Assessing High-Speed Internet Access in the State of Iowa: Sixth Assessment, January 2008

This Assessment gauges the availability of highspeed Internet access to both rural and non-rural Iowans. The Board continues to evaluate the progress in the deployment of high-speed Internet access through this Sixth Assessment, including information related to Internet speeds available to consumers and pricing of high-speed Internet services. Comparison of this Assessment with the earlier efforts is critical if a clear perspective on the developing availability of high-speed Internet access to all residents of the State of Iowa is desired.

Electronic journals, scholarly communication and libraries

The recent surge in scientific electronic journals began when libraries began having access to the WWW in the mid-1990s. The shift from paper to digital has affected the traditional alignment and role of the primary "stakeholders" -mainly authors, publishers, universities and libraries. The author offers a brief review of the history of the scholarly journal followed by the evolution of e-journals in during the past two decades. The article then focuses on the implications that these have had on traditional library processes and services such as selection, acquisitions, cataloguing, storage, preservation and user services. In the conclusion the author speculates on the long term effect of Web-based publishing on the format of the traditional scholarly journal as it has existed for over 300 years.

Cheminformatic studies of molecular properties and their influence on bioactivity in the context of drug discovery

Molecular shape has long been known to be an important property for the process of molecular recognition. Previous studies postulated the existence of a drug-like shape space that could be used to artificially bias the composition of screening libraries, with the aim to increase the chance of success in Hit Identification. In this work, it was analysed to which extend this assumption holds true. Normalized Principal Moments of Inertia Ratios (NPRs) have been used to describe the molecular shape of small molecules. It was investigated, whether active molecules of diverse targets are located in preferred subspaces of the NPR shape space. Results illustrated a significantly stronger clustering than could be expected by chance, with parts of the space unlikely to be occupied by active compounds. Furthermore, a strong enrichment of elongated, rather flat shapes could be observed, while globular compounds were highly underrepresented. This was confirmed for a wide range of small molecule datasets from different origins. Active compounds exhibited a high overlap in their shape distributions across different targets, making a purely shape­ based discrimination very difficult. An additional perspective was provided by comparing the shapes of protein binding pockets with those of their respective ligands. Although more globular than their ligands, it was observed that binding sites shapes exhibited a similarly skewed distribution in shape space: spherical shapes were highly underrepresented. This was different for unoccupied binding pockets of smaller size. These were on the contrary identified to possess a more globular shape. The relation between shape complementarity and exhibited bioactivity was analysed; a moderate correlation between bioactivity and parameters including pocket coverage, distance in shape space, and others could be identified, which reflects the importance of shape complementarity. However, this also suggests that other aspects are of relevance for molecular recognition. A subsequent analysis assessed if and how shape and volume information retrieved from pocket or respective reference ligands could be used as a pre-filter in a virtual screening approach. ln Lead Optimization compounds need to get optimized with respect to a variety of pararneters. Here, the availability of past success stories is very valuable, as they can guide medicinal chemists during their analogue synthesis plans. However, although of tremendous interest for the public domain, so far only large corporations had the ability to mine historical knowledge in their proprietary databases. With the aim to provide such information, the SwissBioisostere database was developed and released during this thesis. This database contains information on 21,293,355 performed substructural exchanges, corresponding to 5,586,462 unique replacements that have been measured in 35,039 assays against 1,948 molecular targets representing 30 target classes, and on their impact on bioactivity . A user-friendly interface was developed that provides facile access to these data and is accessible at http//www.swissbioisostere.ch. The ChEMBL database was used as primary data source of bioactivity information. Matched molecular pairs have been identified in the extracted and cleaned data. Success-based scores were developed and integrated into the database to allow re-ranking of proposed replacements by their past outcomes. It was analysed to which degree these scores correlate with chemical similarity of the underlying fragments. An unexpectedly weak relationship was detected and further investigated. Use cases of this database were envisioned, and functionalities implemented accordingly: replacement outcomes are aggregatable at the assay level, and it was shawn that an aggregation at the target or target class level could also be performed, but should be accompanied by a careful case-by-case assessment. It was furthermore observed that replacement success depends on the activity of the starting compound A within a matched molecular pair A-B. With increasing potency the probability to lose bioactivity through any substructural exchange was significantly higher than in low affine binders. A potential existence of a publication bias could be refuted. Furthermore, often performed medicinal chemistry strategies for structure-activity-relationship exploration were analysed using the acquired data. Finally, data originating from pharmaceutical companies were compared with those reported in the literature. It could be seen that industrial medicinal chemistry can access replacement information not available in the public domain. In contrast, a large amount of often-performed replacements within companies could also be identified in literature data. Preferences for particular replacements differed between these two sources. The value of combining different endpoints in an evaluation of molecular replacements was investigated. The performed studies highlighted furthermore that there seem to exist no universal substructural replacement that always retains bioactivity irrespective of the biological environment. A generalization of bioisosteric replacements seems therefore not possible. - La forme tridimensionnelle des molécules a depuis longtemps été reconnue comme une propriété importante pour le processus de reconnaissance moléculaire. Des études antérieures ont postulé que les médicaments occupent préférentiellement un sous-ensemble de l'espace des formes des molécules. Ce sous-ensemble pourrait être utilisé pour biaiser la composition de chimiothèques à cribler, dans le but d'augmenter les chances d'identifier des Hits. L'analyse et la validation de cette assertion fait l'objet de cette première partie. Les Ratios de Moments Principaux d'Inertie Normalisés (RPN) ont été utilisés pour décrire la forme tridimensionnelle de petites molécules de type médicament. Il a été étudié si les molécules actives sur des cibles différentes se co-localisaient dans des sous-espaces privilégiés de l'espace des formes. Les résultats montrent des regroupements de molécules incompatibles avec une répartition aléatoire, avec certaines parties de l'espace peu susceptibles d'être occupées par des composés actifs. Par ailleurs, un fort enrichissement en formes allongées et plutôt plates a pu être observé, tandis que les composés globulaires étaient fortement sous-représentés. Cela a été confirmé pour un large ensemble de compilations de molécules d'origines différentes. Les distributions de forme des molécules actives sur des cibles différentes se recoupent largement, rendant une discrimination fondée uniquement sur la forme très difficile. Une perspective supplémentaire a été ajoutée par la comparaison des formes des ligands avec celles de leurs sites de liaison (poches) dans leurs protéines respectives. Bien que plus globulaires que leurs ligands, il a été observé que les formes des poches présentent une distribution dans l'espace des formes avec le même type d'asymétrie que celle observée pour les ligands: les formes sphériques sont fortement sous­ représentées. Un résultat différent a été obtenu pour les poches de plus petite taille et cristallisées sans ligand: elles possédaient une forme plus globulaire. La relation entre complémentarité de forme et bioactivité a été également analysée; une corrélation modérée entre bioactivité et des paramètres tels que remplissage de poche, distance dans l'espace des formes, ainsi que d'autres, a pu être identifiée. Ceci reflète l'importance de la complémentarité des formes, mais aussi l'implication d'autres facteurs. Une analyse ultérieure a évalué si et comment la forme et le volume d'une poche ou de ses ligands de référence pouvaient être utilisés comme un pré-filtre dans une approche de criblage virtuel. Durant l'optimisation d'un Lead, de nombreux paramètres doivent être optimisés simultanément. Dans ce contexte, la disponibilité d'exemples d'optimisations réussies est précieuse, car ils peuvent orienter les chimistes médicinaux dans leurs plans de synthèse par analogie. Cependant, bien que d'un extrême intérêt pour les chercheurs dans le domaine public, seules les grandes sociétés pharmaceutiques avaient jusqu'à présent la capacité d'exploiter de telles connaissances au sein de leurs bases de données internes. Dans le but de remédier à cette limitation, la base de données SwissBioisostere a été élaborée et publiée dans le domaine public au cours de cette thèse. Cette base de données contient des informations sur 21 293 355 échanges sous-structuraux observés, correspondant à 5 586 462 remplacements uniques mesurés dans 35 039 tests contre 1948 cibles représentant 30 familles, ainsi que sur leur impact sur la bioactivité. Une interface a été développée pour permettre un accès facile à ces données, accessible à http:/ /www.swissbioisostere.ch. La base de données ChEMBL a été utilisée comme source de données de bioactivité. Une version modifiée de l'algorithme de Hussain et Rea a été implémentée pour identifier les Matched Molecular Pairs (MMP) dans les données préparées au préalable. Des scores de succès ont été développés et intégrés dans la base de données pour permettre un reclassement des remplacements proposés selon leurs résultats précédemment observés. La corrélation entre ces scores et la similarité chimique des fragments correspondants a été étudiée. Une corrélation plus faible qu'attendue a été détectée et analysée. Différents cas d'utilisation de cette base de données ont été envisagés, et les fonctionnalités correspondantes implémentées: l'agrégation des résultats de remplacement est effectuée au niveau de chaque test, et il a été montré qu'elle pourrait également être effectuée au niveau de la cible ou de la classe de cible, sous réserve d'une analyse au cas par cas. Il a en outre été constaté que le succès d'un remplacement dépend de l'activité du composé A au sein d'une paire A-B. Il a été montré que la probabilité de perdre la bioactivité à la suite d'un remplacement moléculaire quelconque est plus importante au sein des molécules les plus actives que chez les molécules de plus faible activité. L'existence potentielle d'un biais lié au processus de publication par articles a pu être réfutée. En outre, les stratégies fréquentes de chimie médicinale pour l'exploration des relations structure-activité ont été analysées à l'aide des données acquises. Enfin, les données provenant des compagnies pharmaceutiques ont été comparées à celles reportées dans la littérature. Il a pu être constaté que les chimistes médicinaux dans l'industrie peuvent accéder à des remplacements qui ne sont pas disponibles dans le domaine public. Par contre, un grand nombre de remplacements fréquemment observés dans les données de l'industrie ont également pu être identifiés dans les données de la littérature. Les préférences pour certains remplacements particuliers diffèrent entre ces deux sources. L'intérêt d'évaluer les remplacements moléculaires simultanément selon plusieurs paramètres (bioactivité et stabilité métabolique par ex.) a aussi été étudié. Les études réalisées ont souligné qu'il semble n'exister aucun remplacement sous-structural universel qui conserve toujours la bioactivité quel que soit le contexte biologique. Une généralisation des remplacements bioisostériques ne semble donc pas possible.

Médecine interne générale en pratique hospitalière: l'année 2011 mise en perspective par les chefs de clinique [Hospital-based internal medicine: year 2011 in chief resident's perspective].

The year 2011 was full of significant advances in all areas of medicine. Whether small or large issues, they all have an impact on daily practice in general internal medicine. For example, intravenous administration of diuretics in heart failure shows no benefit. But double dose may improve symptoms faster. Direct Xa inhibitors are emerging as alternative to anti-vitamin K. beta-blockers reduce overall mortality in COPD and do not worsen lung function significantly. Each year, the chief residents from the Department of internal medicine at the University hospital of Lausanne meet to share their readings. Twelve new therapeutic considerations of 2011 are reviewed here.

Automated scoring of AFLPs using RawGeno v 2.0, a free R CRAN library.

Amplified Fragment Length Polymorphisms (AFLPs) are a cheap and efficient protocol for generating large sets of genetic markers. This technique has become increasingly used during the last decade in various fields of biology, including population genomics, phylogeography, and genome mapping. Here, we present RawGeno, an R library dedicated to the automated scoring of AFLPs (i.e., the coding of electropherogram signals into ready-to-use datasets). Our program includes a complete suite of tools for binning, editing, visualizing, and exporting results obtained from AFLP experiments. RawGeno can either be used with command lines and program analysis routines or through a user-friendly graphical user interface. We describe the whole RawGeno pipeline along with recommendations for (a) setting the analysis of electropherograms in combination with PeakScanner, a program freely distributed by Applied Biosystems; (b) performing quality checks; (c) defining bins and proceeding to scoring; (d) filtering nonoptimal bins; and (e) exporting results in different formats.

Web-based reference databases and subject gateways to locate current research information in agricultural and food sciences : a Finnish perspective

Selostus: Maatalous- ja elintarviketieteiden www-pohjaiset viitetietokannat ja aihehakemistot - suomalaisen tiedonetsijän näkökulma

Building the future: the Brazilian university library in 2010

Information technology will affect academic activities as well as the nature of the high education sector. This sector besides the need to assimilate these technologies will need to attend the requisites of market globalization and, as consequence, all theses changes will be reflected in the university library. Prospectives impacts will affect the structure (emphasis in user services, outsourcing of several services), in the financing aspect (growing of consortia in order to reduce costs), in services (electronic reference, support to long distance education programs, intelligent agents) and in the clientele (attending the great demand por high education which implies a diversity of people).

Constructability in the Bridge Design Process, HR-320, 1991

In the United States many bridge structures have been designed without consideration for their unique construction problems. Many problems could have been avoided if construction knowledge and experience was utilized in the design process. A systematic process is needed to create and capture construction knowledge for use in the design process. This study was conducted to develop a system to capture construction considerations from field people and incorporate it into a knowledge-base for use by the bridge designers. This report presents the results of this study. As a part of this study a microcomputer-based constructability system has been developed. The system is a user-friendly microcomputer database which codifies construction knowledge, provides easy access to specifications, and provides simple design computation checks for the designer. A structure for the final database was developed and used in the prototype system. A process for collecting, developing and maintaining the database is presented and explained. The study involved a constructability survey, interviews with designers and constructors, and visits to construction sites to collect constuctability concepts. The report describes the development of the constructability system and addresses the future needs for the Iowa Department of Transportation to make the system operational. A user's manual for the system is included along with the report.

ISBN (international standard book number) -an international perspective

Esitelmä Suomen ISBN-keskus 30 vuotta -juhlassa Helsingin yliopistossa 7.11.2002

Liability and Traffic Control Considerations for Low Water Stream Crossings, HR-218, 1981

The current shortage of highway funds precludes the immediate replacement of most of the bridges that have been evaluated as structurally deficient or functionally obsolete or both. A low water stream crossing (LWSC) affords an economical alternative to the replacement of a bridge with another bridge in many instances. However, the potential liability that might be incurred from the use of LWSCs has served as a deterrent to their use. Nor have guidelines for traffic control devices been developed for specific application to LWSCs. This research addressed the problems of liability and traffic control associated with the use of LWSCs. Input to the findings from this research was provided by several persons contacted by telephone plus 189 persons who responded to a questionnaire concerning their experience with LWSCs. It was concluded from this research that a significant potential for accidents and liability claims could result from the use of LWSCs. However, it was also concluded that this liability could be reduced to within acceptable limits if adequate warning of the presence of an LWSC were afforded to road users. The potential for accidents and liability could further be reduced if vehicular passage over an LWSC were precluded during periods when the road was flooded. Under these conditions, it is believed, the potential for liability from the use of an LWSC on an unpaved, rural road would be even less than that resulting from the continuing use of an inadequate bridge. The signs recommended for use in advance of an LWSC include two warning signs and one regulatory sign with legends as follows: FLOOD AREA AHEAD, IMPASSABLE DURING HIGH WATER, DO NOT ENTER WHEN FLOODED. Use of the regulatory sign would require an appropriate resolution by the Board of Supervisors having responsibility for a county road. Other recommendations include the optional use of either a supple mental distance advisory plate or an advisory speed plate, or both, under circumstances where these may be needed. It was also recommended HR-218 Liability & Traffic Control Considerations for Low Water Stream Crossings that LWSCs be used only on unpaved roads and that they not be used in locations where flooding of an LWSC would deprive dwelling places of emergency ground access.

New reference tables and user-friendly Internet application for predicted heart weights.

BACKGROUND: Knowledge of normal heart weight ranges is important information for pathologists. Comparing the measured heart weight to reference values is one of the key elements used to determine if the heart is pathological, as heart weight increases in many cardiac pathologies. The current reference tables are old and in need of an update. AIMS: The purposes of this study are to establish new reference tables for normal heart weights in the local population and to determine the best predictive factor for normal heart weight. We also aim to provide technical support to calculate the predictive normal heart weight. METHODS: The reference values are based on retrospective analysis of adult Caucasian autopsy cases without any obvious pathology that were collected at the University Centre of Legal Medicine in Lausanne from 2007 to 2011. We selected 288 cases. The mean age was 39.2 years. There were 118 men and 170 women. Regression analyses were performed to assess the relationship of heart weight to body weight, body height, body mass index (BMI) and body surface area (BSA). RESULTS: The heart weight increased along with an increase in all the parameters studied. The mean heart weight was greater in men than in women at a similar body weight. BSA was determined to be the best predictor for normal heart weight. New reference tables for predicted heart weights are presented as a web application that enable the comparison of heart weights observed at autopsy with the reference values. CONCLUSIONS: The reference tables for heart weight and other organs should be systematically updated and adapted for the local population. Web access and smartphone applications for the predicted heart weight represent important investigational tools.

Browsing a component library using Non-functional Information

This paper highlights the role of non-functional information when reusing from a component library. We describe a method for selecting appropriate implementations of Ada packages taking non-functional constraints into account; these constraints model the context of reuse. Constraints take the form of queries using an interface description language called NoFun, which is also used to state non-functional information in Ada packages; query results are trees of implementations, following the import relationships between components. We define two different situations when reusing components, depending whether we take the library being searched as closed or extendible. The resulting tree of implementations can be manipulated by the user to solve ambiguities, to state default behaviours, and by the like. As part of the proposal, we face the problem of computing from code the non-functional information that determines the selection process.

La gestión de los libros electrónicos en la Biblioteca Virtual de la UOC

El texto que se presenta muestra cómo se lleva a cabo la gestión de los libros electrónicos en la Biblioteca Virtual (en adelante BV) de la Universitat Oberta de Catalunya (en adelante UOC). La BV pone especial énfasis en la adquisición de libros digitales para mejorar el acceso de los usuarios a los recursos y a lascolecciones de una universidad caracterizada por su virtualidad. El documento presenta, en primer lugar, el entorno en el que se adquieren y se utilizan los libros electrónicos: se describen los distintos escenarios de adquisición en los que se puede encontrar la BV y se definen los circuitos internos que permiten su gestión, así como los procesos técnicos de los documentos. A continuación, se muestran las distintas opciones de acceso y consulta de libros electrónicos que actualmente se ofrecen desde la BV y se exponenlos análisis de uso de dichos documentos. Por último, se presentan las conclusiones a las que llega la BV sobre el nuevo contexto de libros electrónicos.