Effects of stitching on delamination of satin weave carbon-epoxy laminates under mode I, mode II and mixed-mode I/II loadings

The objective of the present study is to characterize the effect of modified chain stitching on the delamination growth under mixed-mode I/II loading conditions. Delamination toughness under mode I is experimentally determined, for unstitched and stitched laminates, by using untabbed and tabbed double cantilever beam (TDCB) tests. The effect of the reinforcing tabs on mode I toughness is investigated. Stitching improves the energy release rate (ERR) up to 4 times in mode I. Mode II delamination toughness is evaluated in end-notched flexure (ENF) tests. Different geometries of stitched specimens are tested. Crack propagation occurs without any failure of stitching yarns. The final crack length attains the mid-span or it stops before and the specimen breaks in bending. The ERR is initially low and gradually increases with crack length to very high values. The mixedmode delamination behaviour is investigated using a mixed-mode bending (MMB) test. For unstitched specimens, a simple mixed-mode criterion is identified. For stitched specimens, stitching yarns do not break during 25% of mode I ratio tests and the ERR increase is relatively small compared to unstitched values. For 70% and 50% of mode I ratios, failures of yarns are observed during crack propagation and tests are able to capture correctly the effect of the stitching: it clearly improves the ERR for these two mixed modes, as much as threefold

Visualizing the Feature Importance for Black Box Models

In recent years, a large amount of model-agnostic methods to improve the transparency, trustability and interpretability of machine learning models have been developed. We introduce local feature importance as a local version of a recent model-agnostic global feature importance method. Based on local feature importance, we propose two visual tools: partial importance (PI) and individual conditional importance (ICI) plots which visualize how changes in a feature affect the model performance on average, as well as for individual observations. Our proposed methods are related to partial dependence (PD) and individual conditional expectation (ICE) plots, but visualize the expected (conditional) feature importance instead of the expected (conditional) prediction. Furthermore, we show that averaging ICI curves across observations yields a PI curve, and integrating the PI curve with respect to the distribution of the considered feature results in the global feature importance. Another contribution of our paper is the Shapley feature importance, which fairly distributes the overall performance of a model among the features according to the marginal contributions and which can be used to compare the feature importance across different models.Comment: To Appear in Machine Learning and Knowledge Discovery in Databases: European Conference, ECML PKDD 2018, Dublin, Ireland, September 10 to 14, 2018, Proceedings, Part

Association between psoas abscess and prosthetic hip infection: a case-control study

Background and purpose The relationship between prosthetic hip infection and a psoas abscess is poorly documented. We determined the frequency of prosthetic hip infections associated with psoas abscesses and identified their determinants

Cell-based expression cloning for identification of polypeptides that hypersensitize mammalian cells to mitotic arrest

Microtubule inhibitors such as Vinblastine and Paclitaxel are chemotherapy agents that activate the mitotic spindle checkpoint, arresting cells in mitosis and leading to cell death. The pathways that connect mitotic arrest to cell death are not well characterized. We developed a mammalian cell-based cDNA cloning method to isolate proteins and protein fragments whose expression inhibits colony formation in the presence of microtubule inhibitors. Understanding how these proteins impact cellular responses to microtubule drugs will lead to better understanding of the biochemical pathways connecting mitotic arrest and cell death in mammalian cells and may provide novel targets that can enhance microtubule inhibitor-mediated chemotherapy

Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies.

IntroductionQuantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design.MethodsPittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally.ResultsGlobal amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers.DiscussionAlthough the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers

DNA replication stress restricts ribosomal DNA copy number

Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number

Full deflection profile calculation and Young’s modulus optimisation for engineered high performance materials

New engineered materials have critical applications in different fields in medicine, engineering and technology but their enhanced mechanical performances are significantly affected by the microstructural design and the sintering process used in their manufacture. This work introduces (i) a methodology for the calculation of the full deflection profile from video recordings of bending tests, (ii) an optimisation algorithm for the characterisation of Young’s modulus, (iii) a quantification of the effects of optical distortions and (iv) a comparison with other standard tests. The results presented in this paper show the capabilities of this procedure to evaluate the Young’s modulus of highly stiff materials with greater accuracy than previously possible with bending tests, by employing all the available information from the video recording of the tests. This methodology extends to this class of materials the possibility to evaluate both the elastic modulus and the tensile strength with a single mechanical test, without the need for other experimental tools

Lower edge of locked Main Himalayan Thrust unzipped by the 2015 Gorkha earthquake

Large earthquakes are thought to release strain on previously locked faults. However, the details of how earthquakes are initiated, grow and terminate in relation to pre-seismically locked and creeping patches is unclear ^1-4. The 2015 Mw 7.8 Gorkha, Nepal earthquake occurred close to Kathmandu in a region where the prior pattern of fault locking is well documented ^5. Here we analyze this event using seismological records measured at teleseismic distances and Synthetic Aperture Radar imagery. We show that the earthquake originated northwest of Kathmandu within a cluster of background seismicity that fringes the bottom of the locked portion of the Main Himalayan Thrust fault (MHT). The rupture propagated eastwards for about 140 km, unzipping the lower edge of the locked portion of the fault. High-frequency seismic waves radiated continuously as the slip pulse propagated at about 2.8 km s-1 along this zone of presumably high and heterogeneous pre-¬seismic stress at the seismic-aseismic transition. Eastward unzipping of the fault resumed during the Mw 7.3 aftershock on May 12. The transfer of stress to neighbouring regions during the Gorkha earthquake should facilitate future rupture of the areas of the MHT adjacent and up-dip of the Gorkha earthquake rupture.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ngeo251

Decreased antibody response after severe acute respiratory syndrome coronavirus 2 vaccination in patients with Down syndrom

The risk of a severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in adults with Down syndrome is increased, resulting in an up to 10-fold increase in mortality, in particular in those >40 years of age. After primary SARS-CoV-2 vaccination, the higher risks remain. In this prospective observational cohort study, SARS-CoV-2 spike S1-specific antibody responses after routine SARS-CoV-2 vaccination (BNT162b2, messenger RNA [mRNA]-1273, or ChAdOx1) in adults with Down syndrome and healthy controls were compared. Adults with Down syndrome showed lower antibody concentrations after 2 mRNA vaccinations or after 2 ChAdOx1 vaccinations. After 2 mRNA vaccinations, lower antibody concentrations were seen with increasing age. In this prospective cohort study that included 222 adults with Down syndrome, a significantly lower antibody response was found after SARS-CoV-2 mRNA or vector vaccination compared to healthy controls. After mRNA vaccination, lower antibodies were found with increasing age

Validation of a rapid, non-radioactive method to quantify internalisation of G-protein coupled receptors

Agonist exposure can cause internalisation of G-protein coupled receptors (GPCRs), which may be a part of desensitisation but also of cellular signaling. Previous methods to study internalisation have been tedious or only poorly quantitative. Therefore, we have developed and validated a quantitative method using a sphingosine-1-phosphate (S1P) receptor as a model. Because of a lack of suitable binding studies, it has been difficult to study S1P receptor internalisation. Using a N-terminal HisG-tag, S1P1 receptors on the cell membrane can be visualised via immunocytochemistry with a specific anti-HisG antibody. S1P-induced internalisation was concentration dependent and was quantified using a microplate reader, detecting either absorbance, a fluorescent or luminescent signal, depending on the antibodies used. Among those, the fluorescence detection method was the most convenient to use. The relative ease of this method makes it suitable to measure a large number of data points, e.g. to compare the potency and efficacy of receptor ligands