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Graphic-based musculoskeletal model for biomechanical analyses and animation.

The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the 'Virtual Human' reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. This paper details the design, capabilities, and features of the VIMS development at Johns Hopkins University, an effort possible only through academic and commercial collaborations. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of this unique database and simulation technology. This integrated system will impact on medical education, basic research, device development and application, and clinical patient care related to musculoskeletal diseases, trauma, and rehabilitation.

Algorithms↗

Molecular engineering of fluorescent penicillins for molecularly imprinted polymer assays.

The interaction of seven novel fluorescent labeled beta-lactams with a library of six polymer materials molecularly imprinted (MI) with penicillin G (PenG) has been evaluated using both radioactive and fluorescence competitive assays. The highly fluorescent competitors (emission quantum yields of 0.4-0.95) have been molecularly engineered to contain pyrene or dansyl labels while keeping intact the 6-aminopenicillanic acid moiety for efficient recognition by the cross-linked polymers. Pyrenemethylacetamidopenicillanic acid (PAAP) is the tagged antibiotic that provides the highest selectivity when competing with PenG for the specific binding sites in a MI polymer prepared with methacrylic acid and trimethylolpropane trimethacrylate (10:15 molar ratio) in acetonitrile in the presence of PenG. Molecular modeling shows that recognition of the fluorescent analogues of PenG by the MI material is due to a combination of size and shape selectivity and demonstrates how critical the choice of label and tether chain is. PAAP has been applied to the development of a fluorescence competitive assay for PenG analysis with a dynamic range of 3-890 muM in 99:1 acetonitrile-water solution. Competitive binding studies demonstrate various degrees of cross-reactivity for some antibiotics derived from 6-aminopenicillanic acid, particularly amoxicillin, ampicillin, and penicillin V (but not oxacillin, cloxacillin, dicloxacillin, or nafcillin). Other antibiotics, such as chloramphenicol, tetracycline, or cephapirin, do not compete with PAAP for binding to the imprinted polymer. The MI assay has successfully been tested for PenG analysis in a pharmaceutical formulation.

Binding, Competitive↗

Isolation and functional characterization of the C-terminus of rice phosphatidylinositol 4-kinase in vitro.

A partial rice (Oryza sativa L.) cDNA clone, OsPI4K1c, was isolated through screening of a cDNA library constructed from tillering materials. OsPI4K1c encoded a peptide of 608 amino acids with a calculated molecular mass of 68.4 kDa. The OsPI4K1c peptide shared high homology and possessed the highly conserved domains present in most isolated cloned PI4-kinases, i.e. a lipid kinase unique (LKU) domain and a catalytic (CAT) domain. A region with similarity to pleckstrin homology (PH) domain was present in OsPI4K1c as well. Further comparison with genomic sequences in databases revealed that OsPI4K1c is located at the 3'-end of a putative rice PI 4-kinase coding gene OsPI4K1, and its coding region corresponded to the C-terminal half of OsPI4K1 protein. Twelve exons (49-562 bp in size) and 11 introns (77-974 bp in size) were identified in OsPI4K1c. The recombinant protein expressed in Escherichia coli phosphorylates phosphatidylinositol at the D4 position of the inositol ring. OsPI4K1 transcript levels were detected in a low but constitutive manner in shoot, stem, leaf, spike and root tissues and did not change upon treatment with different hormones, calcium and jasmonic acid (JA). However, treatment with salicylic acid (SA) elevated the mRNA level of the OsPI4K1 gene, which suggested the involvement of OsPI4K1 in wounding responses.

1-Phosphatidylinositol 4-Kinase↗

Correlation of the endoscopic and radiological anatomy of congenital obstruction of the posterior urethra and the external sphincter.

OBJECTIVE: To determine whether the external sphincter is distal to congenital occlusion of the posterior urethra in boys by correlating endoscopic video-recorded information with cysto-urethrographic observations and assessing the anatomy of the disease. PATIENTS AND METHODS: This study reviewed the endoscopic and radiographic findings in 42 boys (mean age 42 months, range newborn to 14 years), using material from a videotape library, and correlated these with the pre-operative cystogram. The nature of the obstructive lesion and its relationship to the verumontanum and the external sphincter was assessed. RESULTS: Of the 42 boys, 36 had the proximal extent of the external sphincter identified on the endoscopic video recording to be above the posterior urethral membrane; 22 of the membranes were obstructive. The proximal extent of the external sphincter was identified on the static cystogram images of only 31 of the 38 boys examined, but only ever above the posterior urethral membrane. CONCLUSION: The proximal extent of the external sphincter, i.e. that portion which is most prominent endoscopically, is proximal to the membrane in congenital obstruction of the posterior urethra.

Adolescent↗

Directed evolution of ampicillin-resistant activity from a functionally unrelated DNA fragment: A laboratory model of molecular evolution.

To establish an experimental system to directly observe molecular evolution, a DNA fragment that confers ampicillin resistance on Escherichia coli was cloned from an archaeal genomic DNA. The activity of this clone was enhanced by 50 rounds of directed evolution by using DNA shuffling. Analysis of the evolved DNA fragments shows that two genetic regions have coevolved: One region, which has no obvious ORF, is essential for the activity, whereas the other, which appears to encode a protein, is not essential but enhances the activity of the former region. Analysis of the evolutionary intermediates shows that negative mutations are effectively removed while beneficial mutations accumulate and illustrates how a protein has evolved over the course of the evolution experiments. Although the mechanism of the activity remains unclear, the evolved DNA fragments also confer resistance to other drugs that inhibit bacterial cell-wall synthesis. The present system would serve as an experimental model to study evolutionary dynamics in the laboratory and provide the concept of screening natural libraries to obtain starting materials for directed evolution.

Ampicillin↗

South Cheshire Local Multi-disciplinary Evidence Centre: an evaluation.

The South Cheshire Local Multidisciplinary Evidence Centre (LMEC) was a two-year project commenced in March 1998 and completed in April 2000. The project aimed to develop an information service to enable all primary and community care staff in South Cheshire to access high-quality evidence and thus to improve patient care. The LMEC gave access from the workplace to both physical and electronic resources to support clinical governance and lifelong learning, with a strong emphasis on evidence-based material. Automation of the library catalogue enabled its inclusion on the website. The project developed enquiry and document delivery services and provided training on using the LMEC and on critical appraisal. An evaluation carried out at the end of the project showed that over 120 primary and community care staff had used the LMEC and were positive about the service. As Clinical Governance, the NHSnet, and plans for continuing professional development are implemented, the LMEC is one model for a Local Health Information Service outlined in the NHS IT strategy.

Education, Medical, Continuing↗

Off-flavour release from packaging materials and its prevention: a foods company's approach.

Off-flavours in packed food are causes for consumer complaints. Often, they are related to packaging materials. For food companies, this represents not only costs related to production, but also a possible loss of brand confidence and market share. The origin of packaging-related off-odours are many sided. Odours derive from the degradation of base packaging materials and their converting processes, including printing, coating and lamination as well as the interaction between food and packaging. Many substances and groups of substances have been identified so far. In spite of the fact that the quality of packaging materials is clearly defined in the specifications (e.g. limit for residual solvents, standardized odour and taste transfer tests), off-flavour cases still do occur. This paper sets out ways of avoiding such problems, even in factories and laboratories which are not so well equipped. Prevention at Nestlé is based on several pillars. For a number of years, a sensory panel at the central laboratory has been specialized in and trained on packaging off-favours. The panel can describe and identify odours and their origin. To confirm the results by instrumental analysis, various extraction and separation techniques are available, including distillation/extraction techniques and direct thermal desorption followed by gas chromatography coupled with mass spectroscopy and an olfactory sniffing port. However, this knowledge must also be present in the operational plants where the problem usually originates. To manage this knowledge transfer, two tools were introduced to build up sensory panels that can evaluate packaging material. First, an aroma library kit was developed that contained odours that are often involved in off-odour cases. For each odour, a typical descriptor and the chemical composition are given. Beside that, information is added about the occurrence. Second, a glossary, which contains descriptors for packaging-related off-odours, was published. This small booklet helps to unify the odour descriptions, especially thanks to its translation into three important languages. This paper describes the tools mentioned above, as well as examples and limitations for their application.

Food Contamination↗

A brassinolide-suppressed rice MADS-box transcription factor, OsMDP1, has a negative regulatory role in BR signaling.

The MADS-box transcription factor-encoding genes are expressed mainly during plant reproductive development, where they play important roles in controlling floral organ initiation and identity. Few previous reports have investigated the functions of MADS-box transcription factors expressed in vegetative tissues. Here we describe the functional characterization of a rice AG-like MADS-box protein, OsMDP1 (Oryza sativa MADS-domain-containing protein 1). A partial cDNA encoding a MADS-box domain was identified via high-throughput screening of rice brassinolide-regulated genes, and the full-length cDNA was subsequently isolated via screening of a cDNA library constructed from rice materials at tillering stage. Expression pattern analyses indicated that OsMDP1 is transcribed mainly in vegetative tissues, including the mature leaf, coleoptile, root-elongation zone, culm internode, and especially the joint region between the leaf blade and sheath. Further studies revealed that transcription of OsMDP1 is stimulated by darkness and suppressed by brassinolide treatment. OsMDP1 deficiency resulted in shortened primary roots, elongated coleoptiles and enhanced lamina joint inclinations. Moreover, transgenic plants showed hypersensitivities to exogenous brassinolide in terms of lamina joint inclination and coleoptile elongation. OsMDP1 deficiency resulted in enhanced expression of OsXTR1, which encodes xyloglucan endotransglycosylase, the cell-wall loosening enzyme necessary for cell elongation, and modulated expressions of multiple genes involved in cell signalling and gene transcription, indicating the key negative regulatory role of OsMDP1 in BR signalling.

Amino Acid Sequence↗

Identification of Epichloë endophytes in planta by a microsatellite-based PCR fingerprinting assay with automated analysis.

Epichloë endophytes are a group of filamentous fungi that include both sexual (Epichloë) and asexual (Neotyphodium) species. As a group they are genetically diverse and form both antagonistic and mutualistic associations with temperate grasses. We report here on the development of a microsatellite-based PCR system for fingerprinting this group of fungi with template isolated from either culture or infected plant material. M13mp19 partial genomic libraries were constructed for size-fractionated genomic DNA from two endophyte strains. These libraries were screened with a mixture of DIG-labeled dinucleotide and trinucleotide repeat probes. Positive clones were sequenced, and nine unique microsatellite loci were identified. An additional microsatellite was serendipitously identified in the 3' untranscribed region of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase gene from N. lolii Lp19. Primers were designed for each locus and a panel of endophytes, from different taxonomic groupings, was screened to determine the degree of polymorphism. On the basis of these results a multiplex assay was developed for strain identification with fluorescently labeled primers for five of these loci. Using this system the size of the products amplified can be precisely determined by automated analysis, and an allele profile for each strain can be readily generated. The assay was shown to resolve endophyte groupings to the level of known isozyme phenotype groupings. In a blind test the assay was used successfully to identify a set of endophytes in planta. A reference database of allele sizes has been established for the panel of endophytes examined, and this will be expanded as new strains are analyzed.

Alleles↗

Identification of bacterial spores using statistical analysis of Fourier transform infrared photoacoustic spectroscopy data.

Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) has been applied for the first time to the identification and speciation of bacterial spores. A total of forty specimens representing five strains of Bacillus spores (Bacillus subtilis ATCC 49760, Bacillus atrophaeus ATCC 49337, Bacillus subtilis 6051, Bacillus thuringiensis subsp. kurstaki, and Bacillus globigii Dugway) were analyzed. Spores were deposited, with minimal preparation, into the photoacoustic sample cup and their spectra recorded. Principal component analysis (PCA), classification and regression trees (CART), and Mahalanobis distance calculations were used on this spectral library to develop algorithms for step-wise classification at three levels: (1) bacterial/nonbacterial, (2) membership within the spore library, and (3) bacterial strain. Internal cross-validation studies on library spectra yielded classification success rates of 87% or better at each of these three levels. Analysis of fifteen blind samples, which included five samples of spores already in the spectral library, two samples of closely related Bacillus globigii 01 spores not in the library, and eight samples of nonbacterial materials, yielded 100% accuracy in distinguishing among bacterial/nonbacterial samples, membership in the library, and bacterial strains within the library.

Acoustics↗

Variation between geographical populations of Lutzomyia (Nyssomyia) whitmani (Antunes & Coutinho, 1939) sensu lato (Diptera:Psychodidae:Phlebotominae) in Brazil.

Phylogenetic analysis of morphometric and biological characters indicated that there are two distinct forms of Lutzomyia whitmani in Brazil: one is present both north and south of the River Amazonas in the State of Pará while the other occurs in northeast Brazil, in the State of Ceará, and further south, including the type locality in State of Bahia. The Amazonian form is reportedly neither strongly anthropophilic nor synanthropic, and it is the vector of Leishmania shawi; whereas the southern form is often collected peridomestically, while biting man, and has been found infected with Le.(V.) braziliensis. The ratio of the length of the genital filaments to that the genital pump was found to be consistently smaller in males of the Amazonian populations. A middle repetitive DNA element was isolated by differentially screening a genomic library made using Amazonian material, and the sequence was diagnostic for this form of Lu. whitmani (being absent or occurring in low copy number in the southern form). The total evidence suggests there are at least two, geographically-isolated forms of Lu. whitmani, which may represent different cryptic species.

Animals↗

Computer-assisted reader software versus expert reviewers for polyp detection on CT colonography.

OBJECTIVE: The purpose of our study was to assess the sensitivity of computer-assisted reader (CAR) software for polyp detection compared with the performance of expert reviewers. MATERIALS AND METHODS: A library of colonoscopically validated CT colonography cases were collated and separated into training and test sets according to the time of accrual. Training data sets were annotated in consensus by three expert radiologists who were aware of the colonoscopy report. A subset of 45 training cases containing 100 polyps underwent batch analysis using ColonCAR version 1.2 software to determine the optimum polyp enhancement filter settings for polyp detection. Twenty-five consecutive positive test data sets were subsequently interpreted individually by each expert, who was unaware of the endoscopy report, and before generation of the annotated reference via an unblinded consensus interpretation. ColonCAR version 1.2 software was applied to the test cases, at optimized polyp enhancement filter settings, to determine diagnostic performance. False-positive findings were classified according to importance. RESULTS: The 25 test cases contained 32 nondiminutive polyps ranging from 6 to 35 mm in diameter. The ColonCAR version 1.2 software identified 26 (81%) of 32 polyps compared with an average sensitivity of 70% for the expert reviewers. Eleven (92%) of 12 polyps > or = 10 mm were detected by ColonCAR version 1.2. All polyps missed by experts 1 (n = 4) and 2 (n = 3) and 12 (86%) of 14 polyps missed by expert 3 were detected by ColonCAR version 1.2. The median number of false-positive highlights per case was 13, of which 91% were easily dismissed. CONCLUSION: ColonCAR version 1.2 is sensitive for polyp detection, with a clinically acceptable false-positive rate. ColonCAR version 1.2 has a synergistic effect to the reviewer alone, and its standalone performance may exceed even that of experts.

Adult↗

What a day!

Explore the source record for details and available documents.

Communication↗

[How Charcot got his chair].

Charcot's career, as is well-known, reached a summit with his acquisition of the Faculty clinical chair of diseases of the nervous system inaugurated in 1882. Based upon previously untapped archival materials at the Charcot Library and the National Archives, this paper explores four questions: I. Was "Charcot's chair" really the first specialized chair for neurology?; 2. Was it founded specifically for Charcot?; 3. What role did the Faculty of Medicine play and did it offer any opposition?; 4. How important was the creation of the chair for the flourishing of the Salpêtrière school. Evidence is presented to show that Charcot considered a specialized chair in nervous diseases a high priority for his career and his school. Sometime around 1880, convinced of the importance of this project, he began to assemble arguments in its behalf from French and foreign sources, particularly from his German colleagues, Westphal and Erb. He learned that there were no precedents, not even in Berlin. Charcot's carefully prepared manuscript memoir presented a strong case for the "necessity" of the chair based on the recent progress and theoretical as well as practical importance of his subject. He described psychiatry, which already had a Faculty clinical chair, as but a "small part" of neuropathology and rejected the idea of combining the two disciplines. Although the project encountered opposition from several Faculty colleagues, who claimed that it was a personal favor for Charcot, powerful support from political allies such as Gambetta and Ferry ensured government funding. In fact, government action in behalf of the creation of the chair for Charcot preceded and surprised the medical Faculty. This paper shows the extent to which Charcot's own initiatives and arguments set the agenda and defined the role he envisaged for the new foundation at the center of the clinical research and teaching centre emerging under his direction at the Salpêtrière.

Clinical Medicine↗

[Health education and AIDS. A randomized controlled trial].

In 1987 a small health education research team in Montpellier became interested in AIDS prevention among high school students (15-19 years old). Studies at that time indicated that the majority of the youth were relatively well informed about AIDS, for example 99% of those questioned knew that the disease was transmitted by sexual intercourse or by the exchange of contaminated needles. Further studies indicated, however, that the young people did not feel that the subject concerned them personally--it was considered a problem like many others. The team decided therefore to design a programme which would involve the young people, and thus motivate them not only to question, but to look for answers and implicate themselves in the search for information. The programme design consisted in creating video workshops in selected high schools. Adults with different backgrounds were trained in video production and communication skills in order to develop sufficient staff for workshop supervision. A network of available specialists was recruited for consulting purposes and a specialized library which included audiovisual materials was created so that the young people would have sufficient resources available for their research. In order to incite the students to contemplate the subject of AIDS and all that it involves, a contest was held. The theme was simply, "AIDS" and the duration was the length of the 1988-89 school year. Eight workshops were created in eight different schools. The teams were created quite spontaneously and the dynamic of interrogation anticipated was realized. With the help of trained adult supervisors, each team started their project by designing a five minute video.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

[Non-A, non-B hepatitis: hepatitis C].

Non-A, non-B hepatitis (NANB), whether following the transfusion of blood products or occurring sporadically without percutaneous exposure, is complicated in approximately 50% of cases by the development of chronic hepatitis. Emerging as a consistent observation is the insidious progression of such cases of chronic NANB hepatitis to cirrhosis. Among patients with chronic NANB hepatitis followed for up to 10 years, cirrhosis is demonstrable in 20%. In May, 1988, the identification of the agent of NANB hepatitis was described by Houghton and colleagues of the Chiron Corporation. Hepatitis C, a 10,000 nucleotide single-stranded RNA virus with properties similar to those of flavivirus, was identified by developing a cDNA library from the genetic material in a chimpanzee inoculum of high infectivity and locating a clone which elaborated a virus-specific protein. Serologic evidence for HCV infection can be detected in 60-90% of cases of transfusion-associated hepatitis and 50% of cases of sporadic NANB hepatitis. Antibody to HCV (anti-HCV) can be detected in 30% of chronic hepatitis B, in 10-46% of alcoholic cirrhosis, in 40-70% of cases of hepatocellular carcinoma HBsAg negative and in 0-83% of patients with auto-immune chronic active hepatitis. Assays for HCV antigen will require technology more sensitive such than current immunoassays, such as the polymerase chain reaction. The introduction into blood banks of a screening test for anti-HCV is expected to reduce the risk of transfusion-associated NANB hepatitis and is highly recommended.

Acute Disease↗