http://crossmark.crossref.org/dialog/?doi=10.1007/s12109-015-9427-2&domain=pdf Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s12109-015-9427-2&domain=pdf Web End = ...http://crossmark.crossref.org/dialog/?doi=10.1007/s12109-015-9427-2&domain=pdf Web End = Pub Res Q (2015) 31:321323 DOI 10.1007/s12109-015-9427-2 BOOK REVIEW Published online: 14 October 2015 Springer Science+Business Media New York 2015 I interviewed Ashok Chopra for the One to One column in Publishing Today in January 2008 and I asked him how he will dene a good book. The author has been in publishing industry for four decades, starting his career as a journalist with Indian Express and moving to Vikas Publishing House as executive editor, vice president of Macmillan India, publishing director of UBS Publishers, publisher of the India Today Book Club and Books Today, as well as chief executive and publisher of HarperCollins India. The readers will love the background stories of publishing books like Freedom at Midnightthe story of the Indian Independence in 1947 and the assassination of Mahatma Gandhiby Dominique Lapierre and Larry Collins, which became a bestseller.
This article is a description and guide to the contents of al-Maqāmāt al-Ǧalāliyya by al-Ḥasan b. Abī Muḥammad al-Ṣafadī (fl. first quarter of the 8th/14th c.). The article begins with a discussion ...of the life of the author al-Ṣafadī and his works. It provides evidence for his biography derived from unpublished manuscript sources. The article then considers features of the authorial context of al-Maqāmāt al-Ǧalāliyya, including notes found in Laleli ms 1929, and evidence for the dedication of al-Maqāmāt al-Ǧalāliyya to the famed geographer, historian, and ruler of Hama, al-Malik al-Muʾayyad Abū l-Fidāʾ (672/1273-732/1332). The remainder of the article provides a description of al-Maqāmāt al-Ǧalāliyya, its narrative structures, the contents of the thirty individual maqāmāt, and explores parallels between al-Maqāmāt al-Ǧalāliyya and other works of the maqāma genre. The final section includes a sample text of al-Maqāma l-Tīzīniyya and an accompanying commentary.
Hitherto accredited prion tests use the PK resistance of PrP
Sc, the pathogenic isoform of the prion protein, as a marker for the disease. Because of variations in the amount of disease-related ...aggregated PrP, which is not PK-resistant, these prion tests offer only limited sensitivity. Therefore, a prion detection method that does not rely on PK digestion would allow for the detection of both PK-resistant as well as PK-sensitive PrP
Sc. Furthermore, single particle counting is more sensitive than methods measuring an integrated signal. Our new test system is based on dual-colour fluorescence correlation spectroscopy (FCS). This method quantifies the number of protein aggregates that have been simultaneously labelled with two different antibodies using dual-colour fluorescence intensity distribution analysis (2D-FIDA). This only counts PrP aggregates, and not PrP monomers. To increase the sensitivity, PrP
Sc was concentrated in a two-dimensional space by immobilizing it so that the antibodies could be captured on the surface of the slide (surface-FIDA). When the surface was systematically scanned, even single prion particles were detected. Using this new technique, the sensitivity to identify samples from scrapie-infected hamster as well as BSE-infected cattle can be dramatically increased in comparison with identification using FIDA in solution.
A characteristic feature of prion diseases such as bovine spongiform encephalopathy (BSE) is the accumulation of a pathological isoform of the host-encoded prion protein, PrP. In contrast to its ...cellular isoform PrPC, the pathological isoform PrPSc forms insoluble aggregates. All commercial BSE tests currently used for routine testing are based on the proteinase K (PK) resistance of PrP, but not all pathological PrP is PK-resistant. In the present study, single prion particles were counted by fluorescence correlation spectroscopy (FCS). The property of PK resistance is not required, i.e., both the PK-resistant and the PK-sensitive parts of the prion particles are detectable. PrP aggregates were prepared from the brains of BSE-infected cattle, as well as from scrapie-infected hamsters, by the NaPTA precipitation method without PK digestion. They were labeled using two different PrP-specific antibodies for FCS measurements in the dual-color mode (2D-FIDA). Within the limited number of samples tested, BSE-infected cattle and scrapie-infected hamsters in the clinical stage of the disease could be distinguished with 100% specificity from a control group. Thus, a diagnostic tool for BSE detection with complete avoidance of PK treatment is presented, which should have particular advantages for testing animals in the preclinical stage.
Objective
The objective of this study was to evaluate the prediction of ambulation in adults with myelomeningocele from muscle strength testing and ambulation in early life.
Materials and methods
...Fifty-two myelomeningocele (MMC) individuals at the age 18–37 years at follow-up were studied. Information on muscle strength and ambulatory function in early life was retrieved from medical records. The motor levels determined by the muscle strength were used to predict ambulatory function later in life. At follow-up, a clinical examination was performed.
Results
Of 20 MMC individuals assessed with muscle strength within the first year of life, 7 achieved the predicted ambulatory function, 6 had a better, and 7 a poorer function. Of 32 individuals with known muscle strength at the age of 5–8 years, 10 had function as predicted, 5 a better ambulatory function, and 17 had a poorer ambulation in adult life than predicted. Good strength in quadriceps muscles gave significant better prospect for adult walking. Of the 52 participants, 41 retained their ambulation status from 5–8 years of age.
Conclusion
For MMC individuals with motor levels L3–L5, adult ambulatory function cannot be determined from muscle strength in early life, while it to some extend can be predicted for motor levels at or above L2 and at or below S1. The majority of the participants who at the age 5–8 years were community walkers without walking aid kept that function.
The rapid increase of compound libraries as well as new targets emerging from the Human Genome Project require constant progress in pharmaceutical research. An important tool is High-Throughput ...Screening (HTS), which has evolved as an indispensable instrument in the pre-clinical target-to-IND (Investigational New Drug) discovery process. HTS requires machinery, which is able to test more than 100,000 potential drug candidates per day with respect to a specific biological activity. This calls for certain experimental demands especially with respect to sensitivity, speed, and statistical accuracy, which are fulfilled by using fluorescence technology instrumentation. In particular the recently developed family of fluorescence techniques, FIDA (Fluorescence Intensity Distribution Analysis), which is based on confocal single-molecule detection, has opened up a new field of HTS applications. This report describes the application of these new techniques as well as of common fluorescence techniques--such as confocal fluorescence lifetime and anisotropy--to HTS. It gives experimental examples and presents advantages and disadvantages of each method. In addition the most common artifacts (auto-fluorescence or quenching by the drug candidates) emerging from the fluorescence detection techniques are highlighted and correction methods for confocal fluorescence read-outs are presented, which are able to circumvent this deficiency.
Este trabajo estudia de manera exploratoria la cooperación recibida por el MERCOSUR de la Unión Europea y del Fondo Internacional de Desarrollo Agrícola en cuatro ejes: dimensión parlamentaria, ...agenda de educación superior, política de ciencia y tecnología y agenda para la agricultura familiar. Se argumenta aquí que la cooperación internacional al desarrollo coloca incentivos a un conjunto de actores (nacionales y regionales, gubernamentales y no gubernamentales) para el desarrollo de capacidades institucionales y de incidencia para presionar sobre la agenda política regional e incorporar nuevas iniciativas de políticas en áreas no contempladas y/o no reguladas por el MERCOSUR.
Measurement of fluorescence lifetime is a well-established technique, which has recently been introduced into the portfolio of assay formats used in high-throughput screening (HTS). This ...investigation establishes appropriate conditions for using lifetime measurements to reduce the impact of compound interference effects during large-scale HTS of corporate screening files. Experimental data on mixtures of standard fluorophores and interfering compounds (from 5 HTS campaigns) have been combined with a theoretical model to identify the minimum data quality required, defined by the photon count in the peak channel, for discrimination of biological activity. Single-component fluorophore lifetimes can be recovered with an error of 1%, with a peak photon count of 10(2), but the same accuracy with a 2-component decay requires a peak photon count of 10(3). When a 3rd component is introduced, the minimum peak count increases to 10(4). The influence of scattered light on lifetime determination was investigated using an emulsion (diameters 25-675 nm). The measured decays of interfering compounds, identified as autofluorescent, show that the vast majority have a very short lifetime that can readily be resolved from the reporter fluorophore, using appropriate data-fitting methods.
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