Continuous Experimentation for Automotive Software on the Example of a Heavy Commercial Vehicle in Daily Operation

As the automotive industry focuses its attention more and more towards the software functionality of vehicles, techniques to deliver new software value at a fast pace are needed. Continuous Experimentation, a practice coming from the web-based systems world, is one of such techniques. It enables researchers and developers to use real-world data to verify their hypothesis and steer the software evolution based on performances and user preferences, reducing the reliance on simulations and guesswork. Several challenges prevent the verbatim adoption of this practice on automotive cyber-physical systems, e.g., safety concerns and limitations from computational resources; nonetheless, the automotive field is starting to take interest in this technique. This work aims at demonstrating and evaluating a prototypical Continuous Experimentation infrastructure, implemented on a distributed computational system housed in a commercial truck tractor that is used in daily operations by a logistic company on public roads. The system comprises computing units and sensors, and software deployment and data retrieval are only possible remotely via a mobile data connection due to the commercial interests of the logistics company. This study shows that the proposed experimentation process resulted in the development team being able to base software development choices on the real-world data collected during the experimental procedure. Additionally, a set of previously identified design criteria to enable Continuous Experimentation on automotive systems was discussed and their validity confirmed in the light of the presented work.Comment: Paper accepted to the 14th European Conference on Software Architecture (ECSA 2020). 16 pages, 5 figure

Reproductive expression dynamics and comparative toxicological perspective of beta estrogen receptor gene in the male wall lizard, Podarcis sicula Rafinesque, 1810 (Chordata: Reptilia)

Over the last few decades, due to its relevant function in male reproduction assessment, important molecular achievements have been made in the molecular characterization of estrogen receptor genes in various species. Our work focuses on a male seasonal breeder, the bioindicator Podarcis sicula, because of its peculiar gonadal anatomy, similar to that of humans. Based on the cloned lizard's gene sequence fragment of estrogen receptor beta, esr2 (GenBank JN705543.1), we found DNA binding domain identity of 99% as well as a homologous sequence with humans. Furthermore, in order to better illustrate how this gene is regulated in the lizard's reproductive system organs, we investigated the transcriptional activity of esr2 in brain and testis tissues during mating and winter stasis phases of the reproductive cycle. Quantitative real time-polymerase chain reaction (qRT-PCR) analyses performed on male gonadal tissues demonstrate a significant increase in esr2 expression during mating compared to the winter stasis period, while in the brain, esr2 shows the opposite trend. Next, we provide morphological evidence of the detrimental effect on spermatogenesis of a pure anti-estrogen treatment (ICI 182,780) and the corresponding effect on esr2 expression in lizard specimens during the mating period which, upon treatment, was found to be no different from the expression levels in winter stasis both in the brain and in the testis. In this study, we explore the potential use of Podarcis sicula as a model for human testis development and maturation, as well as esr2 expression for toxicological screening in one-testis gonadectomy

Non-cell-autonomous regulation of interneuron specification mediated by extracellular vesicles

Disruption in neurogenesis and neuronal migration can influence the assembly of cortical circuits, affecting the excitatory-inhibitory balance and resulting in neurodevelopmental and neuropsychiatric disorders. Using ventral cerebral organoids and dorsoventral cerebral assembloids with mutations in the extracellular matrix gene LGALS3BP, we show that extracellular vesicles released into the extracellular environment regulate the molecular differentiation of neurons, resulting in alterations in migratory dynamics. To investigate how extracellular vesicles affect neuronal specification and migration dynamics, we collected extracellular vesicles from ventral cerebral organoids carrying a mutation in LGALS3BP, previously identified in individuals with cortical malformations and neuropsychiatric disorders. These results revealed differences in protein composition and changes in dorsoventral patterning. Proteins associated with cell fate decision, neuronal migration, and extracellular matrix composition were altered in mutant extracellular vesicles. Moreover, we show that treatment with extracellular vesicles changes the transcriptomic profile in neural progenitor cells. Our results indicate that neuronal molecular differentiation can be influenced by extracellular vesicles

Analysis of Bacterial Stent Colonization: The Role of Urine and Device Microbiological Cultures

: In this study, we explored the incidence of double J (JJ) contamination of patients who underwent an endourological procedure for urinary stones and ureteral stenosis. We developed a prospective study between January 2019 and December 2021. Ninety-seven patients, 54 male and 43 female, were enrolled. Urine culture was taken during four steps: before stent insertion, a sample from selective renal pelvis catheterization, a sample two days after the JJ insertion and finally, after the stent removal procedure. At the time of the stent removal, 1 cm of proximal and distal ends were cut off and placed in the culture for bacterial evaluation. Cohen's kappa coefficient value (k) and concordance rates of microbiological culture results were evaluated. The study group comprised 56% of male patients. Proximal and distal stent cultures were positive in 81 and 78 patients. The concordance rate of microbiological cultures between proximal and distal double J stent is 88% (k 0.6). The most common pathogens isolated from urine and stent cultures were Enterococcus spp. in 52 cases and Klebsiella spp. in 27 cases

Hydroxylation of the NOTCH1 intracellular domain regulates Notch signaling dynamics

Notch signaling plays a pivotal role in the development and, when dysregulated, it contributes to tumorigenesis. The amplitude and duration of the Notch response depend on the posttranslational modifications (PTMs) of the activated NOTCH receptor - the NOTCH intracellular domain (NICD). In normoxic conditions, the hydroxylase FIH (factor inhibiting HIF) catalyzes the hydroxylation of two asparagine residues of the NICD. Here, we investigate how Notch-dependent gene transcription is regulated by hypoxia in progenitor T cells. We show that the majority of Notch target genes are downregulated upon hypoxia. Using a hydroxyl-specific NOTCH1 antibody we demonstrate that FIH-mediated NICD1 hydroxylation is reduced upon hypoxia or treatment with the hydroxylase inhibitor dimethyloxalylglycine (DMOG). We find that a hydroxylation-resistant NICD1 mutant is functionally impaired and more ubiquitinated. Interestingly, we also observe that the NICD1-deubiquitinating enzyme USP10 is downregulated upon hypoxia. Moreover, the interaction between the hydroxylation-defective NICD1 mutant and USP10 is significantly reduced compared to the NICD1 wild-type counterpart. Together, our data suggest that FIH hydroxylates NICD1 in normoxic conditions, leading to the recruitment of USP10 and subsequent NICD1 deubiquitination and stabilization. In hypoxia, this regulatory loop is disrupted, causing a dampened Notch response

GC Content Increased at CpG Flanking Positions of Fish Genes Compared with Sea Squirt Orthologs as a Mechanism for Reducing Impact of DNA Methylation

Background: Fractional DNA methylation in sea squirts evolved to global DNA methylation in fish. The impact of global DNA methylation is reflected by more CpG depletions and/or more A/T to G/C changes at CpG flanking positions due to context-dependent mutations of methylated CpG sites. Methods and Findings: In this report, we demonstrate that the sea squirt genes have undergone more CpG to TpG/CpA substitutions than the fish orthologs using homologous fragments from orthologous genes among Ciona intestinalis, Ciona savignyi, fugufish and zebrafish. To avoid premature transcription, the TGA sites derived from CGA were largely converted to TGG in sea squirt genes. By contrast, a significant increment of GC content at CpG flanking positions was shown in fish genes. The positively selected A/T to G/C substitutions, in combination with the CpG to TpG/CpA substitutions, are the sources of the extremely low CpG observed/expected ratios in vertebrates. The nonsynonymous substitutions caused by the GC content increase have resulted in frequent amino acid replacements in the directions that were not noticed previously. Conclusion: The increased GC content at CpG flanking positions can reduce CpG loss in fish genes and attenuate the impact of DNA methylation on CpG-containing codons, probably accounting for evolution towards vertebrates. © 2008 Wang, Leung.published_or_final_versio

Tollip Is a Mediator of Protein Sumoylation

Tollip is an interactor of the interleukin-1 receptor involved in its activation. The endosomal turnover of ubiquitylated IL-1RI is also controlled by Tollip. Furthermore, together with Tom1, Tollip has a general role in endosomal protein traffic. This work shows that Tollip is involved in the sumoylation process. Using the yeast two-hybrid technique, we have isolated new Tollip partners including two sumoylation enzymes, SUMO-1 and the transcriptional repressor Daxx. The interactions were confirmed by GST-pull down experiments and immunoprecipitation of the co-expressed recombinants. More specifically, we show that the TIR domain of the cytoplasmic region of IL-1RI is a sumoylation target of Tollip. The sumoylated and unsumoylated RanGAP-1 protein also interacts with Tollip, suggesting a possible role in RanGAP-1 modification and nuclear-cytoplasmic protein translocation. In fact, Tollip is found in the nuclear bodies of SAOS-2/IL-1RI cells where it colocalizes with SUMO-1 and the Daxx repressor. We conclude that Tollip is involved in the control of both nuclear and cytoplasmic protein traffic, through two different and often contrasting processes: ubiquitylation and sumoylation

Milan: A City Lost in the Transition from the Growth Machine Paradigm Towards a Social Innovation Approach

Milan can be described as a city lost in transition. For more than two decades, Milan has been ruled by a system of strongly market-oriented governance, following the rhetoric that creating a "good business climate" is an effective way to not only foster growth and innovation but also eradicate poverty and deliver higher standards of living. This approach has led to: (a) a disinvestment in welfare services directly provided by the municipality, in favour of a more residual welfare system based on non-profit and private involvement; (b) a huge investment in neo-liberal tools of government for the economic development of the city, such as the promotion of international events (Expo 2015) and large real estate investments through public–private partnerships. After some scandals as well as a huge increase of social inequalities, municipal elections rewarded a new coalition following a style of governance oriented to a social innovation approach. However, the difficult financial situation of the municipality has reduced ambitions of the current government

Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity.

Basal progenitors (BPs), including intermediate progenitors and basal radial glia, are generated from apical radial glia and are enriched in gyrencephalic species like humans, contributing to neuronal expansion. Shortly after generation, BPs delaminate towards the subventricular zone, where they further proliferate before differentiation. Gene expression alterations involved in BP delamination and function in humans are poorly understood. Here, we study the role of LGALS3BP, so far known as a cancer biomarker, which is a secreted protein enriched in human neural progenitors (NPCs). We show that individuals with LGALS3BP de novo variants exhibit altered local gyrification, sulcal depth, surface area and thickness in their cortex. Additionally, using cerebral organoids, human fetal tissues and mice, we show that LGALS3BP regulates the position of NPCs. Single-cell RNA-sequencing and proteomics reveal that LGALS3BP-mediated mechanisms involve the extracellular matrix in NPCs' anchoring and migration within the human brain. We propose that its temporal expression influences NPCs' delamination, corticogenesis and gyrification extrinsically