Broadening personal competence profiles through transdisciplinary project modules

Engineering education today is often organised in discipline-specific modules. Although it is essential to build up basic knowledge, cross-disciplinary knowledge is fundamental for solving complex problems. Transdisciplinary approaches can provide the necessary hard and soft skills, improve self-determination in education and broaden personal competence profiles. The experience gained is conveyed using the example of project-based modules on the topics of a) AI applications to minimise racial biasing in medical technology and b) construction of microfluidic systems to avoid animal testing. These were developed over several semesters by interdisciplinary student groups involving industry and research partners. The concept was initially carried out online in an interdisciplinary project module focusing on individual learning objectives, composed of the disciplines "Mechanical Engineering", "Computational Engineering Science", "Physical Engineering Sciences" as well as "Biomedical Engineering" and is being expanded in a hybrid-transdisciplinary manner through gradual additions including systems engineering, philosophy and sustainability in technology, ergonomics and human-machine systems. Through active participation in researching and solving real challenges, collaboration of transdisciplinary teams over several group generations and setting individual learning goals, profound knowledge and new methodological competences can be acquired beyond engineering disciplines. The integration of non-technical methods and approaches allows students to recognise complex problems and identify the necessary competences in order to realise a successful project. To further expand this approach, a new module concept for interdisciplinary cooperation in production engineering was developed. It takes up the aspects of individual, project-based learning and brings together all the competences of the institute in transdisciplinary exchange

Tree species traits but not diversity mitigate stem breakage in a subtropical forest following a rare and extreme ice storm

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Spontaneous pneumothorax can be associated with TGFBR2 mutation.

TGFBR2 mutations that cause Loeys-Dietz Syndrome can present as pneumothorax. In vitro kinase assays can help confirm pathogenicity of novel variants.SJM is an MRC Senior Clinical FellowThis is the author accepted manuscript. The final version is available from the European Respiratory Society via http://dx.doi.org/10.1183/13993003.00952-201

A multi-exon deletion within WWOX is associated with a 46,XY disorder of sex development

Disorders of sex development (DSD) are congenital conditions where chromosomal, gonad or genital development is atypical. In a significant proportion of 46,XY DSD cases it is not possible to identify a causative mutation, making genetic counseling difficult and potentially hindering optimal treatment. Here, we describe the analysis of a 46,XY DSD patient that presented at birth with ambiguous genitalia. Histological analysis of the surgically removed gonads showed bilateral undifferentiated gonadal tissue and immature testis, both containing malignant germ cells. We screened genomic DNA from this patient for deletions and duplications using an Illumina whole-genome SNP microarray. This analysis revealed a heterozygous deletion within the WWOX gene on chromosome 16, removing exons 6-8. Analysis of parental DNA showed that the deletion was inherited from the mother. cDNA analysis confirmed that the deletion maintained the reading frame, with exon 5 being spliced directly onto exon 9. This deletion is the first description of a germline rearrangement affecting the coding sequence of WWOX in humans. Previously described Wwox knockout mouse models showed gonadal abnormalities, supporting a role for WWOX in human gonad development

Transfer Functions for Protein Signal Transduction: Application to a Model of Striatal Neural Plasticity

We present a novel formulation for biochemical reaction networks in the context of signal transduction. The model consists of input-output transfer functions, which are derived from differential equations, using stable equilibria. We select a set of 'source' species, which receive input signals. Signals are transmitted to all other species in the system (the 'target' species) with a specific delay and transmission strength. The delay is computed as the maximal reaction time until a stable equilibrium for the target species is reached, in the context of all other reactions in the system. The transmission strength is the concentration change of the target species. The computed input-output transfer functions can be stored in a matrix, fitted with parameters, and recalled to build discrete dynamical models. By separating reaction time and concentration we can greatly simplify the model, circumventing typical problems of complex dynamical systems. The transfer function transformation can be applied to mass-action kinetic models of signal transduction. The paper shows that this approach yields significant insight, while remaining an executable dynamical model for signal transduction. In particular we can deconstruct the complex system into local transfer functions between individual species. As an example, we examine modularity and signal integration using a published model of striatal neural plasticity. The modules that emerge correspond to a known biological distinction between calcium-dependent and cAMP-dependent pathways. We also found that overall interconnectedness depends on the magnitude of input, with high connectivity at low input and less connectivity at moderate to high input. This general result, which directly follows from the properties of individual transfer functions, contradicts notions of ubiquitous complexity by showing input-dependent signal transmission inactivation.Comment: 13 pages, 5 tables, 15 figure

Pre-Operative Continued Oral Anticoagulation Impact on Early Outcomes after Transcatheter Aortic Valve Implantation

Considering that there is a lack of evidence and guideline-based recommendations on the best preoperative oral anticoagulation management (OAC) for transcatheter aortic valve implantation (TAVI), this cohort study aimed to evaluate bleeding, access site complications, and early safety in patients undergoing TAVI on continued OAC therapy vs no-OAC therapy. Three-hundred forty-four patients submitted to a TAVI procedure (66.3% no-OAC vs 33.7% OAC) were consecutively enrolled. Primary endpoint was defined as in-hospital VARC-2 life-threatening or disabling bleeding. Secondary endpoints were in-hospital VARC-2 major vascular complications and VARC-2 early safety at 30 days. Propensity score matching analysis was performed to reduce potential distribution bias, resulting in 2 well-balanced groups (92 patients in each arm). In the overall cohort, mean age, median EuroScore II, and STS-score were 78.7±7.6 years, 2.9% (1.7-5.9), and 2.3% (1.6-3.6), respectively. Despite being older (78 ± 8 vs 80 ± 6, p = 0.004) and having higher STS score (2.1 vs 2.6, p = 0.001), patients on OAC had similar incidence of in-hospital VARC-2 life-threatening or disabling bleeding (1.3% vs. 0.9%, p = 0.711), major vascular complications (4.8% vs 5.2%, p = 0.888), and VARC-2 early safety at 30 days (10.1% vs 12.1%, p = 0.575). No significant differences in the main outcomes were observed when propensity score matching was applied. In conclusion, the management of patients on OAC submitted to a TAVI procedure is challenging and requires balancing the risk of bleeding with the risk of thromboembolic events. The present study suggests that continued OAC was not associated with increased in-hospital VARC-2 life-threatening or disabling bleeding, major vascular complications, and VARC-2 early safety at 30 days

Interleukin-1 receptor-associated kinase-M suppresses systemic lupus erythematosus

Interleukin-1 receptor-associated kinase (IRAK)-M suppresses Toll-like receptor (TLR)-mediated activation of innate immunity during infection. A similar role was hypothesised for IRAK-M in autoimmunity

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Spectrophotometric analysis of the Ryugu rock seen by MASCOT: Searching for a carbonaceous chondrite analog

We analyze images of a rock on Ryugu acquired in situ by MASCam, camera of the MASCOT lander, with the aim of identifying possible carbonaceous chondrite (CC) analogs. The rock's reflectance ($r_{\rm F} = 0.034 \pm 0.003$ at phase angle $4.5^\circ \pm 0.1^\circ$) is consistent with Ryugu's average reflectance, suggesting that the rock is typical for this asteroid. A spectrophotometric analysis of the rock's inclusions provides clues to CC group membership. Inclusions are generally brighter than the matrix. The dominant variation in their color is a change of the visible spectral slope, with many inclusions being either red or blue. Spectral variation in the red channel hints at the presence of the 0.7~$\mu$m absorption band linked to hydrated phyllosilicates. The inclusions are unusually large for a CC; we find that their size distribution may best match that of the Renazzo (CR2) and Leoville (CV3) meteorites. The Ryugu rock does not easily fit into any of the CC groups, consistent with the idea that typical Ryugu-type meteorites are too fragile to survive atmospheric entry