A direct kinematical derivation of the relativistic Sagnac effect for light or matter beams

The Sagnac time delay and the corresponding Sagnac phase shift, for relativistic matter and electromagnetic beams counter-propagating in a rotating interferometer, are deduced on the ground of relativistic kinematics. This purely kinematical approach allows to explain the ''universality'' of the effect, namely the fact that the Sagnac time difference does not depend on the physical nature of the interfering beams. The only prime requirement is that the counter-propagating beams have the same velocity with respect to any Einstein synchronized local co-moving inertial frame.Comment: 10 pages, 1 EPS figure, to appear in General Relativity and Gravitatio

Cladribine Tablets Mode of Action, Learning from the Pandemic: A Narrative Review

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system, characterized by chronic, inflammatory, demyelinating, and neurodegenerative processes. MS management relies on disease-modifying drugs that suppress/modulate the immune system. Cladribine tablets (CladT) have been approved by different health authorities for patients with various forms of relapsing MS. The drug has been demonstrated to deplete CD4+ and CD8+ T-cells, with a higher effect described in the former, and to decrease total CD19+, CD20+, and naive B-cell counts. COVID-19 is expected to become endemic, suggesting its potential infection risk for immuno-compromised patients, including MS patients treated with disease-modifying drugs. We report here the available data on disease-modifying drug-treated-MS patients and COVID-19 infection and vaccination, with a focus on CladT. MS patients treated with CladT are not at higher risk of developing severe COVID-19. While anti-SARS-CoV-2 vaccination is recommended in all MS patients with guidelines addressing vaccination timing according to the different disease-modifying drugs, no vaccination timing restrictions seem to be necessary for cladribine, based on its mechanism of action and available evidence. Published data suggest that CladT treatment does not impact the production of anti-SARS-CoV-2 antibodies after COVID-19 vaccination, possibly due to its relative sparing effect on naïve B-cells and the rapid B-cell reconstitution following treatment. Slightly lower specific T-cell responses are likely not impacting the risk of breakthrough COVID-19. It could be stated that cladribine’s transient effect on innate immune cells likely contributes to maintaining an adequate first line of defense against the SARS-CoV-2 virus

Synchronization Gauges and the Principles of Special Relativity

The axiomatic bases of Special Relativity Theory (SRT) are thoroughly re-examined from an operational point of view, with particular emphasis on the status of Einstein synchronization in the light of the possibility of arbitrary synchronization procedures in inertial reference frames. Once correctly and explicitly phrased, the principles of SRT allow for a wide range of `theories' that differ from the standard SRT only for the difference in the chosen synchronization procedures, but are wholly equivalent to SRT in predicting empirical facts. This results in the introduction, in the full background of SRT, of a suitable synchronization gauge. A complete hierarchy of synchronization gauges is introduced and elucidated, ranging from the useful Selleri synchronization gauge (which should lead, according to Selleri, to a multiplicity of theories alternative to SRT) to the more general Mansouri-Sexl synchronization gauge and, finally, to the even more general Anderson-Vetharaniam-Stedman's synchronization gauge. It is showed that all these gauges do not challenge the SRT, as claimed by Selleri, but simply lead to a number of formalisms which leave the geometrical structure of Minkowski spacetime unchanged. Several aspects of fundamental and applied interest related to the conventional aspect of the synchronization choice are discussed, encompassing the issue of the one-way velocity of light on inertial and rotating reference frames, the GPS's working, and the recasting of Maxwell equations in generic synchronizations. Finally, it is showed how the gauge freedom introduced in SRT can be exploited in order to give a clear explanation of the Sagnac effect for counter-propagating matter beams.Comment: 56 pages, 3 eps figures, invited paper; to appear in Foundations of Physics (Special Issue to honor Prof. Franco Selleri on his 70th birthday

Locality hypothesis and the speed of light

The locality hypothesis is generally considered necessary for the study of the kinematics of non-inertial systems in special relativity. In this paper we discuss this hypothesis, showing the necessity of an improvement, in order to get a more clear understanding of the various concepts involved, like coordinate velocity and standard velocity of light. Concrete examples are shown, where these concepts are discussed.Comment: 23 page

Reference frames and rigid motions in relativity: Applications

The concept of rigid reference frame and of constricted spatial metric, given in the previous work [\emph{Class. Quantum Grav.} {\bf 21}, 3067,(2004)] are here applied to some specific space-times: In particular, the rigid rotating disc with constant angular velocity in Minkowski space-time is analyzed, a new approach to the Ehrenfest paradox is given as well as a new explanation of the Sagnac effect. Finally the anisotropy of the speed of light and its measurable consequences in a reference frame co-moving with the Earth are discussed.Comment: 13 pages, 1 figur

The Sagnac Phase Shift suggested by the Aharonov-Bohm effect for relativistic matter beams

The phase shift due to the Sagnac Effect, for relativistic matter beams counter-propagating in a rotating interferometer, is deduced on the bases of a a formal analogy with the the Aharonov-Bohm effect. A procedure outlined by Sakurai, in which non relativistic quantum mechanics and newtonian physics appear together with some intrinsically relativistic elements, is generalized to a fully relativistic context, using the Cattaneo's splitting technique. This approach leads to an exact derivation, in a self-consistently relativistic way, of the Sagnac effect. Sakurai's result is recovered in the first order approximation.Comment: 18 pages, LaTeX, 2 EPS figures. To appear in General Relativity and Gravitatio

S. aureus and IgE-mediated diseases: pilot or copilot? A narrative review

Introduction: S. aureus is a major opportunistic pathogen that has been implicated in the pathogenesis of several chronic inflammatory diseases including bronchial asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), chronic spontaneous urticaria (CSU), and atopic dermatitis. S. aureus can induce the production of both polyclonal and specific IgE that can elicit an inflammatory cascade. Areas covered: The link between the sensitization to S. aureus enterotoxins and the severity of several chronic inflammatory diseases is reviewed in detail, as well as its therapeutic implications. Expert opinion: An anti-IgE strategy to inhibit S. aureus enterotoxins would be a valid approach to treat several endotypes of severe asthma, CRSwNP and CSU in which IgE against S. aureus enterotoxins should represent, not only a marker of severity of the diseases but also a target of a treatment

The down-regulation of clusterin expression enhances the αsynuclein aggregation process

Parkinson’s Disease (PD) is a progressive neurodegenerative disease characterized by the presence of proteinaceous aggregates of αSynuclein (αSyn) in the dopaminergic neurons. Chaperones are key components of the proteostasis network that are able to counteract αSyn’s aggregation, as well as its toxic effects. Clusterin (CLU), a molecular chaperone, was consistently found to interfere with Aβ aggregation in Alzheimer’s Disease (AD). However, its role in PD pathogenesis has yet to be extensively investigated. In this study, we assessed the involvement of CLU in the αSyn aggregation process by using SH-SY5Y cells stably overexpressing αSyn (SH-Syn). First, we showed that αSyn overexpression caused a strong increase in CLU expression without affecting levels of Hsp27, Hsp70, and Hsp90, which are the chaperones widely recognized to counteract αSyn burden. Then, we demonstrated that αSyn aggregation, induced by proteasome inhibition, determines a strong increase of CLU in insoluble aggregates. Remarkably, we revealed that CLU down-regulation results in an increase of αSyn aggregates in SH-Syn without significantly affecting cell viability and the Unfolded Protein Response (UPR). Furthermore, we demonstrated the direct molecular interaction between CLU and αSyn via a co-immunoprecipitation (co-IP) assay. All together, these findings provide incontrovertible evidence that CLU is an important player in the response orchestrated by the cell to cope with αSyn burden