Generation of long, fully modified, and serum-resistant oligonucleotides by rolling circle amplification

Rolling Circle Amplification (RCA) is an isothermal enzymatic method generating single-stranded DNA products consisting of concatemers containing multiple copies of the reverse complement of the circular template precursor. Little is known on the compatibility of modified nucleoside triphosphates (dN*TPs) with RCA, which would enable the synthesis of long, fully modified ssDNA sequences. Here, dNTPs modified at any position of the scaffold were shown to be compatible with rolling circle amplification, yielding long (>1 kb), and fully modified single-stranded DNA products. This methodology was applied for the generation of long, cytosine-rich synthetic mimics of telomeric DNA. The resulting modified oligo-nucleotides displayed an improved resistance to fetal bovine serum.

Generation of Aptamers with an Expanded Chemical Repertoire

The enzymatic co-polymerization of modified nucleoside triphosphates (dN*TPs and N*TPs) is a versatile method for the expansion and exploration of expanded chemical space in SELEX and related combinatorial methods of in vitro selection. This strategy can be exploited to generate aptamers with improved or hitherto unknown properties. In this review, we discuss the nature of the functionalities appended to nucleoside triphosphates and their impact on selection experiments. The properties of the resulting modified aptamers will be described, particularly those integrated in the fields of biomolecular diagnostics, therapeutics, and in the expansion of genetic systems (XNAs).

Development of a method for fast and automatic radiocarbon measurement of aerosol samples by online coupling of an elemental analyzer with a MICADAS AMS

A fast and automatic method for radiocarbon analysis of aerosol samples is presented. This type of analysis requires high number of sample measurements of low carbon masses, but accepts precisions lower than for carbon dating analysis. The method is based on online Trapping CO2 and coupling an elemental analyzer with a MICADAS AMS by means of a gas interface. It gives similar results to a previously validated reference method for the same set of samples. This method is fast and automatic and typically provides uncertainties of 1.5–5% for representative aerosol samples. It proves to be robust and reliable and allows for overnight and unattended measurements. A constant and cross contamination correction is included, which indicates a constant contamination of 1.4 ± 0.2 μg C with 70 ± 7 pMC and a cross contamination of (0.2 ± 0.1)% from the previous sample. A Real-time online coupling version of the method was also investigated. It shows promising results for standard materials with slightly higher uncertainties than the Trapping online approach.

Improving residency training with the help of multisource feedback: Generation of a model of influencing factors

Background: Feedback is considered to be one of the most important drivers of learning. One form of structured feedback used in medical settings is multisource feedback (MSF). This feedback technique provides the opportunity to gain a differentiated view on a doctor’s performance from several perspectives using a questionnaire and a facilitating conversation, in which learning goals are formulated. While many studies have been conducted on the validity, reliability and feasibility of the instrument, little is known about the impact of factors that might influence the effects of MSF on clinical performance. Summary of Work: To study under which circumstances MSF is most effective, we performed a literature review on Google Scholar with focus on MSF and feedback in general. Main key-words were: MSF, multi-source-feedback, multi source feedback, and feedback each combined with influencing/ hindering/ facilitating factors, effective, effectiveness, doctors-intraining, and surgery. Summary of Results: Based on the literature, we developed a preliminary model of facilitating factors. This model includes five main factors influencing MSF: questionnaire, doctor-in-training, group of raters, facilitating supervisor, and facilitating conversation. Discussion and Conclusions: Especially the following points that might influence MSF have not yet been sufficiently studied: facilitating conversation with the supervisor, individual aspects of doctors-in-training, and the causal relations between influencing factors. Overall there are only very few studies focusing on the impact of MSF on actual and long-term performance. We developed a preliminary model of hindering and facilitating factors on MSF. Further studies are needed to better understand under which circumstances MSF is most effective. Take-home messages: The preliminary model might help to guide further studies on how to implement MSF to use it at its full potential.

Generation of an hTERT-restricted, CMV-augmented oncolytic adenovirus capable of tumor-specific transgene expression: Development, characterization, and optimization

Current shortcomings in cancer therapy require the generation of new, broadly applicable, potent, targeted treatments. Here, an adenovirus is engineered to replicate specifically in cells with active human telomerase promotion using a modified hTERT promoter, fused to a CMV promoter element. The virus was also modified to contain a visible reporter transgene, GFP. The virus, Ad/hTC-GFP-E1 was characterized in vitro and demonstrated tumor specific activity both by dose and over time course experiments in a variety of cell lines. In vivo, Ad/hTC-GFP-E1 was affected at suppressing tumor growth and providing a survival benefit without causing any measurable toxicity. To increase the host range of the vector, the fiber region was modified to contain an RGD-motif. The vector, AdRGD/hTC-GFP-E1, was recharacterized in vitro, revealing heightened levels of infectivity and toxicity however maintaining a therapeutic window between cancer and normal cell toxicity. AdRGD/hTC-GFP-E1 was administered in vivo by limb perfusion and was observed to be tumor specific both in expression and replication. To further enhance the efficacy of viral vectors in lung delivery, asthma medications were investigated for their abilities to enhance transgene delivery and expression. A combination of bronchodilators, mast cell inhibitors, and mucolytic agents was devised which demonstrated fold increases in expression in immunocompetent mouse lungs as single agents and more homogenous, intense levels of expression when done in combination of all agents. To characterize the methods in which some cancers are resistant or may become resistant to oncolytic treatments, several small molecule inhibitors of metabolic pathways were applied in combination with oncolytic infection in vitro. SP600125 and PD 98059, respective JNK and ERK inhibitors, successfully suppressed oncolytic toxicity, however did not affect infectivity or transgene expression of Ad/hTC-GFP-E1. JNK and ERK inhibition did significantly suppress viral replication, however, as analyzed by lysate transfer and titration assays. In contrast, SB 203580, an inhibitor for p38, did not demonstrate any protective effects with infected cells. Flow cytometric analysis indicated a possible correlation with G1 arrest and suppressed viral production, however more compounds must be investigated to clarify this observation. ^

Policies and Education in Latin America : From the 'competitive quality' to 'quality for the generation of bicentenary'

En América Latina la injerencia de los organismos internacionales en la política nacional constituye un fenómeno que no se puede soslayar. Se trata de una cuestión candente en el contexto actual y remite a la presencia creciente en los países de la región de una serie de papers, documentos, boletines que, generados en el seno de dichas entidades, señalan desafíos presentes y futuros que deberá atender América Latina. En el campo educativo, marcan las orientaciones de política para la región y representan discursos sobre la educación que es menester analizar críticamente. El objetivo de este trabajo es analizar una serie de ideas, recomendaciones y retóricas político-pedagógicas de los Organismos Internacionales respecto de la denominada calidad de la educación en América Latina con la intención de poner de manifiesto su productividad discursiva en tanto su incidencia está ligada a significantes que operan ordenando las disputas político-discursivas del campo educativo

Policies and Education in Latin America : From the 'competitive quality' to 'quality for the generation of bicentenary'

En América Latina la injerencia de los organismos internacionales en la política nacional constituye un fenómeno que no se puede soslayar. Se trata de una cuestión candente en el contexto actual y remite a la presencia creciente en los países de la región de una serie de papers, documentos, boletines que, generados en el seno de dichas entidades, señalan desafíos presentes y futuros que deberá atender América Latina. En el campo educativo, marcan las orientaciones de política para la región y representan discursos sobre la educación que es menester analizar críticamente. El objetivo de este trabajo es analizar una serie de ideas, recomendaciones y retóricas político-pedagógicas de los Organismos Internacionales respecto de la denominada calidad de la educación en América Latina con la intención de poner de manifiesto su productividad discursiva en tanto su incidencia está ligada a significantes que operan ordenando las disputas político-discursivas del campo educativo

Policies and Education in Latin America : From the 'competitive quality' to 'quality for the generation of bicentenary'

En América Latina la injerencia de los organismos internacionales en la política nacional constituye un fenómeno que no se puede soslayar. Se trata de una cuestión candente en el contexto actual y remite a la presencia creciente en los países de la región de una serie de papers, documentos, boletines que, generados en el seno de dichas entidades, señalan desafíos presentes y futuros que deberá atender América Latina. En el campo educativo, marcan las orientaciones de política para la región y representan discursos sobre la educación que es menester analizar críticamente. El objetivo de este trabajo es analizar una serie de ideas, recomendaciones y retóricas político-pedagógicas de los Organismos Internacionales respecto de la denominada calidad de la educación en América Latina con la intención de poner de manifiesto su productividad discursiva en tanto su incidencia está ligada a significantes que operan ordenando las disputas político-discursivas del campo educativo

Next Generation of Energy Residential Gateways for Demand Response and Dynamic Pricing

Predictions about electric energy needs, based on current electric energy models, forecast that the global energy consumption on Earth for 2050 will double present rates. Using distributed procedures for control and integration, the expected needs can be halved. Therefore implementation of Smart Grids is necessary. Interaction between final consumers and utilities is a key factor of future Smart Grids. This interaction is aimed to reach efficient and responsible energy consumption. Energy Residential Gateways (ERG) are new in-building devices that will govern the communication between user and utility and will control electric loads. Utilities will offer new services empowering residential customers to lower their electric bill. Some of these services are Smart Metering, Demand Response and Dynamic Pricing. This paper presents a practical development of an ERG for residential buildings.

Methodology for automated generation of multiple choice questions in self assessment

Current trends in the European Higher Education Area (EHEA) are moving towards the continuous evaluation of the students in substitution of the traditional evaluation based on a single test or exam. This fact and the increase in the number of students during last years in Engineering Schools, requires to modify evaluation procedures making them compatible with the educational and research activities. This work presents a methodology for the automatic generation of questions. These questions can be used as self assessment questions by the student and/or as queries by the teacher. The proposed approach is based on the utilization of parametric questions, formulated as multiple choice questions and generated and supported by the utilization of common programs of data sheets and word processors. Through this approach, every teacher can apply the proposed methodology without the use of programs or tools different from those normally used in his/her daily activity

Generation of reduced certificates in abstraction-carrying code

Abstraction-Carrying Code (ACC) has recently been proposed as a framework for mobile code safety in which the code supplier provides a program together with an abstraction whose validity entails compliance with a predefined safety policy. The abstraction plays thus the role of safety certifícate and its generation is carried out automatically by a fixed-point analyzer. The advantage of providing a (fixedpoint) abstraction to the code consumer is that its validity is checked in a single pass of an abstract interpretation-based checker. A main challenge is to reduce the size of certificates as much as possible while at the same time not increasing checking time. In this paper, we first introduce the notion of reduced certifícate which characterizes the subset of the abstraction which a checker needs in order to validate (and re-construct) the full certifícate in a single pass. Based on this notion, we then instrument a generic analysis algorithm with the necessary extensions in order to identify the information relevant to the checker.

e-MIR2: a public online inventory of medical informatics resources

Background. Over the last years, the number of available informatics resources in medicine has grown exponentially. While specific inventories of such resources have already begun to be developed for Bioinformatics (BI), comparable inventories are as yet not available for Medical Informatics (MI) field, so that locating and accessing them currently remains a hard and time-consuming task. Description. We have created a repository of MI resources from the scientific literature, providing free access to its contents through a web-based service. Relevant information describing the resources is automatically extracted from manuscripts published in top-ranked MI journals. We used a pattern matching approach to detect the resources? names and their main features. Detected resources are classified according to three different criteria: functionality, resource type and domain. To facilitate these tasks, we have built three different taxonomies by following a novel approach based on folksonomies and social tagging. We adopted the terminology most frequently used by MI researchers in their publications to create the concepts and hierarchical relationships belonging to the taxonomies. The classification algorithm identifies the categories associated to resources and annotates them accordingly. The database is then populated with this data after manual curation and validation. Conclusions. We have created an online repository of MI resources to assist researchers in locating and accessing the most suitable resources to perform specific tasks. The database contained 282 resources at the time of writing. We are continuing to expand the number of available resources by taking into account further publications as well as suggestions from users and resource developers.