188,265 research outputs found
Du dummer Junge merk Dir’s mal
No full textDU DUMMER JUNGE MERK DIR’S MAL
Du dummer Junge merk Dir’s mal ( -
STK11 Prevents Invasion Through STAT3/5 and FAK Repression in Cutaneous Melanoma
No full textThe serine/threonine kinase 11 (STK11/LKB1) is a tumor suppressor involved in metabolism and cell motility. In BRAFV600E melanoma, STK11 is inactivated by ERK and RSK, preventing it from binding and activating AMPK and promoting melanoma cell proliferation. Although STK11 mutations occur in 5-10% of cutaneous melanoma, few functional studies have been performed. By knocking out STK11 with CRISPR/Cas9 in two human BRAF-mutant melanoma cell lines, we found that STK11-loss reduced the sensitivity to a BRAF inhibitor (BRAFi). More strikingly, STK11 loss led to an increased invasive phenotype in both 3-dimensional spheroids and in vivo zebrafish xenograft models. STK11 overexpression consistently reverted the invasive phenotype.
Interestingly, STK11 knockout increased invasion also in an NRAS-mutant melanoma cell line. Furthermore, while STK11 was expressed in primary human melanoma tumors, its expression significantly decreased in melanoma metastases especially in brain metastases. In the STK11-knockout cells we observed increased activating phosphorylation of STAT3/5 and FAK. Using inhibitors of STAT3/5 and FAK, we reverted the invasive phenotype in both BRAF and NRAS mutated cells. Our findings confirm an increased invasive phenotype upon STK11-inactivation in BRAF and NRAS-mutant cutaneous melanoma that can be targeted by STAT3/5 and FAK-inhibition
3D micro-CT analysis of the interface voids associated with Thermafil root fillings used with AH Plus or a flowable MTA sealer
No full textAim
To investigate nondestructively the percentage of 3D voids and marginal gaps in a pre-defined interface volume of interest (VOI) within root fillings produced by Thermafil Obturators with either a hydrophobic epoxy-resin-based sealer (AH Plus) or a hydrophilic flowable calcium-silicate sealer [mineral trioxide aggregate (MTA) Flow].
Methodology
Sixteen single root canals from extracted premolar teeth were prepared with ProTaper rotary instruments, randomly allocated into two groups (n = 8) and filled with size 30 Thermafil Obturators in association with AH Plus or MTA Flow sealers. The filled roots were stored at 37 °C in 5 mL of Hank's balanced salt solution (HBSS) used to represent body fluids and scanned after 7 days and 6 months using a high-resolution micro-CT. From each root, images of 3000 sections were analysed in 3D and binarized using a high-resolution micro-CT (4-μ resolution). The 3D distribution of voids (porosity and marginal gaps) at the gutta-percha-sealer-dentine interface was detected through a threshold grey level and expressed as percentage of the 40-μ-thick pre-defined interface VOI (20 μ of interface dentine and 20 μ of gutta-percha/sealer). A method of analysis based on the root canal segmentation was used, and coronal, middle and apical thirds considered separately. The percentage of 3D void volume was compared statistically using one-way anova (significance for P < 0.05). Environmental Scanning Electron Microscope with Energy Dispersive X-ray (ESEM-EDX) analysis was performed on the surface of both sealers after soaking in HBSS.
Results
Micro-CT detected gaps at the dentine-sealer interface in both groups. Void volumes wider than 10.21 μm3 with 1.35 μm diameter were detected. Cul-de-sac-type voids (blind pores) and through-and-through voids (continuous pores) were discriminated. The apical thirds had a significantly lower 3D void volume (P < 0.05) than the middle and coronal thirds. The 3D void volume reduced significantly (P < 0.05) over time. ESEM-EDX analysis revealed that MTA Flow sealer created a dense apatite layer after 7 days of immersion in HBSS, whilst only sparse calcium phosphate deposits were detected on AH Plus even after 28 days.
Conclusions
Micro-CT proved to be a powerful nondestructive 3D analysis tool for visualizing the porous internal microstructure of dental/endodontic materials at the interface with dentine. The proportion of voids was least in the apical third of root canals. Voids reduced over time in the presence of simulated body fluid
God the judge, putting down one, and setting up another. A sermon upon occasion of the death of our late sovereign lord King George, and the accession of His present Majesty, King George II to the British throne. / By Thomas Foxcroft, A.M. Minister of the Old Church in Boston.
No full text[4], v [i.e., iv], 39, [1] p. ; 18 cm. (8vo)Dedicated to the Honorable William Dummer, Esq.Half-title: Mr. Foxcroft's sermon on the death of His late Majesty King George, &c.Error in paging: p. iv misnumbered v
Computer-Based Diagnostics and Systematic Analysis of Knowledge
No full textWhat is knowledge? How can it be successfully assessed? How can we best use the results? As questions such as these continue to be discussed and the learning sciences continue to deal with expanding amounts of data, the challenge of applying theory to diagnostic methods takes on more complexity. Computer-Based Diagnostics and Systematic Analysis of Knowledge meets this challenge head-on as an international panel of experts reviews current and emerging assessment methodologies in the psychological and educational arenas. Emphasizing utility, effectiveness, and ease of interpretation, contributors critically discuss practical innovations and intriguing possibilities (including mental representations, automated knowledge visualization, modeling, and computer-based feedback) across fields ranging from mathematics education to medicine. These contents themselves model the steps of systematic inquiry, from theoretical construct to real-world application: •Historical and theoretical foundations for the investigation of knowledge •Current opportunities for understanding knowledge empirically •Strategies for the aggregation and classification of knowledge •Tools and methods for comparison and empirical testing •Data interfaces between knowledge assessment tools •Guidance in applying research results to particular fields Researchers and professionals in education psychology, instructional technology, computer science, and linguistics will find Computer-Based Diagnostics and Systematic Analysis of Knowledge a stimulating guide to a complex present and a rapidly evolving future. © Springer Science+Business Media, LLC 2010. All rights reserved
The structure pf austrobailignan-1 from the leaves of <i>K</i>. <i>henryi</i> Dummer.
No full text<p>(A) The image of K. henryi Dummer (adopted from Herbanum, Academic Sinica, <a href="http://digiarch.sinica.edu.tw/content/repository/resource_content.jsp?oid=3819630" target="_blank">http://digiarch.sinica.edu.tw/content/repository/resource_content.jsp?oid=3819630</a>). (B) The structure of austrobailignan-1 was established via <sup>1</sup>H- and <sup>13</sup>C-NMR. <sup>13</sup>C-NMR assignments were based on HETCOR and long-range HECTOR spectral results.</p
Foundations and Methodologies of Mental Models Research
No full textFor more than 25 years, the pioneering research and theories of Norbert Seel have had a profound impact on educational thought in mathematics. In this special tribute, an international panel of researchers present the current state of model-based education: its research, methodology, and technology. Fifteen stimulating, sometimes playful chapters link the multiple ways of constructing knowledge (and domains as diverse as cognitive science, computer science, and philosophy) to the complex real world of skill development; generalize model-based theories into educational settings; and explain how to design and evaluate model-centered learning environments. Extensive reading lists, provocative graphics, and a wealth of cultural touchstones from the Bible to Bob Dylan make Understanding Models for Learning and Instruction an accessible yet thought provoking collection. A sampling of the topics covered: Evidence-based assessment of learning models Translating cognitive theory into educational practice New approaches to tracking mental change over time Applying psychoeducational theory to the hands-on classroom Using games as a strategy for constructing model-centered learning environments Externalizing mental models with Mindtools This synthesis of latest innovations and fresh perspectives on classic constructs makes Understanding Models for Learning and Instruction cutting-edge reading for the researchers and educators in mathematics instruction building the next generation of educational models. © 2008 Springer Science+Business Media, LLC. All rights reserved
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
A preliminary assessment of a new dedicated endodontic software for use with CBCT images to evaluate the canal complexity of mandibular molars
No full textAim To investigate in vivo the complexity of canals
within mesial roots of mandibular molars using 3D
EndoTM software linked to CBCT images.
Methodology The CBCT images of 100 mandibular
first molars were analysed using the 3D EndoTM
software. The number of canals in the mesial roots,
the presence of apical confluences, the canal lengths
and the canal configurations using Vertucci’s classification
were evaluated in buccolingual (BL) and
mesiodistal (MD) views. The software allowed the
visualization of canal trajectories in three dimensions
using a coloured outline, which was used to develop
a new objective scoring system to provide an overall
assessment of canal complexity. Data were analysed
statistically using ANOVA and t-tests with the significance
set at P < 0.05.
Results Vertucci type IV canals were found in 44% of
the cases, whilst 54% were type II. The mean distance
from the apical foramen to the orifice was 13.15 mm
(1.21) and that between a confluence and the foramen,
2.81 mm (1.13). The number of curvatures and the
canal complexity scores in the MD view were significantly
higher than in the BL view (P < 0.05). The scores
were not directly correlated to the canal (MB versus ML),
to the canal length or to the presence of confluences.
Conclusions 3D Endo software features the automatic
detection and measurement of several anatomical
canal parameters, and is a promising tool for the
study of canal complexity in vivo. The unpredictable
anatomy of the mesial roots of mandibular molars
highlights the value of a three-dimensional preoperative
evaluation of each case. The proposed scoring
system aims to provide the clinician with an overall
assessment of canal complexity
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