Development and validation of AMANDA, a new algorithm for selecting highly relevant regions in Molecular Interaction Fields

Descriptors based on Molecular Interaction Fields (MIF) are highly suitable for drug discovery, but their size (thousands of variables) often limits their application in practice. Here we describe a simple and fast computational method that extracts from a MIF a handful of highly informative points (hot spots) which summarize the most relevant information. The method was specifically developed for drug discovery, is fast, and does not require human supervision, being suitable for its application on very large series of compounds. The quality of the results has been tested by running the method on the ligand structure of a large number of ligand-receptor complexes and then comparing the position of the selected hot spots with actual atoms of the receptor. As an additional test, the hot spots obtained with the novel method were used to obtain GRIND-like molecular descriptors which were compared with the original GRIND. In both cases the results show that the novel method is highly suitable for describing ligand-receptor interactions and compares favorably with other state-of-the-art methods.

Monitoring of posture allocations and activities by a shoe-based wearable sensor.

Monitoring of posture allocations and activities enables accurate estimation of energy expenditure and may aid in obesity prevention and treatment. At present, accurate devices rely on multiple sensors distributed on the body and thus may be too obtrusive for everyday use. This paper presents a novel wearable sensor, which is capable of very accurate recognition of common postures and activities. The patterns of heel acceleration and plantar pressure uniquely characterize postures and typical activities while requiring minimal preprocessing and no feature extraction. The shoe sensor was tested in nine adults performing sitting and standing postures and while walking, running, stair ascent/descent and cycling. Support vector machines (SVMs) were used for classification. A fourfold validation of a six-class subject-independent group model showed 95.2% average accuracy of posture/activity classification on full sensor set and over 98% on optimized sensor set. Using a combination of acceleration/pressure also enabled a pronounced reduction of the sampling frequency (25 to 1 Hz) without significant loss of accuracy (98% versus 93%). Subjects had shoe sizes (US) M9.5-11 and W7-9 and body mass index from 18.1 to 39.4 kg/m2 and thus suggesting that the device can be used by individuals with varying anthropometric characteristics.

Strategic Plan Iowa Workforce Development October, 2004

For the 2004 strategic planning process at Iowa Workforce Development, Director Richard Running asked for as much input from all staff as possible. As a result, planning staff designed an extensive process to gather input over about a three month period during the late spring and summer: • A Guide to Staff Involvement was drafted and distributed to staff in offices throughout the state. This guide provided a brief explanation of the planning process and quoted extensively from the Vilsack/Pederson Leadership Agenda and the 2003 IWD strategic plan to illustrate each step and to show examples of alignment. The guide also provided suggestions for staff in various locations and work units to conduct their own planning sessions. The structure was designed to solicit feedback regarding elements (vision, mission, guiding principles, goals and strategies) of the existing 2003 plan. Particular attention was devoted to securing non-management staff’s perspective during the internal and external assessment exercises. • Several local offices did conduct their own structured input sessions following the suggested guidelines and sent the results to planning staff in the central administrative offices. • Other work units in many locations opted to ask planning staff to facilitate planning sessions for them. The results of these sessions were also gathered by planning staff. In all, dozens of input sessions were held and hundreds of IWD staff participated directly in the process. Because all the sessions followed similar guidelines, it was relatively easy to combine all of the input received and spot common themes that surfaced from the many sessions. A composite of all the flip chart notes was compiled into one large document (for those who like lots of detail) and another document summarized the key themes that emerged. This information was used in a day-long planning retreat on August 20. Management staff members from throughout the department were invited and each work unit and sub-state region also brought a non-management staff person as well. This group reviewed the themes from the earlier sessions and then addressed each element of the 2003 plan, proposing refinements for almost all sections. Subsequently, senior management reviewed the results of the retreat and made the final decisions for the new 2004 plan. This thorough approach, with its special emphasis on input from line staff, did result in some significant changes to IWD’s plan. Local office staff, for example, consistently expressed the need to step up our marketing efforts, especially with employers. Another need that was expressed clearly and often was the need to beef up staff training efforts, much of the capacity for which had been lost in budget and staff reductions a few years ago. Neither of these issues is new, but the degree of concern expressed by IWD staff has caused us to elevate their importance in this year’s plan.

Progress in cardiovascular anastomoses: will the vascular join replace Carrel's technique?

BACKGROUND: Vascular reconstructions are becoming challenging due to the comorbidity of the aging population and since the introduction of minimally invasive approaches. Many sutureless anastomosis devices have been designed to facilitate the cardiovascular surgeon's work and the vascular join (VJ) is one of these. We designed an animal study to assess its reliability and long-term efficacy. METHODS: VJ allows the construction of end-to-end and end-to-side anastomoses. It consists of two metallic crowns fixed to the extremity of the two conduits so that vessel edges are joined layer by layer. There is no foreign material exposed to blood. In adult sheep both carotid arteries were prepared and severed. End-to-end anastomoses were performed using the VJ device on one side and the classical running suture technique on the other side. Animals were followed-up with Duplex-scan every 3 months and sacrificed after 12 months. Histopathological analysis was carried out. RESULTS: In 20 animals all 22 sutureless anastomoses were successfully completed in less than 2 min versus 6 +/- 3 min for running suture. Duplex showed the occlusion of three controls and one sutureless anastomosis. Two controls and one sutureless had stenosis >50%. Histology showed very thin layer of myointimal hyperplasia (50 +/- 10 microm) in the sutureless group versus 300 +/- 27 microm in the control. No significant inflammatory reaction was detected. CONCLUSIONS: VJ provides edge-to-edge vascular repair that can be considered the most physiological way to restore vessel continuity. For the first time, in healthy sheep, an anastomotic device provided better results than suture technique.

Activity and exploratory behavior after lesions of the medial entorhinal cortex in the woodmouse (Apodemus sylvaticus).

The effects of bilateral electrolytic lesions of the entorhinal cortex were studied in male adult woodmice. Experiments were designed to allow separate analysis of the basal activity level and exploratory behavior. Activity recording was conducted in three situations: (a) 24-hr wheel running in the home cage pre- and postoperatively; (b) 24-hr activity composition in a large enclosure over 4 days, 5 to 9 days postoperatively; and (c) sequence and duration of visits in a residential plus maze 11 to 14 days postoperatively. Medial entorhinal cortex lesion involving the para- and presubiculum increased the 24-hr amount of movements in the enclosure (b) without increasing wheel running in any situation (a or b). This lesion also enhanced the locomotor reactivity to being introduced into the plus maze and impaired exploratory behavior. This last effect was equally apparent when the whole situation was new or when part of the familiar maze was modified. Lesioned woodmice did notice the new element but did not show active focalization of their behavior on that element. Data showed that lesion induced hyperactivity and changes of exploratory behavior were not necessarily associated. Novelty detection was performed but it is not clear now on what information this discrimination was based.

Topographic organization of V1 projections through the corpus callosum in humans.

The visual cortex in each hemisphere is linked to the opposite hemisphere by axonal projections that pass through the splenium of the corpus callosum. Visual-callosal connections in humans and macaques are found along the V1/V2 border where the vertical meridian is represented. Here we identify the topography of V1 vertical midline projections through the splenium within six human subjects with normal vision using diffusion-weighted MR imaging and probabilistic diffusion tractography. Tractography seed points within the splenium were classified according to their estimated connectivity profiles to topographic subregions of V1, as defined by functional retinotopic mapping. First, we report a ventral-dorsal mapping within the splenium with fibers from ventral V1 (representing the upper visual field) projecting to the inferior-anterior corner of the splenium and fibers from dorsal V1 (representing the lower visual field) projecting to the superior-posterior end. Second, we also report an eccentricity gradient of projections from foveal-to-peripheral V1 subregions running in the anterior-superior to posterior-inferior direction, orthogonal to the dorsal-ventral mapping. These results confirm and add to a previous diffusion MRI study (Dougherty et al., 2005) which identified a dorsal/ventral mapping of human splenial fibers. These findings yield a more detailed view of the structural organization of the splenium than previously reported and offer new opportunities to study structural plasticity in the visual system.

Analyse en actographe et dans sa cage, de la réponse comportementale du mulot sylvestre (Apodemus sylvaticus L.) à un jeûne de 24

1. The "general activity" of Apodemus Sylvaticus L. has been recorded and analysed using two techniques: a) in an actograph, several components of the "general activity" have been recorded and quantified over 24 hours, including wheel running, locomotion in various areas of the enclosure, nest occupancy, drinking, eating and hoarding; b) in a breeding cage, ten times smaller than the actograph and where the possibilities of locomotion are considerably reduced, the wheel running only has been recorded. In these two situations, we have compared the effects of a food deprivation for 24 hours. 2. In the actograph, starvation increases the general locomotion in the enclosure without detectable changes in wheel running. On the other hand, in the breeding cage, wheel running is somewhat increased. 3. Refeeding results in decreased wheel running under both experimental conditions, and restores general locomotion in the actograph to the predeprivation level. 4. These results are discussed in view of the current literature. The apparent disagreement between our results and those of other workers is attributed to the fact that the latter used experimental conditions where the measured response was predetermined by the lack of choice in expressed responses which were offered to the animal. Consequently, we suggest that the interpretation of such experiments can be improved by allowing a choice of possible behavioural response and that each of them should be recorded separately.

The electric revolution in Latin America

Latin America participated in the electric revolution which profoundly transformed the most developed Western economies between 1880 and 1930. The electrification of Latin America began relatively soon after these economies, but it was incapable of keeping up with them. Public electric lighting was introduced early in the big Latin American cities, where electric trams started running at almost the same time as in Europe, and electricity spread rapidly in the mining sector. In the most advanced countries or areas in the region, the manufacturing industry substituted the steam engine with the electric motor, following the example of industry in the United States and Europe. Nevertheless, towards 1930 electricity consumption per inhabitant for Latin America was far below that of the more advanced economies, and only the Latin American countries which lead the process of electrification had reached levels of electric consumption that were similar to those of the late industrialised European countries. One of the most striking features of the electric revolution in Latin America is rooted precisely in the enormous national differences. These differences are indicative of the great economic inequalities existing in the heart of the region and these nations highly diverse capacity for economic modernisation.

Insuring California earthquakes and the role for catastrophe bonds

The 1994 Northridge earthquake sent ripples to insurance conpanieseverywhere. This was one in a series of natural disasters such asHurricane Andrew which together with the problems in Lloyd's of Londonhave insurance companies running for cover. This paper presents a calibration of the U.S. economy in a model with financial markets forinsurance derivatives that suggests the U.S. economy can deal with thedamage of natural catastrophe far better than one might think.

Implementação do sistema de custeio baseado em actividades (CBA) numa Instituição de Ensino Superior em Cabo Verde

Actualmente, a gestão de gastos assume um papel fundamental nas empresas modernas. A globalização, aliada às novas tecnologias, exige que essas empresas sejam ágeis e competentes. Neste contexto, a gestão eficiente dos recursos e a obtenção de informações precisas que apoiem na tomada de decisão, dependerão em grande parte, de um sistema de custo. A utilização de diversas tecnologias e ferramentas faz com que as empresas tenham cada vez mais gastos indiretos relativamente aos gastos diretos. Logo, o método CBA surgiu como alternativa aos sistemas de custeio tradicionais numa tentativa de solucionar ou, pelo menos, minimizar o problema de atribuição dos gastos indiretos. O presente trabalho pretende abordar o método CBA e propor uma metodologia de implementação do sistema numa Instituição de Ensino Superior, evidenciando e discutindo as principais vantagens e desvantagens associadas a esta metodologia e identificando as suas contribuições para a gestão das IES. De acordo com as pesquisas feitas, conclui-se que nenhuma das IES em São Vicente possui um sistema de contabilidade de gestão, mas verificou-se que todas têm conhecimento deste sistema e consideram-no o melhor método de gestão para análise dos gastos. Os resultados obtidos no estudo de caso demonstram que o objetivo foi atingido, apurandose que o método CBA é o mais adequado para o suporte à gestão, tendo em conta que ultrapassa as insuficiências de informação sobre os gastos. Currently, cost management plays a key role in modern business. The globalization, allied to the new technologies, demands that those companies are agile and qualified. In this context, an efficient management of the resources and the gathering of precise information which support the decision-making process will depend, largely, of an effective cost management system. The use of different technologies and tools makes companies have more indirect costs than direct. Therefore, the ABC method was devised as an alternative to the conventional means of costing in an attempt of solving or, at least, minimizing the problem of the attribution of indirect costs. Our work intends to analyze the ABC method and to propose a methodology of implementation of such system in an Institution of Higher Education, showing and discussing the main advantages and disadvantages associated with this methodology and identifying its contributions for the administration of these Institutions. Our research has shown that, none of the IHEs in São Vicente has a management accounting system, although all have knowledge of it and consider it as being the best administration method for the analysis of expenses. The results obtained in the case study demonstrate that the objective was reached: to conclude the ABC method is the most adequate to support the administration, as it overcomes the problem of lack of information on the running costs.

Quality safeguards and regulation of online pharmacies

Using econometric evidence, this article confirms that distribution ofmedicines online is split into two market segments of very diversequality, and identifies the factors that drive quality and qualityassurance in this activity. Unlike fraudulent, rogue, websites, whichoffer scant guarantees and usually sell just a few medicines withoutprescription, online pharmacies offering insurance coverage and linkedto conventional pharmacies typically sell a wholerange of drugs, require third-party medical prescriptions and provideabundant information to patients. It is shown that, where onlinepharmacies are allowed to act legally, market forces enhance quality,as private insurers require professional standards, and specialized thirdparties make a business of certifying them. Furthermore, older onlinepharmacies and those running conventional operations offer higherquality, probably because of reputational investments. Overall, this evidence supports licensing online pharmacies, especiallyconsidering that prohibiting them is ineffective against fraudulent sites.

O poder local em Timor em contexto multicultural

O trabalho que agora se apresenta é fruto, antes de mais, de uma relação especial com Timor. Não necessariamente pela dimensão histórica das várias presenças naquele território mas, e acima de tudo, pela relação pessoal e afectiva com alguns dos responsáveis políticos e religiosos daquele jovem país. Um convite, formulado em 2007 por Xanana Gusmão, levou-nos a calcorrear todo o território num curto espaço de três semanas, corria o Verão de 2008. O objectivo era a análise, no terreno, da viabilidade da instalação de um poder local num país recentemente tornado independente. Timor, fruto da sua história e, muito em especial, das características antropológicas do seu povo, é uma nação assumidamente multicultural. Das origens ancestrais das suas comunidades, dos reinos dispersos que pulverizam o pequeno território, das suas lideranças e dos vários dilectos, associados à longa e marcante presença portuguesa, bem como outras ocupações de países estrangeiros, com destaque para a Indonésia, resulta um caldo cultural, a todos os níveis peculiar. Aqui e acolá ouvimos o povo, entrevistámos e reunimos com os 432 chefes de suco existentes no país, entrevistámos chefes de aldeia e anciãos, reunimos com políticos, sacerdotes, professores e jornalistas. Interpretámos, ou tentámos interpretar, as condicionantes e os cuidados que se devem observar na preparação do quadro jurídico para reger a municipalidade em Timor: as suas vertentes electivas, funcionais, financeiras e fiscalizadoras. Revistámos a História de Timor e passámos por Cabo Verde, país de referência internacional ao nível da sua gestão pública, muito em especial a autárquica. Fizemos, também, óbvia referência à história do poder local em Portugal. Das consultas, do muito que observámos e estudámos, resulta um desinteressado contributo para a implementação do poder local em Timor, com as conclusões que incorporam alertas e sugestões.

O poder local em Timor em contexto multicultural

This study, now on presentation, comes as a result of a special relationship established with East Timor. Not necessarily through the several historical presences in that territory but, above all, through the emotional and personal relationships with some of the political and religious leaders of this young country. An invitation, made in 2007 by Xanana Gusmão, led us throughout the whole territory in a short time of three weeks, running the summer of 2008. Its purpose was the analysis, on the ground, of the possibility of installing local administration in a country which had recently became independent. Timor, as a result of its history, but mostly of the anthropological characteristics of its people, is an openly multicultural nation. The ancestral origins of their communities, its scattered kingdoms that spray along such a small territory, its leaders and many dialects, associated with the long portuguese presence, as well as other occupations made by foreign countries, especially Indonesia, became a cultural melting pot truly unique. Here and there we heard the people and interviewed and met the 432 local elected leaders of the country. We interviewed village elders and meet with politicians, priests, teachers and journalists. We have interpreted, or tried to, the actual conditions and cautions that must be observed in preparing the legal framework to govern the municipality in East Timor: its elective, functional, financial and oversight aspects. We have reviewed Timor’s history and took Cape Verde’s example as an international reference on its public administration, mostly its local authorities. We made also the obvious reference to the portuguese local government’s history. From search, and much of the observed and studied, remains a selfless contribution to the implementation of local government in East Timor, with alerts that incorporate conclusions and suggestions.

Strategic ambiguity in electoral competition

Many have observed that political candidates running for election areoften purposefully expressing themselves in vague and ambiguous terms. In thispaper we provide a simple formal model of this phenomenon. We model theelectoral competition between two candidates as a two--stage game. In thefirst stage of the game two candidates simultaneously choose their ideologies,and in the second stage they simultaneously choose their level of ambiguity.Our results show that ambiguity, although disliked by voters, may be sustainedin equilibrium. The introduction of ambiguity as a strategic choice variablefor the candidates can also serve to explain why candidates with the sameelectoral objectives end up ``separating'', that is, assuming different ideological positions.

Competition amongst contests

This article analyses the allocation of prizes in contests. While existing models consider a single contest with an exogenously given set of players, in our model several contests compete for participants. As a consequence, prizes not only induce incentive effects but also participation effects. We show that contests that aim to maximize players aggregate effort will award their entire prize budget to the winner. In contrast, multiple prizes will be awarded in contests that aim to maximize participation and the share of the prize budget awarded to the winner increases in the contests randomness. We also provide empirical evidence for this relationship using data from professional road running. In addition, we show that prize structures might be used to screen between players of differing ability.