Optical orbital angular momentum analogy to the Stern-Gerlach experiment.

Symmetry breaking has been shown to reveal interesting phenomena in physical systems. A notable example is the fundamental work of Otto Stern and Walther Gerlach [Stern and Zerlach, Z. Physik9, 349 (1922)10.1007/BF01326983] nearly 100 years ago demonstrating a spin angular momentum (SAM) deflection that differed from classical theory. Here we use non-separable states of SAM and orbital angular momentum (OAM), known as vector vortex modes, to demonstrate how a classical optics analogy can be used to reveal this non-separability, reminiscent of the work carried out by Stern and Gerlach. We show that by implementing a polarization insensitive device to measure the OAM, the SAM states can be deflected to spatially resolved positions.

Big Data Warehouse for Healthcare-Sensitive Data Applications.

Obesity is a major public health problem worldwide, and the prevalence of childhood obesity is of particular concern. Effective interventions for preventing and treating childhood obesity aim to change behaviour and exposure at the individual, community, and societal levels. However, monitoring and evaluating such changes is very challenging. The EU Horizon 2020 project "Big Data against Childhood Obesity (BigO)" aims at gathering large-scale data from a large number of children using different sensor technologies to create comprehensive obesity prevalence models for data-driven predictions about specific policies on a community. It further provides real-time monitoring of the population responses, supported by meaningful real-time data analysis and visualisations. Since BigO involves monitoring and storing of personal data related to the behaviours of a potentially vulnerable population, the data representation, security, and access control are crucial. In this paper, we briefly present the BigO system architecture and focus on the necessary components of the system that deals with data access control, storage, anonymisation, and the corresponding interfaces with the rest of the system. We propose a three-layered data warehouse architecture: The back-end layer consists of a database management system for data collection, de-identification, and anonymisation of the original datasets. The role-based permissions and secured views are implemented in the access control layer. Lastly, the controller layer regulates the data access protocols for any data access and data analysis. We further present the data representation methods and the storage models considering the privacy and security mechanisms. The data privacy and security plans are devised based on the types of collected personal, the types of users, data storage, data transmission, and data analysis. We discuss in detail the challenges of privacy protection in this large distributed data-driven application and implement novel privacy-aware data analysis protocols to ensure that the proposed models guarantee the privacy and security of datasets. Finally, we present the BigO system architecture and its implementation that integrates privacy-aware protocols.

BigO: A public health decision support system for measuring obesogenic behaviors of children in relation to their local environment.

Obesity is a complex disease and its prevalence depends on multiple factors related to the local socioeconomic, cultural and urban context of individuals. Many obesity prevention strategies and policies, however, are horizontal measures that do not depend on context-specific evidence. In this paper we present an overview of BigO (http://bigoprogram.eu), a system designed to collect objective behavioral data from children and adolescent populations as well as their environment in order to support public health authorities in formulating effective, context-specific policies and interventions addressing childhood obesity. We present an overview of the data acquisition, indicator extraction, data exploration and analysis components of the BigO system, as well as an account of its preliminary pilot application in 33 schools and 2 clinics in four European countries, involving over 4,200 participants.

Experimental realization of arbitrary activation functions for optical neural networks.

We experimentally demonstrate an on-chip electro-optic circuit for realizing arbitrary nonlinear activation functions for optical neural networks (ONNs). The circuit operates by converting a small portion of the input optical signal into an electrical signal and modulating the intensity of the remaining optical signal. Electrical signal processing allows the activation function circuit to realize any optical-to-optical nonlinearity that does not require amplification. Such line shapes are not constrained to those of conventional optical nonlinearities. Through numerical simulations, we demonstrate that the activation function improves the performance of an ONN on the MNIST image classification task. Moreover, the activation circuit allows for the realization of nonlinearities with far lower optical signal attenuation, paving the way for much deeper ONNs.

Compact OAM microscope for edge enhancement of biomedical and object samples.

The production of orbital angular momentum (OAM) by using a q-plate, which functions as an electrically tunable spatial frequency filter, provides a simple and efficient method of edge contrast in biological and medical sample imaging for histological evaluation of tissue, smears, and PAP smears. An instrument producing OAM, such as a q-plate, situated at the Fourier plane of a 4f lens system, similar to the use of a high-pass spatial filter, allows the passage of high spatial frequencies and enables the production of an image with highly illuminated edges contrasted against a dark background for both opaque and transparent objects. Compared with ordinary spiral phase plates and spatial light modulators, the q-plate has the added advantage of electric control and tunability.

Spatial frequency analysis of anisotropic drug transport in tumor samples.

Directional Fourier spatial frequency analysis was used on standard histological sections to identify salient directional bias in the spatial frequencies of stromal and epithelial patterns within tumor tissue. This directional bias is shown to be correlated to the pathway of reduced fluorescent tracer transport. Optical images of tumor specimens contain a complex distribution of randomly oriented aperiodic features used for neoplastic grading that varies with tumor type, size, and morphology. The internal organization of these patterns in frequency space is shown to provide a precise fingerprint of the extracellular matrix complexity, which is well known to be related to the movement of drugs and nanoparticles into the parenchyma, thereby identifying the characteristic spatial frequencies of regions that inhibit drug transport. The innovative computational methodology and tissue validation techniques presented here provide a tool for future investigation of drug and particle transport in tumor tissues, and could potentially be used a priori to identify barriers to transport, and to analyze real-time monitoring of transport with respect to therapeutic intervention.

Late paleozoic fusulinoidean gigantism driven by atmospheric hyperoxia.

Atmospheric hyperoxia, with pO(2) in excess of 30%, has long been hypothesized to account for late Paleozoic (360-250 million years ago) gigantism in numerous higher taxa. However, this hypothesis has not been evaluated statistically because comprehensive size data have not been compiled previously at sufficient temporal resolution to permit quantitative analysis. In this study, we test the hyperoxia-gigantism hypothesis by examining the fossil record of fusulinoidean foraminifers, a dramatic example of protistan gigantism with some individuals exceeding 10 cm in length and exceeding their relatives by six orders of magnitude in biovolume. We assembled and examined comprehensive regional and global, species-level datasets containing 270 and 1823 species, respectively. A statistical model of size evolution forced by atmospheric pO(2) is conclusively favored over alternative models based on random walks or a constant tendency toward size increase. Moreover, the ratios of volume to surface area in the largest fusulinoideans are consistent in magnitude and trend with a mathematical model based on oxygen transport limitation. We further validate the hyperoxia-gigantism model through an examination of modern foraminiferal species living along a measured gradient in oxygen concentration. These findings provide the first quantitative confirmation of a direct connection between Paleozoic gigantism and atmospheric hyperoxia.

Improvement of cyclophosphamide activation by CYP2B6 mutants: from in silico to ex vivo.

Cyclophosphamide (CPA) is a chemotherapeutic agent that is primarily activated in the liver by cytochrome P4502B6 (CYP2B6) and then transported to the tumor via blood flow. To prevent deleterious secondary effects, P450-based gene-directed enzyme prodrug therapy (GDEPT) consists of expressing CYP2B6 in tumor cells before CPA treatment. Given the relatively low affinity of CYP2B6 for CPA, the aim of our work was to modify CYP2B6 to increase its catalytic efficiency (V(max)/K(m)) to metabolize CPA into 4'-OH CPA. A molecular model of CYP2B6 was built, and four residues in close contact with the substrate were subjected to mutagenesis. Canine CYP2B11 exhibiting a particularly low K(m) to CPA, the amino acids exclusively present in the CYP2B11 substrate recognition sequences were substituted in human CYP2B6. All mutants (n = 26) were expressed in Saccharomyces cerevisiae and their enzymatic constants (K(m), V(max)) evaluated using CPA as substrate. Five mutants exhibited a 2- to 3-fold higher catalytic efficiency than wild-type CYP2B6. A double mutant, comprising the two most effective mutations, showed a 4-fold increase in K(m)/V(max). Molecular dynamic simulations of several mutants were found to be consistent with the observed modifications in catalytic efficiency. Finally, expression of the CYP2B6 114V/477W double mutant, contrary to wt CYP2B6, allowed switching of a resistant human head and neck cancer cell line (A-253) into a sensitive cell line toward CPA. Thus, we were able to obtain a new efficient CYP2B6 mutant able to metabolize CPA, an important step in the GDEPT strategy for human cancer treatment.