Smart Lighting Clinical Testbed Pilot Study on Circadian Phase Advancement

Objective: Lighting is a strong synchronizer for circadian rhythms, which in turn drives a wide range of biological functions. The objective of our work is a) to construct a clinical in-patient testbed with smart lighting, and b) evaluate its feasibility for use in future clinical studies. Methods: A feedback capable, variable spectrum lighting system was installed at the University of New Mexico Hospital. The system consists of variable spectrum lighting troffers, color sensors, occupancy sensors, and computing and communication infrastructure. We conducted a pilot study to demonstrate proof of principle, that 1) this new technology is capable of providing continuous lighting and sensing in an active clinical environment, 2) subject recruitment and retention is feasible for round-the-clock, multi-day studies, and 3) current techniques for circadian regulation can be deployed in this unique testbed. Unlike light box studies, only troffer-based lighting was used, and both lighting intensity and spectral content were varied. Results: The hardware and software functioned seamlessly to gather biometric data and provide the desired lighting. Salivary samples that measure dim-light melatonin onset showed phase advancement for all three subjects. Conclusion: We executed a five-day circadian rhythm study that varied intensity, spectrum, and timing of lighting as proof-of-concept or future clinical studies with troffer-based, variable spectrum lighting. Clinical Impact: The ability to perform circadian rhythm experiments in more realistic environments that do not overly constrain the subject is important for translating lighting research into practice, as well as for further research on the health impacts of lighting

Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer

Osteopontin (OPN), also known as SPP1 (secreted phosphoprotein), is an integrin binding glyco-phosphoprotein produced by a variety of tissues. In cancer patients expression of OPN has been associated with poor prognosis in several tumor types including breast, lung, and colorectal cancers. Despite wide expression in tumor cells and stroma, there is limited evidence supporting role of OPN in tumor progression and metastasis. Using phage display technology we identified a high affinity anti-OPN monoclonal antibody (hereafter AOM1). The binding site for AOM1 was identified as SVVYGLRSKS sequence which is immediately adjacent to the RGD motif and also spans the thrombin cleavage site of the human OPN. AOM1 efficiently inhibited OPNa binding to recombinant integrin αvβ3 with an IC50 of 65 nM. Due to its unique binding site, AOM1 is capable of inhibiting OPN cleavage by thrombin which has been shown to produce an OPN fragment that is biologically more active than the full length OPN. Screening of human cell lines identified tumor cells with increased expression of OPN receptors (αvβ3 and CD44v6) such as mesothelioma, hepatocellular carcinoma, breast, and non-small cell lung adenocarcinoma (NSCLC). CD44v6 and αvβ3 were also found to be highly enriched in the monocyte, but not lymphocyte, subset of human peripheral blood mononuclear cells (hPBMCs). In vitro, OPNa induced migration of both tumor and hPBMCs in a transwell migration assay. AOM1 significantly blocked cell migration further validating its specificity for the ligand. OPN was found to be enriched in mouse plasma in a number of pre-clinical tumor model of non-small cell lung cancers. To assess the role of OPN in tumor growth and metastasis and to evaluate a potential therapeutic indication for AOM1, we employed a KrasG12D-LSLp53fl/fl subcutaneously implanted in vivo model of NSCLC which possesses a high capacity to metastasize into the lung. Our data indicated that treatment of tumor bearing mice with AOM1 as a single agent or in combination with Carboplatin significantly inhibited growth of large metastatic tumors in the lung further supporting a role for OPN in tumor metastasis and progression

The Ross Sea 2013 geological expedition: the Italian-Korean collaboration and preliminary results.

In February 2013 the Korean oceanographic cruise ANA03B was conducted on board of the IBRV ARAON (Kopri) in the Ross Sea (Antarctica). During the cruise a collaborative work between Korea and Italy was performed. The Italian participation was supported by PNRA in the framework of the ROSSLOPE Project (Past and present sedimentary dynamic in the ROSS Sea: a multidisciplinary approach to study the continental SLOPE ). The goal of the Rosslope and Kopri team collaboration was to collect geophysical and sedimentological data in the Central Basin area. In this presentation we report the preliminary results