Förster resonance energy transfer (FRET) imaging is an essential analytical method in biomedical research. The limited photon-budget experimentally available, however, imposes compromises between spatiotemporal and biochemical resolutions, photodamage and phototoxicity. The study of photon-statistics in biochemical imaging is thus important in guiding the efficient design of instrumentation and assays. Here, we show a comparative analysis of photon-statistics in FRET imaging demonstrating how the precision of FRET imaging varies vastly with imaging parameters. Therefore, we provide analytical and numerical tools for assay optimization. Fluorescence lifetime imaging microscopy (FLIM) is a very robust technique with excellent photon-efficiencies. However, we show that also intensity-based FRET imaging can reach high precision by utilizing information from both donor and acceptor fluorophores.

Cargo containers constitute the most critical component of global trade: 108 million containers represent the movement of about 95% of the world's manufactured goods. The steady increase in cargo container shipments has had a profound effect on world security: the threat associated with smuggling of shielded special nuclear material is elevated every year. Containers reaching the borders of the U.S. are currently not radiographically inspected due to time and dose considerations stemming from the use of bremsstrahlung beams for imaging. Bremsstrahlung spectra are low-energy peaked, resulting in low penetration values, especially through dense cargoes. The use of monoenergetic radiography beams could alleviate many of these problems due to higher energy and low background continuum. Using Monte Carlo simulations of a realistic imaging scenario with support from previous experimental measurements, we demonstrate how the use of monoenergetic photon beams in radiography can simultaneously reduce the radiation dose imparted to the cargo and any potential stowaways while increasing image quality. Dual-energy methods are leveraged to calculate material atomic number. Image quality is evaluated by measuring the noise standard deviation, contrast-to-noise ratio, and the pixel error as the dose is decreased.

Posttraumatic stress disorder (PTSD) is a serious psychosis leading to cognitive impairment. To restore cognitive functions for patients, the main treatments are based on medication or rehabilitation training but with limited effectiveness and strong side effects. Here, we demonstrate a new treatment approach for PTSD by using terahertz (THz) photons stimulating the hippocampal CA3 subregion. We verified that this method can nonthermally restore cognitive function in PTSD rats in vivo. After THz photon irradiation, the PTSD rats' recognitive index improved by about 10% in a novel object recognition test, the PTSD rats' accuracy improved by about 100% in a shuttler box test, the PTSD rats' numbers to identify target box was about 5 times lower in a Barnes maze test, and the rate of staying in new arm increased by approximately 40% in a Y-maze test. Further experimental studies found that THz photon (34.5 THz) irradiation could improve the expression of NR2B (increased by nearly 40%) and phosphorylated NR2B (increased by about 50%). In addition, molecular dynamics simulations showed that THz photons at a frequency of 34.5 THz are mainly absorbed by the pocket of glutamate receptors rather than by glutamate molecules. Moreover, the binding between glutamate receptors and glutamate molecules was increased by THz photons. This study offers a nondrug, nonthermal approach to regulate the binding between the excitatory neurotransmitter (glutamate) and NR2B. By increasing synaptic plasticity, it effectively improves the cognitive function of animals with PTSD, providing a promising treatment strategy for NR2B-related cognitive disorders.

Despite decades of research, the mechanism of anesthetic-induced unconsciousness remains incompletely understood, with some advocating for a quantum mechanical basis. Despite associations between general anesthesia and changes in physical properties such as electron spin, there has been no empirical demonstration that general anesthetics are capable of functional quantum interactions. In this work, we studied the linear and non-linear optical properties of the halogenated ethers sevoflurane (SEVO) and isoflurane (ISO), using UV-Vis spectroscopy, time dependent-density functional theory (TD-DFT) calculations, classical two-photon spectroscopy, and entangled two-photon spectroscopy. We show that both of these halogenated ethers interact with pairs of 800 nm entangled photons while neither interact with 800 nm classical photons. By contrast, nonhalogenated diethyl ether does not interact with entangled photons. This is the first experimental evidence that halogenated anesthetics can directly undergo quantum interaction mechanisms, offering a new approach to understanding their physicochemical properties.

The nervous system is one of the most complex expressions of biological evolution. Its high performance mostly relies on the basic principle of the action potential, a sequential activation of local ionic currents along the neural fiber. The implications of this essentially electrical phenomenon subsequently emerged in a more comprehensive electromagnetic perspective of neurotransmission. Several studies focused on the possible role of photons in neural communication and provided evidence of the transfer of photons through myelinated axons. A hypothesis is that myelin sheath would behave as an optical waveguide, although the source of photons is controversial. In a previous work, we proposed a model describing how photons would arise at the node of Ranvier. In this study we experimentally detected photons in the node of Ranvier by Ag+ photoreduction measurement technique, during electrically induced nerve activity. Our results suggest that in association to the action potential a photonic radiation takes place in the node.

In thin polymeric layers, external molecular analytes may well be confined within tiny surface nano/microcavities, or they may be attached to ligand adhesion binding sites via electrical dipole forces. Even though molecular trapping is followed by a variation of the entropic potential, the experimental evidence of entropic energy variation from molecular confinement is scarce because tiny thermodynamic energy density diverseness can be tracked only by sub-nm surface strain. Here, it is shown that water confinement within photon-induced nanocavities in Poly (2-hydroxyethyl methacrylate), (PHEMA) layers could be trailed by an entropic potential variation that competes with a thermodynamic potential from electric dipole attachment of molecular adsorbates in polymeric ligands. The nano/microcavities and the ligands were fabricated on a PHEMA matrix by vacuum ultraviolet laser photons at 157 nm. The entropic energy variation during confinement of water analytes on the photon processed PHEMA layer was monitored via sub-nm surface strain by applying white light reflectance spectroscopy, nanoindentation, contact angle measurements, Atomic Force Microscopy (AFM) imaging, and surface and fractal analysis. The methodology has the potency to identify entropic energy density variations less than 1 pJm-3 and to monitor dipole and entropic fields on biosurfaces.

Many of the quantum information applications rely on indistinguishable sources of polarization-entangled photons. Semiconductor quantum dots are among the leading candidates for a deterministic entangled photon source; however, due to their random growth nature, it is impossible to find different quantum dots emitting entangled photons with identical wavelengths. The wavelength tunability has therefore become a fundamental requirement for a number of envisioned applications, for example, nesting different dots via the entanglement swapping and interfacing dots with cavities/atoms. Here we report the generation of wavelength-tunable entangled photons from on-chip integrated InAs/GaAs quantum dots. With a novel anisotropic strain engineering technique based on PMN-PT/silicon micro-electromechanical system, we can recover the quantum dot electronic symmetry at different exciton emission wavelengths. Together with a footprint of several hundred microns, our device facilitates the scalable integration of indistinguishable entangled photon sources on-chip, and therefore removes a major stumbling block to the quantum-dot-based solid-state quantum information platforms.

Monolayers of transition metal dichalcogenide materials emerged as a new material class to study excitonic effects in solid state, as they benefit from enormous Coulomb correlations between electrons and holes. Especially in WSe2, sharp emission features have been observed at cryogenic temperatures, which act as single photon sources. Tight exciton localization has been assumed to induce an anharmonic excitation spectrum; however, the evidence of the hypothesis, namely the demonstration of a localized biexciton, is elusive. Here we unambiguously demonstrate the existence of a localized biexciton in a monolayer of WSe2, which triggers an emission cascade of single photons. The biexciton is identified by its time-resolved photoluminescence, superlinearity and distinct polarization in micro-photoluminescence experiments. We evidence the cascaded nature of the emission process in a cross-correlation experiment, which yields a strong bunching behaviour. Our work paves the way to a new generation of quantum optics experiments with two-dimensional semiconductors.

Quantum optics largely relies on the fundamental concept that the diffraction and interference patterns of a multi-partite state are determined by its de Broglie wavelength. In this paper we show that this is still true for a mixed state with one sub-system being in a classical coherent state and one being in entangled state. We demonstrate the quantum-classical light discrimination using de Broglie wavelength for the states with all classical parameters being the same.

Vertebrate rod photoreceptors evolved the astonishing ability to respond reliably to single photons. In parallel, the proximate neurons of the visual system evolved the ability to reliably encode information from a few single-photon responses (SPRs) as arising from the presence of an object of interest in the visual environment. These amazing capabilities were first inferred from measurements of human visual threshold by Hecht et al. (1942), whose paper has since been cited over 1,000 times. Subsequent research, in part inspired by Hecht et al.'s discovery, has directly measured rod SPRs, characterized the molecular mechanism responsible for their generation, and uncovered much about the specializations in the retina that enable the reliable transmission of SPRs in the teeth of intrinsic neuronal noise.

In vivo vibrational spectroscopic imaging is inhibited by relatively slow spectral acquisition on the second scale and low photon collection efficiency for a highly scattering system. Recently developed multiplex coherent anti-Stokes Raman scattering and stimulated Raman scattering techniques have improved the spectral acquisition time down to microsecond scale. These methods using a spectrometer setting are not suitable for turbid systems in which nearly all photons are scattered. We demonstrate vibrational imaging by spatial frequency multiplexing of incident photons and single photodiode detection of a stimulated Raman spectrum within 60 μs. Compared to the spectrometer setting, our method improved the photon collection efficiency by two orders of magnitude for highly scattering specimens. We demonstrated in vivo imaging of vitamin E distribution on mouse skin and in situ imaging of human breast cancerous tissues. The reported work opens new opportunities for spectroscopic imaging in a surgical room and for development of deep-tissue Raman spectroscopy toward molecular level diagnosis.

Entangled light sources are considered as core technology for multiple quantum network architectures. Of particular interest are sources that are based on a single quantum system as these offer intrinsic security due to the sub-Poissonian nature of the photon emission process. This is important for applications in quantum communication where multi-pair emission generally compromises performance. A large variety of sources has been developed, but the generated photons remained far from being utilized in established standard fiber networks, mainly due to lack of compatibility with telecommunication wavelengths. In this regard, single semiconductor quantum dots are highly promising photon pair sources as they can be engineered for direct emission at telecom wavelengths. In this work we demonstrate the feasibility of this approach. We report a week-long transmission of polarization-entangled photons from a single InAs/GaAs quantum dot over a metropolitan network fiber. The photons are in the telecommunication O-band, favored for fiber optical communication. We employ a polarization stabilization system overcoming changes of birefringence introduced by 18.23 km of installed fiber. Stable transmission of polarization-encoded entanglement with a high fidelity of 91% is achieved, facilitating the operation of sub-Poissonian quantum light sources over existing fiber networks.

Many quantum photonic technologies require the efficient generation of entangled pairs of photons, but to date there have been few ways to produce them reliably. Sources based on parametric down conversion operate at very low efficiency per pulse due to the probabilistic generation process. Semiconductor quantum dots can emit single pairs of entangled photons deterministically but they fall short due to the extremely low-extraction efficiency. Strategies for extracting single photons from quantum dots, such as embedding them in narrowband optical cavities, are difficult to translate to entangled photons. Here, we build a broadband optical antenna with an extraction efficiency of 65% ± 4% and demonstrate a highly-efficient entangled-photon source by collecting strongly entangled photons (fidelity of 0.9) at a pair efficiency of 0.372 ± 0.002 per pulse. The high brightness achieved by our source represents a step forward in the development of optical quantum technologies.

The aim of this work is to develop a discrete ordinates Boltzmann solver that can be used for calculation of absorbed dose from both photons and protons within an inverse planning optimiser, so as to perform accurate dose calculation throughout the whole of the inverse planning process. With photons, five transport sweeps were performed to obtain scattered photon fluence, and unscattered electron fluence was then obtained and used as a fixed source for solution of the electron transport equations. With protons, continuous slowing down was treated as a fixed source, and five transport sweeps were used to calculate scattered fluence. The total electron or proton fluence was multiplied by the stopping power ratio for the transport medium to obtain absorbed dose. The method was evaluated in homogeneous media and in a lung case where the planning target volume was surrounded by low-density lung material. Photon arc, proton passive scattering and proton arc treatments were considered. The results were compared to a clinically validated convolution dose calculation for photons, and with an analytical method for protons. In water-equivalent media, the discrete ordinates method agrees with the alternative algorithms to within 2%. Convergence is found to be sufficiently complete for water-, lung- and bone-equivalent materials after five iterations. The dose calculated by the relatively simple angular quadrature is seen to be very close to that calculated by a more comprehensive quadrature. For inhomogeneous lung plans, the method shows more heterogeneity of dose to the planning target volume than the comparative methods. The discrete ordinates Boltzmann solver provides a general framework for dose calculation with both photons and protons. The method is suitable for incorporation into an inverse planning optimiser, so that accurate dose calculation in a heterogeneous medium can be obtained throughout inverse planning, with the result that the final dose distribution is as predicted by the optimiser.

Treatment of uveal melanoma (UM) is generally successful, with local primary tumour control being at 90%-95%. Localized radiotherapy in the form of plaque brachytherapy or proton beam radiotherapy is the most common treatment modality in the UK. However, the basic mechanisms of radiation response, DNA repair and tissue reactions in UM have not been well documented previously. We have investigated the comparative radiosensitivity of four UM cell lines in response to exogenous radiation sources (both X-rays and protons), and correlated this with DNA repair protein expression and repair efficiency. We observed a broad range of radiosensitivity of different UM cell lines to X-rays and protons, with increased radioresistance correlating with elevated protein expression of ataxia telangiectasia mutated (ATM), a protein kinase involved in the signaling and repair of DNA double strand breaks. The use of an ATM inhibitor in UM cell lines enhanced radiosensitivity following both X-ray and proton irradiation, particularly in cells that contained high levels of ATM protein which are otherwise comparatively radioresistant. In proton-irradiated compared with non-irradiated primary enucleated UM patient samples, there was no significant difference in ATM protein expression. Our study therefore suggests that ATM is a potential target for increasing the radiosensitivity of more resistant UM subgroups.

The interactions between the electromagnetic field and the biological systems were extensively investigated, with remarkable results and advanced technologies. Nevertheless, the visible domain of the spectrum has been rather neglected, since the classic physics did not allow electronic transitions induced by visible light. Recently, the interaction of light with the matter has generated a new scientific domain known in Physics as optical manipulation, with the new concepts of optical matter and optical force. This article presents the results of our work concerning in vitro effects of High Density Green Photons (HDGP) irradiation on cell cultures: stimulation of cell proliferation and migration and a possible antioxidant action.

Strong interaction between two single photons is a long standing and important goal in quantum photonics. This would enable a new regime of nonlinear optics and unlock several applications in quantum information science, including photonic quantum gates and deterministic Bell-state measurements. In the context of quantum networks, it would be important to achieve interactions between single photons from independent photon pairs storable in quantum memories. So far, most experiments showing nonlinearities at the single-photon level have used weak classical input light. Here we demonstrate the storage and retrieval of a paired single photon emitted by an ensemble quantum memory in a strongly nonlinear medium based on highly excited Rydberg atoms. We show that nonclassical correlations between the two photons persist after retrieval from the Rydberg ensemble. Our result is an important step towards deterministic photon-photon interactions, and may enable deterministic Bell-state measurements with multimode quantum memories.

Low-energy X-rays induce Auger cascades by photoelectric absorption in iodine present in the DNA of cells labeled with 5-iodo-2'-deoxyuridine (IUdR). This photoactivation therapy results in enhanced cellular sensitivity to radiation which reaches its maximum with 50 keV photons. Synchrotron core facilities are the only way to generate such monochromatic beams. However, these structures are not adapted for the routine treatment of patients. In this study, we generated two beams emitting photon energy means of 42 and 50 keV respectively, from a conventional 225 kV X-ray source. Viability assays performed after pre-exposure to 10 μM of IUdR for 48h suggest that complex lethal damage is generated after low energy photons irradiation compared to 137Cs irradiation (662KeV). To further decipher the molecular mechanisms leading to IUdR-mediated radiosensitization, we analyzed the content of DNA damage-induced foci in two glioblastoma cell lines and showed that the decrease in survival under these conditions was correlated with an increase in the content of DNA damage-induced foci in cell lines. Moreover, the follow-up of repair kinetics of the induced double-strand breaks showed the maximum delay in cells labeled with IUdR and exposed to X-ray irradiation. Thus, there appears to be a direct relationship between the reduction of radiation survival parameters and the production of DNA damage with impaired repair of these breaks. These results further support the clinical potential use of a halogenated pyrimidine analog combined with low-energy X-ray therapy.

Postoperative radiation therapy substantially decreases local relapse and moderately reduces breast cancer mortality, but can be associated with increased late mortality due to cardiovascular morbidity and secondary malignancies. Sophistication of breast irradiation techniques, including conformal radiotherapy and intensity modulated radiation therapy, has been shown to markedly reduce cardiac and lung irradiation. The delivery of more conformal treatment can also be achieved with particle beam therapy using protons. Protons have superior dose distributional qualities compared to photons, as dose deposition occurs in a modulated narrow zone, called the Bragg peak. As a result, further dose optimization in breast cancer treatment can be reasonably expected with protons. In this review, we outline the potential indications and benefits of breast cancer radiotherapy with protons. Comparative planning studies and preliminary clinical data are detailed and future developments are considered.

The differential diagnosis between brain tumors recurrence and early neuroinflammation or late radionecrosis is still an unsolved problem. The new emerging magnetic resonance imaging, computed tomography, and positron emission tomography diagnostic modalities still lack sufficient accuracy. In the last years, a great effort has been made to develop radiotracers able to detect specific altered metabolic pathways or tumor receptor markers. Our research project aims to evaluate irradiation effects on radiopharmaceutical uptake and compare the kinetic of the fluorinate tracers. T98G glioblastoma cells were irradiated at doses of 2, 10, and 20 Gy with photons, and 18F-DOPA and 18F-FET tracer uptake was evaluated. Activity and cell viability at different incubation times were measured. 18F-FET and 18F-DOPA are accumulated via the LAT-1 transporter, but 18F-DOPA is further incorporated, whereas 18F-FET is not metabolized. Therefore, time-activity curves (TACs) tend to plateau with 18F-DOPA and to a rapid washout with 18F-FET. After irradiation, 18F-DOPA TAC resembles the 18F-FET pattern. 18F-DOPA activity peak we observed at 20 min might be fictitious, because earlier time points have not been evaluated, and a higher activity peak before 20 min cannot be excluded. In addition, the activity retained in the irradiated cells remains higher in comparison to the sham ones at all time points investigated. This aspect is similar in the 18F-FET TAC but less evident. Therefore, we can hypothesize the presence of a second intracellular compartment in addition to the amino acidic pool one governed by LAT-1, which could explain the progressive accumulation of 18F-DOPA in unirradiated cells.