Distributed Smoothed Tree Kernel

In this paper we explore the possibility to merge the world of Compositional Distributional Semantic Models (CDSM) with Tree Kernels (TK). In particular, we will introduce a specific tree kernel (smoothed tree kernel, or STK) and then show that is possibile to approximate such kernel with the dot product of two vectors obtained compositionally from the sentences, creating in such a way a new CDSM

In Situ Geophysical Exploration by Humans in Mars Analog Environments

We carried out three geophysical experiments in Mars analog environments in order to better understand the challenges future astronauts will face when conducting similar surveys on Mars or the Moon. The experiments included a passive seismometer deployment and a time-domain electromagnetic survey at the Flashline Mars Arctic Research Station (FMARS) on Devon Island, Canada and a seismic refraction survey in southeastern Utah at the Mars Desert Research Station (MDRS). FMARS is located on the rim of the 23 Ma Haughton Crater in a polar desert environment. MDRS is located in an area with sedimentary plateaus and canyons of Jurassic to Cretaceous age. Both facilities were built by The Mars Society to help develop key knowledge about human Mars exploration. Crews of six spend 2-4 weeks in the habitats and conduct eld research on simulated extravehicular activities (EVAs) wearing mock spacesuits. The work reported here was conducted in July 2009 at FMARS and February 2010 at MDRS

Compositional Distributional Semantics Models in Chunk-based Smoothed Tree Kernels

The field of compositional distributional semantics has proposed very interesting and reliable models for accounting the distributional meaning of simple phrases. These models however tend to disregard the syntactic structures when they are applied to larger sentences. In this paper we propose the chunk-based smoothed tree kernels (CSTKs) as a way to exploit the syntactic structures as well as the reliability of these compositional models for simple phrases. We experiment with the recognizing textual entailment datasets. Our experiments show that our CSTKs perform better than basic compositional distributional semantic models (CDSMs) recursively applied at the sentence level, and also better than syntactic tree kernels

STAT1 contributes to HLA class I upregulation and CTL reactivity after anti-EGFR mAb cetuximab therapy in head and neck cancer patients

Squamous cell carcinoma of head and neck (HNSCC) cells express low HLA class I and antigen processing machinery (APM) components, such as transporter TAP-1/2, which is associated with the reduced sensitivity to cytotoxic T lymphocyte (CTL) mediated lysis. Epidermal growth factor receptor (EGFR) is overexpressed in HNSCC and is associated with the poor prognosis. FDA approved anti-EGFR blockade mAb cetuximab inhibits HNSCC proliferation, and induces EGFR-specific CTL. However, the molecular mechanism(s) underlying the EGFR-specific CTL recognition of HNSCC in the therapeutic efficacy of anti-EGFR mAb is still emerging. We show that cetuximab or EGFR knockdown enhanced expression of HLA class I antigens, which is associated with the EGFR expression level on HNSCC. These findings were validated in a prospective trial of neoadjuvant cetuximab therapy. Interestingly, upregulation of HLA-B/C alleles were more pronounced than HLA-A alleles after cetuximab or EGFR knockdown treatment. EGFR signaling blockade or EGFR depletion also enhanced IFN gamma receptor (IFNAR) on HNSCC and augmented induction of HLA class I and TAP-1/2 caused by IFN gamma treatment. Cetuximab or EGFR knockdown enhanced the level of HLA class I, STAT-1, TAP-1/2 in a STAT-1+/+ cell line but not in STAT-1-/- cell line, documenting the STAT-1 dependence of this effect. We also found that Src homology domain-containing phosphatase 2 (SHP-2), which is downstream of EGFR and also overexpressed in SCCHN, can suppress the immunostimulatory effect of cetuximab treatment on HLA class I/STAT-1 upregulation, and dual targeting of EGFR and SHP-2 co-operates in the most efficient reversal of immune escape phenotype. In addition, cetuximab-based EGFR inhibition and SHP-2 depletion enhanced the recognition of HNSCC cells by EGFR 853-861 specific CTL, and enhanced surface presentation of non-EGFR TA, such as MAGE-3 271-279 , indicating that a broad tumor antigen repertoire is processed and presented by HLA/APM upregulation. These findings elucidate a novel immune escape mechanism associated with EGFR signaling through STAT1 suppression and the reversal with cetuximab, which may provide additional targets for on-going mAb-based immunotherapy

EGFR-mediated tumor immunoescape: The imbalance between phosphorylated STAT1 and phosphorylated STAT3

The epidermal growth factor receptor (EGFR) supports the escape of malignant cells from immunosurveillance by inhibiting the activation of signal transducer and activator of transcription 1 (STAT1) while promoting that of STAT3. We have recently demonstrated that protein tyrosine phosphatase, non-receptor type 11 (PTNP11, best known as SHP2), a phosphatase that operates downstream of EGFR, is responsible for the dephosphorylation of active STAT1 and for the inhibition of the antigen-processing machinery (APM), hence favoring tumor immunoescape. Thus, EGFR signaling may skew the tumor microenvironment to suppress cellular immune responses

Evaluating the implementation of a chronic obstructive pulmonary disease management program using the Consolidated Framework for Implementation Research: a case study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent chronic disease that requires comprehensive approaches to manage; it accounts for a significant portion of Canada\u27s annual healthcare spending. Interprofessional teams are effective at providing chronic disease management that meets the needs of patients. As part of an ongoing initiative, a COPD management program, the Best Care COPD program was implemented in a primary care setting. The objectives of this research were to determine site-specific factors facilitating or impeding the implementation of a COPD program in a new setting, while evaluating the implementation strategy used. METHODS: A qualitative case study was conducted using interviews, focus groups, document analysis, and site visits. Data were deductively analyzed using the Consolidated Framework for Implementation Research (CFIR) to assess the impact of each of its constructs on Best Care COPD program implementation at this site. RESULTS: Eleven CFIR constructs were determined to meaningfully affect implementation. Five were identified as the most influential in the implementation process. Cosmopolitanism (partnerships with other organizations), networks and communication (amongst program providers), engaging (key individuals to participate in program implementation), design quality and packaging (of the program), and reflecting and evaluating (throughout the implementation process). A peer-to-peer implementation strategy included training of registered respiratory therapists (RRT) as certified respiratory educators and the establishment of a communication network among RRTs to discuss experiences, collectively solve problems, and connect with the program lead. CONCLUSIONS: This study provides a practical example of the various factors that facilitated the implementation of the Best Care COPD program. It also demonstrates the potential of using a peer-to-peer implementation strategy. Focusing on these factors will be useful for informing the continued spread and success of the Best Care COPD program and future implementation of other chronic care programs

Diversity of Extracellular Vesicles (EV) in Plasma of Cancer Patients

Extracellular vesicles (EVs) are produced by all cells and are found in all body fluids. They function as intercellular messengers that carry and deliver signals regulating cellular interactions in health and disease. EVs are emerging as potential biomarkers of diseases and responses to therapies, and much attention is being devoted to understanding their role in physiological as well as pathological events. EVs are heterogenous in their origin, size, molecular characteristics, genetic content and functions. Isolation of EV subsets from plasma and characterization of their distinct properties have been a limiting factor in ongoing efforts to understand their biological importance. Here, we discuss the immunoaffinity-based strategies that are available for isolating distinct subsets of EVs from plasma and provide a road-map to their successful immunocapture and molecular profiling, with special attention to tumor-derived EVs or TEX

Simple Synthesis of Fe3O4@-Activated Carbon from Wastepaper for Dispersive Magnetic Solid-Phase Extraction of Non-Steroidal Anti-Inflammatory Drugs and Their UHPLC–PDA Determination in Human Plasma

In the present society, the recycling and reuse of valuable substances are of utmost im- portance for economic and environmental purposes. At the same time, there is a pressing need to develop new methods to protect the ecosystem from many human activities, including those that have contributed to an ever-increasing presence of pharmaceutical pollutants. In this study, a straightforward approach that applies a magnetic carbon composite for the effective removal of NSAIDs from biological fluids is reported. The composite was produced by recycling wasted hand- kerchiefs, to provide cellulose to the reactive system and then transformed into carbon via calcination at high temperature. The morphological and structural features of the prepared “Fe3O4@-activated carbon” samples were investigated via thermal analysis, X-ray diffraction, Raman spectroscopy, and scanning electron microscopy. Magnetic solid-state extraction was carried out to reveal the adsorption capabilities of the magnetic carbon composite and then combined with UHPLC–PDA for the determination and quantification of five NSAIDs (furprofen, indoprofen, ketoprofen, flurbiprofen, and indomethacin). The method developed herein proved to be fast and accurate. The adsorbent could be reused for up to 10 cycles, without any decrease in performance; thus, it contributes to an intelligent and sustainable economic strategy projected toward minimal waste generation

Canine Melanoma Immunology and Immunotherapy: Relevance of Translational Research

In veterinary oncology, canine melanoma is still a fatal disease for which innovative and long-lasting curative treatments are urgently required. Considering the similarities between canine and human melanoma and the clinical revolution that immunotherapy has instigated in the treatment of human melanoma patients, special attention must be paid to advancements in tumor immunology research in the veterinary field. Herein, we aim to discuss the most relevant knowledge on the immune landscape of canine melanoma and the most promising immunotherapeutic approaches under investigation. Particular attention will be dedicated to anti-cancer vaccination, and, especially, to the encouraging clinical results that we have obtained with DNA vaccines directed against chondroitin sulfate proteoglycan 4 (CSPG4), which is an appealing tumor-associated antigen with a key oncogenic role in both canine and human melanoma. In parallel with advances in therapeutic options, progress in the identification of easily accessible biomarkers to improve the diagnosis and the prognosis of melanoma should be sought, with circulating small extracellular vesicles emerging as strategically relevant players. Translational advances in melanoma management, whether achieved in the human or veterinary fields, may drive improvements with mutual clinical benefits for both human and canine patients; this is where the strength of comparative oncology lies