Data managers: A survey of the European Society of Breast Cancer Specialists in certified multi-disciplinary breast centers.

The European Society of Breast Cancer Specialists (EUSOMA) requires that the breast centers' core team includes a trained person responsible for data collection and analysis. We addressed a questionnaire to the data managers of the EUSOMA breast centers network in order to acquire information with regard to their education, training, role, activity, recognition, and satisfaction. Breast centers' data managers are highly educated individuals with a variety of backgrounds carrying out, more frequently part-time and as temporary employees, a job for which they received little specific training. These findings support the importance of defining a core curriculum and a training program

Quartz Crystal Microbalances for Space: Design and Testing of a 3D Printed Quasi-Kinematic Support

Outgassing or thruster’s generated contaminants are critical for optical surfaces and optical payloads because scientific measurements and, in general, the performances can be degraded or jeopardized by uncontrolled contamination. This is a well-known issue in space technology that is demonstrated by the growing usage of quartz crystal microbalances as a solution for measuring material outgassing properties data and characterizing the on-orbit contamination environment. Operation in space requires compatibility with critical requirements, especially the mechanical and thermal environments to be faced throughout the mission. This work provides the design of a holding structure based on 3D printing technology conceived to meet the environmental characteristics of space application, and in particular, to face harsh mechanical and thermal environments. A kinematic mounting has been conceived to grant compatibility with a large temperature range, and it has been designed by finite element methods to overcome loading during the launch phases and cope with a temperature working range down to cryogenic temperatures. Qualification in such environments has been performed on a mockup by testing a prototype of the holding assembly between −110 °C and 110 °C and allowing verification of the mechanical resistance and stability of the electrical contacts for the embedded heater and sensor in that temperature range. Moreover, mechanical testing in a random environment characterized by an RMS acceleration level of 500 m/s2 and excitation frequency from 20 to 2000 Hz was successfully performed. The testing activity allowed for validation of the proposed design and opened the road to the possible implementation of the proposed design for future flight opportunities, also onboard micro or nanosatellites. Moreover, exploiting the manufacturing technology, the proposed design can implement an easy assembling and mounting of the holding system. At the same time, 3D printing provides a cost-effective solution even for small series production for ground applications, like monitoring the contaminants in thermo-vacuum chambers or clean rooms, or depositions chambers

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator–like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration

Epilepsy and intellectual disability linked protein Shrm4 interaction with GABA B Rs shapes inhibitory neurotransmission

Shrm4, a protein expressed only in polarized tissues, is encoded by the KIAA1202 gene, whose mutations have been linked to epilepsy and intellectual disability. However, a physiological role for Shrm4 in the brain is yet to be established. Here, we report that Shrm4 is localized to synapses where it regulates dendritic spine morphology and interacts with the C terminus of GABA B receptors (GABA B Rs) to control their cell surface expression and intracellular trafficking via a dynein-dependent mechanism. Knockdown of Shrm4 in rat severely impairs GABA B R activity causing increased anxiety-like behaviour and susceptibility to seizures. Moreover, Shrm4 influences hippocampal excitability by modulating tonic inhibition in dentate gyrus granule cells, in a process involving crosstalk between GABA B Rs and extrasynaptic \uce-subunit-containing GABA A Rs. Our data highlights a role for Shrm4 in synaptogenesis and in maintaining GABA B R-mediated inhibition, perturbation of which may be responsible for the involvement of Shrm4 in cognitive disorders and epilepsy

Design and testing of selective laser melted structural component in AlSi9Cu3 alloy for a space dust analyser

Space is one of the most avant-garde sectors for additive manufacturing as the inherent characteristics of this technology allow the creation of complex and lightweight 3D structures. Using this brand-new design tool, it was possible to design the pumping system holder of the MicroMED instrument, a particle analyser developed for ExoMars 2022 mission. The geometry of the holder was optimized using a finite element approach. The effectiveness of the proposed solution was evaluated by comparing the performance of two different designs using the AlSi9Cu3 alloy. One solution was based on micro-milling and the other on Selective Laser Melting. In order to validate the designed SLMed holder, a mockup was produced and successfully tested in the mission's mechanical environment

Oligophrenin-1 regulates synaptic activity dependent shuttling between synapses and nucleus of Rev-erbAalpha

Oligophrenin-1 (OPHN1) is a synaptic RhoGTPase-activating protein involved in X-linked mental retardation that regulates dendritic spines shape and outgrowth of axons in brain (Govek et al., 2004). By using the C-terminal fragment of Oligophrenin 1 as bait in a two-hybrid screening of a human fetal brain cDNA library we identified as an interactor, NR1D1 (Rev-erbAalpha). Rev-erbAalpha is an orphan nuclear receptor that constitutively suppresses gene transcription and regulates the circadian clock in the CNS (Preitner et al. 2002). We confirmed the interaction in vitro and in vivo by co-immunoprecipitation and GST-pull down. In COS-7 cells we observed that overexpressed Oligophrenin-1 is able to recruit Rev-erbAalpha (normally localized in the nucleus) to the cytoplasm. Furthermore, overexpression Oligophrenin-1 induces an accumulation of endogenous Rev-erbAalpha in dendritic spines in hippocampal neurons. The Oligophrenin-1deltaC (deleted of C-terminus), a mutant that mimics the mutation present in the XLMR patients, wasn\u2019t able to induce this effect in COS7 and in hippocampal neurons. In HEK cells we observed that Oligophrenin-1 protects Rev-erbAalpha from degradation by GSK3beta We also have found that RNAi knockdown of Oligophrenin-1 inhibited the translocation of Rev-erbAalpha into the dendritic spines. More remarkable, synaptic activity mediated by AMPA receptors induces translocation of Rev-erbAalpha to the dendritic spines. RNAi experiments showed that Oligophrenin-1 is required for the translocation of Rev-erbAalpha in spines induced by synaptic activity. Moreover we observed an alteration of Rev-erbAalpha expression in Oligophrenin-1 KO mouse: there is a reduction of Rev-erbAalpha in hippocampus. Our results demonstrate for the first time the interaction between an orphan receptor (Rev-erbAalpha) and a synaptic protein (Oligophrenin-1). This interaction regulates the localization of Rev-erbAalpha between synapse and nucleus induced by synaptic activation

Qualification of MEMS differential pressure sensors in Martian-like environment

This work describes the qualification of MEMS differential pressure sensors to be used in a particle analyzer for Mars 2020. Two different types of sensors have been initially considered MEMS-33A-001D and NPH-8-002.5-GH, in order to select the most suitable in terms of S/N ratio and sensitivity. Sensors have been calibrated at ambient pressure using as reference a water column differential manometers, selected for the unmatchable stability, key property for tests expected to span across many days. The pressure signal has been generated using the water column manometer itself, allowing to reach the full scale of the instruments and by means of a vane pump in low pressure environment where a capacitive manometer has been used as reference. No variation in the sensor sensitivity has been evidenced after exposure to the expected temperature range for the instruments mounted on the platform of the ExoMars Lander. The final selection of the sensor to be flight-qualified has been made on the SNR because both candidates proved to be compatible with the mechanical loads expected during launch and Martian landing and the expected space environment through all mission phases