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Large-scale analysis of 73 329 physcomitrella plants transformed with different gene disruption libraries: production parameters and mutant phenotypes.

Gene targeting in the moss Physcomitrella patens has created a new platform for plant functional genomics. We produced a mutant collection of 73 329 Physcomitrella plants and evaluated the phenotype of each transformant in comparison to wild type Physcomitrella. Production parameters and morphological changes in 16 categories, such as plant structure, colour, coverage with gametophores, cell shape, etc., were listed and all data were compiled in a database (mossDB). Our mutant collection consists of at least 1804 auxotrophic mutants which showed growth defects on minimal Knop medium but were rescued on supplemented medium. 8129 haploid and 11 068 polyploid transformants had morphological alterations. 9 % of the haploid transformants had deviations in the leaf shape, 7 % developed less gametophores or had a different leaf cell shape. Other morphological deviations in plant structure, colour, and uniformity of leaves on a moss colony were less frequently observed. Preculture conditions of the plant material and the cDNA library (representing genes from either protonema, gametophore or sporophyte tissue) used to transform Physcomitrella had an effect on the number of transformants per transformation. We found correlations between ploidy level and plant morphology and growth rate on Knop medium. In haploid transformants correlations between the percentage of plants with specific phenotypes and the cDNA library used for transformation were detected. The number of different cDNAs present during transformation had no effect on the number of transformants per transformation, but it had an effect on the overall percentage of plants with phenotypic deviations. We conclude that by linking incoming molecular, proteome, and metabolome data of the transformants in the future, the database mossDB will be a valuable biological resource for systems biology.

Bryopsida↗

The construction of a genetic linkage map of red raspberry (Rubus idaeus subsp. idaeus) based on AFLPs, genomic-SSR and EST-SSR markers.

Breeding in raspberry is time-consuming due to the highly heterozygous nature of this perennial fruit crop, coupled with relatively long periods of juvenility. The speed and precision of raspberry breeding can be improved by genetic linkage maps, thus facilitating the development of diagnostic markers for polygenic traits and the identification of genes controlling complex phenotypes. A genetic linkage map (789 cM) of the red raspberry Rubus idaeus has been constructed from a cross between two phenotypically different cultivars; the recent European cultivar Glen Moy and the older North American cultivar Latham. SSR markers were developed from both genomic and cDNA libraries from Glen Moy. These SSRs, together with AFLP markers, were utilised to create a linkage map. In order to test the utility of the genetic linkage map for QTL analysis, morphological data based on easily scoreable phenotypic traits were collected. The segregation of cane spininess, and the root sucker traits of density and spread from the mother plant, was quantified in two different environments. These traits were analysed for significant linkages to mapped markers using MapQTL and were found to be located on linkage group 2 for spines and group 8 for density and diameter. The availability of co-dominant markers allowed heterozygosities to be calculated for both cultivars.

Chromosome Mapping↗

A virtual-reality-based telerehabilitation system with force feedback.

A PC-based orthopedic rehabilitation system was developed for use at home, while allowing remote monitoring from the clinic. The home rehabilitation station has a Pentium II PC with graphics accelerator, a Polhemus tracker, and a multipurpose haptic control interface. This novel interface is used to sample a patient's hand positions and to provide resistive forces using the Rutgers Master II (RMII) glove. A library of virtual rehabilitation routines was developed using WorldToolKit software. At the present time, it consists of three physical therapy exercises (DigiKey, ball, and power putty) and two functional rehabilitation exercises (peg board and ball game). These virtual reality exercises allow automatic and transparent patient data collection into an Oracle database. A remote Pentium II PC is connected with the home-based PC over the Internet and an additional video conferencing connection. The remote computer is running an Oracle server to maintain the patient database, monitor progress, and change the exercise level of difficulty. This allows for patient progress monitoring and repeat evaluations over time. The telerehabilitation system is in clinical trails at Stanford Medical School (CA), with progress being monitored from Rutgers University (NJ). Other haptic interfaces currently under development include devices for elbow and knee rehabilitation connected to the same system.

Computer Graphics↗

[Research on quality of life: review of the scientific production of public universities from the state of Sao Paulo].

This descriptive and exploratory study aims to analyze the scientific production regarding quality of life by the public universities in São Paulo State on the basis of data collected from the elected universities' virtual libraries. The preliminary analysis resulted in 84 studies: 71.4% were Master's Theses, 23.8% doctoral dissertations and 4.7% associate professor's theses from 1993 to 2001. 1 studies were excluded from this total. The 53 (100%) remaining studies had been developed with male and female adults (71.7%) who presented some type of pathology (69.8%) and used existing instruments to assess quality of life (77.3%). The most frequently used instrument was the Medical Outcomes Studies 36-item Short-Form (MOS SF-36), found in 18 (34%) of these studies.

Brazil↗

Health information networking via the Internet with the former Soviet Union.

Because of the severe financial hardships associated with the transition to a market economy in the Newly Independent States (NIS) of the former Soviet Union, the Internet has become a major link to health care resources for many health care workers. In 1992, the University of Illinois at Chicago Library of the Health Sciences (UIC LHS) initiated a special support project with goals of enhancing access to international biomedical information and facilitating international professional networking for interested NIS organizations and individuals. Project objectives included an information needs assessment, development of culturally sensitive Internet training applications, information and referral services, and follow-up e-mail consultations for NIS participants. This paper reviews the historical context of the health care partnerships between the United States and the NIS, and of the UIC LHS International Health Information Networking Project. In the context of UIC, international networking cross-cultural observations, teaching techniques, a Russian training experience, and the development of a Web-based course are reported.

Computer Communication Networks↗

Online search patterns: NLM CATLINE database.

In this article the authors present their analysis of the online search patterns within user searching sessions of the National Library of Medicine ELHILL system and examine the user search patterns on the CATLINE database. In addition to the CATLINE analysis, a comparison is made using data previously analyzed on the MEDLINE database for the same time period, thus offering an opportunity to compare the performance parameters of different databases within the same information system. Data collection covers eight weeks and includes 441,282 transactions and over 11,067 user sessions, which accounted for 1680 hours of system usage. The descriptive analysis contained in this report can assists system design activities, while the predictive power of the transaction log analysis methodology may assists the development of real-time aids.

Cataloging↗

A human chromosome 7 yeast artificial chromosome (YAC) resource: construction, characterization, and screening.

The paradigm of sequence-tagged site (STS)-content mapping involves the systematic assignment of STSs to individual cloned DNA segments. To date, yeast artificial chromosomes (YACs) represent the most commonly employed cloning system for constructing STS maps of large genomic intervals, such as whole human chromosomes. For developing a complete YAC-based STS-content map of human chromosome 7, we wished to utilize a limited set of YAC clones that were highly enriched for chromosome 7 DNA. Toward that end, we have assembled a human chromosome 7 YAC resource that consists of three major components: (1) a newly constructed library derived from a human-hamster hybrid cell line containing chromosome 7 as its only human DNA; (2) a chromosome 7-enriched sublibrary derived from the CEPH mega-YAC collection by Alu-polymerase chain reaction (Alu-PCR)-based hybridization; and (3) a set of YACs isolated from several total genomic libraries by screening for > 125 chromosome 7 STSs. In particular, the hybrid cell line-derived YACs, which comprise the majority of the clones in the resource, have a relatively low chimera frequency (10-20%) based on mapping isolated insert ends to panels of human-hamster hybrid cell lines and analyzing individual clones by fluorescence in situ hybridization. An efficient strategy for polymerase chain reaction (PCR)-based screening of this YAC resource, which totals 4190 clones, has been developed and utilized to identify corresponding YACs for > 600 STSs. The results of this initial screening effort indicate that the human chromosome 7 YAC resource provides an average of 6.9 positive clones per STS, a level of redundancy that should support the assembly of large YAC contigs and the construction of a high-resolution STS-content map of the chromosome.

Animals↗

Target specificity analysis of the Abl kinase using peptide microarray data.

Protein kinases play an important role in cellular signalling. The reliable prediction of their substrates is of high importance for the deciphering of signalling pathways. A recently developed peptide microarray technology for the charcterisation of protein kinases delivers data on the individual phosphorylation status of each single member of a large peptide library. This data can be used to approximate the substrate specificity of the investigated kinase. We present an approach to process the collected information using a combination of a weight matrix approach and a nearest neighbor approach. Experiments with the protein-tyrosine kinase Abl are conducted to validate the results. Randomly selected peptides (1433) are used to estimate the substrate preferences of the kinase. The obtained prediction results are compared with standard methods. The new approach is tested further on bona fide Abl phosphorylation sites.

Binding Sites↗

Organometallic chemistry on solid phase. An overview.

Solid-phase organic synthesis (SPOS) is the most important method for the production of combinatorial libraries and with the development of high-throughput screening, libraries are widespread in pharmaceutical and agricultural chemistry. Amongst all the synthetic transformations successfully applied to solid phase, the use of organometallic reagents for the formation of a new carbon-carbon bond has been scarcely pursued. In this overview we collected the most recent examples of the use of organometallic reagents of Li, Mg, Cu, Zn, Si and B for C-C bond formation. The use of organometallic reagents in Pd-catalysed cross-coupling reactions was not reviewed. Highly basic organometallics as organo-lithium and -magnesium reagents have been more largely employed than cuprates and zincates, suggesting that several kinds of resins can withstand relatively strong reaction conditions.

Boranes↗

Kolmogorov-Smirnov statistic and its application in library design.

After several years of frantic development, the dream of an "ideal" library remains elusive. Traditionally, combinatorial chemistry has been used primarily for lead generation, and molecular diversity has been the method of choice for designing and prioritizing experiments. One aspect that often has been overlooked is the drug likeness of the resulting collections. Recently, there have been several attempts to quantify this concept and incorporate it directly into the design process. This article demonstrates the limitations of some conventional methodologies and proposes a new paradigm for experimental design based on the principles of multiobjective optimization. This method allows traditional design objectives such as diversity or similarity to be combined with secondary selection criteria in order to bias the selection toward more pharmacologically relevant regions of chemical space. The method is robust, general, and easily extensible, and it allows the medicinal chemist to create designs that represent the best compromise between several, often conflicting, objectives. Two types of designs are discussed (singles, arrays), and a novel criterion based on the Kolmogorov-Smirnov statistic is proposed as a means to enforce a particular distribution on key molecular properties that are related to drug likeness. The potential of this approach is illustrated in the design of an exploratory library based on the simultaneous optimization of five different parameters. These parameters are combined in an intuitive manner to produce a design that is sufficiently diverse, exhibits a molecular weight and logP profile that is consistent with the respective distributions of known drugs, requires a small number of reagents, and can be synthesized easily in array format using robotic hardware.

Databases, Factual↗

The 'market' for medical and health information in transition: the case of the Hong Kong Hospital Authority libraries.

The last few years have been a period of transition not only for hospitals and their governance but also for post-graduate medical education in Hong Kong. Both trends have a direct impact on the information market place. This article starts by studying the provision of medical and health-related information in Hong Kong. The two university medical and dental libraries, together with the hospital and health sciences libraries in government hospitals and the Department of Health, house the major collections on medicine and health care. The demand for medical and health care information is increasingly felt with the takeover of 39 hospitals by the statutory Hong Kong Hospital Authority in 1991. The major problems and issues in planning for library information services are the historically uneven development of libraries, discrepancies in funding, the changes in organizational and management structure, and the competition with higher development priorities within the organization. In view of current technology and the availability of rich external resources, the adopted strategies tend towards the formation of 10 library service networks, development of integrated library information systems on the Health Authority-wide area network, and the devolution of management responsibilities. The future challenges in store for the information professional are examined.

Community Networks↗

Client value models provide a framework for rational library planning (or, phrasing the answer in the form of a question).

Libraries often do not know how clients value their product/ service offerings. Yet at a time when the mounting costs for library support are increasingly difficult to justify to the parent institution, the library's ability to gauge the value of its offerings to clients has never been more critical. Client Value Models (CVMs) establish a common definition of value elements-or a "value vocabulary"-for libraries and their clients, thereby providing a basis upon which to make rational planning decisions regarding product/service acquisition and development. The CVM concept is borrowed from business and industry, but its application has a natural fit in libraries. This article offers a theoretical consideration and practical illustration of CVM application in libraries.

Consumer Behavior↗

Aspirin in diabetic retinopathy. A systematic review.

Diabetes mellitus is a risk factor for eye disease that can lead to blindness. There have been both concerns that aspirin use might worsen diabetic retinopathy, as well as hopes that aspirin might be beneficial in treating it. We investigated whether there are beneficial effects of aspirin alone and in combination with other antiplatelet agents in the treatment of diabetic retinopathy, and the relative hazards for the development of high-risk proliferative retinopathy following aspirin treatment. We conducted a sensitive search for randomized controlled trials combined with index terms for identifying studies on aspirin treatment in diabetic retinopathy in the Cochrane Library (issue 4, 2001) and Medline (1966 to October, 2001). We examined randomized controlled clinical trials in diabetic patients with (non) proliferative diabetic retinopathy and aspirin treatment alone or in combination with dipyramidole versus placebo administration. Two independent reviewers judged trial eligibility, collected details of study population, interventions, and outcomes using a standard data extraction form. One reviewer assessed the quality of trial reporting. We identified six publications pertinent to our objective. Aspirin dosages ranged from 650 mg to 990 mg daily, the dose of dipyridamole, used in only one trial, was 225 mg per day. Studies lasted 8 weeks to 5 years. All trials showed that aspirin alone or in combination with dipyridamole neither lowered nor increased the risk of the development of diabetic retinopathy. The results suggest that there are no ocular contraindications to taking aspirin if required as part of a treatment for cardiovascular diseases or other medical indications.

Anti-Inflammatory Agents, Non-Steroidal↗

Can the Internet help to meet the challenges in ADME and e-ADME?

The high-throughput screening (HTS) of large proprietary compound collections and combinatorial libraries has put an increased pressure on getting pharmacokinetic and drug metabolism data as early as possible. Properties related to absorption, distribution, metabolism and excretion (ADME) can be estimated by a range of in vivo and in vitro methods. Most are now available or under development in high(er) throughput modus. In addition progress has been made in in silico methods using various QSAR and modeling techniques using a range of recently introduced descriptors tailored to e-ADME. These approaches are promising as a filter for virtual libraries to decide on synthesis as well as in the selection of compounds for acquisition and screening. This paper will discuss a number of Internet resources relevant to ADME studies and predictions. We have focused on areas related to metabolism including metabolic pathways and P450 metabolism, transporters, bioavailability and absorption, pharmacokinetics and pharmacodynamics, molecular properties and tools for data analysis.

Adsorption↗

Introducing the National Library for Health Skin Conditions Specialist Library.

BACKGROUND: This paper introduces the new National Library for Health Skin Conditions Specialist Library http://www.library.nhs.uk/skin. DESCRIPTION: The aims, scope and audience of the new NLH Skin Conditions Specialist Library, and the composition and functions of its core Project Team, Editorial Team and Stakeholders Group are described. The Library's collection building strategy, resource and information types, editorial policies, quality checklist, taxonomy for content indexing, organisation and navigation, and user interface are all presented in detail. The paper also explores the expected impact and utility of the new Library, as well as some possible future directions for further development. CONCLUSION: The Skin Conditions Specialist Library is not just another new Web site that dermatologists might want to add to their Internet favourites then forget about it. It is intended to be a practical, "one-stop shop" dermatology information service for everyday practical use, offering high quality, up-to-date resources, and adopting robust evidence-based and knowledge management approaches.

Databases as Topic↗

[Malnutrition: a secular challenge to child nutrition]

OBJECTIVE: To review current knowledge about child malnutrition, including the historical aspects of the problem, its dimension as a childhood public health problem, its natural history, physiopathology, clinical features, diagnosis and treatment, and strategies used by the health sector to control this disease. METHODS: Information was collected by researching the Medline system, the Bireme library, internet sites of interest, catalogues of publications produced by Brazilian governmental organizations and international institutions dealing with child nutrition. RESULTS: The review pointed out that despite recent world prevalence reduction, child malnutrition is a major public health problem in developing countries. Malnutrition, in any of its forms, contributes for more than 50% of deaths among children under 5 years in those countries. Mortality rates of severely malnourished children treated as in patients have been unchanged for the last five decades. Guidelines for improving the treatment and reducing mortality rates of severely malnourished children treated in hospitals were recently defined by the World Health Organization. Even though some positive results have been achieved by the health sector in reducing child malnutrition prevalence, the effectivity of the interventions is often low. Lack of food might limit the success in treating and preventing malnutrition. Factors that may contribute to the effectiveness of interventions against malnutrition include approaches which reassure the confidence of health professionals about achieving positive results with the proper treatment of malnourished children, establishment of an effective relationship between health professionals and mothers, as well as practical support to mothers in recognizing them as valuable active agents for their children nutrition rehabilitation at the household level. CONCLUSIONS: Throughout the centuries, malnutrition has been the biggest challenge faced by developing countries in order to guarantee to children under five years of age their right of being well nourished and healthy. The current challenge is the proper use of the available scientific knowledge on child nutrition to further reduce the figures for all the types of child malnutrition.

Journal Article↗

Development of a method for evaluating drug-likeness and ease of synthesis using a data set in which compounds are assigned scores based on chemists' intuition.

The concept of drug-likeness, an important characteristic for any compound in a screening library, is nevertheless difficult to pin down. Based on our belief that this concept is implicit within the collective experience of working chemists, we devised a data set to capture an intuitive human understanding of both this characteristic and ease of synthesis, a second key characteristic. Five chemists assigned a pair of scores to each of 3980 diverse compounds, with the component scores of each pair corresponding to drug-likeness and ease of synthesis, respectively. Using this data set, we devised binary classifiers with an artificial neural network and a support vector machine. These models were found to efficiently eliminate compounds that are not drug-like and/or hard-to-synthesize derivatives, demonstrating the suitability of these models for use as compound acquisition filters.

Combinatorial Chemistry Techniques↗

Molecular assays for targeting human and bovine enteric viruses in coastal waters and their application for library-independent source tracking.

Rapid population growth and urban development along waterways and coastal areas have led to decreasing water quality. To examine the effects of upstream anthropogenic activities on microbiological water quality, methods for source-specific testing are required. In this study, molecular assays targeting human enteroviruses (HEV), bovine enteroviruses (BEV), and human adenoviruses (HAdV) were developed and used to identify major sources of fecal contamination in the lower Altamaha River, Georgia. Two-liter grab samples were collected monthly from five tidally influenced stations between July and December 2002. Samples were analyzed by reverse transcription- and nested-PCR. PCR results were confirmed by dot blot hybridization. Eleven and 17 of the 30 surface water samples tested positive for HAdV and HEV, respectively. Two-thirds of the samples tested positive for either HEV or HAdV, and the viruses occurred simultaneously in 26% of samples. BEV were detected in 11 of 30 surface water samples. Binary logistic regression analysis showed that the presence of both human and bovine enteric viruses was not significantly related to either fecal coliform or total coliform levels. The presence of these viruses was directly related to dissolved oxygen and streamflow but inversely related to water temperature, rainfall in the 30 days preceding sampling, and chlorophyll-a concentrations. The stringent host specificity of enteric viruses makes them good library-independent indicators for identification of water pollution sources. Viral pathogen detection by PCR is a highly sensitive and easy-to-use tool for rapid assessment of water quality and fecal contamination when public health risk characterization is not necessary.

Adenoviruses, Human↗