Limits and opportunities of risk analysis application in railway systems

Risk Analysis is a collection of methods widely used in many industrial sectors. In the transport sector it has been particularly used for air transport applications. The reasons for this wide use are well-known: risk analysis allows to approach the safety theme in a stochastic - rather than deterministic - way, it forces to break down the system in sub-components, last but not least it allows a comparison between solutions with different costs, introducing de facto an element of economic feasibility of the project alternatives in the safety field. Apart from the United Kingdom, in Europe the application of this tool in the railway sector is relatively recent. In particular Directive 2004/49/EC (the "railway safety directive") provides for compulsory risk assessment in relation to the activities of railway Infrastructure Managers (IMs) and of Railway Undertakings (RUs). Nevertheless the peculiarity of the railway system - in which human, procedural, environmental and technological components have a continuous interchange and in which human responsibilities and technological functions often overlap - induced the EC to allow wide margins of subjectivity in the interpretation of risk assessment. When enacting Commission Regulation (EC) No 352/2009 which further regulates this subject, a risk assessment is considered positive also if the IM or RU declare to take safety measures widely used in normal practice. The paper shows the results of a structured comparative analysis of the rail sector and other industrial sectors, which illustrate the difficulties, but also the opportunities, of a transfer towards the railway system of the risk analysis methods currently in use for the other systems

The present and future of sustainability disclosure in equity investment funds’ pre-contractual documents: Mapping ESG discourse through STM

To show how pre-contractual documents are currently employed to disclose sustainability and ESG-related information, we map and examine the contents of 945 Key Investor Information Documents (KIIDs) from ten major asset managers, including sustainable and non-sustainable funds. Through a Structural Topic Modelling approach, we infer sustainability-related topics and compare their contents and prevalence in different sections of these documents. Sustainability is a cross-cutting and multifaceted issue, discussed coherently with the SFDR fund classification across multiple sections of the KIID, making the option to convey sustainable information in a single section complex to implement

METTL3 regulates WTAP protein homeostasis

The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumors, including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also a regulator of the nuclear complex required for the deposition of N6-methyladenosine (m6A) into mRNAs, containing the METTL3 methyltransferase. However, it is not clear if WTAP may have m6A-independent regulatory functions that might contribute to its oncogenic role. Here, we show that both knockdown and overexpression of METTL3 protein results in WTAP protein upregulation, indicating that METTL3 levels are critical for WTAP protein homeostasis. However, we show that WTAP upregulation is not sufficient to promote cell proliferation in the absence of a functional METTL3. Therein, these data indicate that the reported oncogenic function of WTAP is strictly connected to a functional m6A methylation complex

Management of Obesity and Obesity-Related Disorders: From Stem Cells and Epigenetics to Its Treatment

: Obesity is a complex worldwide disease, characterized by an abnormal or excessive fat accumulation. The onset of this pathology is generally linked to a complex network of interactions among genetic and environmental factors, aging, lifestyle, and diets. During adipogenesis, several regulatory mechanisms and transcription factors are involved. As fat cells grow, adipose tissue becomes increasingly large and dysfunctional, losing its endocrine function, secreting pro-inflammatory cytokines, and recruiting infiltrating macrophages. This long-term low-grade systemic inflammation results in insulin resistance in peripheral tissues. In this review we describe the main mechanisms involved in adipogenesis, from a physiological condition to obesity. Current therapeutic strategies for the management of obesity and the related metabolic syndrome are also reported

Cerebellar Non-Invasive Brain Stimulation: A Frontier in Chronic Pain Therapy

Chronic pain poses a widespread and distressing challenge; it can be resistant to conventional therapies, often having significant side effects. Non-invasive brain stimulation (NIBS) techniques offer promising avenues for the safe and swift modulation of brain excitability. NIBS approaches for chronic pain management targeting the primary motor area have yielded variable outcomes. Recently, the cerebellum has emerged as a pivotal hub in human pain processing; however, the clinical application of cerebellar NIBS in chronic pain treatment remains limited. This review delineates the cerebellum’s role in pain modulation, recent advancements in NIBS for cerebellar activity modulation, and novel biomarkers for assessing cerebellar function in humans. Despite notable progress in NIBS techniques and cerebellar activity assessment, studies targeting cerebellar NIBS for chronic pain treatment are limited in number. Nevertheless, positive outcomes in pain alleviation have been reported with cerebellar anodal transcranial direct current stimulation. Our review underscores the potential for further integration between cerebellar NIBS and non-invasive assessments of cerebellar function to advance chronic pain treatment strategies

Analysis of the human Y-chromosome haplogroup Q characterizes ancient population movements in Eurasia and the Americas

Background: Recent genome studies of modern and ancient samples have proposed that Native Americans derive from a subset of the Eurasian gene pool carried to America by an ancestral Beringian population, from which two well-differentiated components originated and subsequently mixed in different proportion during their spread in the Americas. To assess the timing, places of origin and extent of admixture between these components, we performed an analysis of the Y-chromosome haplogroup Q, which is the only Pan-American haplogroup and accounts for virtually all Native American Y chromosomes in Mesoamerica and South America. Results: Our analyses of 1.5 Mb of 152 Y chromosomes, 34 re-sequenced in this work, support a "coastal and inland routes scenario" for the first entrance of modern humans in North America. We show a major phase of male population growth in the Americas after 15 thousand years ago (kya), followed by a period of constant population size from 8 to 3 kya, after which a secondary sign of growth was registered. The estimated dates of the first expansion in Mesoamerica and the Isthmo-Colombian Area, mainly revealed by haplogroup Q-Z780, suggest an entrance in South America prior to 15 kya. During the global constant population size phase, local South American hints of growth were registered by different Q-M848 sub-clades. These expansion events, which started during the Holocene with the improvement of climatic conditions, can be ascribed to multiple cultural changes rather than a steady population growth and a single cohesive culture diffusion as it occurred in Europe. Conclusions: We established and dated a detailed haplogroup Q phylogeny that provides new insights into the geographic distribution of its Eurasian and American branches in modern and ancient samples

Study of the Synthetic Approach Influence in Ni/CeO2-Based Catalysts for Methane Dry Reforming

This study focuses on the synthetic approach influence in morphostructural features and catalytic performances for Ni/CeO2 catalysts. Incipient wetness impregnation, coprecipitation and nitrate combustion were studied as catalyst preparation approaches, and the materials were then tested at 700 C for methane dry reforming (MDR). The morphostructural properties of the materials were deeply studied using several techniques, such as temperature programmed reduction (TPR), to investigate reducibility and support-metal interaction, N2 physisorption to evaluate the porosity and the surface area, scanning electron microscopy (SEM) and X-ray diffraction (XRD) to estimate Ni dispersion, and temperature programmed oxidation (TPO) to identify the type and amount of coke formed on catalysts’ surface after reaction. From the data obtained, coprecipitation turned out to be the most suitable technique for this application because this catalyst was able to reach 70% of CO2 conversion and 30% methane conversion, with an H2 yield of 15% and 30% yield of CO at the end of the 30 h test. Moreover, it was also the catalyst with the highest metal dispersion, the strongest interaction with the support, and the lowest coke deposition

Changes in Cortical Activation by Transcranial Magnetic Stimulation Due to Coil Rotation Are Not Attributable to Cranial Muscle Activation

Transcranial magnetic stimulation coupled with electroencephalography (TMS-EEG) allows for the study of brain dynamics in health and disease. Cranial muscle activation can decrease the interpretability of TMS-EEG signals by masking genuine EEG responses and increasing the reliance on preprocessing methods but can be at least partly prevented by coil rotation coupled with the online monitoring of signals; however, the extent to which changing coil rotation may affect TMS-EEG signals is not fully understood. Our objective was to compare TMS-EEG data obtained with an optimal coil rotation to induce motor evoked potentials (M1standard) while rotating the coil to minimize cranial muscle activation (M1emg). TMS-evoked potentials (TEPs), TMS-related spectral perturbation (TRSP), and intertrial phase clustering (ITPC) were calculated in both conditions using two different preprocessing pipelines based on independent component analysis (ICA) or signal-space projection with source-informed reconstruction (SSP-SIR). Comparisons were performed with cluster-based correction. The concordance correlation coefficient was computed to measure the similarity between M1standard and M1emg TMS-EEG signals. TEPs, TRSP, and ITPC were significantly larger in M1standard than in M1emg conditions; a lower CCC than expected was also found. These results were similar across the preprocessing pipelines. While rotating the coil may be advantageous to reduce cranial muscle activation, it may result in changes in TMS-EEG signals; therefore, this solution should be tailored to the specific experimental context

Phonon-Mediated KIDs as Light Detectors for Rare-Event Search: The CALDER Project

Background suppression plays a crucial role in experiments searching for rare events, like neutrino-less double beta decay (0 $$\nu$$ DBD) and dark matter. Large mass bolometers that are among the most competitive devices in this field would largely benefit from the development of ultrasensitive light detectors, as the combined readout of the bolometric and light signals enables the particle identification. The CALDER collaboration is developing cryogenic light detectors that will match the requirements of next generation experiments: noise lower than 20 eV RMS, large active area (several cm $$^{2}$$ ), wide temperature range of operation, and ease in fabricating and operating a thousand of detectors. For this purpose, we are exploiting the excellent energy resolution and the natural multiplexed read-out provided by kinetic inductance detectors (KIDs). These devices can be operated in a phonon-mediated approach, in which KIDs are coupled to a large insulating substrate in order to increase the active surface from a few mm $$^{2}$$ to 25 cm $$^{2}$$ . Our current best prototype, based on aluminum LEKIDs, reached a baseline sensitivity of 80 eV with an overall efficiency of about 20 %