Predicting loss in magnetic steels under arbitrary induction waveform and with minor hysteresis loops

We have studied ways of predicting power losses in soft magnetic laminations for generic time dependence of the periodic magnetic polarization J(t). We found that, whatever the frequency and the induction waveform, the loss behavior can be quantitatively assessed within the theoretical framework of the statistical loss model. The prediction requires a limited set of preemptive experimental data, depending on whether or not the arbitrary J(t) waveform is endowed with local slope inversions (i.e., minor hysteresis loops) in its periodic time behavior. In the absence of minor loops, such data reduce, for any peak polarization value Jp, to the loss figures obtained under sinusoidal J(t) at two different frequency values. In the presence of minor loops of semiamplitude Jm, the two-frequency loss experiment should be carried out for both peak polarization values Jp and Jm. Additional knowledge of the quasi-static major loop, to be used for modeling hysteresis loss, does improve the accuracy of the prediction method. A more general approach to loss in soft magnetic laminations is obtained in this way, the only limitation apparently being the onset of skin effect at high frequencie

Axion-sourced fireballs from supernovae

New feebly interacting particles would emerge from a supernova core with 100-MeV-range energies and produce $\gamma$-rays by subsequent decays. These would contribute to the diffuse cosmic $\gamma$-ray background or would have shown up in the Solar Maximum Mission (SMM) satellite from SN~1987A. However, we show for the example of axion-like particles (ALPs) that, even at distances beyond the progenitor star, the decay photons may not escape, and can instead form a fireball, a plasma shell with $T\lesssim 1$ MeV. Thus, existing arguments do not exclude ALPs with few 10 MeV masses and a two-photon coupling of a few $10^{-10}~{\rm GeV}^{-1}$. However, the energy would have showed up in sub-MeV photons, which were not seen from SN 1987A in the Pioneer Venus Orbiter (PVO), closing again this new window. A careful re-assessment is required for other particles that were constrained in similar ways.Comment: 11 pages, 6 figure

Learning mutational graphs of individual tumour evolution from single-cell and multi-region sequencing data

Background. A large number of algorithms is being developed to reconstruct evolutionary models of individual tumours from genome sequencing data. Most methods can analyze multiple samples collected either through bulk multi-region sequencing experiments or the sequencing of individual cancer cells. However, rarely the same method can support both data types. Results. We introduce TRaIT, a computational framework to infer mutational graphs that model the accumulation of multiple types of somatic alterations driving tumour evolution. Compared to other tools, TRaIT supports multi-region and single-cell sequencing data within the same statistical framework, and delivers expressive models that capture many complex evolutionary phenomena. TRaIT improves accuracy, robustness to data-specific errors and computational complexity compared to competing methods. Conclusions. We show that the application of TRaIT to single-cell and multi-region cancer datasets can produce accurate and reliable models of single-tumour evolution, quantify the extent of intra-tumour heterogeneity and generate new testable experimental hypotheses

Participatory risk assessment of pluvial floods in four towns of Niger

Intense rainfalls in Sub-Saharan Africa are increasing in frequency. Land degradation, watercourses siltation, and flood defence failure turn these events into disastrous floods. Over the last decade flood risk assessments have been prepared to face these disasters. However, they have frequent limitations in design, accuracy, and completeness. The objectives of this study are (i) to integrate local and scientific knowledge into a participated pluvial flood risk assessment (ii) to identify assets and (iii) to estimate the potential impact and efficiency of risk-reduction measures. The assessment is developed in four rapidly expanding towns of Niger, flooded several times in recent years. Flood-prone areas and assets are identified according four flood scenarios using local knowledge, 2D hydraulic modelling, and visual photointerpretation of very-high-resolution satellite images. Risk-reduction measures are singled-out through public participation. The residual risk and benefit/cost analyses provide a decision-making tool to accept or treat risk. During the last decade the expansion of the four towns has been more rapid in flood-prone zones than in safe areas. Nowadays more than half of the housing stock could be flooded by rainfalls with 20 years return period. Catchment treatment and building retrofitting can reduce risk. from 100 to 29–82. Nevertheless, the benefit/cost of risk reduction is high for towns settled in small catchments only

Method for pluvial flood risk assessment in rural settlements characterised by scant information availability

In tropical regions, heavy precipitations may lead to catastrophic flooding due to the degradation of catchments and the expansion of settlements in flood prone zones. In the current situation, where information on rainfall and exposed assets is either scant, or requires significant time to be collected, pluvial flood risk assessments are conducted using participatory tools, without any scientific support. Another option is to use satellite precipitation products, digital terrain models and satellite images at high to moderate-resolution. However, these datasets do not reach the required accuracy at the local scale. Consequently, the potential damages and the evaluation component of risk assessment are often missing. Risk evaluation is pivotal for informed decision making, with regards to the choice of treating or accepting the risk, implementing more effective measures, and for determining the safest areas for development. We proposed an improved method for assessing the risk of pluvial floods, which merges local and scientific knowledge and is consistent with the ISO 31010 standard. The method was successfully applied in five rural settlements in Niger and can be replicated in areas where information is scarce

Recent Changes in Hydroclimatic Patterns over Medium Niger River Basins at the Origin of the 2020 Flood in Niamey (Niger)

Niamey, the capital of Niger, is particularly prone to floods, since it is on the banks of the Niger River, which in its middle basin has two flood peaks: one in summer (the red flood) and one in winter (the black flood). In 2020, the Niger River in Niamey reached its all-time highest levels following an abundant rainy season. On the other hand, the floods in Niamey have been particularly frequent in the last decade, a symptom of a change in hydroclimatic behaviour already observed since the end of the great droughts of the 1970s and 1980s and which is identified with the name of Sahelian Paradox. This study, starting from the analysis of the 2020 flood and from the update of the rating curve of the Niamey hydrometric station, analyses the rainfall–runoff relationship on the Sahelian basins of the Medium Niger River Basin (MNRB) that are at the origin of the local flood. The comparative analysis of runoffs, annual maximum flows (AMAX) and runoff coefficients with various rainfall indices calculated on gridded datasets allowed to hydroclimatically characterise the last decade as a different period from the wet one before the drought, the dry one and the postdrought one. Compared to the last one, the current period is characterised by a sustained increase in hydrological indicators (AMAX +27%) consistent with the increase in both the accumulation of precipitation (+11%) and the number (+51%) and magnitude (+54%) of extreme events in the MNRB. Furthermore, a greater concentration of rainfall and extremes (+78%) in August contributes to reinforcing the red flood’s positive anomalies (+2.23 st.dev in 2020). The study indicates that under these conditions the frequency of extreme hydrological events in Niamey will tend to increase further also because of the concurrence of drivers such as river-bed silting and levee effects. Consequently, the study concludes with the need for a comprehensive flood-risk assessment on the Niamey city that considers both recent hydroclimatic trends and urbanisation dynamics in flood zones hence defining the most appropriate risk-reduction strategies

Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian multiple sclerosis patients, a follow-up study

Monitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) help to establish the optimal strategies to ensure adequate COVID-19 protection without compromising disease control offered by DMTs. Following our previous observations on the humoral response one month after two doses of BNT162b2 vaccine (T1) in MS patients differently treated, here we present a cross-sectional and longitudinal follow-up analysis six months following vaccination (T2, n=662) and one month following the first booster (T3, n=185). Consistent with results at T1, humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients also at the time points considered here (T2 and T3). Interestingly, a strong upregulation one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. Although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells.

A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-function phosphatase that causes alterations in thymic negative selection and/or thymic output of regulatory T cells (Treg) through inhibition of thymic TCR signaling. To test this model, we generated mice in which the human LYP-W620 variant or its phosphatase-inactive mutant are expressed in developing thymocytes under control of the proximal Lck promoter. We found that LYP-W620 expression results in diminished thymocyte TCR signaling, thus modeling a "gain-of-function" of LYP at the signaling level. However, LYP-W620 transgenic mice display no alterations of thymic negative selection and no anomalies in thymic output of CD4(+)Foxp3(+) Treg were detected in these mice. Lck promoter-directed expression of the human transgene also causes no alteration in thymic repertoire or increase in disease severity in a model of rheumatoid arthritis, which depends on skewed thymic selection of CD4(+) T cells. Our data suggest that a gain-of-function of LYP is unlikely to increase risk of autoimmunity through alterations of thymic selection and that LYP likely acts in the periphery perhaps selectively in regulatory T cells or in another cell type to increase risk of autoimmunity

Chronic Immune Activation in Systemic Lupus Erythematosus and the Autoimmune PTPN22 Trp620 Risk Allele Drive the Expansion of FOXP3+ Regulatory T Cells and PD-1 Expression.

In systemic lupus erythematosus (SLE), perturbed immunoregulation underpins a pathogenic imbalance between regulatory and effector CD4+ T-cell activity. However, to date, the characterization of the CD4+ regulatory T cell (Treg) compartment in SLE has yielded conflicting results. Here we show that patients have an increased frequency of CD4+FOXP3+ cells in circulation owing to a specific expansion of thymically-derived FOXP3+HELIOS+ Tregs with a demethylated FOXP3 Treg-specific demethylated region. We found that the Treg expansion was strongly associated with markers of recent immune activation, including PD-1, plasma concentrations of IL-2 and the type I interferon biomarker soluble SIGLEC-1. Since the expression of the negative T-cell signaling molecule PTPN22 is increased and a marker of poor prognosis in SLE, we tested the influence of its missense risk allele Trp620 (rs2476601C>T) on Treg frequency. Trp620 was reproducibly associated with increased frequencies of thymically-derived Tregs in blood, and increased PD-1 expression on both Tregs and effector T cells (Teffs). Our results support the hypothesis that FOXP3+ Tregs are increased in SLE patients as a consequence of a compensatory mechanism in an attempt to regulate pathogenic autoreactive Teff activity. We suggest that restoration of IL-2-mediated homeostatic regulation of FOXP3+ Tregs by IL-2 administration could prevent disease flares rather than treating at the height of a disease flare. Moreover, stimulation of PD-1 with specific agonists, perhaps in combination with low-dose IL-2, could be an effective therapeutic strategy in autoimmune disease and in other immune disorders