Interplay of spin waves and vortices in the two-dimensional XY model at small vortex-core energy

The Berezinskii-Kosterlitz-Thouless (BKT) mechanism describes universal vortex unbinding in many two-dimensional systems, including the paradigmatic XY model. However, most of these systems present a complex interplay between excitations at different length scales that complicates theoretical calculations of nonuniversal thermodynamic quantities. These difficulties may be overcome by suitably modifying the initial conditions of the BKT flow equations to account for noncritical fluctuations at small length scales. In this work, we perform a systematic study of the validity and limits of this two-step approach by constructing optimised initial conditions for the BKT flow. We find that the two-step approach can accurately reproduce the results of Monte Carlo simulations of the traditional XY model. To systematically study the interplay between vortices and spin-wave excitations, we introduce a modified XY model with increased vortex fugacity. We present large-scale Monte Carlo simulations of the spin stiffness and vortex density for this modified XY model and show that even at large vortex fugacity, vortex unbinding is accurately described by the nonperturbative functional renormalization group

Ingress of Coolant Event simulation with TRACE code with accuracy evaluation and coupled DAKOTA Uncertainty Analysis

Among the Postulated Initiating Events in nuclear fusion plants, the Ingress of Coolant Event (ICE) in the Plasma Chamber is one of the main safety issues. In the present paper, the best estimate thermal-hydraulic system code TRACE, developed by USNRC, has been adopted to study the ICE, and it has been qualified based on experimental results obtained in the Integrated ICE facility at JAERI. A nodalization has been developed in the SNAP environment/architecture, using also the TRACE 3D Vessel component where multidimensional phenomena could occur. The accuracy of the code calculation has been assessed both from a qualitative and quantitative point of view. In addition, an Uncertainty Analysis (UA), with the probabilistic method to propagate the input uncertainties, has been performed to characterize the dispersion of the results. The analysis has been carried out with the DAKOTA toolkit coupled with TRACE code in the SNAP environment/architecture. Results show the adequacy of the 3D nodalization and the capability of the code to follow the transient evolution also at a very low pressure. Response correlations have been computed to characterize the correlation between the selected uncertain input parameters and the Plasma Chamber pressure

Toward Open Integrated Access and Backhaul with O-RAN

Millimeter wave (mmWave) communications has been recently standardized for use in the fifth generation (5G) of cellular networks, fulfilling the promise of multi-gigabit mobile throughput of current and future mobile radio network generations. In this context, the network densification required to overcome the difficult mmWave propagation will result in increased deployment costs. Integrated Access and Backhaul (IAB) has been proposed as an effective mean of reducing densification costs by deploying a wireless mesh network of base stations, where backhaul and access transmissions share the same radio technology. However, IAB requires sophisticated control mechanisms to operate efficiently and address the increased complexity. The Open Radio Access Network (RAN) paradigm represents the ideal enabler of RAN intelligent control, but its current specifications are not compatible with IAB. In this work, we discuss the challenges of integrating IAB into the Open RAN ecosystem, detailing the required architectural extensions that will enable dynamic control of 5G IAB networks. We implement the proposed integrated architecture into the first publiclyavailable Open-RAN-enabled experimental framework, which allows prototyping and testing Open-RAN-based solutions over end-to-end 5G IAB networks. Finally, we validate the framework with both ideal and realistic deployment scenarios exploiting the large-scale testing capabilities of publicly available experimental platforms

Mental retardation in mucopolysaccharidoses correlates with high molecular weight urinary heparan sulphate derived glucosamine

none11noMucopolysaccharidoses (MPS) are characterized by mental retardation constantly present in the severe forms of Hurler (MPS I), Hunter (MPS II) and Sanfilippo (MPS III) diseases. On the contrary, mental retardation is absent in Morquio (MPS IV) and Maroteaux-Lamy (MPS VI) diseases and absent or only minimal in the attenuated forms of MPS I, II and III. Considering that MPS patients affected by mental disease accumulate heparan sulfate (HS) due to specific enzymatic defects, we hypothesized a possible correlation between urinary HS-derived glucosamine (GlcN) accumulated in tissues and excreted in biological fluids and mental retardation. 83 healthy subjects were found to excrete HS in the form of fragments due to the activity of catabolic enzymes that are absent or impaired in MPS patients. On the contrary, urinary HS in 44 patients was observed to be composed of high molecular weight polymer and fragments of various lengths depending on MPS types. On this basis we correlated mental retardation with GlcN belonging to high and low molecular weight HS. We demonstrate a positive relationship between the accumulation of high molecular weight HS and mental retardation in MPS severe compared to attenuated forms. This is also supported by the consideration that accumulation of other GAGs different from HS, as in MPS IV and MPS VI, and low molecular weight HS fragments do not impact on central nervous system disease.Coppa, G.V; Gabrielli, O.; Zampini, L.; Maccari, F.; Mantovani, V.; Galeazzi, T.; Santoro, L.; Padella, L.; Marchesiello, R.L.; Galeotti, F.; Volpi, N.Coppa, Giovanni Valentino; Gabrielli, Orazio; Zampini, Lucia; Maccari, F.; Mantovani, V.; Galeazzi, Tiziana; Santoro, Lucia; Padella, Lucia; Marchesiello, R. L.; Galeotti, F.; Volpi, N

In search for multi-target ligands as potential agents for diabetes mellitus and its complications—a structure-activity relationship study on inhibitors of aldose reductase and protein tyrosine phosphatase 1b

Diabetes mellitus (DM) is a complex disease which currently affects more than 460 million people and is one of the leading cause of death worldwide. Its development implies numerous metabolic dysfunctions and the onset of hyperglycaemia-induced chronic complications. Multiple ligands can be rationally designed for the treatment of multifactorial diseases, such as DM, with the precise aim of simultaneously controlling multiple pathogenic mechanisms related to the disease and providing a more effective and safer therapeutic treatment compared to combinations of selective drugs. Starting from our previous findings that highlighted the possibility to target both aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP1B), two enzymes strictly implicated in the development of DM and its complications, we synthesised 3-(5-arylidene-4-oxothiazolidin-3-yl)propanoic acids and analogous 2-butenoic acid derivatives, with the aim of balancing the effectiveness of dual AR/PTP1B inhibitors which we had identified as designed multiple ligands (DMLs). Out of the tested compounds, 4f exhibited well-balanced AR/PTP1B inhibitory effects at low micromolar concentrations, along with interesting insulin-sensitizing activity in murine C2C12 cell cultures. The SARs here highlighted along with their rationalization by in silico docking experiments into both target enzymes provide further insights into this class of inhibitors for their development as potential DML antidiabetic candidates

Approccio globale alle mucopolisaccaridosi: applicazione di metodi altamente specifici per la diagnosi neonatale: risultati preliminari su campione di urina

Scopo dello studio Le Mucopolisaccaridosi (MPS) sono patologie multisistemiche ed invalidanti ad alto grado di mortalit\ue0 e morbidit\ue0, spesso diagnosticate in ritardo quando si sono gi\ue0 verificati danni irreversibili agli organi. Una diagnosi precoce ed accurata risulta quindi importante per la consulenza genetica alla famiglia e per ottimizzare le terapie che risultano pi\uf9 efficaci se attuate sin dalle prime settimane di vita del neonato, anche in assenza di un\u2019evidente sintomatologia. Obiettivo dello studio \ue8 quello di individuare marker affidabili, in grado di identificare diverse forme di MPS in una singola analisi. Campioni di sangue su spot (DBS) saranno analizzati attraverso una tecnica HPLC per la determinazione quantitativa e qualitativa dei disaccaridi che compongono i GAG, dopo il trattamento con enzimi specifici. Come controllo, i campioni di urine degli stessi soggetti verranno analizzati attraverso metodi standard: il saggio al colorante DMB e l\u2019elettroforesi su acetato di cellulosa. Vengono qui presentati i risultati della valutazione quantitativa e qualitativa dei GAG urinari. Metodi utilizzati Sono stati raccolti campioni di urina da 450 neonati sani a termine, dal 3\ub0 al 5\ub0 giorno di vita. La determinazione quantitativa dei GAG urinari totali \ue8 stata condotta mediante DMB test ed elettroforesi su acetato di cellulosa per identificare il pattern dei GAG escreti. Risultati La valutazione quantitativa dei GAG totali, con un valore medio di 227 \ub1 91 \ub5g GAG/mg di creatinina, ha messo in evidenza quantit\ue0 di GAG superiori (>50%) rispetto al valore medio di riferimento (114 \ub1 57 \ub5g GAG/mg di creatinina nella fascia di et\ue0 0-1 anno). Tutti i soggetti finora analizzati hanno mostrato all\u2019elettroforesi un pattern qualitativo normale rispetto ai patologici utilizzati come controllo. Conclusioni Lo studio si inserisce nell\u2019ambito di un progetto multicentrico triennale e fornir\ue0 un\u2019analisi di distribuzione dei valori normali dei GAG urinari nei primi giorni di vita, una valutazione dell\u2019affidabilit\ue0 del nuovo metodo per la determinazione dei disaccaridi su DBS e una stima della sua applicabilit\ue0. Ricerca in parte finanziata con fondi Progetto PRIN 201

Plasmatic and urinary glycosaminoglycans characterization in mucopolysaccharidosis II Patient treated with enzyme-replacement therapy with Idursulfase

We report the structural characterization of plasmatic and urinary GAGs in a Patient affected by MPS II (Hunter syndrome) before and during the first ten months of enzyme-replacement therapy (ERT). Plasmatic GAGs before ERT were rich in pathological DS consisting of iduronic acid (IdoA) and composed of ~90% \uf044Di4s and trace amounts of disulfated disaccharides. DS was also characterized as the main (~90%) urinary GAG mainly composed of ~90% \uf044Di4s with minor percentages of monosulfated and disulfated disaccharides, in particular \u394Di2,4dis. After 300 days of ERT, plasmatic DS strongly decreased but ~14% of IdoA-rich \uf044Di4s was still detected. Similarly, urinary galactosaminoglycans were mainly composed of 78% \uf044Di4s, ~11% \uf044Di6s and ~4% \uf044Di0s with the persistence of \u394Di2,4dis (~4%). About 40% of IdoA-formed \uf044Di4s were also calculated thus confirming that pathological DS is still present in excreted urinary GAGs during ERT. By considering the % of IdoA, we observed rather similar kinetics of excretion in fluids from the beginning of the treatment. Immediately after the first enzyme infusion, a large amount of abnormal DS is removed from tissues reaching the blood compartment and eliminated via the urine, and this process lasts for about two weeks. After this, the percentage of IdoA-rich material present in biological fluids remains fairly constant over the following nine months of treatment. To date, these are the first data regarding plasmatic and urinary kinetics directly measured on products released by the activity of the recombinant enzyme Idursulfase, iduronate-2-sulfatase, evaluated using specific and sensitive analytical procedures

Fluoxetine during Development Reverses the Effects of Prenatal Stress on Depressive-Like Behavior and Hippocampal Neurogenesis in Adolescence

Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity

A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS.

The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune lymphoproliferative syndrome to identify a population of FAS-controlled TCRαβ+ T cells. They include CD4+, CD8+, and double-negative T cells and can be defined by a CD38+CD45RA+T-BET- expression pattern. These unconventional T cells are present in healthy individuals, are generated before birth, are enriched in lymphoid tissue, and do not expand during acute viral infection. They are characterized by a unique molecular signature that is unambiguously different from other known T cell differentiation subsets and independent of CD4 or CD8 expression. Functionally, FAS-controlled T cells represent highly proliferative, noncytotoxic T cells with an IL-10 cytokine bias. Mechanistically, regulation of this physiological population is mediated by FAS and CTLA4 signaling, and its survival is enhanced by mTOR and STAT3 signals. Genetic alterations in these pathways result in expansion of FAS-controlled T cells, which can cause significant lymphoproliferative disease