Visualization of molecular fingerprints

A visualization plot of a data set of molecular data is a useful tool for gaining insight into a set of molecules. In chemoinformatics, most visualization plots are of molecular descriptors, and the statistical model most often used to produce a visualization is principal component analysis (PCA). This paper takes PCA, together with four other statistical models (NeuroScale, GTM, LTM, and LTM-LIN), and evaluates their ability to produce clustering in visualizations not of molecular descriptors but of molecular fingerprints. Two different tasks are addressed: understanding structural information (particularly combinatorial libraries) and relating structure to activity. The quality of the visualizations is compared both subjectively (by visual inspection) and objectively (with global distance comparisons and local k-nearest-neighbor predictors). On the data sets used to evaluate clustering by structure, LTM is found to perform significantly better than the other models. In particular, the clusters in LTM visualization space are consistent with the relationships between the core scaffolds that define the combinatorial sublibraries. On the data sets used to evaluate clustering by activity, LTM again gives the best performance but by a smaller margin. The results of this paper demonstrate the value of using both a nonlinear projection map and a Bernoulli noise model for modeling binary data.

On the solution of a class of capital investment problems

In this work the solution of a class of capital investment problems is considered within the framework of mathematical programming. Upon the basis of the net present value criterion, the problems in question are mainly characterized by the fact that the cost of capital is defined as a non-decreasing function of the investment requirements. Capital rationing and some cases of technological dependence are also included, this approach leading to zero-one non-linear programming problems, for which specifically designed solution procedures supported by a general branch and bound development are presented. In the context of both this development and the relevant mathematical properties of the previously mentioned zero-one programs, a generalized zero-one model is also discussed. Finally,a variant of the scheme, connected with the search sequencing of optimal solutions, is presented as an alternative in which reduced storage limitations are encountered.

Increased diversity of libraries from libraries: chemoinformatic analysis of bis-diazacyclic libraries

Combinatorial libraries continue to play a key role in drug discovery. To increase structural diversity, several experimental methods have been developed. However, limited efforts have been performed so far to quantify the diversity of the broadly used diversity-oriented synthetic (DOS) libraries. Herein we report a comprehensive characterization of 15 bis-diazacyclic combinatorial libraries obtained through libraries from libraries, which is a DOS approach. Using MACCS keys, radial and different pharmacophoric fingerprints as well as six molecular properties, it was demonstrated the increased structural and property diversity of the libraries from libraries over the individual libraries. Comparison of the libraries to existing drugs, NCI Diversity and the Molecular Libraries Small Molecule Repository revealed the structural uniqueness of the combinatorial libraries (mean similarity < 0.5 for any fingerprint representation). In particular, bis-cyclic thiourea libraries were the most structurally dissimilar to drugs retaining drug-like character in property space. This study represents the first comprehensive quantification of the diversity of libraries from libraries providing a solid quantitative approach to compare and contrast the diversity of DOS libraries with existing drugs or any other compound collection.

Spain:countries of the world

Spain has been the home of some of the world's great artists and has museums and galleries to match. In the cities, narrow twisting old streets suddenly open up to views of the daring modern architecture, as a culture of old and new mix and mingle in the city's nightlife. There are endless tracts of wild and crinkled sierra to explore, as well as some spectacularly rugged stretches of coast. Culturally, the country is littered with superb old buildings, from Roman aqueducts to Gothic cathedrals, and almost every second village has a medieval castle. With more than 115 years exploring the globe with its writers, photographers, and research expeditions, "National Geographic" is uniquely positioned to introduce your readers to everything they need to know about the countries of the world.

From the medicalisation of dementia to the politics of memory and identity in three Spanish documentary films:Bicicleta, cullera, poma, Las voces de la memoria and Bucarest: la memòria perduda

This paper explores how the concept of Alzheimer’s disease (AD) is constructed through Spanish media and documentary films and how it is represented. The article analyses three documentary films and the cultural and social contexts in and from which they emerged: Solé´s Bucarest: la memòria perduda [Bucharest: Memory Lost] (2007), Bosch´s Bicicleta, cullera, poma [Bicycle, Spoon, Apple] (2010) , and Frabra’s Las voces de la memoria [Memory´s Voices] (2011). The three documentary films approach AD from different perspectives, creating well-structured discourses of what AD represents for contemporary Spanish society, from medicalisation of AD to issues of personhood and citizenship. These three films are studied from an interdisciplinary perspective, in an effort to strengthen the links between ageing and dementia studies and cultural studies. Examining documentary film representations of AD from these perspectives enables semiotic analyses beyond the aesthetic perspectives of film studies, and the exploration of the articulation of knowledge and power in discourses about AD in contemporary Spain

Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall

Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference +/- 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38 degrees C (-5.33, -1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [-35.9 (-60, -11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.

Who speaks up for Inés Fonseca? Representing violence against vulnerable subjects and the ethics of care in fictional narrative about Alzheimer’s disease:Ahora tocad música de baile (2004) by Andrés Barba

This paper studies the Spanish fictional novel by Andrés Barba, Ahora tocad música de baile (2004), one of the first cultural texts dealing entirely with Alzheimer’s disease (AD) to appear in Spain. It argues that the significance of Barba’s fictional novel rests on two important issues: the ethics of representation of violence against vulnerable subjects and the ethics of care. The paper analyses how these two issues allow Barba to create a story in which the verbal and physical abuse to which the person living with Alzheimer’s disease is subjected places the reader, on the one hand, as voyeur/witness of the abuse; and, on the other, as interpreter, and ultimately judge, of the fine line that separates euthanasia, assisted suicide, and murder. The open ending of the novel defers all ethical and moral judgment to the reader. It examines how the novel offers a monolithic perspective about AD, in which care is presented as a burden. In fact, this study shows that the novel’s multi-layered structure and polyphonic nature places the emphasis on stigmas, stereotypes and negative metaphors around AD, as found in contemporary social discourses.

‘Let’s talk about feedback’:an exploration of academic feedback practices in pharmacy education

Feedback is considered one of the most effective mechanisms to aid learning and achievement (Hattie and Timperley, 2007). However, in past UK National Student Surveys, perceptions of academic feedback have been consistently rated lower by final year undergraduate students than other aspects of the student experience (Williams and Kane, 2009). For pharmacy students in particular, Hall and colleagues recently reported that almost a third of students surveyed were dissatisfied with feedback and perceived feedback practice to be inconsistent (Hall et al, 2012). Aims of the Workshop: This workshop has been designed to explore current academic feedback practices in pharmacy education across a variety of settings and cultures as well as to create a toolkit for pharmacy academics to guide their approach to feedback. Learning Objectives: 1. Discuss and characterise academic feedback practices provided by pharmacy academics to pharmacy students in a variety of settings and cultures. 2. Develop academic feedback strategies for a variety of scenarios. 3. Evaluate and categorise feedback strategies with use of a feedback matrix. Description of Workshop Activities: Introduction to workshop and feedback on pre-reading exercise (5 minutes). Activity 1: A short presentation on theoretical models of academic feedback. Evidence of feedback in pharmacy education (10 minutes). Activity 2: Discussion of feedback approaches in participants’ organisations for differing educational modalities. Consideration of the following factors will be undertaken: experiential v. theoretical education, formative v. summative assessment, form of assessment and the effect of culture (20 minutes, large group discussion). Activity 3: Introduction of a feedback matrix (5 minutes). Activity 4: Development of an academic feedback toolkit for pharmacy education. Participants will be divided into 4 groups and will discuss how to provide effective feedback for 2 scenarios. Feedback strategies will be categorised with the feedback matrix. Results will be presented back to the workshop group (20 minutes, small group discussion, 20 minutes, large group presentation). Summary (10 minutes). Additional Information: Pre-reading: Participants will be provided with a list of definitions for academic feedback and will be asked to rank the definitions in order of perceived relevance to pharmacy education. References Archer, J. C. (2010). State of the science in health professional education: effective feedback. Medical education, 44(1), 101-108. Hall, M., Hanna, L. A., & Quinn, S. (2012). Pharmacy Students’ Views of Faculty Feedback on Academic Performance. American journal of pharmaceutical education, 76(1). Hattie, J., & Timperley, H. (2007). The power of feedback. Review of educational research, 77(1), 81-112. Medina, M. S. (2007). Providing feedback to enhance pharmacy students’ performance. American Journal of Health-System Pharmacy, 64(24), 2542-2545.