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  • PMC (PubMed Central)  (74)
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  • 1
    Language: English
    In: Scientific reports, 16 May 2018, Vol.8(1), pp.7702
    Description: East Asia has experienced strong warming since the 1960s accompanied by an increased frequency of heat waves and shrinking glaciers over the Tibetan Plateau and the Tien Shan. Here, we place the recent warmth in a long-term perspective by presenting a new spatially resolved warm-season (May-September) temperature reconstruction for the period 1-2000 CE using 59 multiproxy records from a wide range of East Asian regions. Our Bayesian Hierarchical Model (BHM) based reconstructions generally agree with earlier shorter regional temperature reconstructions but are more stable due to additional temperature sensitive proxies. We find a rather warm period during the first two centuries CE, followed by a multi-century long cooling period and again a warm interval covering the 900-1200 CE period (Medieval Climate Anomaly, MCA). The interval from 1450 to 1850 CE (Little Ice Age, LIA) was characterized by cooler conditions and the last 150 years are characterized by a continuous warming until recent times. Our results also suggest that the 1990s were likely the warmest decade in at least 1200 years. The comparison between an ensemble of climate model simulations and our summer reconstructions since 850 CE shows good agreement and an important role of internal variability and external forcing on multi-decadal time-scales.
    Keywords: Article;
    E-ISSN: 2045-2322
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  • 2
    Language: English
    In: Journal of Biotechnology, 10 July 2015, Vol.205, pp.3-13
    Description: Physiologically relevant models can serve as biological analytical platforms for testing novel treatments and drug delivery systems. We describe the first steps in the development of a 3D human brain tumour co-culture model that includes the interplay between normal and tumour tissue along with nutrient gradients, cell-cell and cell-matrix interactions. The human medulloblastoma cell line UW228-3 and human foetal brain tissue were marked with two supravital fluorescent dyes (CDCFDASE, Celltrace Violet) and cultured together in ultra-low attachment 96-well plates to form reproducible single co-culture spheroids ( = 600 μm, CV% = 10%). Spheroids were treated with model cytotoxic drug etoposide (0.3–100 μM) and the viability of normal and tumour tissue quantified separately using flow cytometry and multiphoton microscopy. Etoposide levels of 10 μM were found to maximise toxicity to tumours (6.5% viability) while stem cells maintained a surviving fraction of 40%. The flexible cell marking procedure and high-throughput compatible protocol make this platform highly transferable to other cell types, primary tissues and personalised screening programs. The model's key anticipated use is for screening and assessment of drug delivery strategies to target brain tumours, and is ready for further developments, e.g. differentiation of stem cells to a range of cell types and more extensive biological validation.
    Keywords: Three-Dimensional Tumor Model ; Cancer Drug Screening in 3d ; Co-Culture Spheroid ; Human Stem Cell Neurosphere ; Medulloblastoma ; Engineering
    ISSN: 0168-1656
    ISSN: 19326203
    E-ISSN: 1873-4863
    E-ISSN: 19326203
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  • 3
    Language: English
    In: Nature, 24 December 2015, Vol.528(7583), pp.560-564
    Description: Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch and epidermal growth factor (EGF) signals supporting Lgr5(+) crypt base columnar ISCs for normal epithelial maintenance. However, little is known about the regulation of the ISC compartment after tissue damage. Using ex vivo organoid cultures, here we show that innate lymphoid cells (ILCs), potent producers of interleukin-22 (IL-22) after intestinal injury, increase the growth of mouse small intestine organoids in an IL-22-dependent fashion. Recombinant IL-22 directly targeted ISCs, augmenting the growth of both mouse and human intestinal organoids, increasing proliferation and promoting ISC expansion. IL-22 induced STAT3 phosphorylation in Lgr5(+) ISCs, and STAT3 was crucial for both organoid formation and IL-22-mediated regeneration. Treatment with IL-22 in vivo after mouse allogeneic bone marrow transplantation enhanced the recovery of ISCs, increased epithelial regeneration and reduced intestinal pathology and mortality from graft-versus-host disease. ATOH1-deficient organoid culture demonstrated that IL-22 induced epithelial regeneration independently of the Paneth cell niche. Our findings reveal a fundamental mechanism by which the immune system is able to support the intestinal epithelium, activating ISCs to promote regeneration.
    Keywords: Regeneration ; Epithelial Cells -- Cytology ; Interleukins -- Immunology ; Intestinal Mucosa -- Cytology ; Intestine, Small -- Cytology ; Stem Cells -- Cytology
    ISSN: 00280836
    E-ISSN: 1476-4687
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  • 4
    In: PLoS ONE, 2018, Vol.13(7)
    Description: Background This study investigates the effect of a new computer-based visual search training (VST) that was adapted for children with homonymous hemianopia (HH). Methods 22 children with HH (median age 11 years, 8 months: 6y6m-19y2m) trained at home for 15 minutes twice/day, 5 days/week, for 6 weeks. To assess performance before training (T1), directly after training (T2) and 6 weeks after the end of training (T3), we measured search times (STs) during on-screen search (with eye tracking), and in a real life search task. Additional variables analyzed during on-screen search were numbers, amplitudes, and durations of saccades, their directional patterns and the proportional number of saccades into the non-seeing field. The latter was the main variable during free viewing. Sixteen healthy age-matched children, who did not undergo the training, served as comparison group. Quality of Life (QoL)-questionnaires were also applied. Results STs of the patients decreased significantly during the training and all search performance tests. This improvement persisted 6 weeks after the end of the training. Saccade amplitudes increased, total number of saccades to find the target decreased, and the proportional number of saccades to the non-seeing side increased. These changes were maintained at T3. Saccade durations did not change. During free viewing, saccades were equally distributed to both sides before and after training. Patients reported improvements in QoL and activities of daily living. Performance in the healthy children did not change by simply repeating the visual search test. Conclusions The improvement in STs in all search tasks, larger and fewer saccades, and an improved search strategy after VST suggests that the children with HH benefited from the training. The maintained improvement at T3 and the improvement in the real life search task indicate that the newly developed search strategy persists and can be applied to everyday life.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; People And Places ; People And Places ; Biology And Life Sciences ; Biology And Life Sciences ; Social Sciences ; Research And Analysis Methods ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: Frontiers in Neuroscience, 01 November 2017, Vol.11
    Description: Hemodynamic responses, in general, and the blood oxygenation level-dependent (BOLD) fMRI signal, in particular, provide an indirect measure of neuronal activity. There is strong evidence that the BOLD response correlates well with post-synaptic changes, induced by changes in the excitatory...
    Keywords: Excitatory-Inhibitory ; Multi-Modal Data ; Fmri Signal Modeling ; Response Transients ; Neuronal Adaptation ; Post-Stimulus Bold Undershoot ; Anatomy & Physiology
    ISSN: 16624548
    E-ISSN: 1662-453X
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  • 6
    Language: English
    In: TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik, July 2011, Vol.123(2), pp.219-30
    Description: Tobacco (Nicotiana tabacum L.) is a species in the large family of the Solanaceae and is important as an agronomic crop and as a model system in plant biotechnology. Despite its importance, only limited molecular marker resources are available that can be used for genome analysis, genetic mapping and breeding. We report here on the development and characterization of 5,119 new and functional microsatellite markers and on the generation of a high-resolution genetic map for the tetraploid tobacco genome. The genetic map was generated using an F2 mapping population derived from the intervarietal cross of Hicks Broadleaf × Red Russian and merges the polymorphic markers from this new set with those from a smaller set previously used to produce a lower density map. The genetic map described here contains 2,317 microsatellite markers and 2,363 loci, resulting in an average distance between mapped microsatellite markers which is less than 2 million base pairs or 1.5 cM. With this new and expanded marker resource, a sufficient number of markers are now available for multiple applications ranging from tobacco breeding to comparative genome analysis. The genetic map of tobacco is now comparable in marker density and resolution with the best characterized genomes of the Solanaceae: tomato and potato.
    Keywords: Chromosome Mapping ; Genome, Plant ; Microsatellite Repeats ; Sequence Analysis, DNA ; Tobacco -- Genetics
    ISSN: 00405752
    E-ISSN: 1432-2242
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  • 7
    Language: English
    In: Science advances, August 2018, Vol.4(8), pp.eaat3962
    Description: Autoionizing resonances are paradigmatic examples of two-path wave interferences between direct photoionization, which takes a few attoseconds, and ionization via quasi-bound states, which takes much longer. Time-resolving the evolution of these interferences has been a long-standing goal, achieved recently in the helium atom owing to progress in attosecond technologies. However, already for the hydrogen molecule, similar time imaging has remained beyond reach due to the complex interplay between fast nuclear and electronic motions. We show how vibrationally resolved photoelectron spectra of H allow one to reconstruct the associated subfemtosecond autoionization dynamics by using the ultrafast nuclear dynamics as an internal clock, thus forgoing ultrashort pulses. Our procedure should be general for autoionization dynamics in molecules containing light nuclei, which are ubiquitous in chemistry and biology.
    Keywords: Research Article ; Research Articles ; Sciadv R-Articles ; Chemistry ; Chemistry;
    E-ISSN: 2375-2548
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  • 8
    Language: English
    In: Clinical ophthalmology (Auckland, N.Z.), 2017, Vol.11, pp.1601-1606
    Description: Nowadays, complex digital imaging systems allow detailed retinal imaging without dilating patients' pupils. These so-called non-mydriatic cameras have advantages in common circumstances (eg, for screening or emergency purposes) but present limitations in terms of image quality and field of view. We compare the usefulness of two non-mydriatic camera systems (ie, a handheld versus a stand-alone device) for fundus imaging. The primary outcome was image quality. The secondary outcomes were learning effects and quality grade-influencing factors. The imaging procedures followed standard protocol and were all performed by the same investigator. Camera 1 (DRS) was a stand-alone system, while Camera 2 (Smartscope PRO) was a mobile system. In order to evaluate possible learning effects, we selected an examiner with no prior training in the use of these systems. The images were graded separately by two experienced and "blinded" ophthalmologists following a defined protocol. In total, 211 people were enrolled. Quality grade comparisons showed significantly better grades for Camera 1. Both systems achieved better quality grades for macular images than for disc-centered images. No remarkable learning effects could be demonstrated. Both camera systems are useful for fundus imaging. The greater mobility of Camera 2 was associated with lower image quality. For screening scenarios or telemedicine, it must be determined whether image quality or mobility is more important.
    Keywords: Handheld Camera ; Imaging ; Learning Curve ; Non-Mydriatic
    ISSN: 1177-5467
    E-ISSN: 11775483
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  • 9
    Language: English
    In: Journal of Investigative Dermatology, January 2016, Vol.136(1), pp.154-160
    Description: Several thermosensitive transient receptor potential channels (transient receptor potential vanilloid type-1, -3; transient receptor potential cation channel, subfamily A, member 1) have been implicated in itch. In contrast, the role of transient receptor potential vanilloid type-4 (TRPV4) in itch is unknown. Therefore, we investigated if TRPV4, a temperature-sensitive cation channel, plays an important role in acute itch in mice. Four different pruritogens, including serotonin (5-hydroxytryptamine [5-HT]), histamine, SLIGRL (protease-activated receptors 2/mas-related G-protein-coupled receptor C11 agonist), and chloroquine (mas-related G-protein-coupled receptor A3 agonist), were intradermally injected into mice and itch-related scratching behavior was assessed. TRPV4 knockout mice exhibited significantly fewer 5-HT-evoked scratching bouts compared with wild-type mice. Notably, no differences between TRPV4 knockout and wild-type mice were observed in the number of scratch bouts elicited by SLIGRL and histamine. Pretreatment with a TRPV4 antagonist significantly attenuated 5-HT-evoked scratching in vivo. Using calcium imaging in cultured primary murine dorsal root ganglion neurons, the response of neurons after 5-HT application, but not other pruritogens, was significantly lower in TRPV4 knockout compared with wild-type mice. A TRPV4 antagonist significantly suppressed 5-HT-evoked responses in dorsal root ganglion cells from wild-type mice. Approximately 90% of 5-HT-sensitive dorsal root ganglion neurons were immunoreactive for an antibody to TRPV4, as assessed by calcium imaging. These results indicate that 5-HT-induced itch is linked to TRPV4.
    Keywords: Medicine
    ISSN: 0022-202X
    E-ISSN: 1523-1747
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  • 10
    Language: English
    In: Applied Magnetic Resonance, 2018, Vol.49(3), pp.293-307
    Description: We provide a detailed evaluation of nuclear magnetic resonance (NMR) parameters of the cis - and trans -isomers of azobenzene (AB). For determining the NMR parameters, such as proton–proton and proton–nitrogen J -couplings and chemical shifts, we compared NMR spectra of three different isotopomers of AB: the doubly 15 N labeled azobenzene, 15 N, 15 N′-AB, and two partially deuterated AB isotopomers with a single 15 N atom. For the total lineshape analysis of NMR spectra, we used the recently developed ANATOLIA software package. The determined NMR parameters allowed us to optimize experiments for investigating singlet long-lived spin states (LLSs) of 15 N spin pairs and to measure LLS lifetimes in cis -AB and trans -AB. Magnetization-to-singlet-to-magnetization conversion has been performed using the SLIC and APSOC techniques, providing a degree of conversion up to 17 and 24% of the initial magnetization, respectively. Our approach is useful for optimizing the performance of experiments with singlet LLSs; such LLSs can be exploited for preserving spin hyperpolarization, for probing slow molecular dynamics, slow chemical processes and also slow transport processes.
    Keywords: Magnetization – Analysis ; Molecular Dynamics – Analysis ; Azo Compounds – Analysis ; Nuclear Magnetic Resonance Spectroscopy – Analysis;
    ISSN: 0937-9347
    E-ISSN: 1613-7507
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