Regulatable and modulable background expression control in prokaryotic synthetic circuits by auxiliary repressor binding sites.

Expression control in synthetic genetic circuitry, for example, for construction of sensitive biosensors, is hampered by the lack of DNA parts that maintain ultralow background yet achieve high output upon signal integration by the cells. Here, we demonstrate how placement of auxiliary transcription factor binding sites within a regulatable promoter context can yield an important gain in signal-to-noise output ratios from prokaryotic biosensor circuits. As a proof of principle, we use the arsenite-responsive ArsR repressor protein from Escherichia coli and its cognate operator. Additional ArsR operators placed downstream of its target promoter can act as a transcription roadblock in a distance-dependent manner and reduce background expression of downstream-placed reporter genes. We show that the transcription roadblock functions both in cognate and heterologous promoter contexts. Secondary ArsR operators placed upstream of their promoter can also improve signal-to-noise output while maintaining effector dependency. Importantly, background control can be released through the addition of micromolar concentrations of arsenite. The ArsR-operator system thus provides a flexible system for additional gene expression control, which, given the extreme sensitivity to micrograms per liter effector concentrations, could be applicable in more general contexts.

Governance mode vs. governance fit: Performance implications of make-or-ally choices for product innovation in the worldwide aircraft industry, 1942-2000

We examine the impact of governance mode and governance fit on performance in make-or-ally decisions. We argue that while horizontal collaboration and autonomous governance have direct and countervailing performance implications, the alignment of make-or-ally choices with the focal firm's resource endowment and the activity's resource requirements leads to better performance. Data on the aircraft industry show that relative to aircraft developed autonomously, collaborative aircraft exhibit greater sales but require longer time-to-market. However, governance fit increases unit sales and reduces time-to-market. We contribute to the alliance and economic organization literatures. (Copyright © 2013 John Wiley & Sons, Ltd.)

Doses monitoring in radiology: calibration of air kerma-area product (PKA) meters

Objective The authors have sought to study the calibration of a clinical PKA meter (Diamentor E2) and a calibrator for clinical meters (PDC) in the Laboratory of Ionizing Radiation Metrology at Instituto de Energia e Ambiente - Universidade de São Paulo. Materials and Methods Different qualities of both incident and transmitted beams were utilized in conditions similar to a clinical setting, analyzing the influence from the reference dosimeter, from the distance between meters, from the filtration and from the average beam energy. Calibrations were performed directly against a standard 30 cm3 cylindrical chamber or a parallel-plate monitor chamber, and indirectly against the PDC meter. Results The lowest energy dependence was observed for transmitted beams. The cross calibration between the Diamentor E2 and the PDC meters, and the PDC presented the greatest propagation of uncertainties. Conclusion The calibration coefficient of the PDC meter showed to be more stable with voltage, while the Diamentor E2 calibration coefficient was more variable. On the other hand, the PDC meter presented greater uncertainty in readings (5.0%) than with the use of the monitor chamber (3.5%) as a reference.

Synthetic long peptide-based vaccine formulations for induction of cell mediated immunity: A comparative study of cationic liposomes and PLGA nanoparticles.

Nanoparticulate formulations for synthetic long peptide (SLP)-cancer vaccines as alternative to clinically used Montanide ISA 51- and squalene-based emulsions are investigated in this study. SLPs were loaded into TLR ligand-adjuvanted cationic liposomes and PLGA nanoparticles (NPs) to potentially induce cell-mediated immune responses. The liposomal and PLGA NP formulations were successfully loaded with up to four different compounds and were able to enhance antigen uptake by dendritic cells (DCs) and subsequent activation of T cells in vitro. Subcutaneous vaccination of mice with the different formulations showed that the SLP-loaded cationic liposomes were the most efficient for the induction of functional antigen-T cells in vivo, followed by PLGA NPs which were as potent as or even more than the Montanide and squalene emulsions. Moreover, after transfer of antigen-specific target cells in immunized mice, liposomes induced the highest in vivo killing capacity. These findings, considering also the inadequate safety profile of the currently clinically used adjuvant Montanide ISA-51, make these two particulate, biodegradable delivery systems promising candidates as delivery platforms for SLP-based immunotherapy of cancer.

Compostos de platina em quimioterapia do câncer

The vast majority of clinically used antitumor drugs are either synthetic or natural product based organic compounds. In this review we describe different aspects, such as structure-activity relationships, mechanism of action, clinical uses and possible future prospects, of the platinum antitumor complexes, a distinct class of antitumor agents.

The wide synthetic versatility of five membered rings containing phosphorus

The chemistry of cyclopentadiene rings has been widely studied. This review article deals with a similar chemistry of new compounds containing from 1 to 5 phosphorus atoms on the ring substituting the carbon atoms. The neutral rings containing one, two and three phosphorus atoms can be used as building blocks for the synthesis of new organic compounds containing phosphorus. These rings plus the anionic ones also show great potential as ligands in coordination chemistry. The aim of this article is to show how important this new area is and how diverse the chemistry related to a single type of ring can be.

Economia de átomos, engenharia molecular e catálise organometálica bifásica: conceitos moleculares para tecnologias limpas

For economical and ecological reasons, synthetic chemists are confronted with the increasing obligation of optimizing their synthetic methods. Maximizing efficiency and minimizing costs in the production of molecules and macromolecules constitutes, therefore, one of the most exciting challenges of synthetic chemistry. The ideal synthesis should produce the desired product in 100% yield and selectivity, in a safe and environmentally acceptable process. In this highlight the concepts of atom economy, molecular engineering and biphasic organometallic catalysis, which address these issues at the molecular level for the generation of "green" technologies, are introduced and discussed.

Offering planning process development: Bridging the Offering Gaps and Consolidating Top Priority Needs in Product Offering

The aim of this Thesis is to study how to manage the front-end of the offering planning process. This includes actual process development and methods to gather and analyze information to achieve the best outcome in customer oriented product offering. Study is carried out in two parts: theoretical part and company related part. Theoretical framework is created introducing different types of approaches to manage product planning processes. Products are seen as platforms and they are broken down to subsystems to show different parts of the development. With the help of the matrix-based approaches product platform related information is gathered and analyzed. In this kind of analysis business/market drivers and cus-tomer/competitor information are connected with product subsystems. This gives possibilities to study product gaps/needs and possible future ideas/scenarios in different customer segments. Company related part consists of offering planning process development in real company environment. Process formation includes documents and tools that guide planning from the information gathering to the prioritization and decision making.

Assessment of an information product project success: case business blueprint

The objective of this study was to find out how project success can be measured in a case where the output of a project is an intangible information product, what kind of framework can be used to evaluate the project success, and how the project assessment can be done in practice. As a case example, the success of a business blueprint project was assessed from the product point of view. A framework for assessing business blueprint project success was made based on a literature review. Furthermore, separate frameworks for measuring information product quality and project costs were developed. The theory of business blueprinting was discovered not to be firmly institutionalized and it is briefly covered in the thesis. The possible net benefits from the strategic business process harmonization were noted to be much more significant than the costs of the business blueprint project. The project was seen as a sufficient success from the viewpoint of the created output.

Creating Global Competitive Advantage by Global Product Technology Transfers

Globalization is the trend which is realized in all areas in today’s business world. Pressure for cost reduction, changes in market situation and available scale economies have changed business environment more global than ever. To respond to new situation, companies are establishing global strategies. In this thesis, available global competitive advantages in electrical machine industry are studied in context of gaining them by global technology transfers. In theory part, establishing global strategy and competitive advantage is considered with connection to global sourcing and supply chain management. Additionally, market development in 21st century and its impact on global strategies is studied. In practice, global manufacturing is enabled by technology transfer projects. Smooth and fast project implementation enables faster and more flexible production ramp up. By starting the production available competitive advantages can be realized. In this thesis the present situation of technology transfer projects and the risks and advantages related to global manufacturing are analyzed. The analysis of implemented technology transfer projects indicates that project implementation is in good level. For further development of project execution 10 minor suggestions could be presented with two major ones: higher level standardization and development of product information model to support better global manufacturing.

Preparation and phytotoxicity of sorgoleone analogues

3,5-Dimethoxybenzylic alcohol was converted into the 2-acetoxy-5-methoxy-3-(pent-1-yl)-1,4-benzoquinone (12), in seven steps, with an overall yield of 14.6%. The natural quinone sorgoleone (1) was isolated from Sorghum bicolor and converted into the corresponding quinone (13) having a saturated side chain. The selective effects of these compounds (1, 12 and 13), at the dose of 5.6 mug of a.i./ g of substrate, on the growth of Cucumis sativus, Lactuca sativa, Desmodium tortuosum, Hyptis suaveolens and Euphorbia heterophylla were evaluated. All three compounds caused some inhibition on the root growth of the test plants (0.0-69.19%) with the aerial parts less affected. The results showed that the triene unit of the sorgoleone side chain is not essential for the phytotoxicity and also the synthetic quinone was as active as the natural product.

Structuration and branding of a religious tourism product: Catalonia sacra

This article aims to provide an overview of the products Catalonia has to offer in terms of religious tourism. The growing interest in this kind of tourism worldwide, and in Catalonia itself, along with the region's wealth of religious heritage (particularly connected to the Christian Church) contrast with the lack of religion-based tourism products available, which results in its absence from the region's image as a tourism destination. In view of this, the Faculty of Tourism (University of Girona), the Vic Bishopric's Albergueria-Centre for Cultural Dissemination and the Tarraconense Episcopal Conference's Interdiocese Secretariat for the Custody and Promotion of Holy Art (SICPAS) decided to address the situation with the help of funding from the Autonomous Government of Catalonia. In order to re-position Christian religious heritage in the image of Catalonia as a tourist destination, the aforementioned parties embarked upon a project to set up a series of routes throughout the region, branded under the name Catalonia Sacra

Estratégia de simplificação molecular no planejamento racional de fármacos: a descoberta de novo agente cardioativo

In this article are described examples of the successful use of molecular simplification strategy in the discovery of new drugs from bioactive natural products and synthetic compounds. The discovery of a new cardiotonic derivative (37, 2-thienylidene-3,4-methylenedioxybenzoylhydrazine; LASSBio-294), efficiently synthesized from Brazilian natural product and structurally designed by molecular simplification of active pyridazinone compounds reported in the literature, is described. A brief description of the pharmacological profile of this new cardiotonic lead-compound, belonging to the N-acylhydrazone (NAH) class, is also reported herein.