Comparison of elastic moduli from seismic diving-wave and ice-core microstructure analysis in Antarctic polar firn

The densification of firn depends on the elastic properties of firn, processes which are still not fully explained by the usual models. Geophysical methods provide spatially distributed data, while the analysis of firn cores is restricted to finite locations, but with a different vertical resolution. In this study, we compared elastic moduli in polar firn derived from refraction seismic velocity analysis and vertical density profiles from the firn-core measurements to elastic properties derived from microstructure modelling based on firn-core data. The seismic data were obtained with a small electrodynamic vibrator source (ElViS) near Kohnen Station, East Antarctica. The analysis of divingwaves resulted in velocity–depth profiles for P-, SH- and SV-wave velocities. Elastic moduli of firn were derived by combining P- and S-wave velocities and densities obtained from firn-core measurements. P-wave velocities derived from diving-wave analysis range from 2060 m s−1at 10 m depth to 3400 m s−1at 70 m depth, S-wave velocities from 1250 m s−1 to 1700 m s−1, respectively. The structural finite-element method (FEM) was used to calculate the components of the elastic tensor from firn microstructure derivedfrom X-ray tomography of firn-core samples at depths of 10, 42, 71 and 99 m. Shear and bulk moduli range from 0.39 GPa to 2.42 GPa and 0.68 GPa to 2.42 GPa, respectively. The elastic moduli from seismic observations and the structural FEM agree within 8.5% for the values derived at a depth of 71 m, and are within the uncertainty range. Our study demonstrates that elastic moduli of firn can be consistently obtained from two independent methods, which are based on dynamic (seismic) and static (tomography and FEM) observations, respectively. The agreement of the results for both methods indicates that elastic properties in firn can be acquired as spatially distributed data with the seismic approach, supported by local density information. Thus, information about elastic properties can be derived over larger lateral distances than would be possible with the static method. This enables the analysis of the firn and conclusions of the densification models might be drawn from observations of spatial and temporal changes in elastic properties

Intrabiliary infusion of naked DNA vectors targets periportal hepatocytes in mice

Hydrodynamic tail vein injection (HTV) is the "gold standard" for delivering naked DNA vectors to mouse liver, thereby transfecting predominately perivenous hepatocytes. While HTV corrects metabolic liver defects such as phenylketonuria or cystathionine β-synthase deficiency, correction of spf ash mice with ornithine transcarbamylase (OTC) deficiency was not possible despite overexpression in the liver, as the OTC enzyme is primarily expressed in periportal hepatocytes. To target periportal hepatocytes, we established hydrodynamic retrograde intrabiliary injection (HRII) in mice and optimized minicircle (MC) vector delivery using luciferase as a marker gene. HRII resulted in a transfection efficiency below 1%, 100-fold lower than HTV. While HRII induced minimal liver toxicity compared with HTV, overexpression of luciferase by both methods, but not of a natural liver-specific enzyme, elicited an immune response that led to the elimination of luciferase expression. Further testing of MC vectors delivered via HRII in spf ash mice did not result in sufficient therapeutic efficacy and needs further optimization and/or selection of the corrected cells. This study reveals that luciferase expression is toxic for the liver. Furthermore, physical delivery of MC vectors via the bile duct has the potential to treat defects restricted to periportal hepatocytes, which opens new doors for non-viral liver-directed gene therapy. Keywords: FLAG-tagged OTC; OTC deficiency; hydrodynamic retrograde intrabiliary injection; hydrodynamic tail vein injection; immune response; liver toxicity; liver-directed gene therapy; luciferase expression; naked DNA minicircle vector; non-viral; urea cycle disorder

Comparison of elastic moduli from seismic diving-wave and ice-core microstructure analysis in Antarctic polar firn

We compared elastic moduli in polar firn derived from diving wave refraction seismic velocity analysis, firn-core density measurements and microstructure modelling based on firn-core data. The seismic data were obtained with a small electrodynamic vibrator source near Kohnen Station, East Antarctica. The analysis of diving waves resulted in velocity–depth profiles for different wave types (P-, SH- and SV-waves). Dynamic elastic moduli of firn were derived by combining P- and S-wave velocities and densities obtained from firn-core measurements. The structural finite-element method (FEM) was used to calculate the components of the elastic tensor from firn microstructure derived from X-ray tomography of firn-core samples at depths of 10, 42, 71 and 99 m, providing static elastic moduli. Shear and bulk moduli range from 0.39 to 2.42 GPa and 0.68 to 2.42 GPa, respectively. The elastic moduli from seismic observations and the structural FEM agree within 8.5% for the deepest achieved values at a depth of 71 m, and are within the uncertainty range. Our observations demonstrate that the elastic moduli of the firn can be consistently obtained from two independent methods which are based on dynamic (seismic) and static (tomography and FEM) observations, respectively, for deeper layers in the firn below ∼10 m depth

5-teilige Sonderausgabe des KOBV-Newsletters – 24. bis 30. Oktober 2016

An der internationalen Open-Access-Woche 2016 vom 24.-28. Oktober war der KOBV erstmalig mit einem Online „Publishing Event“ beteiligt. An fünf aufeinanderfolgenden Tagen erschien täglich eine Sonderausgabe des KOBV- Newsletters zu ausgewählten Open-Access-Themen. Die einzelnen Beiträge sind in dieser Sonderedition als Online-Reader zusammengestellt. Der aktuelle Diskussionsstand zum jeweiligen Thema wird von Expertinnen und Experten in kurzen Übersichtsartikeln vorgestellt und mit Praxistipps ergänzt. Zielgruppe sind vor allem Bibliothekare und Bibliothekarinnen, die sich einen schnellen Überblick zu Open Access verschaffen wollen

Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) Following Blinatumomab-Induced Remission in Pediatric Patients with Relapsed/Refractory (r/r) B-Precursor Acute Lymphoblastic Leukemia (ALL): Preliminary Results from a Phase I/II Stud

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Frequent and sex-biased deletion of SLX4IP by illegitimate V(D)J-mediated recombination in childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) accounts for ∼25% of pediatric malignancies. Of interest, the incidence of ALL is observed ∼20% higher in males relative to females. The mechanism behind the phenomenon of sex-specific differences is presently not understood. Employing genome-wide genetic aberration screening in 19 ALL samples, one of the most recurrent lesions identified was monoallelic deletion of the 5′ region of SLX4IP. We characterized this deletion by conventional molecular genetic techniques and analyzed its interrelationships with biological and clinical characteristics using specimens and data from 993 pediatric patients enrolled into trial AIEOP-BFM ALL 2000. Deletion of SLX4IP was detected in ∼30% of patients. Breakpoints within SLX4IP were defined to recurrent positions and revealed junctions with typical characteristics of illegitimate V(D)J-mediated recombination. In initial and validation analyses, SLX4IP deletions were significantly associated with male gender and ETV6/RUNX1-rearranged ALL (both overall P < 0.0001). For mechanistic validation, a second recurrent deletion affecting TAL1 and caused by the same molecular mechanism was analyzed in 1149 T-cell ALL patients. Validating a differential role by sex of illegitimate V(D)J-mediated recombination at the TAL1 locus, 128 out of 1149 T-cell ALL samples bore a deletion and males were significantly more often affected (P = 0.002). The repeatedly detected association of SLX4IP deletion with male sex and the extension of the sex bias to deletion of the TAL1 locus suggest that differential illegitimate V(D)J-mediated recombination events at specific loci may contribute to the consistent observation of higher incidence rates of childhood ALL in boys compared with girl

The Rest-Frame Optical Luminosity Function of Cluster Galaxies at z<0.8 and the Assembly of the Cluster Red Sequence

We present the rest-frame optical luminosity function (LF) of red sequence galaxies in 16 clusters at 0.4<z<0.8 drawn from the ESO Distant Cluster Survey (EDisCS). We compare our clusters to an analogous sample from the Sloan Digital Sky Survey (SDSS) and match the EDisCS clusters to their most likely descendants. We measure all LFs down to M M* + (2.5 - 3.5). At z<0.8, the bright end of the LF is consistent with passive evolution but there is a significant build-up of the faint end of the red sequence towards lower redshift. There is a weak dependence of the LF on cluster velocity dispersion for EDisCS but no such dependence for the SDSS clusters. We find tentative evidence that red sequence galaxies brighter than a threshold magnitude are already in place, and that this threshold evolves to fainter magnitudes toward lower redshifts. We compare the EDisCS LFs with the LF of co-eval red sequence galaxies in the field and find that the bright end of the LFs agree. However, relative to the number of bright red galaxies, the field has more faint red galaxies than clusters at 0.6<z<0.8 but fewer at 0.4<z<0.6, implying differential evolution. We compare the total light in the EDisCS cluster red sequences to the total red sequence light in our SDSS cluster sample. Clusters at 0.4<z<0.8 must increase their luminosity on the red sequence (and therefore stellar mass in red galaxies) by a factor of 1-3 by z=0. The necessary processes that add mass to the red sequence in clusters predict local clusters that are over-luminous as compared to those observed in the SDSS. The predicted cluster luminosities can be reconciled with observed local cluster luminosities by combining multiple previously known effects.Comment: Accepted for publication in the Astrophysical Journal. 36 pages, 16 figures, 10 table

Inhibition of radiation induced migration of human head and neck squamous cell carcinoma cells by blocking of EGF receptor pathways

<p>Abstract</p> <p>Background</p> <p>Recently it has been shown that radiation induces migration of glioma cells and facilitates a further spread of tumor cells locally and systemically. The aim of this study was to evaluate whether radiotherapy induces migration in head and neck squamous cell carcinoma (HNSCC). A further aim was to investigate the effects of blocking the epidermal growth factor receptor (EGFR) and its downstream pathways (Raf/MEK/ERK, PI3K/Akt) on tumor cell migration in vitro.</p> <p>Methods</p> <p>Migration of tumor cells was assessed via a wound healing assay and proliferation by a MTT colorimeritric assay using 3 HNSCC cell lines (BHY, CAL-27, HN). The cells were treated with increasing doses of irradiation (2 Gy, 5 Gy, 8 Gy) in the presence or absence of EGF, EGFR-antagonist (AG1478) or inhibitors of the downstream pathways PI3K (LY294002), mTOR (rapamycin) and MEK1 (PD98059). Biochemical activation of EGFR and the downstream markers Akt and ERK were examined by Western blot analysis.</p> <p>Results</p> <p>In absence of stimulation or inhibition, increasing doses of irradiation induced a dose-dependent enhancement of migrating cells (p < 0.05 for the 3 HNSCC cell lines) and a decrease of cell proliferation (p < 0.05 for the 3 HNSCC cell lines). The inhibition of EGFR or the downstream pathways reduced cell migration significantly (almost all p < 0.05 for the 3 HNSCC cell lines). Stimulation of HNSCC cells with EGF caused a significant increase in migration (p < 0.05 for the 3 HNSCC cell lines). After irradiation alone a pronounced activation of EGFR was observed by Western blot analysis.</p> <p>Conclusion</p> <p>Our results demonstrate that the EGFR is involved in radiation induced migration of HNSCC cells. Therefore EGFR or the downstream pathways might be a target for the treatment of HNSCC to improve the efficacy of radiotherapy.</p