Looking for an axion in a haystack of muons

The search for axion-like particles $X$ in muon decays is an excellent opportunity for the MEG II and Mu3e experiments to extend their horizons beyond $\mu^+ \to e^+ \gamma$ and $\mu^+ \to e^+ e^- e^+$. A suitable process for both experiments is the two-body decay $\mu^+ \to e^+ X$, whose only signature is a monochromatic peak close to the kinematic endpoint of the positron energy spectrum of the $\mu^+ \to e^+ \nu_e \bar\nu_\mu$ background. The hunt for such an elusive signal in a vast amount of irreducible background requires extremely accurate theoretical predictions to be implemented in a Monte Carlo event generator. This work presents a new state-of-the-art computation of $\mu^+ \to e^+ \nu_e \bar\nu_\mu$ for polarised muons, accomplished with the McMule framework. The calculation includes next-to-next-leading order QED corrections and logarithmically enhanced terms at even higher orders. The results are also used to estimate the sensitivity of both experiments on the branching ratio of $\mu^+ \to e^+ X$, in order to evaluate the impact of the theoretical error.Comment: 4 pages, 2 figures, contribution to NFLF23, version accepted for publicatio

The effects of interbank networks on efficiency and stability in a macroeconomic agent-based model

We develop a macroeconomic agent-based model that consists of firms, banks, unions and households who interact on labour, goods, credit and interbank markets. The model endogenises pricing decisions by firms, wage setting by unions and interest rate setting by banks on both firm and interbank lending. Banks also set leverage targets and precautionary liquidity buffers on the basis of internal risk models. Our model produces endogenous fluctuations driven by the pricing behaviour of firms and the wage setting behaviour of unions. Fluctuations lead to loan defaults which are exacerbated as lenders reduce lending and charge higher interest rates, inducing a credit crunch. We also study how making the inter-banking network more connected affects the key outcomes of the economy and find that while the flow of funds from surplus banks to firms can be increased, the latter effect is soon dominated by increasing instability in the real sector as firms default at higher rates. While the banking sector experiences fewer defaults as a whole, losses on the interbank market increase as a source of bank defaults

A multi-agent methodology to assess the effectiveness of alternative systemic risk adjusted capital requirements

We propose a multi-agent approach to compare the effectiveness of macro-prudential capital requirements, where banks are embedded in an artificial macroeconomy. Capital requirements are derived from systemic- risk metrics that reflect both the vulnerability or impact of financial in- stitutions. Our objective is to explore how systemic-risk measures could be translated in capital requirements and test them in a comprehensive framework. Based on our counterfactual scenarios, we find that macro- prudential capital requirements can mitigate systemic risk, but there is a trade-off between market- and balance-sheet-based policies in terms of banks’ losses and credit supply

High-precision muon decay predictions for ALP searches

We present an improved theoretical prediction of the positron energy spectrum for the polarised Michel decay $\mu^+\to e^+ \nu_e\bar{\nu}_\mu$. In addition to the full next-to-next-to-leading order correction of order $\alpha^2$ in the electromagnetic coupling, we include logarithmically enhanced terms at even higher orders. Logarithms due to collinear emission are included at next-to-leading accuracy up to order $\alpha^4$. At the endpoint of the Michel spectrum, soft photon emission results in large logarithms that are resummed up to next-to-next-to-leading logarithmic accuracy. We apply our results in the context of the MEG II and Mu3e experiments to estimate the impact of the theory error on the branching ratio sensitivity for the lepton-flavour-violating decay $\mu^+\to e^+ X$ of a muon into an axion-like particle $X$.Comment: 36 pages, 14 figure

Exploiting Intrinsic Kinematic Null Space for Supernumerary Robotic Limbs Control

Supernumerary robotic limbs (SRLs) gained increasing interest in the last years for their applicability as healthcare and assistive technologies. These devices can either support or augment human sensorimotor capabilities, allowing users to complete tasks that are more complex than those feasible for their natural limbs. However, for a successful coordination between natural and artificial limbs, intuitiveness of interaction and perception of autonomy are key enabling features, especially for people suffering from motor disorders and impairments. The development of suitable human-robot interfaces is thus fundamental to foster the adoption of SRLs.With this work, we describe how to control an extra degree of freedom by taking advantage of what we defined the Intrinsic Kinematic Null Space, i.e. the redundancy of the human kinematic chain involved in the ongoing task. Obtained results demonstrated that the proposed control strategy is effective for performing complex tasks with a supernumerary robotic finger, and that practice improves users' control ability

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE-/-Mice via Nanoformulated Lipid-Methotrexate Conjugates

Macrophage inflammation and maturation into foam cells, following the engulfment of oxidized low-density lipoproteins (oxLDL), are major hallmarks in the onset and progression of atherosclerosis. Yet, chronic treatments with anti-inflammatory agents, such as methotrexate (MTX), failed to modulate disease progression, possibly for the limited drug bioavailability and plaque deposition. Here, MTX-lipid conjugates, based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), were integrated in the structure of spherical polymeric nanoparticles (MTX-SPNs) or intercalated in the lipid bilayer of liposomes (MTX-LIP). Although, both nanoparticles were colloidally stable with an average diameter of ∼200 nm, MTX-LIP exhibited a higher encapsulation efficiency (>70%) and slower release rate (∼50% at 10 h) compared to MTX-SPN. In primary bone marrow derived macrophages (BMDMs), MTX-LIP modulated the transcellular transport of oxLDL more efficiently than free MTX mostly by inducing a 2-fold overexpression of ABCA1 (regulating oxLDL efflux), while the effect on CD36 and SRA-1 (regulating oxLDL influx) was minimal. Furthermore, in BMDMs, MTX-LIP showed a stronger anti-inflammatory activity than free MTX, reducing the expression of IL-1β by 3-fold, IL-6 by 2-fold, and also moderately of TNF-α. In 28 days high-fat-diet-fed apoE-/- mice, MTX-LIP reduced the mean plaque area by 2-fold and the hematic amounts of RANTES by half as compared to free MTX. These results would suggest that the nanoenhanced delivery to vascular plaques of the anti-inflammatory DSPE-MTX conjugate could effectively modulate the disease progression by halting monocytes' maturation and recruitment already at the onset of atherosclerosis

The intellectual disability protein RAB39B selectively regulates GluA2 trafficking to determine synaptic AMPAR composition

RAB39B is a member of the RAB family of small GTPases that controls intracellular vesicular trafficking in a compartment-specific manner. Mutations in the RAB39B gene cause intellectual disability comorbid with autism spectrum disorder and epilepsy, but the impact of RAB39B loss of function on synaptic activity is largely unexplained. Here we show that protein interacting with C-kinase 1 (PICK1) is a downstream effector of GTP-bound RAB39B and that RAB39B-PICK1 controls trafficking from the endoplasmic reticulum to the Golgi and, hence, surface expression of GluA2, a subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). The role of AMPARs in synaptic transmission varies depending on the combination of subunits (GluA1, GluA2 and GluA3) they incorporate. RAB39B downregulation in mouse hippocampal neurons skews AMPAR composition towards non GluA2-containing Ca(2+)-permeable forms and thereby alters synaptic activity, specifically in hippocampal neurons. We posit that the resulting alteration in synaptic function underlies cognitive dysfunction in RAB39B-related disorders

Age-related cognitive and motor decline in a mouse model of CDKL5 deficiency disorder is associated with increased neuronal senescence and death

open20noThis work was supported by grants to E.C. and M.G. from Telethon (GGP19045) and from the Italian parent Association “CDKL5 insieme verso la cura”, and to M.G. from the Association “l’Albero di Greta”, from the International Foundation for CDKL5 Research (IFCR 2019), from the CDKL5 Program of Excellence - LouLou Fundation (CDKL5-17-106-01) and from the Association Française du Syndrome de Rett (ASFR 2017).CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene. Children affected by CDD display a clinical phenotype characterized by early-onset epilepsy, intellectual disability, motor impairment, and autistic-like features. Although the clinical aspects associated with CDKL5 mutations are well described in children, adults with CDD are still under-characterized. Similarly, most animal research has been carried out on young adult Cdkl5 knockout (KO) mice only. Since age represents a risk factor for the worsening of symptoms in many neurodevelopmental disorders, understanding age differences in the development of behavioral deficits is crucial in order to optimize the impact of therapeutic interventions. Here, we compared young adult Cdkl5 KO mice with middle-aged Cdkl5 KO mice, at a behavioral, neuroanatomical, and molecular level. We found an age-dependent decline in motor, cognitive, and social behaviors in Cdkl5 KO mice, as well as in breathing and sleep patterns. The behavioral decline in older Cdkl5 KO mice was not associated with a worsening of neuroanatomical alterations, such as decreased dendritic arborization or spine density, but was paralleled by decreased neuronal survival in different brain regions such as the hippocampus, cortex, and basal ganglia. Interestingly, we found increased β-galactosidase activity and DNA repair protein levels, γH2AX and XRCC5, in the brains of older Cdkl5 KO mice, which suggests that an absence of Cdkl5 accelerates neuronal senescence/death by triggering irreparable DNA damage. In summary, this work provides evidence that CDKL5 may play a fundamental role in neuronal survival during brain aging and suggests a possible worsening with age of the clinical picture in CDD patients.openGennaccaro L.; Fuchs C.; Loi M.; Pizzo R.; Alvente S.; Berteotti C.; Lupori L.; Sagona G.; Galvani G.; Gurgone A.; Raspanti A.; Medici G.; Tassinari M.; Trazzi S.; Ren E.; Rimondini R.; Pizzorusso T.; Zoccoli G.; Giustetto M.; Ciani E.Gennaccaro L.; Fuchs C.; Loi M.; Pizzo R.; Alvente S.; Berteotti C.; Lupori L.; Sagona G.; Galvani G.; Gurgone A.; Raspanti A.; Medici G.; Tassinari M.; Trazzi S.; Ren E.; Rimondini R.; Pizzorusso T.; Zoccoli G.; Giustetto M.; Ciani E