Serre's "formule de masse" in prime degree

For a local field F with finite residue field of characteristic p, we describe completely the structure of the filtered F_p[G]-module K^*/K^*p in characteristic 0 and $K^+/\wp(K^+) in characteristic p, where K=F(\root{p-1}\of F^*) and G=\Gal(K|F). As an application, we give an elementary proof of Serre's mass formula in degree p. We also determine the compositum C of all degree p separable extensions with solvable galoisian closure over an arbitrary base field, and show that C is K(\root p\of K^*) or K(\wp^{-1}(K)) respectively, in the case of the local field F. Our method allows us to compute the contribution of each character G\to\F_p^* to the degree p mass formula, and, for any given group \Gamma, the contribution of those degree p separable extensions of F whose galoisian closure has group \Gamma.Comment: 36 pages; most of the new material has been moved to the new Section

L-Idose: an attractive substrate alternative to d-glucose for measuring aldose reductase activity

Although glucose is one of the most important physio-pathological substrates of aldose reductase, it is not an easy molecule for in vitro investigation into the enzyme. In many cases alternative aldoses have been used for kinetic characterization and inhibition studies. However these molecules do not completely match the structural features of glucose, thus possibly leading to results that are not fully applicable to glucose. We show how aldose reductase is able to act efficiently on L-idose, the C-5 epimer of D-glucose. This is verified using both the bovine lens and the human recombinant enzymes. While the kcat values obtained are essentially identical to those measured for D-glucose, a significant decrease in KM was observed. This can be due to the significantly higher level of the free aldehyde form present in L-idose compared to D-glucose. We believe that L-idose is the best alternative to D-glucose in studies on aldose reductase

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

Comparison of drugs for active eosinophilic oesophagitis: systematic review and network meta-analysis

Background There is currently no recommendation regarding preferred drugs for active eosinophilic oesophagitis (EoE) because their relative efficacy is unclear. We conducted an up-to-date network meta-analysis to compare proton pump inhibitors, off-label and EoE-specific topical steroids, and biologics in EoE. Methods We searched MEDLINE, Embase, Embase Classic and the Cochrane Central Register of Controlled Trials from inception to June 2023. We included randomised controlled trials (RCTs) comparing efficacy of all drugs versus each other, or placebo, in adults and adolescents with active EoE. Results were reported as pooled relative risks with 95% CIs to summarise effect of each comparison tested, with drugs ranked according to P score Results Seventeen RCTs were eligible for systematic review. Of these, 15 studies containing 1813 subjects with EoE reported extractable data for the network meta-analysis. For histological remission defined as ≤6 eosinophils/high-power field (HPF), lirentelimab 1 mg/kg monthly ranked first. For histological remission defined as ≤15 eosinophils/HPF, budesonide orally disintegrating tablet (BOT) 1 mg two times per day ranked first. For failure to achieve symptom improvement, BOT 1 mg two times per day and budesonide oral suspension (BOS) 2 mg two times per day were significantly more efficacious than placebo. For failure to achieve endoscopic improvement based on the EoE Endoscopic Reference Score, BOT 1 mg two times per day and BOS 1 mg two times per day or 2 mg two times per day were significantly more efficacious than placebo. Conclusions Although this network meta-analysis supports the efficacy of most available drugs over placebo for EoE treatment, significant heterogeneity in eligibility criteria and outcome measures among available trials hampers the establishment of a solid therapeutic hierarchy

Study of a Nonlocal Density scheme for electronic--structure calculations

An exchange-correlation energy functional beyond the local density approximation, based on the exchange-correlation kernel of the homogeneous electron gas and originally introduced by Kohn and Sham, is considered for electronic structure calculations of semiconductors and atoms. Calculations are carried out for diamond, silicon, silicon carbide and gallium arsenide. The lattice constants and gaps show a small improvement with respect to the LDA results. However, the corresponding corrections to the total energy of the isolated atoms are not large enough to yield a substantial improvement for the cohesive energy of solids, which remains hence overestimated as in the LDA.Comment: 4 postscript figure

Calculated optical properties of Si, Ge, and GaAs under hydrostatic pressure

The macroscopic dielectric function in the random-phase-approximation without local field effect has been implemented using the local density approximation with an all electron, full-potential linear muffin-tin orbital basis-set. This method is used to investigate the optical properties of the semiconductors Si, Ge, and GaAs under hydrostatic pressure. The pressure dependence of the effective dielectric function is compared to the experimental data of Go\~ni and coworkers, and an excellent agreement is found when the so called ``scissors-operator'' shift (SOS) is used to account for the correct band gap at $\Gamma$. The effect of the $3d$ semi-core states in the interband transitions hardly changes the static dielectric function, $\epsilon_\infty$; however, their contribution to the intensity of absorption for higher photon energies is substantial. The spin-orbit coupling has a significant effect on $\epsilon_\infty$ of Ge and GaAs, but not of Si. The $E_1$ peak in the dynamical dielectric function is strongly underestimated for Si, but only slightly for Ge and GaAs, suggesting that excitonic effects might be important only for Si.Comment: 29 RevTex pages and 12 figs; in press in Physical Review

Risk factors for bronchiolitis hospitalization during the first year of life in a multicenter Italian birth cohort

BACKGROUND: Respiratory Syncytial Virus (RSV) is one of the main causes of respiratory infections during the first year of life. Very premature infants may contract more severe diseases and 'late preterm infants' may also be more susceptible to the infection. The aim of this study is to evaluate the risk factors for hospitalization during the first year of life in children born at different gestational ages in Italy. METHODS: A cohort of 33-34 weeks gestational age (wGA) newborns matched by sex and age with two cohort of newborns born at 35-37 wGA and > 37 wGA were enrolled in this study for a three-year period (2009-2012). Hospitalization for bronchiolitis (ICD-9 code 466.1) during the first year of life was assessed through phone interview at the end of the RSV season (November-March) and at the completion of the first year of life. RESULTS: The study enrolled 2314 newborns, of which 2210 (95.5 %) had a one year follow-up and were included in the analysis; 120 (5.4 %) were hospitalized during the first year of life for bronchiolitis. Children born at 33-34 wGA had a higher hospitalization rate compared to the two other groups. The multivariate analysis carried out on the entire population associated the following factors with higher rates for bronchiolitis hospitalization: male gender; prenatal treatment with corticosteroids; prenatal exposure to maternal smoking; singleton delivery; respiratory diseases in neonatal period; surfactant therapy; lack of breastfeeding; siblings <10 years old; living in crowded conditions and/or in unhealthy households and early exposure to the epidemic RSV season. When analysis was restricted to preterms born at 33-34 wGA the following variables were associated to higher rates of bronchiolitis hospitalization: male gender, prenatal exposure to maternal smoking, neonatal surfactant therapy, having siblings <10 years old, living in crowded conditions and being exposed to epidemic season during the first three months of life. CONCLUSION: Our study identified some prenatal, perinatal and postnatal conditions proving to be relevant and independent risk factors for hospitalization for bronchiolitis during the first year of life. The combination of these factors may lead to consider palivizumab prophylaxis in Italy

EBP1 and DRBP76/NF90 binding proteins are included in the major histocompatibility complex class II RNA operon

Major histocompatibility complex class II mRNAs encode heterodimeric proteins involved in the presentation of exogenous antigens during an immune response. Their 3′UTRs bind a protein complex in which we identified two factors: EBP1, an ErbB3 receptor-binding protein and DRBP76, a double-stranded RNA binding nuclear protein, also known as nuclear factor 90 (NF90). Both are well-characterized regulatory factors of several mRNA molecules processing. Using either EBP1 or DRBP76/NF90-specific knockdown experiments, we established that the two proteins play a role in regulating the expression of HLA-DRA, HLA-DRB1 and HLA-DQA1 mRNAs levels. Our study represents the first indication of the existence of a functional unit that includes different transcripts involved in the adaptive immune response. We propose that the concept of ‘RNA operon’ may be suitable for our system in which MHCII mRNAs are modulated via interaction of their 3′UTR with same proteins

Search for anomalies in the neutrino sector with muon spectrometers and large LArTPC imaging detectors at CERN

A new experiment with an intense ~2 GeV neutrino beam at CERN SPS is proposed in order to definitely clarify the possible existence of additional neutrino states, as pointed out by neutrino calibration source experiments, reactor and accelerator experiments and measure the corresponding oscillation parameters. The experiment is based on two identical LAr-TPCs complemented by magnetized spectrometers detecting electron and muon neutrino events at Far and Near positions, 1600 m and 300 m from the proton target, respectively. The ICARUS T600 detector, the largest LAr-TPC ever built with a size of about 600 ton of imaging mass, now running in the LNGS underground laboratory, will be moved at the CERN Far position. An additional 1/4 of the T600 detector (T150) will be constructed and located in the Near position. Two large area spectrometers will be placed downstream of the two LAr-TPC detectors to perform charge identification and muon momentum measurements from sub-GeV to several GeV energy range, greatly complementing the physics capabilities. This experiment will offer remarkable discovery potentialities, collecting a very large number of unbiased events both in the neutrino and antineutrino channels, largely adequate to definitely settle the origin of the observed neutrino-related anomalies.Comment: Contribution to the European Strategy for Particle Physics - Open Symposium Preparatory Group, Kracow 10-12 September 201