The Automatic Control Telelab: a remote control engineering laboratory

Describes the realization of a remote laboratory of automatic control developed at the University of Siena. The Automatic Control Telelab (ACT) allows the on-line interaction between remote users and a set of remote physical processes through the Internet. The key feature of this project is the user-defined controller facility. The remote user can design his/her own controller through the well-known Simulink environment. The overall architecture of the Automatic Control Telelaboratory has been designed with the goal of simplifying the upgrading procedure and the procedures to add new experiments

Optimal Management of Energy Communities Hosting a Fleet of Electric Vehicles

In this paper, we study the problem of managing an energy community hosting a fleet of electric vehicles for rent. On the day-ahead, service requests of electric vehicles are submitted to the community. Then, the optimal request-to-vehicle assignment has to be found, as well as the optimal charging schedule of vehicle batteries. A suitable model is presented and included in an existing energy community architecture. The overall community management problem is formulated as a bilevel model, featuring two nested optimization problems. The optimal request-to-vehicle assignment requires the solution of a mixed-integer linear program. To reduce the computational complexity, a heuristic solution to the assignment problem is presented. Numerical results show that the participation in the community grants a remarkable reduction of the electric vehicle charging cost. The adoption of the heuristic assignment solution provides a dramatic reduction of the computation time required to solve the bilevel model. At the same time, the level of suboptimality introduced appears to be negligible, being less than 1% in most of the considered cases

A severe case of neuroleukemiosis caused by B cell chronic lymphocytic leukemia, presenting as mononeuritis multiplex.

To report an exceptional case of nerve infiltration by an otherwise benign chronic B cell leukemia, inducing severe mononeuritis multiplex. The patient underwent extensive evaluation, including nerve conduction study and myography, brain and plexus MRI, and nerve biopsy. The clinical and electrophysiological diagnosis was a mononeuritis multiplex with severe motor and sensory involvement; only the nerve biopsy allowed definite diagnosis and introduction of chemotherapy, leading to resolution of sensory deficit and progressive motor improvement. Neuroleukemiosis caused by chronic lymphoid leukemia is an exceptional diagnosis. The presence of other possible causes like cryoglobulinemia could induce avoidance of nerve biopsy thus undertreating patient, since steroid treatment is not expected to be efficient on lymphocytic proliferation. Our case stretches the importance of nerve biopsy and raises neuromuscular specialist's awareness of this rare entity

Winning the Genetic Lottery: Biasing Birth Sex Ratio Results in More Grandchildren.

Population dynamics predicts that on average parents should invest equally in male and female offspring; similarly, the physiology of mammalian sex determination is supposedly stochastic, producing equal numbers of sons and daughters. However, a high quality parent can maximize fitness by biasing their birth sex ratio (SR) to the sex with the greatest potential to disproportionately outperform peers. All SR manipulation theories share a fundamental prediction: grandparents who bias birth SR should produce more grandoffspring via the favored sex. The celebrated examples of biased birth SRs in nature consistent with SR manipulation theories provide compelling circumstantial evidence. However, this prediction has never been directly tested in mammals, primarily because the complete three-generation pedigrees needed to test whether individual favored offspring produce more grandoffspring for the biasing grandparent are essentially impossible to obtain in nature. Three-generation pedigrees were constructed using 90 years of captive breeding records from 198 mammalian species. Male and female grandparents consistently biased their birth SR toward the sex that maximized second-generation success. The most strongly male-biased granddams and grandsires produced respectively 29% and 25% more grandoffspring than non-skewing conspecifics. The sons of the most male-biasing granddams were 2.7 times as fecund as those of granddams with a 50:50 bias (similar results are seen in grandsires). Daughters of the strongest female-biasing granddams were 1.2 times as fecund as those of non-biasing females (this effect is not seen in grandsires). To our knowledge, these results are the first formal test of the hypothesis that birth SR manipulation is adaptive in mammals in terms of grandchildren produced, showing that SR manipulation can explain biased birth SR in general across mammalian species. These findings also have practical implications: parental control of birth SR has the potential to accelerate genetic loss and risk of extinction within captive populations of endangered species

A severe case of neuro-Sjögren's syndrome induced by pembrolizumab.

The prevalence of connective tissue disease (CTD) induced by immune checkpoint inhibitors (CPIs) in the absence of pre-existing autoimmunity is unknown. We report the case of a melanoma patient treated for 8 months with pembrolizumab who developed a subacute ataxic sensory neuronopathy (SNN), including a right trigeminal neuropathy. Salivary gland biopsy showed inflammatory changes suggestive of Sjögren's syndrome, while brain MRI revealed enhancement of the right trigeminal ganglia. A high level of protein and pleocytosis was found in the cerebrospinal fluid, with negative cultures. Nerve conduction studies revealed the absence of sensory nerve action potentials in the upper and lower limbs and reduced motor responses in the upper limbs, fulfilling criteria for SNN. Blood tests revealed an important inflammatory syndrome, hemolytic anemia, elevation of total IgG levels and the presence of ANA autoantibodies specific to anti-SSA (52 and 60 kd). All these elements were absent before the initiation of the treatment with pembrolizumab. Initially, there was a clinical response following intravenous frontline methylprednisone, but the subacute relapse required the introduction of second-line treatment with intravenous immunoglobulins and then rituximab, which led to a quick clinical improvement. Herein, we describe the first case of a patient who developed a typical SNN as a complication of severe neuro-Sjögren's syndrome induced by pembrolizumab treatment

Conservative Treatment of Ewing’s Sarcoma of the Uterus in Young Women

Ewing sarcoma-primitive neuroectodermal tumors (ES/PNETs) constitute a family of neoplasms characterized by a continuum of neuroectodermal differentiations. ES/PNET of the uterus is rare. There are 48 cases of ES/PNET of the uterus published in the literature as far as we know. We describe a case of Ewing sarcoma of the uterus occurring in a 17-year-old woman presenting with a two-month history of pelvic pain. After surgical excision and microscopic, immunohistochemical, and electron microscopy examination, the diagnosis of Ewing sarcoma of the uterus was suggested. This report will discuss the diagnosis and surgical and clinical management of Ewing uterine sarcoma in young women, according to the available literature. In spite of the rarity of ES/PNETs, they should be taken into account in the differential diagnosis of uterine neoplasms in young women

A realistic pattern of fermion masses from a five-dimensional SO(10) model

We provide a unified description of fermion masses and mixing angles in the framework of a supersymmetric grand unified SO(10) model with anarchic Yukawa couplings of order unity. The space-time is five dimensional and the extra flat spatial dimension is compactified on the orbifold $S^1/(Z_2 \times Z_2')$, leading to Pati-Salam gauge symmetry on the boundary where Yukawa interactions are localised. The gauge symmetry breaking is completed by means of a rather economic scalar sector, avoiding the doublet-triplet splitting problem. The matter fields live in the bulk and their massless modes get exponential profiles, which naturally explain the mass hierarchy of the different fermion generations. Quarks and leptons properties are naturally reproduced by a mechanism, first proposed by Kitano and Li, that lifts the SO(10) degeneracy of bulk masses in terms of a single parameter. The model provides a realistic pattern of fermion masses and mixing angles for large values of $\tan\beta$. It favours normally ordered neutrino mass spectrum with the lightest neutrino mass below 0.01 eV and no preference for leptonic CP violating phases. The right handed neutrino mass spectrum is very hierarchical and does not allow for thermal leptogenesis. We analyse several variants of the basic framework and find that the results concerning the fermion spectrum are remarkably stable.Comment: 30 pages, 7 figures, 4 table

AAV-mediated photoreceptor transduction of the pig cone-enriched retina

Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy of retinal diseases caused by defects in the retinal pigment epithelium (RPE). In contrast, evidence of the efficacy of AAV-mediated gene transfer to retinal photoreceptors, the major site of inherited retinal diseases, is less robust. In addition, although AAV-mediated RPE transduction appears efficient, independently of the serotype used and species treated, AAV-mediated photoreceptor gene transfer has not been systematically investigated thus so far in large animal models, which also may allow identifying relevant species-specific differences in AAV-mediated retinal transduction. In the present study, we used the porcine retina, which has a high cone/rod ratio. This feature allows to properly evaluate both cone and rod photoreceptors transduction and compare the transduction characteristics of AAV2/5 and 2/8, the two most efficient AAV vector serotypes for photoreceptor targeting. Here we show that AAV2/5 and 2/8 transduces both RPE and photoreceptors. AAV2/8 infects and transduces photoreceptor more efficiently than AAV2/5, similarly to what we have observed in the murine retina. The use of the photoreceptor-specific rhodopsin promoter restricts transgene expression to porcine rods and cones, and results in photoreceptor transduction levels similar to those obtained with the ubiquitous promoters tested. Finally, immunological, toxicological and biodistribution studies support the safety of AAV subretinal administration to the large porcine retina. The data presented here on AAV-mediated transduction of the cone-enriched porcine retina may affect the development of gene-based therapies for rare and common severe photoreceptor diseases

Guillain-Barre syndrome after SARS-CoV-2 infection in an international prospective cohort study

In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barre syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12-22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not