Combined frequency-amplitude nonlinear modulation: theory and applications

In this work we formulate a generalized theoretical model to describe the nonlinear dynamics observed in combined frequency-amplitude modulators whose characteristic parameters exhibit a nonlinear dependence on the input modulating signal. The derived analytical solution may give a satisfactory explanation of recent laboratory observations on magnetic spin-transfer oscillators and fully agrees with results of micromagnetic calculations. Since the theory has been developed independently of the mechanism causing the nonlinearities, it may encompass the description of modulation processes of any physical nature, a promising feature for potential applications in the field of communication systems.Comment: 8 pages, 4 figures, to be published on IEEE Transactions on Magnetic

Villa en Ivrea

This villa has been constructed on sloping ground, and naturally this circumstance has been utilised to give the design a dynamic and stimulating quality. There are two floor levels; a semibasement of 64.3 ms2 and the main part of the house, which has a surface of 203.7 ms2 The former includes a garage, celler and boiler room. The latter comprises the vestibule, a living cum dining room, study, bedrooms, services and terraces. The construction consists mainly of irregularly shaped, partly cut, stone walls, and load bearing concrete pillars. The roof is outstanding and original: it is a plane slab with overhangs in various directions, forming novel and intriguing configurations which help to break any possible monotony of the building. The overall impression conveyed by this villa, on whose pure white surfaces stand out the shaded projection of the roof outline, is most pleasant. The combination of materials, colour patterns, and the dynamic contrasts in shapes and volumes is surprising and charming.Se yergue sobre un terreno en pendiente. Y, como es lógico y usual en estos casos, ha sido aprovechada esta circunstancia para crear una. ambientación y movimiento interesantes. El total de edificación está dispuesto en dos plantas: Un semisótano, de 64,30 m2 de superficie útil, con garaje, bodega y sala de calefacción, y una planta noble, de 208,70 m2, distribuida en vestíbulo, estar-comedor, estudio, dormitorios, servicios y terrazas. La estructura ha sido ejecutada a base de muros de mampostería careada con despiece irregular y machos resistentes de hormigón. Destacan, por su originalidad, las cubiertas planas volando en determinados puntos con formas sencillas y graciosas, que ayudan a romper la monotonía del conjunto. En definitiva, la impresión que nos ofrece esta villa —de nítida blancura, sobre la que destacan las recortadas sombras producidas por los voladizos de cubierta— es sumamente agradable. La combinación de materiales —piedra, madera y paños de color—, junto a la movilidad de plantas y alzados, ofrecen un efecto plástico sorpréndete y gracioso

Nutrient delivery efficiency of a combined sewer along a lake challenged by incipient eutrophication

Although sewage diversion outside of a lake's watershed is now ordinary practice in the restoration of eutrophic lakes, often the observed recovery is slower than expected and the internal load from the lake anoxic sediments is identified as a possible reason. However, in the case of combined sewer, the quantification of the residual nutrient load discharged from sewer spillways must also be questioned. In this paper, the diversion efficiency of the sewer system along the east coast of Lake Iseo, a prealpine Italian lake where eutrophication effects are still severe, is investigated. To this purpose, a representative part of the sewer system was modelled by PCSWMM and calibrated by using an extensive series of discharge measurements. Water quality monitoring during wet weather periods reveals that the first flush is common in tributary sewers, whereas it is absent along the main collector. Moreover, flow discharges are strongly affected by infiltration waters, which are controlled by the lake water level. The calibrated model, including infiltration modeling, was used to assess the annual overflow volumes and the nutrient load through a continuous 10-year simulation. Simulations were conducted both with regard to the current conditions and to a climate change scenario. Results show that the discharged residual load is at least 7 times larger than the design value, with the water infiltration contributing to 17% to the overflow volume and that non-structural practices could considerably reduce the overall impact of the sewer. This research thus provides important insight into the potential impact of combined sewer overflows on lacustrine environments and addresses effective mitigation measures in similar contexts

Light-Scattering Observation Of Surface Acoustic Modes In High-Order Brillouin Zones Of A Si(001) Grating

In Brillouin light-scattering (BLS) measurements of an ion-milled Si(001) surface grating with grating wavelength Lambda(G) =0.35 mu m, we have observed numerous high-order zone-folded surface acoustic modes between the second and third zone boundaries associated with the grating. A surprisingly intense signal from a zone-folded longitudinal resonance was observed in the absence of direct hybridization with the Rayleigh modes. The relative intensities of all of the modes have been calculated by allowing for coupling between modes related by up to two grating reciprocal-lattice vectors, and for a grating profile with nonzero first and second Fourier amplitudes. The Fourier amplitudes inferred from the BLS measurements and calculations agree very well with those obtained from a direct measurement of the grating profile using atomic-force microscopy

Optimizing PD-L1 evaluation on cytological samples from advanced non-small-cell lung cancer

Aim: Programmed cell death-ligand 1 (PD-L1) predicts response to immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) patients. Most NSCLCs are diagnosed at an advanced stage and using minimally invasive diagnostic procedures that yield small biopsies or cytological samples. Methods: Cytological smears and paired histological samples from 52 advanced NSCLC patients were tested for PD-L1 expression by immunocyto/histochemistry (ICC/IHC) and for PD-L1 gene status by FISH. Results: PD-L1 was overexpressed in 9/52 (17%) cytological samples and in seven (13.5%) matched biopsies. The concordance between immunocytochemistry and IHC was 92.3% (48/52; p < 0.001). The concordance between PD-L1 gene status on cytology and histology was 69.2% (18/26; p < 0.001). No correlation between IHC and fluorescence in situ hybridization results was found. Conclusion: Our data support the feasibility and reliability of PD-L1 protein and PD-L1 gene assessment on direct cytological smears from NSCLC patients whenever histological sample are inadequate

Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma

Background: Trastuzumab has recently shown efficacy in the treatment of HER2-positive advanced gastric adenocarcinoma. Although antibody-based therapies target the metastatic disease, HER2 status is usually evaluated in the primary tumour because metastatic sites are rarely biopsied. The aim of this study was to compare HER2 status in primary and paired metastatic sites of gastric adenocarcinoma. Methods: The HER2 status was assessed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in 72 secondary lesions of gastric adenocarcinoma and in the corresponding primary tumours. Results: Concordance of FISH results, evaluable in 68 primary and matched metastatic sites, was 98.5%. Concordance of IHC results, available in 39 of the 72 paired cases, was 94.9%. Only one case showed discordance between primary tumour and metastasis, being negative by both IHC and FISH in the primary and showing HER2 overexpression and amplification in the corresponding pancreatic lymph node metastasis. Conclusion: The high concordance observed between HER2 results obtained by both IHC and FISH on primary tumours and corresponding metastases suggests that in gastric cancer HER2 status is maintained in most cases unchanged during the metastatic process. Keywords: HER2, gastric cancer, FISH, immunohistochemistr

Impact of immunochemotherapy with R-bendamustine or R-CHOP for treatment naïve advanced-stage follicular lymphoma: A subset analysis of the FOLL12 trial by Fondazione Italiana Linfomi

We conducted a post hoc analysis of the FOLL12 trial to determine the impact of different initial immunochemotherapy (ICT) regimens on patient outcomes. Patients were selected from the FOLL12 trial, which included adults with stage II–IV follicular lymphoma (FL) grade 1–3a and high tumor burden. Patients were randomized 1:1 to receive either standard ICT followed by rituximab maintenance (RM) or the same ICT followed by a response-adapted approach. ICT consisted of rituximab-bendamustine (RB) or rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP), per physician's decision. A total of 786 patients were included in this analysis, 341 of whom received RB and 445 R-CHOP. RB was more frequently prescribed to older subjects, females, patients without bulky disease, and those with grade 1–2 FL. After a median of 56 months of follow-up, R-CHOP and RB had similar progression-free survival (PFS) (Hazard Ratio for RB 1.11, 95% CI 0.87–1.42, p = 0.392). Standard RM was associated with improved PFS compared to response-adapted management both after R-CHOP and RB. Grade 3–4 hematologic adverse events were more frequent with R-CHOP during induction treatment and more frequent with RB during RM. Grade 3–4 infections were more frequent with RB. RB was also associated with a higher incidence of transformed FL. R-CHOP and RB showed similar activity and efficacy, but with different safety profiles and long-term events, suggesting that the treating physician should carefully select the most appropriate chemotherapy regimen for each patient based on patient's individual characteristics, choices, and risk profile

Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells

Alteration of the gut microbiota has been associated with different gastrointestinal disorders. Normobiosis restoration by faecal microbiota transplantation (FMT) is considered a promising therapeutic approach, even if the mechanisms underlying its efficacy are at present largely unknown. Here we sought to elucidate the functional effects of therapeutic FMT administration during experimental colitis on innate and adaptive immune responses in the intestinal mucosa. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, ultimately leading to IL-10 production by innate and adaptive immune cells, including CD4+ T cells, iNKT cells and Antigen Presenting Cells (APC), and reduces the ability of dendritic cells, monocytes and macrophages to present MHCII-dependent bacterial antigens to colonic T cells. These results demonstrate the capability of FMT to therapeutically control intestinal experimental colitis and poses FMT as a valuable therapeutic option in immune-related pathologies

Pathogenicity of in-vivo generated intestinal Th17 lymphocytes is IFNγ dependent

Th17 cells are crucially involved in the immunopathogenesis of inflammatory bowel diseases in humans. Nevertheless, pharmacological blockade of IL17A, the Th17 signature cytokine, yielded negative results in patients with Crohn's disease (CD), and attempts to elucidate the determinants of Th17 cells pathogenicity in the gut have so far proved unsuccessful. Here, we aimed to identify and functionally validate the pathogenic determinants of intestinal IL-17-producing T cells