression; partner support and relationship quality. The intervention is structured around key target periods in gestational development and during the early weeks after delivery. Suggestions for each target visit are based on prior research that has demonstrated how psychoeducation about the transition to parenthood, as well as increased communication, can positively affect partner support and relationship quality. The ultimate goal of the intervention is not only to prevent perinatal depression but also to improve the mental health and wellbeing of the entire family system.

Modulation of the Silica Sol–Gel Composition for the Promotion of Direct Electron Transfer to Encapsulated Cytochrome c

The direct electron transfer between indium–tin oxide electrodes (ITO) and cytochrome c encapsulated in different sol–gel silica networks was studied. Cyt c@silica modified electrodes were synthesized by a two-step encapsulation method mixing a phosphate buffer solution with dissolved cytochrome c and a silica sol prepared by the alcohol-free sol–gel route. These modified electrodes were characterized by cyclic voltammetry, UV–vis spectroscopy, and in situ UV–vis spectroelectrochemistry. The electrochemical response of encapsulated protein is influenced by the terminal groups of the silica pores. Cyt c does not present electrochemical response in conventional silica (hydroxyl terminated) or phenyl terminated silica. Direct electron transfer to encapsulated cytochrome c and ITO electrodes only takes place when the protein is encapsulated in methyl modified silica networks.

Endophytic colonization of barley (Hordeum vulgare) roots by the nematophagous fungus Pochonia chlamydosporia reveals plant growth promotion and a general defense and stress transcriptomic response

Plant crop yields are negatively conditioned by a large set of biotic and abiotic factors. An alternative to mitigate these adverse effects is the use of fungal biological control agents and endophytes. The egg-parasitic fungus Pochonia chlamydosporia has been traditionally studied because of its potential as a biological control agent of plant-parasitic nematodes. This fungus can also act as an endophyte in monocot and dicot plants, and has been shown to promote plant growth in different agronomic crops. An Affymetrix 22K Barley GeneChip was used in this work to analyze the barley root transcriptomic response to P. chlamydosporia root colonization. Functional gene ontology (GO) and gene set enrichment analyses showed that genes involved in stress response were enriched in the barley transcriptome under endophytism. An 87.5 % of the probesets identified within the abiotic stress response group encoded heat shock proteins. Additionally, we found in our transcriptomic analysis an up-regulation of genes implicated in the biosynthesis of plant hormones, such as auxin, ethylene and jasmonic acid. Along with these, we detected induction of brassinosteroid insensitive 1-associated receptor kinase 1 (BR1) and other genes related to effector-triggered immunity (ETI) and pattern-triggered immunity (PTI). Our study supports at the molecular level the growth-promoting effect observed in plants endophytically colonized by P. chlamydosporia, which opens the door to further studies addressing the capacity of this fungus to mitigate the negative effects of biotic and abiotic factors on plant crops.

Records of the Society for the Promotion of Theological Education at Harvard University, 1788-1853 (inclusive), 1816-1853 (bulk)

Includes minutes and other records, 1816-1829, of the trustees of the Society and other correspondence relating to the founding of the Society; treasurer's reports, 1843-1844, of J.G. Palfrey; lists of beneficiaries, 1824- 1830; and subscription receipts, 1819-1823. Also records regarding subscriptions for a professorship, 1828, an extract from the will of J.D. Williams, and legal matters. For more detailed information about records, see Harvard Archives LOCATION below.

The European Union's promotion of regional economic integration in Southeast Asia: Norms, markets or both? Bruges Political Research Paper No. 25/May 2012

The EU‘s external action includes a preference for regional interlocutors and a tendency to promote regionalism. This work concentrates on the southeast Asian area and it aims at investigating the nature of EU‘s promotion of ASEAN regional integration. The EU‘s ideas and practices of regionalism as well as the single market experience influence the EU‘s international action. The power deriving from the EU‘s institutionalized market is used by the Union in a normative way to diffuse the EU‘s ideas and principles, advance the EU‘s interests and spread its model of economic integration through political dialogue, development cooperation and preferential trade arrangements. This action seems to result in a certain diffusion of the EU‘s ideas and practices in southeast Asia as well as in a subsequent reappropriation and redefinition of external inputs by ASEAN.

Why EU promotion is at odds with successful crisis management: public relations, news coverage, and the Aceh Monitoring Mission. EU Centre in Singapore Working Paper No. 10, September 2012

The EU’s Common Foreign and Security Policy (CFSP) and its accompanying Common Security and Defence Policy (CSDP) missions can be tools used to increase the international profile of the European Union. Nevertheless, CSDP missions garner little news coverage. This article argues that the very nature of the missions themselves makes them poor vehicles for EU promotion for political, institutional, and logistical reasons. By definition, they are conducted in the middle of crises, making news coverage politically sensitive. The very act of reporting could undermine the mission. Institutionally, all CSDP missions are intergovernmental, making press statements slow, overly bureaucratic, and of little interest to journalists. Logistically, the missions are often located in remote, undeveloped parts of the world, making it difficult and expensive for European and international journalists to cover. Moreover, these regions in crisis seldom have a thriving, local free press. Using the Aceh Monitoring Mission (AMM) as a case study, the author concludes that although a mission may do good, CSDP missions cannot fulfil the political function of raising the profile of the EU.