Optical resonators based on Bloch surface waves

A few recent works suggest the possibility of controlling light propagation at the interface of periodic multilayers supporting Bloch surface waves (BSWs), but optical resonators based on BSWs are yet to demonstrate. Here we discuss the feasibility of exploiting guided BSWs in a ring resonator configuration. In particular, we investigate the main issues related to the design of these structures, and we discuss about their limitations in terms of quality factors and dimensions. We believe these results might be useful for the development of a complete BSW-based platform for application ranging from optical sensing to the study of the light-matter interaction in micro and nano structures.Comment: 10 pages, 10 figures. To be published in JOSA

Nonlinear characterisation of a silicon integrated Bragg waveguide filter

Bragg waveguides are promising optical filters for pump suppression in spontaneous Four-Wave Mixing (FWM) photon sources. In this work, we investigate the generation of unwanted photon pairs in the filter itself. We do this by taking advantage of the relation between spontaneous and classical FWM, which allows for the precise characterisation of the nonlinear response of the device. The pair generation rate estimated from the classical measurement is compared with the theoretical value calculated by means of a full quantum model of the filter, which also allows to investigate the spectral properties of the generated pairs. We find a good agreement between theory and experiment, confirming that stimulated FWM is a valuable approach to characterise the nonlinear response of an integrated filter, and that the pairs generated in a Bragg waveguide are not a serious issue for the operation of a fully integrated nonclassical source

Energy correlations of photon pairs generated by a silicon microring resonator probed by Stimulated Four Wave Mixing

Compact silicon integrated devices, such as micro-ring resonators, have recently been demonstrated as efficient sources of quantum correlated photon pairs. The mass production of integrated devices demands the implementation of fast and reliable techniques to monitor the device performances. In the case of time-energy correlations, this is particularly challenging, as it requires high spectral resolution that is not currently achievable in coincidence measurements. Here we reconstruct the joint spectral density of photons pairs generated by spontaneous four-wave mixing in a silicon ring resonator by studying the corresponding stimulated process, namely stimulated four wave mixing. We show that this approach, featuring high spectral resolution and short measurement times, allows one to discriminate between nearly-uncorrelated and highly-correlated photon pairs.Comment: 7 pages, 4 figure

Regulation of CD45 phosphatase by oncogenic ALK in anaplastic large cell lymphoma

Anaplastic Large Cell Lymphoma (ALCL) is a subtype of non-Hodgkin lymphoma frequently driven by the chimeric tyrosine kinase NPM-ALK, generated by the t (2,5)(p23;q35) translocation. While ALK+ ALCL belongs to mature T cell lymphomas, loss of T cell identity is observed in the majority of ALCL secondary to a transcriptional and epigenetic repressive program induced by oncogenic NPM-ALK. While inhibiting the expression of T cell molecules, NPM-ALK activates surrogate TCR signaling by directly inducing pathways downstream the TCR. CD45 is a tyrosine phosphatase that plays a central role in T cell activation by controlling the TCR signaling and regulating the cytokine responses through the JAK/STAT pathway and exists in different isoforms depending on the stage of T-cell maturation, activation and differentiation. ALK+ ALCL cells mainly express the isoform CD45RO in keeping with their mature/memory T cell phenotype. Because of its regulatory effect on the JAK/STAT pathway that is essential for ALK+ ALCL, we investigated whether CD45 expression was affected by oncogenic ALK. We found that most ALK+ ALCL cell lines express the CD45RO isoform with modest CD45RA expression and that NPM-ALK regulated the expression of these CD45 isoforms. Regulation of CD45 expression was dependent on ALK kinase activity as CD45RO expression was increased when NPM-ALK kinase activity was inhibited by treatment with ALK tyrosine kinase inhibitors (TKIs). Silencing ALK expression through shRNA or degradation of ALK by the PROTAC TL13-112 caused upregulation of CD45RO both at mRNA and protein levels with minimal changes on CD45RA, overall indicating that oncogenic ALK downregulates the expression of CD45. CD45 repression was mediated by STAT3 as demonstrated by ChIP-seq data on ALCL cells treated with the ALK-TKI crizotinib or cells treated with a STAT3 degrader. Next, we found that knocking-out CD45 with the CRISPR/Cas9 system resulted in increased resistance to ALK TKI treatment and CD45 was down-regulated in ALCL cells that developed resistance in vitro to ALK TKIs. Overall, these data suggest that CD45 expression is regulated by ALK via STAT3 and acts as a rheostat of ALK oncogenic signaling and resistance to TKI treatment in ALCL

The Kramers equation simulation algorithm I. Operator analysis

Using an operatorial formalism, we study the Kramers equation and its applications to numerical simulations. We obtain classes of algorithms which may be made precise at every desired order in the time step $\epsilon$ and with a set of free parameters which can be used to reduce autocorrelations. We show that it is possible to use a global Metropolis test to restore Detailed Balance.Comment: 32 pages, REVTeX 3.0, IFUP-TH-2

Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency.

Most of the anaplastic large-cell lymphoma (ALCL) cases carry the t(2;5; p23;q35) that produces the fusion protein NPM-ALK (nucleophosmin-anaplastic lymphoma kinase). NPM-ALK-deregulated kinase activity drives several pathways that support malignant transformation of lymphoma cells. We found that in ALK-rearranged ALCL cell lines, NPM-ALK was distributed in equal amounts between the cytoplasm and the nucleus. Only the cytoplasmic portion was catalytically active in both cell lines and primary ALCL, whereas the nuclear portion was inactive because of heterodimerization with NPM1. Thus, about 50% of the NPM-ALK is not active and sequestered as NPM-ALK/NPM1 heterodimers in the nucleus. Overexpression or relocalization of NPM-ALK to the cytoplasm by NPM genetic knockout or knockdown caused ERK1/2 (extracellular signal-regulated protein kinases 1 and 2) increased phosphorylation and cell death through the engagement of an ATM/Chk2- and γH2AX (phosphorylated H2A histone family member X)-mediated DNA-damage response. Remarkably, human NPM-ALK-amplified cell lines resistant to ALK tyrosine kinase inhibitors (TKIs) underwent apoptosis upon drug withdrawal as a consequence of ERK1/2 hyperactivation. Altogether, these findings indicate that an excess of NPM-ALK activation and signaling induces apoptosis via oncogenic stress responses. A 'drug holiday' where the ALK TKI treatment is suspended could represent a therapeutic option in cells that become resistant by NPM-ALK amplification.We thank Maria Stella Scalzo for technical support, Dr Emanuela Colombo for kindly providing MEFs that lack NPM1 (MEF NPM−/−p53−/−) and control fibroblasts (MEF p53−/−), Dr Guido Serini for the use of his confocal microscopy unit at the Candiolo Cancer Institute—IRCCS, Torino, Italy. We also thank Ariad Pharmaceutical, Pfizer, Astellas and Novartis that kindly provided all drugs used in this study. This work was supported by the Regione Lombardia (ID14546A) and Fondazione Berlucchi Onlus Grant 2014 (to CGP), and by grants FP7 ERC-2009-StG (Proposal No. 242965—‘Lunely’); Associazione Italiana per la Ricerca sul Cancro (AIRC) Grant IG-12023; Koch Institute/DFCC Bridge Project Fund; Ellison Foundation Boston; Worldwide Cancer Research Association (former AICR) grant 12-0216; the Grant for Oncology Innovation by Merck-Serono and R01 CA196703-01 (to RC).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/onc.2015.45

Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors

Non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene is treated with ALK tyrosine kinase inhibitors (TKIs), but is successful for only a limited amount of time; most cases relapse due to the development of drug resistance. Here we show that a vaccine against ALK induced a strong and specific immune response that both prophylactically and therapeutically impaired the growth of ALK-positive lung tumors in mouse models. The ALK vaccine was efficacious also in combination with ALK TKI treatment and significantly delayed tumor relapses after TKI suspension. We found that lung tumors containing ALK rearrangements induced an immunosuppressive microenvironment, regulating the expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression reduced ALK vaccine efficacy, which could be restored by administration of anti-PD-1 immunotherapy. Thus, combinations of ALK vaccine with TKIs and immune checkpoint blockade therapies might represent a powerful strategy for the treatment of ALK-driven NSCLC

Preface of the 31st Italian Symposium on Advanced Database Systems

This volume contains the proceedings of the 31st Italian Symposium on Advanced Database Systems (SEBD - Sistemi Evoluti per Basi di Dati), held in Galzinagno Terme (Padua, Italy) from 2 to 5 July 2023.</p

Preface of the 31st Italian Symposium on Advanced Database Systems

This volume contains the proceedings of the 31st Italian Symposium on Advanced Database Systems (SEBD - Sistemi Evoluti per Basi di Dati), held in Galzinagno Terme (Padua, Italy) from 2 to 5 July 2023.</p