Multi-fluorescent silica colloids for encoding large combinatorial libraries

Large chemical libraries can be synthesized on solid-support beads by the combinatorial split-and-mix method. A major challenge associated with this type of library synthesis is distinguishing between the beads and their attached compounds. A new method of encoding these solid-support beads, 'colloidal bar-coding', involves attaching fluorescent silica colloids ('reporters') to the beads as they pass through the compound synthesis, thereby creating a fluorescent bar code on each bead. In order to obtain sufficient reporter varieties to bar code extremely large libraries, many of the reporters must contain multiple fluorescent dyes. We describe here the synthesis and spectroscopic analysis of various mono- and multi-fluorescent silica particles for this purpose. It was found that by increasing the amount of a single dye introduced into the particle reaction mixture, mono- fluorescent silica particles of increasing intensities could be prepared. This increase was highly reproducible and was observed for six different fluorescent dyes. Multi-fluorescent silica particles containing up to six fluorescent dyes were also prepared. The resultant emission intensity of each dye in the multi-fluorescent particles was found to be dependent upon a number of factors; the hydrolysis rate of each silane-dye conjugate, the magnitude of the inherent emission intensity of each dye within the silica matrix, and energy transfer effects between dyes. We show that by varying the relative concentration of each silane-dye conjugate in the synthesis of multi-fluorescent particles, it is possible to change and optimize the resultant emission intensity of each dye to enable viewing in a fluorescence detection instrument.

Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII

The selection, synthesis and chromatographic evaluation of a synthetic affinity adsorbent for human recombinant factor VIIa is described. The requirement for a metal ion-dependent immunoadsorbent step in the purification of the recombinant human clotting factor, FVIIa, has been obviated by using the X-ray crystallographic structure of the complex of tissue factor (TF) and Factor VIIa and has directed our combinatorial approach to select, synthesise and evaluate a rationally-selected affinity adsorbent from a limited library of putative ligands. The selected and optimised ligand comprises a triazine scaffold bis-substituted with 3-aminobenzoic acid and has been shown to bind selectively to FVIIa in a Ca2+-dependent manner. The adsorbent purifies FVIIa to almost identical purity (>99%), yield (99%), activation/degradation profile and impurity content (∼1000 ppm) as the current immunoadsorption process, while displaying a 10-fold higher static capacity and substantially higher reusability and durability. © 2002 Elsevier Science B.V. All rights reserved.

Exploring privileged structures: the combinatorial synthesis of cyclic peptides

Head-to-tail cyclic peptides have been reported to bind to multiple, unrelated classes of receptor with high affinity. They may therefore be considered to be privileged structures. This review outlines the strategies by which both macrocyclic cyclic peptides and cyclic dipeptides or diketopiperazines have been synthesised in combinatorial libraries. It also briefly outlines some of the biological applications of these molecules, thereby justifying their inclusion as privileged structures.

Teaching and learning mathematics using moodle

This paper summarizes a project that is contributing to a change in the way of teaching and learning Mathematics. Mathematics is a subject of the Accounting and Administration course. In this subject we teach: Functions and Algebra. The aim is that the student understand the basic concepts and is able to apply them in other issues, when possible, establishing a bridge between the issues that they have studied and their application in Accounting. As from this year, the Accounting course falls under in Bologna Process. The teacher and the student roles have changed. The time for theoretical and practical classes has been reduced, so it was necessary to modify the way of teaching and learning. In the theoretical classes we use systems of multimedia projection to present the concepts, and in the practical classes we solve exercises. We also use the Excel and the mathematical open source software wxMaxima. To supplement our theoretical and practical classes we have developed a project called MatActiva based on the Moodle platform offered by PAOL - Projecto de Apoio Online (Online Support Project). With the creation of this new project we wanted to take advantage already obtained results with the previous experiences, giving to the students opportunities to complement their study in Mathematics. One of the great objectives is to motivate students, encourage them to overcome theirs difficulties through an auto-study giving them more confidence. In the MatActiva project the students have a big collection of information about the way of the subject works, which includes the objectives, the program, recommended bibliography, evaluation method and summaries. It works as material support for the practical and theoretical classes, the slides of the theoretical classes are available, the sheets with exercises for the students to do in the classroom and complementary exercises, as well as the exams of previous years. Students can also do diagnostic tests and evaluation tests online. Our approach is a reflexive one, based on the professional experience of the teachers that explore and incorporate new tools of Moodle with their students and coordinate the project MatActiva.

Developing multiple - choice questions in mathematics

In this paper we wish to illustrate different perspectives used to create Multiple-Choice questions and we will show how we can improve these in the construction of math tests. As it is known, web technologies have a great influence on student’s behaviour. Based on an on-line project beginning at 2007 which has been contributing to help students on their individual work, we would like to share our experience and thoughts with colleagues who have a common concern when they have the task of constructing Multiple-Choice tests. We feel that Multiple-Choice tests play an important and a very useful supporting role in selfevaluation or self-examination of our students. Nonetheless, good Multiple–Choice Test Items are generally more complex and time-consuming to create than other types of tests. It requires a certain amount of skill. However, this skill maybe increases through study, practice and experience. This paper discusses a number of issues related to the use of Multiple-Choice questions, lists the advantages and disadvantages of this question format contrasting it with open questions. Some examples are given in this context.

How to teach mathematics with MOODLE

The aim of this article is to present a Project in the Oporto’s Institute of Accounting and Administration, which pretends to contribute for a change in the way of teaching and learning Mathematics. One of the main objectives of this project is to innovate the teaching and learning processes, exploring technologies as a pedagogical resource and to induce higher motivation to students, improve the rate of success and make available to students a set of materials adapted to their needs. This concern is justified due to the fact that students have a weak preparation, without consolidated basis. Since the year 2007/2008 the courses were adjusted to the Bologna process, which requires several changes in teacher’s and student’s roles, methodologies and assessment. The number of weekly classes has been reduced, so it was necessary to develop new strategies and methodologies to support the student. With the implementation of the Bologna Process in the Accounting degree, we felt a great need to provide other types of activities to students. To complement our theoretical and practical classes we have developed a project called MatActiva based on the Moodle platform offered by PAOL - Projecto de Apoio On-Line (Online Support Project). Moodle allows us to use the language TEX to create materials that use mathematical symbols. Using this functionality, we created a set of easy to use interactive resources. In MatActiva project, the students have access to a variety of different materials. We have followed a strategy that makes the project compatible with the theoretical and practical subjects/classes, complementing them. To do so, we created some resources, for instance multiple-choice tests, which are the most accessed by the students. These tests can be realized and corrected on-line and for each wrong answer there is a feedback with the resolution. We can find other types of resources: diagnostic tests, theoretical notes. There are not only the pre-requirements for subjects mathematics, but also materials to help students follow up the programs. We also developed several lessons. This activity consists of a number of pages, where each page has contents and leads to other pages, based on the student's progress. The teacher creates the choices and determines the next page that the student will see, based upon their knowledge. There is also an area of doubts, where the students can place all the mathematical doubts they have, and a teacher gives the answers or clues to help them in their work. MatActiva also offers an area where we can find some humour, curiosities, contests and games including mathematical contents to test the math skills, as well as links to pages about mathematical contents that could be useful for the study. Since ISCAP receives ERASMUS students and some of them attend mathematics, we developed some materials in English, so they can also use MatActiva. The main objectives of our project are not only to bring success in the subjects of mathematics, but also to motivate the students, encourage them to overcome theirs difficulties through an auto-study giving them more confidence and improve their relationship with the mathematics as well as the communication between students and teachers and among students.

The active mathematics project at ISCAP

This paper summarizes a project that is contributing to a change in the way of teaching and learning Mathematics. Mathematics is a subject of the Accounting and Administration course. In this subject we teach: Functions and Algebra. The aim is that the students understand the basic concepts and is able to apply them in other issues, when possible, establishing a bridge between the issues that they have studied and their application in Accounting. As from this year, the Accounting course falls under in Bologna Process. The teacher and the student roles have changed. The time for theoretical and practical classes has been reduced, so it was necessary to modify the way of teaching and learning. In the theoretical classes we use systems of multimedia projection to present the concepts, and in the practical classes we solve exercises. To supplement our theoretical and practical classes we have developed an active mathematics project called MatActiva based on the Moodle platform offered by PAOL - Projecto de Apoio Online (Online Support Project). In the last versions of Moodle, it is possible use the TeX language to create math questions. Using this tool we created a set of interactive materials. With the creation of this new project we wanted to take advantage already obtained results with the previous experiences, giving to the students opportunities to complement their study in Mathematics. One of the great objectives is to motivate students, encourage them to overcome theirs difficulties through an auto-study, giving them more confidence and the opportunity to seeing others perspectives of the mathematics subjects. In the MatActiva project the students have a big collection of information about the way of the subject works, which includes the objectives, the program, recommended bibliography, evaluation method and summaries. It works as material support for the practical and theoretical classes, the slides of the theoretical classes are available, the sheets with exercises for the students to do in the classroom and complementary exercises, as well as the exams of previous years. Students can also do diagnostic tests and evaluation tests online. Our approach is a reflexive one, based on the professional experience of the teachers that explore and incorporate new tools of Moodle with their students and coordinate the project MatActiva.