HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth

n addition to genetic changes, post-transcriptional events strongly contribute to the progression of malignant tumors. The RNA-binding protein HuR (ELAVL1) is able to bind and stabilize a large group of target mRNAs, which contain AU-rich elements (ARE) in their 3′-untranslated region. We found HuR to be upregulated in malignant melanoma in vitro and in vivo, significantly correlating with progression in vivo. Additionally, we could show that miR-194-5p can regulate HuR expression level. HuR knockdown in melanoma cells led to the suppression of proliferation and the induction of cellular senescence. Interestingly, HuR overexpression was sufficient to inhibit senescence in BRAFV600E-expressing melanocytes and to force their growth. Here, MITF (Microphthalmia-associated transcription factor), a key player in suppressing senescence and an ARE containing transcript, is positively regulated by HuR. Our results show for the first time that the overexpression of HuR is an important part of the regulatory pathway in the development of malignant melanoma and functions as a switch to overcome oncogene-induced senescence and to support melanoma formation. These newly defined alterations may provide possibilities for innovative therapeutic approaches

Fatigue behavior of hybrid continuous-discontinuous fiber-reinforced sheet molding compound composites under application-related loading conditions

Hybrid continuous-discontinuous sheet molding compound (SMC) composites are considered suitable candidates for structural automotive applications, due to their high mass-specific mechanical properties combined with high geometrical flexibility and low costs. Since structural automotive parts are subject to repeated loading, profound knowledge of their fatigue behavior is required. This paper presents an experimental study on the bending fatigue behavior of hybrid SMC with discontinuous glass fibers in the core and unidirectional continuous carbon fibers in the face layers. Effects of hybridization on the S-N behavior and stiffness degradation have been analyzed in constant amplitude fatigue tests under 3-point bending load at different temperatures and frequencies. Microscopic investigations on polished specimen edges were used to study the damage behavior. The ultimate flexural strength at quasi-static (UFS$^S$) and fatigue strain rate (UFS$^F$) of the hybrid composite was 54 % and 59 % higher than that of discontinuous SMC, respectively. In contrast, the flexural fatigue strength at 2.6⋅10S$^6$ cycles increased by 258 %. The relative stiffness degradation of the hybrid composites was smaller during most of their fatigue lives due to the continuous carbon fiber reinforcement. The carbon fiber ply on the compression loaded side was the first ply to fail. Fatigue stress significantly decreased at 80 °C due to early kinking of the continuous carbon fiber-reinforced ply on the compression loaded side. Variation of frequency had no significant effect on the fatigue behavior of both discontinuous and continuous-discontinuous SMC

Adapting a practical EPR dosimetry protocol to measure output factors in small fields with alanine.

PURPOSE Modern radiotherapy techniques often deliver small radiation fields. In this work, a practical Electron Paramagnetic Resonance (EPR) dosimetry protocol is adapted and applied to measure output factors (OF) in small fields of a 6 MV radiotherapy system. Correction factors and uncertainties are presented and OFs are compared to the values obtained by following TRS-483 using an ionization chamber (IC). METHODS Irradiations were performed at 10 cm depth inside a water phantom positioned at 90 cm source to surface distance with a 6 MV flattening filter free photon beam of a Halcyon radiotherapy system. OFs for different nominal field sizes (1 × 1, 2 × 2, 3 × 3, 4 × 4, normalized to 10 × 10 cm2 ) were determined with a PinPoint 3D (PTW 31022) IC following TRS-483 as well as with alanine pellets with a diameter of 4 mm and a height of 2.4 mm. EPR readout was performed with a benchtop X-band spectrometer. Correction factors due to volume averaging and due to positional uncertainties were derived from 2D film measurements. RESULTS OFs obtained from both dosimeter types agreed within 0.7% after applying corrections for the volume averaging effect. For the used alanine pellets, volume averaging correction factors of 1.030(2) for the 1 × 1 cm2 field and <1.002 for the larger field sizes were determined. The correction factor for positional uncertainties of 1 mm was in the order of 1.018 for the 1 × 1 cm2 field. Combined relative standard uncertainties uc for the OFs resulting from alanine measurements were estimated to be below 1.5% for all field sizes. For IC measurements, uc was estimated to be below 1.0%. CONCLUSIONS A practical EPR dosimetry protocol is adaptable for precisely measuring OFs in small fields down to 1 × 1 cm2 . It is recommended to consider the effect of positional uncertainties for field sizes <2 × 2 cm2

Progress in the understanding and modelling of components that could drive the overall fragility of a nuclear power plant

International audienc

Study of material homogeneity in the long fiber thermoset injection molding process by image texture analysis

To quantify the homogeneity of fiber dispersion in short fiber-reinforced polymer composites, a method for image texture analysis of 3-dimensional X-ray micro computed tomography (µCT) images is presented in this work. The adaption of the method to the specific requirements of the composite material is accomplished using a statistical region merging approach. Subsequently, the method is applied for evaluating the homogeneity of specimens from an intermediate step of the long fiber thermoset injection molding process as well as molded parts. This new injection molding process enables the manufacturing of parts with a flexible combination of short and long glass fibers. By using a newly developed screw element based on the Maddock mixing element design, the material homogeneity of parts molded in the long fiber injection molding process is improved

Field-Scale Soil Property Changes under Switchgrass Managed for Bioenergy

The capacity of perennial grasses to affect change in soil properties is well documented but information on switchgrass (Panicum virgatum L.) managed for bioenergy is limited. An on-farm study (10 fields) in North Dakota, South Dakota, and Nebraska was sampled before switchgrass establishment and after 5 years to determine changes in soil bulk density (SBD), pH, soil phosphorus (P), and equivalent mass soil organic carbon (SOC). Changes in SBD were largely constrained to near-surface depths (0–0.05 m). SBD increased (0–0.05 m) at the Nebraska locations (mean=0.16 Mgm-3), while most South Dakota and North Dakota locations showed declines in SBD (mean=-0.18 Mgm-3; range=-0.42–0.07 Mgm-3). Soil pH change was significant at five of the 10 locations at near surface depths (0–0.05 m), but absolute changes were modest (range=-0.67–0.44 pH units). Available P declined at all sites where it was measured (North Dakota and South Dakota locations). When summed across the surface 0.3 m depth, annual decreases in available P averaged 1.5 kg P ha-1 yr-1 (range=0.5–2.8 kg P ha-1 yr-1). Averaged across locations, equivalent mass SOC increased by 0.5 and 2.4 Mg Cha-1 yr-1 for the 2500 and 10 000 Mg ha-1 soil masses, respectively. Results from this study underscore the contribution of switchgrass to affect soil property changes, though considerable variation in soil properties exists within and across locations

Low-energy neutron-deuteron reactions with N3LO chiral forces

We solve three-nucleon Faddeev equations with nucleon-nucleon and three-nucleon forces derived consistently in the framework of chiral perturbation theory at next-to-next-to-next-to-leading order in the chiral expansion. In this first investigation we include only matrix elements of the three-nucleon force for partial waves with the total two-nucleon (three-nucleon) angular momenta up to 3 (5/2). Low-energy neutron-deuteron elastic scattering and deuteron breakup reaction are studied. Emphasis is put on Ay puzzle in elastic scattering and cross sections in symmetric-space-star and neutron-neutron quasi-free-scattering breakup configurations, for which large discrepancies between data and theory have been reported.Comment: 22 pages, 7 figure

Implementation and comparison of algebraic and machine learning based tensor interpolation methods applied to fiber orientation tensor fields obtained from CT images

Fiber orientation tensors (FOT) are used as a compact form of representing the mechanically important quantity of fiber orientation in fiber reinforced composites. While they can be obtained via image processing methods from micro computed tomography scans (CT), the specimen size needs to be sufficiently small for adequate resolution – especially in the case of carbon fibers. In order to avoid massive workload by scans and image evaluation when determining full-field FOT distributions for a plaque or a part, e.g., for comparison with process simulations, the possibilities of a direct interpolation of a few measured FOT at specific support points were opened in this paper. Hence, three different tensor interpolation methods were implemented and compared qualitatively with the help of visualization through tensor glyphs and quantitatively by calculating originally measured tensors at support points and evaluating the deviations. The methods compared in this work include two algebraic approaches, firstly, a Euclidean component averaging and secondly, a decomposition approach based on separate invariant and quaternion weighting, as well as an artificial intelligence (AI)-based method using an artificial neural network (ANN). While the decomposition method showed the best results visually, quantitatively the component averaging method and the neural network behaved better (that is for the type of quantitative error assessment used in this paper) with mean absolute errors of 0.105 and 0.114 when calculating previously measured tensors and comparing the components. With each method providing different advantages, the use for further application as well as necessary improvement is discussed. The authors would like to highlight the novelty of the methods being used with small and CT-based tensor datasets