Istituto Nazionale di Fisica Nucleare, Laboratori Acceleratori e Superconduttività Applicata

We present the first observation of self-amplified spontaneous emission (SASE) in a free-electron laser (FEL) in the vacuum ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approximately 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width, and intensity fluctuations, are all consistent with the present models for SASE FELs.

Radioactive emissions into the atmosphere from the damaged reactors of the Fukushima Dai-ichi nuclear power plant (NPP) started on March 12th, 2011. Among the various radionuclides released, iodine-131 ((131)I) and cesium isotopes ((137)Cs and (134)Cs) were transported across the Pacific toward the North American continent and reached Europe despite dispersion and washout along the route of the contaminated air masses. In Europe, the first signs of the releases were detected 7 days later while the first peak of activity level was observed between March 28th and March 30th. Time variations over a 20-day period and spatial variations across more than 150 sampling locations in Europe made it possible to characterize the contaminated air masses. After the Chernobyl accident, only a few measurements of the gaseous (131)I fraction were conducted compared to the number of measurements for the particulate fraction. Several studies had already pointed out the importance of the gaseous (131)I and the large underestimation of the total (131)I airborne activity level, and subsequent calculations of inhalation dose, if neglected. The measurements made across Europe following the releases from the Fukushima NPP reactors have provided a significant amount of new data on the ratio of the gaseous (131)I fraction to total (131)I, both on a spatial scale and its temporal variation. It can be pointed out that during the Fukushima event, the (134)Cs to (137)Cs ratio proved to be different from that observed after the Chernobyl accident. The data set provided in this paper is the most comprehensive survey of the main relevant airborne radionuclides from the Fukushima reactors, measured across Europe. A rough estimate of the total (131)I inventory that has passed over Europe during this period was <1% of the released amount. According to the measurements, airborne activity levels remain of no concern for public health in Europe.

Experimental results are presented from vacuum-ultraviolet free-electron laser (FEL) operating in the self-amplified spontaneous emission (SASE) mode. The generation of ultrashort radiation pulses became possible due to specific tailoring of the bunch charge distribution. A complete characterization of the linear and nonlinear modes of the SASE FEL operation was performed. At saturation the FEL produces ultrashort pulses (30-100 fs FWHM) with a peak radiation power in the GW level and with full transverse coherence. The wavelength was tuned in the range of 95-105 nm.

This work presents the establishment of novel bright-emission small-molecule NIR-II fluorophores for<italic>in vivo</italic>tumor imaging and NIR-II image-guided sentinel lymph node surgery.

BACKGROUND: Bronchial asthma is one of the most prevalent diseases in Arab children. Environmental pollution has been suggested to be considered causative of asthma, nasal symptoms and bronchitis in both children and adult. The objectives of this study were to evaluate the association between serum polycyclic aromatic hydrocarbons (PAHs) levels, asthma and allergic outcomes among Saudi children aged up to 15 yrs. We hypothesized that increased serum PAHs are associated with allergy, asthma, or respiratory symptoms. METHODS: A total of 195 Saudi children (98 asthma pediatric patients and 97 healthy controls) were randomly selected from the Riyadh Cohort Study for inclusion. The diagnosis of Asthma was based on established pediatric diagnosis and medications taken. RESULTS: Asthma related markers showed highly significant differences between children with and without asthma. Thus IgE, resistin and IL-4 were significantly increased (p 0.004, 0.001 and 0.003, respectively) in children with asthma compared with non-asthma control subjects. GMCSF, IFN-γ, IL-5, IL-8 and IL-10, on the other hand, were significantly decreased in children with asthma (p 0.003, 0.03, 0.001, 0.004 and 0.03, respectively). Strong associations between serum PAHs levels and biomarkers of childhood asthma were detected in Arabic children. Data confirmed the role of naphthalene, 4H-cyclobenta[def]phenanthrene, 1,2-benzanthracene, chrysene and benzo(e)acephenanthrylene in childhood asthma; levels of these PAHs were correlated with asthma related biomarkers including IgE, resistin, GMCSF and IFN-γ as well as IL-4, IL-5, IL-8 and IL-10 cytokines. CONCLUSIONS: This data highlight the pivotal role of specific PAHs in childhood asthma.

The present study investigated the ability of Bifidobacterium animalis ssp. lactis (BB-12®) and Lactobacillus paracasei ssp. paracasei (L. casei 431®) to modulate the immune system using a vaccination model in healthy subjects. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 211 subjects (56 % females, mean age 33·2 (sd 13·1) years). Subjects consumed a minimum of 10⁹ colony-forming units of BB-12® (capsule) or L. casei 431® (dairy drink) or a matching placebo once daily for 6 weeks. After 2 weeks, a seasonal influenza vaccination was given. Plasma and saliva samples were collected at baseline and after 6 weeks for the analysis of antibodies, cytokines and innate immune parameters. Changes from baseline in vaccine-specific plasma IgG, IgG1 and IgG3 were significantly greater in both probiotic groups v. the corresponding placebo group (L. casei 431®, P = 0·01 for IgG; P < 0·001 for remaining comparisons). The number of subjects obtaining a substantial increase in specific IgG (defined as ≥ 2-fold above baseline) was significantly greater in both probiotic groups v. placebo (BB-12®, P < 0·001 for IgG, IgG1 and IgG3; L. casei 431®, P < 0·001 for IgG1 and IgG3). Significantly greater mean fold increases for vaccine-specific secretory IgA in saliva were observed in both probiotic groups v. placebo (BB-12®, P = 0·017; L. casei 431®, P = 0·035). Similar results were observed for total antibody concentrations. No differences were found for plasma cytokines or innate immune parameters. Data herein show that supplementation with BB-12® or L. casei 431® may be an effective means to improve immune function by augmenting systemic and mucosal immune responses to challenge.

Abstract The choice on an efficient direct integration procedure for linear structural dynamic equations of motion is discussed. It is suggested that as accuracy parameter the truncation error on the exponential terms contained in the modal contributions of the exact solution be assumed. This error does not always coincide with the local truncation error. These considerations were used to design an unconditionally stable one‐step method whose accuracy is 0( h 4 ). Numerical comparisons with some well‐known integration schemes showed the efficiency of the proposed method.

Nanostructured carbon films consisting of sp chains (polyynes and polycumulenes) embedded in an ${\mathrm{sp}}^{2}$ matrix are grown using supersonic carbon cluster beam deposition in ultrahigh vacuum at room temperature. All the specimens have been analyzed by in situ Raman spectroscopy. The use of different excitation wavelengths (532 and 632.8 nm) confirms the presence of distinct carbynoid species. Chemical stability of the sp species has been studied by exposing the as-deposited films to 500 mbar of ${\mathrm{H}}_{2},$ He, ${\mathrm{N}}_{2},$ and dry air. Gas exposure produces an exponential decay of the carbynoid fraction slightly affecting the ${\mathrm{sp}}^{2}$ component. Helium, hydrogen, and nitrogen do not chemically interact with the sp chains whereas oxygen reacts with the carbynoids species causing their fast and almost complete destruction. The films have been also thermally annealed at $20\ifmmode^\circ\else\textdegree\fi{},$ $100\ifmmode^\circ\else\textdegree\fi{},$ $150\ifmmode^\circ\else\textdegree\fi{},$ and $200\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}.$ The amount of carbynoid species is rapidly and strongly reduced at temperature larger than room temperature. The relevance for material science and interstellar chemistry of the production of a bulk form of carbon where sp and ${\mathrm{sp}}^{2}$ hybridizations coexist is addressed.

The paper presents an acoustic pyrometry method for the reconstruction of temperature maps inside power plant boilers. It is based on measuring times-of-flight of acoustic waves along a number of straight paths in a cross-section of the boiler; via an integral relationship, these times depend on the temperature of the gaseous medium along the paths. On this basis, 2D temperature maps can be reconstructed using suitable inversion techniques. The structure of a particular system for the measurement of the times-of-flight is described, and two classes of reconstruction algorithms are presented. The algorithms proposed have been applied to both simulated and experimental data measured in power plants of the Italian National Electricity Board (ENEL). The results obtained appear fairly satisfactory, considering the small data sets that it was possible to acquire in the tested boilers.

The first small-molecule based αvβ₃-targeted NIR-II/PET dual-modal probes<italic>via</italic>base-catalyzed thiol-addition chemistry were concisely assembled and evaluated.

BACKGROUND: Although cancer cachexia is widely diffuse in the cancer patient population, there is no objective definition and classification of this syndrome. The purpose of this study is to propose a simple and quick classification that relies on the severity of the body weight loss and presence/absence of symptoms that are associated with cancer cachexia. METHODS: The authors used a database of an ongoing multicenter prospective investigation on the screening of the nutrition risk of 1307 cancer outpatients from different (mainly Italian) university or scientific institutes or hospitals. The database included demographic, oncologic, clinical, and nutrition data. The patients were divided into 4 classes based on combinations of body weight loss (< 10%, precachexia; > or = 10%, cachexia) and the presence/absence of at least 1 symptom of anorexia, fatigue, or early satiation. The authors verified statistically whether these 4 classes were associated with the distribution of main clinical, nutrition, and oncologic variables, after adjustment for treatment status, by using the Cochrane-Mantel-Hanszel test for count data and ANOVA for continuous data. RESULTS: Moving from "asymptomatic precachexia" (class 1) to "symptomatic cachexia" (class 4), there were statistically significant trends (P < .0001) in the percentage of gastrointestinal vs nongastrointestinal tumors, severity of cancer stage, percentage of weight loss, number of symptoms per patient, Eastern Cooperative Oncology Group (ECOG) performance status, and nutritional risk score. CONCLUSIONS: The statistical analysis has validated the classification by identifying stages with different severity of cachexia. This classification could be adopted within a comprehensive oncologic approach to the weight-losing patients, until more specific diagnostic techniques are available in clinical practice.

Abstract Local interstellar spectra (LIS) for protons, helium, and antiprotons are built using the most recent experimental results combined with state-of-the-art models for propagation in the Galaxy and heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of cosmic-ray (CR) species at different modulation levels and at both polarities of the solar magnetic field. To do so in a self-consistent way, an iterative procedure was developed, where the GALPROP LIS output is fed into HelMod, providing modulated spectra for specific time periods of selected experiments to compare with the data; the HelMod parameter optimization is performed at this stage and looped back to adjust the LIS using the new GALPROP run. The parameters were tuned with the maximum likelihood procedure using an extensive data set of proton spectra from 1997 to 2015. The proposed LIS accommodate both the low-energy interstellar CR spectra measured by Voyager 1 and the high-energy observations by BESS, Pamela, AMS-01, and AMS-02 made from the balloons and near-Earth payloads; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The found solution is in a good agreement with proton, helium, and antiproton data by AMS-02, BESS, and PAMELA in the whole energy range.

particles per μL under optimal conditions, and the feasibility of the method for exosome detection in complex clinical samples was also proved using simulated serum samples. The detection cost and difficulty are significantly reduced compared to conventional methods, while ensuring sensitivity, and so this method provides a basis for subsequent exosome detection in specific cancer cells.

EuCARD-2 is a project supported by FP7-European Commission that includes, inter alia, a work-package (WP10) called “Future Magnets.” This project is part of the long term development that CERN is launching to explore magnet technology at 16 T to 20 T dipole operating field, within the scope of a study on Future Circular Colliders. The EuCARD2 collaboration is closely liaising with similar programs for high field accelerator magnets in the USA and Japan. The main focus of EuCARD2 WP10 is the development of a 10 kA-class superconducting, high current density cable suitable for accelerator magnets, The cable will be used to wind a stand-alone magnet 500 mm long and with an aperture of 40 mm. This magnet should yield 5 T, when stand-alone, and will enable to reach a 15 to 18 T dipole field by placing it in a large bore background dipole of 12-15 T. REBCO based Roebel cables is the baseline. Various magnet configurations with HTS tapes are under investigation and also use of Bi-2212 round wire based cables is considered. The paper presents the structure of the collaboration and describes the main choices made in the first year of the program, which has a breadth of five to six years of which four are covered by the FP7 frame.

The High Luminosity (HiLumi) Large Hadron Collider (LHC) project has, as the main objective, to increase the LHC peak luminosity by a factor five and the integrated luminosity by a factor ten. This goal will be achieved mainly with a new interaction region layout, which will allow a stronger focusing of the colliding beams. The target will be to reduce the beam size in the interaction points by a factor of two, which requires doubling the aperture of the low- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\beta$</tex-math></inline-formula> (or inner triplet) quadrupole magnets. The use of Nb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> Sn superconducting material and, as a result, the possibility of operating at magnetic field levels in the windings higher than 11 T will limit the increase in length of these quadrupoles, called MQXF, to acceptable levels. After the initial design phase, where the key parameters were chosen and the magnet's conceptual design finalized, the MQXF project, a joint effort between the U.S. LHC Accelerator Research Program and the Conseil Européen pour la Recherche Nucléaire (CERN), has now entered the construction and test phase of the short models. Concurrently, the preparation for the development of the full-length prototypes has been initiated. This paper will provide an overview of the project status, describing and reporting on the performance of the superconducting material, the lessons learnt during the fabrication of superconducting coils and support structure, and the fine tuning of the magnet design in view of the start of the prototyping phase.

A2780 human ovarian carcinoma cells respond to treatment with the synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR) with the production of dihydroceramide and with a concomitant reduction of cell proliferation and induction of apoptosis. The derived HPR-resistant clonal cell line, A2780/HPR, is less responsive to HPR in terms of dihydroceramide generation. In this report, we show that the production of sphingosine 1-phosphate (S1P) is significantly higher in A2780/HPR versus A2780 cells due to an increased sphingosine kinase (SK) activity and SK-1 mRNA and protein levels. Treatment of A2780 and A2780/HPR cells with a potent and highly selective pharmacological SK inhibitor effectively reduced S1P production and resulted in a marked reduction of cell proliferation. Moreover, A2780/HPR cells treated with a SK inhibitor were sensitized to the cytotoxic effect of HPR, due to an increased dihydroceramide production. On the other hand, the ectopic expression of SK-1 in A2780 cells was sufficient to induce HPR resistance in these cells. Challenge of A2780 and A2780/HPR cells with agonists and antagonists of S1P receptors had no effects on their sensitivity to the drug, suggesting that the role of SK in HPR resistance in these cells is not mediated by the S1P receptors. These data clearly demonstrate a role for SK in determining resistance to HPR in ovarian carcinoma cells, due to its effect in the regulation of intracellular ceramide/S1P ratio, which is critical in the control of cell death and proliferation.

Ceramide represents an important sphingoid mediator involved in the signaling pathways that control cell proliferation, differentiation, and death. To determine whether ceramide levels correlate with the malignant progression of human astrocytomas, we investigated these levels in surgical specimens of glial tumors of low-grade and high-grade malignancy. Tumor samples obtained from 52 patients who underwent therapeutic removal of primary brain tumors were used. The tumors were classified according to standard morphologic criteria and were grouped into tumors of low-grade and high-grade malignancy. Sections of normal brain tissue adjacent to the tumor were also analyzed in 11 of the 52 patients. After extraction and partial purification, ceramide was measured by quantitative derivatization to ceramide-1-phosphate using diacylglycerol kinase and [gamma-(32)P]ATP. Ceramide levels were significantly lower in the combined high-grade tumors compared with low-grade tumors and in both tumor groups compared with peritumoral tissue. The results indicate an inverse correlation between the amount of ceramide and tumor malignancy as assessed by both the histological grading and ganglioside pattern. Moreover, overall survival analysis of 38 patients indicates that ceramide levels are significantly associated with patient survival. The present findings indicate that ceramide is inversely associated with malignant progression of human astrocytomas and poor prognosis. The downregulation of ceramide levels in human astrocytomas emerges as a novel alteration that may contribute to glial neoplastic transformation. The low ceramide levels in high-grade tumors may provide an advantage for their rapid growth and apoptotic resistant features. This study appears to support the rationale for the potential benefits of a ceramide-based chemotherapy.

Wound healing is a complex physiological process including overlapping phases (hemostatic/inflammatory, proliferating and remodeling phases). Every alteration in this mechanism might lead to pathological conditions of different medical relevance. Treatments for chronic non-healing wounds are expensive because reiterative treatments are needed. Regenerative medicine and in particular mesenchymal stem cells approach is emerging as new potential clinical application in wound healing. In the past decades, advance in the understanding of molecular mechanisms underlying wound healing process has led to extensive topical administration of growth factors as part of wound care. Currently, no definitive treatment is available and the research on optimal wound care depends upon the efficacy and cost-benefit of emerging therapies. Here we provide an overview on the novel approaches through stem cell therapy to improve cutaneous wound healing, with a focus on diabetic wounds and Systemic Sclerosis-associated ulcers, which are particularly challenging. Current and future treatment approaches are discussed with an emphasis on recent advances.

In silicon nanocrystal based metal–oxide–semiconductor memory structures, tuning of the electron tunneling distance between the Si substrate and Si nanocrystals located in the gate oxide is a crucial requirement for the pinpointing of optimal device architectures. In this work it is demonstrated that this tuning of the “injection distance” can be achieved by varying the Si+ ion energy or the oxide thickness during the fabrication of Si nanocrystals by ultralow-energy silicon implantation. Using an accurate cross-section transmission electron microscopy (XTEM) method, it is demonstrated that two-dimensional arrays of Si nanocrystals cannot be positioned closer than 5 nm to the channel by increasing the implantation energy. It is shown that injection distances down to much smaller values (2 nm) can be achieved only by decreasing the nominal thickness of the gate oxide. Depth profiles of excess silicon measured by time-of-flight secondary ion mass spectroscopy and Si nanocrystal locations determined by XTEM are compared with Monte-Carlo simulations of the implanted Si profiles taking into account dynamic target changes due to ion implantation, ion erosion, and ion beam mixing. This combination of experimental and theoretical studies gives a safe explanation regarding the unique technological route of obtaining Si nanocrystals at distances smaller than 5 nm from the channel: the formation of nanocrystals requires that the interface mixing due to collisional damage does not overlap with the range profile to the extent that there is no more a local maximum of Si excess buried in the SiO2 layer.

Casein phosphopeptides beta-CN(1-25)4P and alpha(s1)-CN(59-79)5P, from beta- and alpha(s1)-casein, respectively, both carrying the characteristic 'acidic motif' Ser(P)-Ser(P)-Ser(P)-Glu-Glu, were chemically synthesized and administered to HT-29 cells differentiated in culture, which are a used model of intestinal epithelium for absorption studies. Both casein phosphopeptides caused an increase of [Ca(2+)](i) due to influx of extracellular Ca(2+). The response was quantitatively higher with beta-CN(1-25)4P than alpha(s1)-CN(59-79)5P. The synthetic peptide corresponding to the 'acidic motif' was ineffective and the dephosphorylated form of beta-CN(1-25)4P almost inactive. The lack of the N-terminally located five amino acids, or sequence modifications within the N-terminal segment of beta-CN(1-25)4P, caused a total loss of activity, whereas the lack of the C-terminal segment preserved activity. In conclusion, the influx of calcium into HT-29 cells caused by beta-CN(1-25)4P appears to depend on the phosphorylated 'acidic motif' and the preceding N-terminal region.