THE DISCOVERY AND CHARACTERIZATION OF NOVEL POTENT 5-SUBSTITUTED 3, 3’, 4’, 7-TETRAMETHOXYFLAVONOID DNA TRIPLEX SPECIFIC BINDING LIGANDS

Chemotherapy works by killing fast dividing cells. Unfortunately, these drugs are not specific to cancer tissue and can damage normal cells. Chemotherapy is like taking poison and hoping it kills the cancer cells before it kills you. As an alternative, many researchers have investigated the use of antigene therapy to selectively target cancer causing genes to avoid off target effects. Although promising, the theory is limited by the stability of the triplex structure. Here, we report the discovery of potent triplex binding ligands derived from the natural product quercetin. Chemical derivatives of 5-substituted 3, 3’, 4’, 7-tetramethoxyquercetin derivatives were characterized using several biophysical methods: thermal denaturation monitored by UV, circular dichroism, viscometry, differential scanning calorimetry, and isothermal titration calorimetry. The data revealed that these derivatives specifically stabilize triplex DNA and do not influence the stability of duplex DNA, triple RNA, or duplex RNA. Structurally, the amino containing side chains at the 5-position and the linker length are critical for the observed binding affinity and specificity. Two derivatives, 5 and 7, are comparable (if not better) to the triplex groove binder Neomycin. Our data confirm the binding mode as enthalpically driven intercalation. Piperidine or pyrrolidine 5-substituted 3, 3’, 4’, 7-tetramethoxyquercetin derivatives with a three-carbon linker are the lead compounds for development as a potential antigene enhancer

Empathic choice involves vmPFC value signals that are modulated by social processing implemented in IPL

Empathic decision-making involves making choices on behalf of others in order to maximize their well-being. Examples include the choices that parents make for their children, as well as the decisions of a politician trying to make good choices on behalf of his constituency. We investigated the neurobiological and computational basis of empathic choice using a human fMRI task in which subjects purchased DVDs for themselves with their own money, or DVDs for others with the other's money. We found that empathic choices engage the same regions of ventromedial prefrontal cortex that are known to compute stimulus values, and that these value signals were modulated by activity from a region of inferior parietal lobule (IPL) known to play a critical role in social processes such as empathy. We also found that the stimulus value signals used to make empathic choices were computed using a mixture of self-simulation and other-simulation processes, and that activity in IPL encoded a variable measuring the distance between the other's and self preferences, which provides a hint for how the mixture of self- and other-simulation might be implemented

Nuevas tecnologías y necesidades formativas de los directivos de comunicación en Andalucía

En esta era que algunos autores denominan mediática-digital, todos los agentes sociales y económicos requieren un amplio conocimiento y una correcta implementación de las estrategias de comunicación para convertir la comunicación en una clara ventaja competitiva y de creación de valor. En Andalucía, el desarrollo paulatino de la sociedad en los últimos 20 años han iniciado una serie de acontecimientos que cristalizan en una nueva etapa económico y social. En concreto, surge un tejido empresarial compuesto en su mayor parte por las denominadas pymes (pequeñas y medianas empresas) donde la comunicación surge como una necesidad. No obstante, carecen de departamentos propios de comunicación razón por la que subcontratan consultoras como departamentos externos de comunicación. Este artículo pretende abordar la formación y las características generales de los directivos del ámbito de las relaciones públicas en Andalucía partiendo de la siguiente premisa: la figura del Director de Comunicación parece cada vez más sólidamente asentada en las estructuras organizacionales con perfiles más precisos y con titulaciones cada vez más relacionadas con las relaciones públicas

Media Naturalness Reduction and Compensatory Channel Expansion: A Study of Online and Face-to-face Sections of the Same Course

The study discussed here provides a test of media naturalness and channel expansion theories’ predictions in the context of university online learning. Data was collected from undergraduate students at the middle and end of a long semester in which the students took an introductory course in management information systems. Approximately half of the students took the course face-to-face, and the other half online. As predicted based on media naturalness theory, perceived communication ambiguity and cognitive effort were higher in the online than in the face-to-face condition. As a result, grades were significantly higher in the face-to-face than the online condition at the middle of the semester. Consistently with predictions based on channel expansion theory, the difference between grades obtained at the middle of the semester disappeared at the end of the semester

Serving Americans Well: Removing Bureaucracy to Help Americans Access Tax Credits

While tax credits can be incredibly effective at helping families afford basic needs and lifting working families out of poverty, the process of claiming them is difficult and confusing for many low- and middle-income families. Even among savvy tax filers, confusion is common. Additional barriers pervade the system for very low-income families, making it difficult for the people who need tax credits the most to get them. The IRS has made progress towards a simpler process, however much more needs to be done to ensure all Americans are served well by our tax filing system. While this issue has sadly become a political football, at root it is simply a matter of making our government work better for taxpayers. Simplifying eligibility for tax credits and removing extra bureaucracy in the process would immediately reduce childhood poverty and material hardship and translate to various long-term positive outcomes for families and society at large. Based on lessons learned from three years of work helping thousands of families in Illinois access their stimulus checks and Child Tax Credits, this paper translates the experiences of hard-working families into a series of policy recommendations from the Chicago team

Performance control considering risks for construction projects

Making decisions during the building phase of a project is much important for their success. To support that process, it has developed the Earned Value Management system which considers scope, time and cost to measure the project performance and to identify variances from the original plan. By identifying performance variances, the Project Manager has to do corrective actions for correcting the course of the project. The EVM is a deterministic method so any variance reported is considered a performance problem that needs to be attended. This characteristic is currently considered a weakness of the method for being applied in daily operations. The paper presents an EVM-based method for controlling time and cost that allows the project manager to determine when really needed corrective actions are. The proposal was applied in a construction project to evaluate its utility

Performance control considering risks for construction projects

Making decisions during the building phase of a project is much important for their success. To support that process, it has developed the Earned Value Management system which considers scope, time and cost to measure the project performance and to identify variances from the original plan. By identifying performance variances, the Project Manager has to do corrective actions for correcting the course of the project. The EVM is a deterministic method so any variance reported is considered a performance problem that needs to be attended. This characteristic is currently considered a weakness of the method for being applied in daily operations. The paper presents an EVM-based method for controlling time and cost that allows the project manager to determine when really needed corrective actions are. The proposal was applied in a construction project to evaluate its utility

Synthesis of FeTi hydrogen storage material via ball milling: effect of milling energy and atmosphere.

Attempts were made earlier to synthesize and activate the FeTi intermetallic during ball milling (BM), for H2 storage using sodium boron tetra-hydride (NaBH4) additive as a process controlling agent. Simple reactive milling starting from Fe and Ti powders resulted in heavy agglomeration of powders, due to the self sustaining nature of the reaction following an incubation period. When NaBH4 was used as the process control agent to avoid agglomeration, this resulted in the production of titanium hydride besides FeTi, and as a consequence unfavorable irreversibility in the subsequent hydrogen charging/discharging cycles [1,2,12]. The present work reports on modifications introduced in the synthesis process by changing two processing parameters, namely the milling energy and atmosphere compositio