Selection of the cross-section design for the LHC main dipole

With the aim of selecting the most suitable design for the series production of the LHC main dipoles, several possible configurations were analysed with respect to admissible component tolerances and structural stability, field level, field quality, number and weight of parts. Two alternatives designs, featuring common collars made out of aluminium alloy and austenitic steel, respectively, were finally compared in detail, Although both designs are almost equivalent at nominal conditions, the austenitic steel collar structure turned out to be far less sensitive to components dimensional variations. This paper reports the main results of the above evaluations, which lead to the choice of austenitic steel collars for the LHC main dipoles     

INSIDIA 2.0 High-Throughput Analysis of 3D Cancer Models: Multiparametric Quantification of Graphene Quantum Dots Photothermal Therapy for Glioblastoma and Pancreatic Cancer

Cancer spheroids are in vitro 3D models that became crucial in nanomaterials science thanks to the possibility of performing high throughput screening of nanoparticles and combined nanoparticle-drug therapies on in vitro models. However, most of the current spheroid analysis methods involve manual steps. This is a time-consuming process and is extremely liable to the variability of individual operators. For this reason, rapid, user-friendly, ready-to-use, high-throughput image analysis software is necessary. In this work, we report the INSIDIA 2.0 macro, which offers researchers high-throughput and high content quantitative analysis of in vitro 3D cancer cell spheroids and allows advanced parametrization of the expanding and invading cancer cellular mass. INSIDIA has been implemented to provide in-depth morphologic analysis and has been used for the analysis of the effect of graphene quantum dots photothermal therapy on glioblastoma (U87) and pancreatic cancer (PANC-1) spheroids. Thanks to INSIDIA 2.0 analysis, two types of effects have been observed: In U87 spheroids, death is accompanied by a decrease in area of the entire spheroid, with a decrease in entropy due to the generation of a high uniform density spheroid core. On the other hand, PANC-1 spheroids’ death caused by nanoparticle photothermal disruption is accompanied with an overall increase in area and entropy due to the progressive loss of integrity and increase in variability of spheroid texture. We have summarized these effects in a quantitative parameter of spheroid disruption demonstrating that INSIDIA 2.0 multiparametric analysis can be used to quantify cell death in a non-invasive, fast, and high-throughput fashion.     

Cyclopenta[d]pyrimidines and dihydropyrrolo[2,3-d]pyrimidines as potent and selective corticotropin-releasing factor 1 receptor antagonists

Two new classes of potent and selective CRF(1) receptor antagonists are presented. Exploration of general templates 3 and 4 through modifications of the top amine and bottom phenyl substituents led to optimization of the in vitro affinity and pharmacokinetic profiles. The typical alkyl chains present in the top region of CRF(1) antagonists were replaced by substituted heteroaryl moieties, leading to a dramatic improvement of the metabolic stability. This improvement was apparent when the compounds were dosed in vivo: several compounds exhibited low plasma clearance, good oral bioavailability, and high brain penetration. As a consequence of their outstanding pharmacokinetic profiles, these CRF(1) antagonists, as exemplified by compound 4 fi (4-(4-bromo-3-methyl-1H-pyrazol-1-yl)-7-(2,4-dichlorophenyl)-2-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine), produced a dose-dependent "anxiolytic-like" effect when administered orally, decreasing the vocalization of rat pups.     

Potential isotopic and chemical markers for characterising organic fruits

Several isotopic (¹³C/¹²C, ¹⁵N/¹⁴N, ¹⁸O/¹⁶O, ²H/¹H, ³⁴S/³²S) and chemical–physical parameters (pH, fruit weight, juice yield, titratable acidity, total soluble solids, skin resistance, flesh firmness, colorimetric characteristics, weight loss after harvesting, antioxidant activity, earliness index, total nitrogen, ascorbic acid, synephrine, anthocyanins and polyphenols, citric acid, malic acid, sucrose, glucose and fructose content) were investigated as potential markers of organically cultivated oranges, clementines, strawberries and peaches produced in Italy between 2006 and 2008, in experimental fields and in certified farms. The ratio ¹⁵N/¹⁴N, ascorbic acid and total soluble solids were shown to be the most significant variables for distinguishing between organically and conventionally cultivated fruits. It was not possible to define general threshold limits typical of organic fruits because these parameters are influenced also by fruit specie, cultivar, year and site of production. Combining isotopic and chemical markers a good discrimination between organic and conventional fruits of different species was achieved.     

Direct Laser Metal Deposition of AISI H13 Cladding on Copper–Beryllium Alloy Substrate Through a Stainless-Steel Buffer Layer Strategy

AISI H13 cladding is deposited on the copper–beryllium (CuBe) alloy substrate by direct laser metal deposition via a buffer layer strategy. The SS316L austenite stainless steel is used as the buffer material attempting to reduce the risk of cracking. Single- and multi-layer samples are deposited, including single-layer SS316L, 1-layer SS316L + 1-layer H13, 2-layers SS316L + 1-layer H13, and 1-layer SS316L + 4-layers H13. The defect-free single-layer SS316L cladding is successfully deposited after the parameter pre-optimization. Two types of defects including porosity and cracking are observed in all multi-layer systems. The cladding microhardness of the 2-layer system is rather low (400HV). A 50% increase in the cladding microhardness is observed when depositing on the five-layer system. The five-layer system shows a better load-bearing capability (LBC) compared with the CuBe substrate in the low loading range. As load increases above 10 kN, the five-layer cladding system shows the worse LBC compared to CuBe due to the low strength of the heat-affected zone. A 2.7% cladding to substrate thickness ratio allows keeping more than 80% of the original thermal conductivity of the CuBe substrate.     

Multielement stable isotope ratios (H,C, N,S) of honey from different European regions

The aim of this study as a part of the food traceability project “TRACE” funded by the EU was to investigate if honeys produced in regions with different climatic and geological characteristics could be discriminated on the basis of the isotopic data. The hydrogen, carbon, nitrogen and sulphur stable isotope ratios of 516 authentic honeys from 20 European regions are presented and discussed. As honey contains only small quantities of nitrogen and sulphur, the honey protein was precipitated in order to obtain measurable amounts of these elements. The mean hydrogen isotopic ratios of the honey protein were found to be significantly correlated with the mean hydrogen isotopic ratios of precipitation and groundwater in the production regions. Carbon isotopic ratios were influenced by climate. The sulphur stable isotope composition is clearly influenced by geographical location (sea spray effect) and surface geology of the production regions. The results show that the stable isotope ratios of the four bio-elements carbon, nitrogen, hydrogen and sulphur in honey protein can be applied to verify the origin of honey. Carbon and sulphur were identified by canonical discriminant analysis as providing the maximum discrimination between honey samples. For seven regions the percentage of correct classified samples is greater than 70%. It was concluded that the methodology in its current state can be used to provide reliable origin information.     

Causes and risks of hyperlipidemia during dialysis and after renal transplantation

The most widely studied hyperlipidemies in patients affected by renal insufficiency or subsequent to kidney transplant present phenotype IIa, IIb or IV. The lipidic alteration most frequently observed in chronic renal insufficiency and/or dialytic treatment is represented by hypertrigliceridemia as a result of: 1) altered VLDL metabolism; 2) reduced activity of lecithin cholesterol acyltransferase (LCAT); 3) decrease in Apo-A1 and HDL3. Furthermore, marked anomalies in lipoprotein Lp (a) have been reported in hemodialysis. In patients undergoing peritoneal dialysis, hyperlipidemia arises from both an anomalous retrograde absorption of glucose and protein dispersion. Following kidney transplant the most frequent hyperlipidemia is hypercholesterolemia, consequent to immunosuppressive treatment (mainly steroids and cyclosporin). The documented significant increase of cardiovascular risk in the presence of hyperlipidemia points to the need for a clearer etiopathogenic definition of this anomaly, as well as the necessity to find an efficacious pharmacological treatment.     

Imipramine in alopecia areata. A double-blind, placebo-controlled study

Alopecia areata (AA) is a dermatologic disease whose onset is significantly associated to life events. Its course may often be characterized by high levels of anxiety and depression. These observations suggested a rationale for using an antidepressant in AA. Thirteen patients were enrolled in a double-blind, placebo-controlled study of efficacy of imipramine in alopecia. After six months clinically significant hair regrowth occurred in 5 of the 7 patients on imipramine, whereas no response was observed in the placebo group. An improvement in psychic symptomatology was present in both groups. Our preliminary results indicate the potential efficacy of imipramine in patients with AA, not acting directly through a reduction of anxiety or depression.