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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Geometriae dedicata 33 (1990), S. 27-35 
    ISSN: 1572-9168
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract The inner and outer automorphism groups of a Lie group are generalized by considering automorphisms in the category of homogeneous principal bundles. These automorphisms are then used to produce certain invariant gauge transformations of such bundles. Some aspects of the resulting action on the space of invariant connections are also described.
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  • 2
    Publication Date: 2009-08-18
    Description: Genome-wide association studies suggest that common genetic variants explain only a modest fraction of heritable risk for common diseases, raising the question of whether rare variants account for a significant fraction of unexplained heritability. Although DNA sequencing costs have fallen markedly, they remain far from what is necessary for rare and novel variants to be routinely identified at a genome-wide scale in large cohorts. We have therefore sought to develop second-generation methods for targeted sequencing of all protein-coding regions ('exomes'), to reduce costs while enriching for discovery of highly penetrant variants. Here we report on the targeted capture and massively parallel sequencing of the exomes of 12 humans. These include eight HapMap individuals representing three populations, and four unrelated individuals with a rare dominantly inherited disorder, Freeman-Sheldon syndrome (FSS). We demonstrate the sensitive and specific identification of rare and common variants in over 300 megabases of coding sequence. Using FSS as a proof-of-concept, we show that candidate genes for Mendelian disorders can be identified by exome sequencing of a small number of unrelated, affected individuals. This strategy may be extendable to diseases with more complex genetics through larger sample sizes and appropriate weighting of non-synonymous variants by predicted functional impact.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844771/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844771/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ng, Sarah B -- Turner, Emily H -- Robertson, Peggy D -- Flygare, Steven D -- Bigham, Abigail W -- Lee, Choli -- Shaffer, Tristan -- Wong, Michelle -- Bhattacharjee, Arindam -- Eichler, Evan E -- Bamshad, Michael -- Nickerson, Deborah A -- Shendure, Jay -- R01 HL094976/HL/NHLBI NIH HHS/ -- R01 HL094976-01/HL/NHLBI NIH HHS/ -- R21 HG004749/HG/NHGRI NIH HHS/ -- R21 HG004749-01/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Sep 10;461(7261):272-6. doi: 10.1038/nature08250. Epub 2009 Aug 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. sarahng@u.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19684571" target="_blank"〉PubMed〈/a〉
    Keywords: Exons/*genetics ; Gene Frequency/genetics ; Gene Library ; Genes, Dominant/genetics ; Genetic Predisposition to Disease/*genetics ; Genetic Testing/*methods ; Genetic Variation/*genetics ; Genome, Human/*genetics ; Haplotypes/genetics ; Humans ; INDEL Mutation/genetics ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; RNA Splice Sites/genetics ; Sample Size ; Sensitivity and Specificity ; Sequence Analysis, DNA/*methods ; Syndrome
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-11-05
    Description: A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages could result from interactions with the companion during the common-envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 +/- 0.59 kiloparsecs from the Sun.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schaefer, G H -- ten Brummelaar, T -- Gies, D R -- Farrington, C D -- Kloppenborg, B -- Chesneau, O -- Monnier, J D -- Ridgway, S T -- Scott, N -- Tallon-Bosc, I -- McAlister, H A -- Boyajian, T -- Maestro, V -- Mourard, D -- Meilland, A -- Nardetto, N -- Stee, P -- Sturmann, J -- Vargas, N -- Baron, F -- Ireland, M -- Baines, E K -- Che, X -- Jones, J -- Richardson, N D -- Roettenbacher, R M -- Sturmann, L -- Turner, N H -- Tuthill, P -- van Belle, G -- von Braun, K -- Zavala, R T -- Banerjee, D P K -- Ashok, N M -- Joshi, V -- Becker, J -- Muirhead, P S -- England -- Nature. 2014 Nov 13;515(7526):234-6. doi: 10.1038/nature13834. Epub 2014 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The CHARA Array of Georgia State University, Mount Wilson Observatory, Mount Wilson, California 91023, USA. ; Center for High Angular Resolution Astronomy and Department of Physics and Astronomy, Georgia State University, PO Box 5060, Atlanta, Georgia 30302, USA. ; Laboratoire Lagrange, UMR 7293, Universite de Sophia-Antipolis (UNS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire de la Cote d'Azur (OCA), Boulevard de l'Observatoire, CS 34229, F-06304 Nice, Cedex 4, France. ; Department of Astronomy, University of Michigan, 941 Dennison Building, Ann Arbor, Michigan 48109, USA. ; National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, Arizona 85719, USA. ; Universite de Lyon; Universite Lyon 1, Observatoire de Lyon, 9 avenue Charles Andre, 69230 Saint Genis Laval; CNRS UMR 5574, Centre de Recherche Astrophysique de Lyon; Ecole Normale Superieure, 69007 Lyon, France. ; Department of Astronomy, Yale University, New Haven, Connecticut 06511, USA. ; Sydney Institute for Astronomy, School of Physics, University of Sydney, New South Wales 2006, Sydney, Australia. ; Research School of Astronomy and Astrophysics, Australian National University, Canberra, Australian Capital Territory 2611, Australia. ; Remote Sensing Division, Naval Research Laboratory, 4555 Overlook Avenue Southwest, Washington, DC 20375, USA. ; Departement de Physique and Centre de Recherche en Astrophysique du Quebec (CRAQ), Universite de Montreal, CP 6128, Succursale Centre-Ville, Montreal, Quebec H3C 3J7, Canada. ; Lowell Observatory, 1400 West Mars Hill Road, Flagstaff, Arizona 86001, USA. ; Max Planck Institute for Astronomy (MPIA), Konigstuhl 17, 69117 Heidelberg, Germany. ; United States Naval Observatory, Flagstaff Station, 10391 West Naval Observatory Road, Flagstaff, Arizona 86001, USA. ; Astronomy and Astrophysics Division, Physical Research Laboratory, Navrangpura, Ahmedabad, Gujarat 380009, India. ; 1] Department of Astronomy, University of Michigan, 941 Dennison Building, Ann Arbor, Michigan 48109, USA [2] Cahill Center for Astronomy and Astrophysics, California Institute of Technology, Pasadena, California 91106, USA. ; Department of Astronomy, Boston University, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363778" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
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  • 4
    Publication Date: 2012-04-13
    Description: It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown. Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported. Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected beta-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350576/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350576/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Roak, Brian J -- Vives, Laura -- Girirajan, Santhosh -- Karakoc, Emre -- Krumm, Niklas -- Coe, Bradley P -- Levy, Roie -- Ko, Arthur -- Lee, Choli -- Smith, Joshua D -- Turner, Emily H -- Stanaway, Ian B -- Vernot, Benjamin -- Malig, Maika -- Baker, Carl -- Reilly, Beau -- Akey, Joshua M -- Borenstein, Elhanan -- Rieder, Mark J -- Nickerson, Deborah A -- Bernier, Raphael -- Shendure, Jay -- Eichler, Evan E -- HD065285/HD/NICHD NIH HHS/ -- HHSN273200800010C/PHS HHS/ -- HL 094976/HL/NHLBI NIH HHS/ -- HL 1029230/HL/NHLBI NIH HHS/ -- HL 102924/HL/NHLBI NIH HHS/ -- HL102926/HL/NHLBI NIH HHS/ -- R01 HD065285/HD/NICHD NIH HHS/ -- R01 HD065285-02/HD/NICHD NIH HHS/ -- R01 HL094976/HL/NHLBI NIH HHS/ -- RC2 HL102923/HL/NHLBI NIH HHS/ -- RC2 HL102926/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Apr 4;485(7397):246-50. doi: 10.1038/nature10989.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22495309" target="_blank"〉PubMed〈/a〉
    Keywords: Autistic Disorder/*genetics ; DNA-Binding Proteins/genetics ; Exome/*genetics ; Exons/*genetics ; GPI-Linked Proteins/genetics ; Genetic Predisposition to Disease/genetics ; Humans ; Laminin/genetics ; NAV1.1 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins/genetics ; Parents ; Point Mutation/*genetics ; Protein Interaction Maps/*genetics ; Receptors, N-Methyl-D-Aspartate/genetics ; Reproducibility of Results ; Siblings ; Signal Transduction ; Sodium Channels/genetics ; Stochastic Processes ; Transcription Factors/genetics ; Tumor Suppressor Protein p53/metabolism ; beta Catenin/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
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  • 5
    Publication Date: 2016-04-28
    Description: The Bacillus thuringiensis delta-endotoxins (Bt toxins) are widely used insecticidal proteins in engineered crops that provide agricultural, economic, and environmental benefits. The development of insect resistance to Bt toxins endangers their long-term effectiveness. Here we have developed a phage-assisted continuous evolution selection that rapidly evolves high-affinity protein-protein interactions, and applied this system to evolve variants of the Bt toxin Cry1Ac that bind a cadherin-like receptor from the insect pest Trichoplusia ni (TnCAD) that is not natively bound by wild-type Cry1Ac. The resulting evolved Cry1Ac variants bind TnCAD with high affinity (dissociation constant Kd = 11-41 nM), kill TnCAD-expressing insect cells that are not susceptible to wild-type Cry1Ac, and kill Cry1Ac-resistant T. ni insects up to 335-fold more potently than wild-type Cry1Ac. Our findings establish that the evolution of Bt toxins with novel insect cell receptor affinity can overcome insect Bt toxin resistance and confer lethality approaching that of the wild-type Bt toxin against non-resistant insects.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865400/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865400/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Badran, Ahmed H -- Guzov, Victor M -- Huai, Qing -- Kemp, Melissa M -- Vishwanath, Prashanth -- Kain, Wendy -- Nance, Autumn M -- Evdokimov, Artem -- Moshiri, Farhad -- Turner, Keith H -- Wang, Ping -- Malvar, Thomas -- Liu, David R -- R01 EB022376/EB/NIBIB NIH HHS/ -- R01EB022376/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 May 5;533(7601):58-63. doi: 10.1038/nature17938. Epub 2016 Apr 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA. ; Monsanto Company, 245 First Street, Suite 200, Cambridge, Massachusetts 02142, USA. ; Department of Entomology, Cornell University, Geneva, New York 14456, USA. ; Monsanto Company, 700 Chesterfield Parkway West, Chesterfield, Missouri 63017, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27120167" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bacillus thuringiensis/*genetics ; Bacterial Proteins/*genetics/*metabolism ; Bacteriophages/genetics ; Biotechnology ; Cadherins/metabolism ; Cell Death ; Consensus Sequence ; Crops, Agricultural/genetics/metabolism ; Directed Molecular Evolution/*methods ; Endotoxins/*genetics/*metabolism ; Genetic Variation/*genetics ; Hemolysin Proteins/*genetics/*metabolism ; *Insecticide Resistance ; Insecticides/metabolism ; Molecular Sequence Data ; Moths/cytology/*physiology ; Mutagenesis/genetics ; Pest Control, Biological/*methods ; Plants, Genetically Modified ; Protein Binding/genetics ; Protein Stability ; Selection, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
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  • 6
    ISSN: 1436-5065
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Description / Table of Contents: Summary Temperature and wind are treated as weather elements which are closely interdependent. The air currents along the valley cross-section are graphically opposed to the temperature pattern, differentiated according to defined weather situations such as “undisturbed fair”, “foehn at high levels”, “bise” (advection of cold dry air from sector N), and “blocking situation” (advection of cold air from NW), as well as with respect to typical diurnal phases (Figs. 3–10). Variations of wind direction and wind speed are shown to be closely related to alterations of temperature gradients between the different measurement stations. Nocturnal inversions above the valley bottom, accompanied by a down valley wind and by independent downslope winds, are established during all nights of clear skies, regardless of weather situation. The temperature inversion is, however, most pronounced during foehn at high levels, when the slopes of middle elevations are heated by advection of warm air in addition to foehn subsidence. Cross-valley winds, closely connected to simultaneous great temperature differences between the both valley sides, occur in the morning and in the late afternoon provided fine weather is established. At these times of the day the inversion between the shaded valley bottom and the sunlit slope is most strongly marked. During the day and fine weather the gradients everywhere on the slopes show positive values, but they are of varying magnitude. Superadiabatic gradients most frequently occur during advection of cold dry air (“bise”). During advections of cold air from NW (blocking situation) the temperature and wind patterns are less evenly distributed than one would expect. In the lowermost layers of the valley atmosphere, presumably below the cloud base, from 1700 to 1900 m the gradient on the slope even with this weather situation reaches the value of nearly 1°C per 100 m, only above this zone the gradient drops to approximately 0.6° C per 100 m.
    Notes: Zusammenfassung Temperatur und Wind werden als direkt voneinander abhängige Elemente gemeinsam behandelt. Die Windströmungen und Temperaturverteilungen werden für die eindeutigen Wetterlagen „ungestört schön”, „Föhn in der Höhe”, „Bis” und „Stau” sowie für typische tageszeitliche Phasen im Talquerschnitt einander graphisch gegenübergestellt. Änderungen der Windrichtung und -geschwindigkeit hängen eng mit Änderungen der Temperaturgradienten zwischen den einzelnen Meßstellen zusammen. Nächtliche Inversionen über dem Talgrund bei gleichzeitigem Bergwind im Tal und davon unabhängigem Abwind an den Hängen finden sich in allen heiteren Nächten unabhängig von der Wetterlage, jedoch ist die Temperaturumkehr bei Föhn in der Höhe am ausgeprägtesten, wenn die Hänge mittlerer Höhe außer durch Subsidenz noch zusätzlich durch Warmluftadvektion erwärmt werden. Bei heiterer Witterung treten morgens und am späteren Nachmittag große Temperaturunterschiede zwischen beiden Hängen und damit verknüpfte Winde quer zur Talachse auf; zu diesen Tageszeiten erreicht auch die Temperaturinversion zwischen beschattetem Talgrund und besonntem Hang ihre stärkste Ausprägung. Tagsüber sind bei solcher Witterung die Gradienten zwar vom Talgrund bis hinauf zu den Kämmen positiv, aber an den verschiedenen Hangabschnitten unterschiedlich groß und untertags variabel. Überadiabatische Gradienten sind bei trockener Kaltluftadvektion (Bise) am häufigsten. Bei Nordstau sind die Temperatur- und Windverhältnisse weniger ausgeglichen als erwartet: Im tiefsten Bereich des Talquerschnittes zwischen 1700 und 1900 m (vermutlich unterhalb der Wolkenbasis) erreicht der Gradient am Hang gelegentlich fast 1° pro 100 m und sinkt erst oberhalb dieser Zone auf rund 0.6° pro 100 m.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Histochemistry and cell biology 19 (1969), S. 272-280 
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Es wird über die Entwicklung einer katecholamin-spezifischen Fluorescenz im Pigmentepithel des Meerschweinchenauges während der Embryonalzeit berichtet. Ab 16. Tragtag ist mit der Methode der „formaldehyde-induced fluorescence“ am Kryostatschnitt eine spezifische Fluorescenz in den Zellen der äußeren Lamelle des Augenbechers nachweisbar. Während die Fluorescenz bei pigmentierten Tieren mit dem Auftreten von Melanin am Ort der Melaninablagerung verschwindet, bleibt sie bei Albinos bis zur Geburt erhalten und erreicht hier bis zum 40. Tag der Embryonalentwicklung ihr Maximum. Es kann angenommen werden, daß wir durch die Fluorescenz Dopa erfassen.
    Notes: Summary The development of the catecholamine-specific fluorescence in the pigment epithelium of the guinea-pig eye during fetal life is investigated. At the 16th day of gestation a specific fluorescence in the outer layer of the optic cup can be demonstrated. It disappears with the onset of melanin synthesis in the pigment cells, while the fluorescence in the pigment epithelium of albinotic animals persists until birth and has its maximun intensity at the 40th day of gestation. The fluorescence is considered to be Dopa-specific.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 56 (2000), S. 19-25 
    ISSN: 1432-1041
    Keywords: Key words Glycaemic control ; Insulin-fixed mixture ; Premixed insulins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Background: Pre-mixed insulins currently represent about 40% of the world market in human insulin. Despite the fact that many patients are being treated with these insulin formulations, there are surprisingly few data about fixed mixtures and comparisons with other administration schedules. The main advantages of using a pre-mixed preparation over a self-mixed insulin are increased accuracy of dosage, efficacy and patient convenience. These benefits may lead to increased compliance resulting in better long-term control of the disease. Insulin mixtures are used by a wide variety of patients with type-1 and type-2 diabetes. Premixed insulins also appear to be useful in elderly and adolescent patients with diabetes, although there are few published data on patients in these groups. Conclusions: It is likely that, in the future, fixed mixtures containing rapid-acting insulin analogues, such as insulin lispro, and possibly newly formulated intermediate-acting insulin analogues, such as neutral protamine lispro, may allow further improvements in both metabolic control and patient convenience.
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  • 9
    Publication Date: 2000-04-26
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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  • 10
    Publication Date: 1969-09-01
    Print ISSN: 0018-2222
    Electronic ISSN: 1432-119X
    Topics: Biology , Medicine
    Published by Springer
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