Ultracompact, low-loss directional couplers on InP based on self-imaging by multimode interference

We report extremely compact (494-µm-long 3 dB splitters, including input/output bends), polarization-insensitive, zero-gap directional couplers on InP with a highly multimode interference region that are based on the self-imaging effect. We measured cross-state extinctions better than 28 dB and on-chip insertion losses of 0.5 dB/coupler plus 1 dB/cm guide propagation loss at 1523 nm wavelength

Designing all-graphene nanojunctions by covalent functionalization

We investigated theoretically the effect of covalent edge functionalization, with organic functional groups, on the electronic properties of graphene nanostructures and nano-junctions. Our analysis shows that functionalization can be designed to tune electron affinities and ionization potentials of graphene flakes, and to control the energy alignment of frontier orbitals in nanometer-wide graphene junctions. The stability of the proposed mechanism is discussed with respect to the functional groups, their number as well as the width of graphene nanostructures. The results of our work indicate that different level alignments can be obtained and engineered in order to realize stable all-graphene nanodevices

Orbital overlap effects in electron transfer reactions across a metal nanowire/electrolyte solution interface

In this paper, we report on calculations of the orbital overlap between Fe(III) and Cr(III) aquacomplexes and different electrode surfaces: Cu(111), Ag (111), Au(111), Pt(111), and corresponding monatomic wires. The electronic structure of the monocrystalline surfaces and nanowires are described in terms of the electronic spillover and density of electronic states at the Fermi level obtained from periodic density functional theory (DFT) calculations. The transmission coefficients (κ) characterizing the first stage of outer-sphere electron transfer for the reduction of aquacomplexes are calculated on the basis of Landau–Zener theory as a function of electrode–reactant separation; the electronic transmission coefficients for the [Cr(H2O)6]3+/2+ redox couple were found to be smaller than those for [Fe(H2O)6]3+/2+. Two different intervals can be clearly distinguished for Cu, Au and Pt: “a catalytic region”, where κ(wire) > κ(Me slab) and “an inhibition region”, where κ(wire) < κ(Me slab). A similar behavior exhibits the coupling constant estimated for a hydrogen atom adsorbed at the Au(111) surface and the Au monatomic wire. These effects originate from some specific features of electronic density profile for metal nanowires: at short distances the electronic density of nanowires is higher compared with the (111) metal surfaces, while at larger separations it decreases more sharply.Fil: Nazmutdinov, Renat R.. Kazan National Research Technological University; RusiaFil: Berezin, Alexander S.. Kazan National Research Technological University; RusiaFil: Soldano, Germán. Universitat Ulm; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schmickler, Wolfgang. Universitat Ulm; Alemani

THU0116 European multicentre pilot survey to assess vitamin d and clinical status in rheumatoid arthritis patients

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Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma

HLA class I loss is a significant mechanism of immune evasion by cervical carcinoma, interfering with the development of immunotherapies and cancer vaccines. We report the systematic investigation of HLA class I and antigen processing machinery component expression and association with clinical outcome. A tissue microarray containing carcinoma lesions from 109 cervical carcinoma patients was stained for HLA class I heavy chains, β2-microglobulin, LMP2, LMP7, LMP10, TAP1, TAP2, ERAP1, tapasin, calreticulin, calnexin and ERp57. A novel staining evaluation method was used to ensure optimal accuracy and reliability of expression data, which were correlated with known clinicopathological parameters. Partial HLA class I loss was significantly associated with decreased 5-years overall survival (61% vs. 83% for normal expression; P < 0.05) and was associated with decreased 5-years disease-free survival (DFS) (65% vs. 82% for normal expression; P = 0.05). All APM components except LMP10, calnexin and calreticulin were down-regulated in a substantial number of cases and, except ERAP1, correlated significantly with HLA class I down-regulation. LMP7, TAP1 and ERAP1 loss was significantly associated with decreased overall and (except LMP7) DFS (P < 0.05 and 0.005, respectively). ERAP1 down-regulation was an independent predictor for worse overall and DFS in multivariate analysis (HR 3.08; P < 0.05 and HR 2.84; P < 0.05, respectively). HLA class I and APM component down-regulation occur frequently in cervical carcinoma, while peptide repertoire alterations due to ERAP1 loss are a major contributing factor to tumour progression and mortality

FUTURE PERSPECTIVES IN MELANOMA RESEARCH. Meeting report from the “Melanoma Research: a bridge from Naples to the World. Napoli, December 5th–6 th2011”

After more than 30 years, landmark progress has been made in the treatment of cancer, and melanoma in particular, with the success of new molecules such as ipilimumab, vemurafenib and active specific immunization

Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells

The breast cancer stem cell (BCSC) hypotheses suggest that breast cancer is derived from a single tumor-initiating cell with stem-like properties, but the source of these cells is unclear. We previously observed that induction of an immune response against an epithelial breast cancer led in vivo to the T-cell-dependent outgrowth of a tumor, the cells of which had undergone epithelial to mesenchymal transition (EMT). The resulting mesenchymal tumor cells had a CD24(-/lo)CD44(+) phenotype, consistent with BCSCs. In the present study, we found that EMT was induced by CD8 T cells and the resulting tumors had characteristics of BCSCs, including potent tumorigenicity, ability to reestablish an epithelial tumor, and enhanced resistance to drugs and radiation. In contrast to the hierarchal cancer stem cell hypothesis, which suggests that breast cancer arises from the transformation of a resident tissue stem cell, our results show that EMT can produce the BCSC phenotype. These findings have several important implications related to disease progression and relapse

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge";: Napoli, December 3rd-6th 2014.

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma