Variational principle for the Wheeler-Feynman electrodynamics

We adapt the formally-defined Fokker action into a variational principle for the electromagnetic two-body problem. We introduce properly defined boundary conditions to construct a Poincare-invariant-action-functional of a finite orbital segment into the reals. The boundary conditions for the variational principle are an endpoint along each trajectory plus the respective segment of trajectory for the other particle inside the lightcone of each endpoint. We show that the conditions for an extremum of our functional are the mixed-type-neutral-equations with implicit state-dependent-delay of the electromagnetic-two-body problem. We put the functional on a natural Banach space and show that the functional is Frechet-differentiable. We develop a method to calculate the second variation for C2 orbital perturbations in general and in particular about circular orbits of large enough radii. We prove that our functional has a local minimum at circular orbits of large enough radii, at variance with the limiting Kepler action that has a minimum at circular orbits of arbitrary radii. Our results suggest a bifurcation at some radius below which the circular orbits become saddle-point extrema. We give a precise definition for the distributional-like integrals of the Fokker action and discuss a generalization to a Sobolev space of trajectories where the equations of motion are satisfied almost everywhere. Last, we discuss the existence of solutions for the state-dependent delay equations with slightly perturbated arcs of circle as the boundary conditions and the possibility of nontrivial solenoidal orbits

Minimizers with discontinuous velocities for the electromagnetic variational method

The electromagnetic two-body problem has \emph{neutral differential delay} equations of motion that, for generic boundary data, can have solutions with \emph{discontinuous} derivatives. If one wants to use these neutral differential delay equations with \emph{arbitrary} boundary data, solutions with discontinuous derivatives must be expected and allowed. Surprisingly, Wheeler-Feynman electrodynamics has a boundary value variational method for which minimizer trajectories with discontinuous derivatives are also expected, as we show here. The variational method defines continuous trajectories with piecewise defined velocities and accelerations, and electromagnetic fields defined \emph{by} the Euler-Lagrange equations \emph{% on} trajectory points. Here we use the piecewise defined minimizers with the Li{\'{e}}nard-Wierchert formulas to define generalized electromagnetic fields almost everywhere (but on sets of points of zero measure where the advanced/retarded velocities and/or accelerations are discontinuous). Along with this generalization we formulate the \emph{generalized absorber hypothesis} that the far fields vanish asymptotically \emph{almost everywhere%} and show that localized orbits with far fields vanishing almost everywhere \emph{must} have discontinuous velocities on sewing chains of breaking points. We give the general solution for localized orbits with vanishing far fields by solving a (linear) neutral differential delay equation for these far fields. We discuss the physics of orbits with discontinuous derivatives stressing the differences to the variational methods of classical mechanics and the existence of a spinorial four-current associated with the generalized variational electrodynamics.Comment: corrected minor typo: piecewise differentiable on closed instead of open interval

"The Social Network" and Muscular Dystrophies: The Lesson Learnt about the Niche Environment as a Target for Therapeutic Strategies

The muscle stem cells niche is essential in neuromuscular disorders. Muscle injury and myofiber death are the main triggers of muscle regeneration via satellite cell activation. However, in degenerative diseases such as muscular dystrophy, regeneration still keep elusive. In these pathologies, stem cell loss occurs over time, and missing signals limiting damaged tissue from activating the regenerative process can be envisaged. It is unclear what comes first: the lack of regeneration due to satellite cell defects, their pool exhaustion for degeneration/regeneration cycles, or the inhibitory mechanisms caused by muscle damage and fibrosis mediators. Herein, Duchenne muscular dystrophy has been taken as a paradigm, as several drugs have been tested at the preclinical and clinical levels, targeting secondary events in the complex pathogenesis derived from lack of dystrophin. We focused on the crucial roles that pro-inflammatory and pro-fibrotic cytokines play in triggering muscle necrosis after damage and stimulating satellite cell activation and self-renewal, along with growth and mechanical factors. These processes contribute to regeneration and niche maintenance. We review the main effects of drugs on regeneration biomarkers to assess whether targeting pathogenic events can help to protect niche homeostasis and enhance regeneration efficiency other than protecting newly formed fibers from further damage

Enhanced second-harmonic generation from magnetic resonance in AlGaAs nanoantennas

We designed AlGaAs-on-aluminium-oxide all-dielectric nanoantennas with magnetic dipole resonance at near-infrared wavelengths

Functional assessment of cancer therapy questionnaire for breast cancer (FACT-B+4): Italian version validation

BACKGROUND: Improvements in breast cancer diagnosis and treatment led to an increased incidence of survivors' rate. The healthcare system has to face new problems related not only to the treatment of the disease, but also to the management of the quality of life after the diagnosis. The aim of this study was to validate the Italian version of the Functional Assessment of Cancer Therapy - Breast (FACT-B+4) questionnaire and to evaluate its reliability. METHODS: The questionnaire was administered twice, with an interval of three days between each administration, to a cohort of women of the Breast Surgical Unit, PoliclincoUmberto I. Cronbach's alpha was used as a measure of the internal consistency of the Italian version. RESULTS: The Italian version of the tool was administered to 55 subjects. The Cronbach's alpha for most scores registered values >0.7, both at baseline and at the follow-up analysis, therefore the subscale showed good internal consistency. CONCLUSIONS: The Italian version of FACT-B+4 demonstrated acceptable reliability properties in the Breast Unit patients. The use of this questionnaire seemed to be effective and in line with the results derived from the English and Spanishversions. Internal consistency and validity had similar performance results

Characterization of a population of Pelodera strongyloides (Nematoda: Rhabditidae) associated with the beetle Lucanus ibericus (Coleoptera:Lucanidae) from Georgia

During a field survey for entomopathogenic nematodes in Georgia, in the territory of Borjomi-Kharagauli, a nematode population was isolated from the body of single dead beetle of Lucanus ibericus Motschulsky 1845 (Coleoptera: Lucanidae). Based on morphological characters and molecular analyses, the nematode species is identical to Pelodera strongyloides (Schneider, 1860, 1866), being the first record of this species in Georgia. Morphometrics of the Georgian population agree with the original description, and females differ from males by very few characters. The Georgian population of P. strongyloides was molecularly characterized by sequencing the D2 to D3 expansion domains of the 28S rRNA gene and two new molecular markers as the ITS and the mitochondrial COI gene. Phylogenetic analyses revealed that all P. strongyloides sequences grouped together along with all other Pelodera species

Extracellular vesicle microRNAs contribute to the osteogenic inhibition of mesenchymal stem cells in multiple myeloma

Osteolytic bone disease is the major complication associated with the progression of multiple myeloma (MM). Recently, extracellular vesicles (EVs) have emerged as mediators of MM-associated bone disease by inhibiting the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Here, we investigated a correlation between the EV-mediated osteogenic inhibition and MM vesicle content, focusing on miRNAs. By the use of a MicroRNA Card, we identified a pool of miRNAs, highly expressed in EVs, from MM cell line (MM1.S EVs), expression of which was confirmed in EVs from bone marrow (BM) plasma of patients affected by smoldering myeloma (SMM) and MM. Notably,we found that miR-129-5p, which targets different osteoblast (OBs) differentiation markers, is enriched in MM-EVs compared to SMM-EVs, thus suggesting a selective packaging correlated with pathological grade. We found that miR-129-5p can be transported to hMSCs by MM-EVs and, by the use of miRNA mimics, we investigated its role in recipient cells. Our data demonstrated that the increase of miR-129-5p levels in hMSCs under osteoblastic differentiation stimuli inhibited the expression of the transcription factor Sp1, previously described as a positive modulator of osteoblastic differentiation, and of its target the Alkaline phosphatase (ALPL), thus identifying miR-129-5p among the players of vesicle-mediated bone disease

Search for the Optical Counterpart of the Vela Pulsar X-ray Nebula

Observations of the Vela pulsar region with the Chandra X-ray observatory have revealed the fine structure of its synchrotron pulsar-wind nebula (PWN), which showed an overall similarity with the Crab PWN. However, contrary to the Crab, no firm detection of the Vela PWN in optical has been reported yet. To search for the optical counterpart of the X-ray PWN, we analyzed deep optical observations performed with different telescopes. We compared the optical images with those obtained with the Chandra ACIS to search for extended emission patterns which could be identified as counterparts of the X-ray nebula elements. Although some features are seen in the optical images, we find no correlation with the X-ray structure. Thus, we conclude that the diffuse optical emission is more likely associated with filaments in the host Vela SNR. The derived upper limits on the optical flux from the PWN are compatibile, within the uncertainties, with the values expected on the basis of the extrapolations of the X-ray data.Comment: 19 pages, 6 figures. Accepted for publication in Ap

Safety issues and harmful pharmacological interactions of nutritional supplements in Duchenne muscular dystrophy: considerations for Standard of Care and emerging virus outbreaks

At the moment, little treatment options are available for Duchenne muscular dystrophy (DMD). The absence of the dystrophin protein leads to a complex cascade of pathogenic events in myofibres, including chronic inflammation and oxidative stress as well as altered metabolism. The attention towards dietary supplements in DMD is rapidly increasing, with the aim to counteract pathology-related alteration in nutrient intake, the consequences of catabolic distress or to enhance the immunological response of patients as nowadays for the COVID-19 pandemic emergency. By definition, supplements do not exert therapeutic actions, although a great confusion may arise in daily life by the improper distinction between supplements and therapeutic compounds. For most supplements, little research has been done and little evidence is available concerning their effects in DMD as well as their preventing actions against infections. Often these are not prescribed by clinicians and patients/caregivers do not discuss the use with their clinical team. Then, little is known about the real extent of supplement use in DMD patients. It is mistakenly assumed that, since compounds are of natural origin, if a supplement is not effective, it will also do no harm. However, supplements can have serious side effects and also have harmful interactions, in terms of reducing efficacy or leading to toxicity, with other therapies. It is therefore pivotal to shed light on this unclear scenario for the sake of patients. This review discusses the supplements mostly used by DMD patients, focusing on their potential toxicity, due to a variety of mechanisms including pharmacodynamic or pharmacokinetic interactions and contaminations, as well as on reports of adverse events. This overview underlines the need for caution in uncontrolled use of dietary supplements in fragile populations such as DMD patients. A culture of appropriate use has to be implemented between clinicians and patients’ groups

rab7b controls trafficking from endosomes to the tgn

Rab7b is a recently identified member of the Rab GTPase protein family and has high similarity to Rab7. It has been reported that Rab7b is lysosome associated, that it is involved in monocytic differentiation and that it promotes lysosomal degradation of TLR4 and TLR9. Here we investigated further the localization and function of this GTPase. We found that wild-type Rab7b is lysosome associated whereas an activated, GTP-bound form of Rab7b localizes to the Golgi apparatus. In contrast to Rab7, Rab7b is not involved in EGF and EGFR degradation. Depletion of Rab7b or expression of Rab7b T22N, a Rab7b dominant-negative mutant, impairs cathepsin-D maturation and causes increased secretion of hexosaminidase. Moreover, expression of Rab7b T22N or depletion of Rab7b alters TGN46 distribution, cation-independent mannose-6-phosphate receptor (CI-MPR) trafficking, and causes an increase in the levels of the late endosomal markers CI-MPR and cathepsin D. Vesicular stomatitis virus G protein (VSV-G) trafficking, by contrast, is normal in Rab7b-depleted or Rab7b-T22N-expressing cells. In addition, depletion of Rab7b prevents cholera toxin B-subunit from reaching the Golgi. Altogether, these data indicate that Rab7b is required for normal lysosome function, and, in particular, that it is an essential factor for retrograde transport from endosomes to the trans-Golgi network (TGN)