Observations on the International Law Commission’s Draft Rules on the Non-Navigational Uses of International Watercourses: “Management and Domestic Remedies

46 pages. Contains 11 pages of endnotes

Simultaneous fluorometry and phosphorometry of Langendorff perfused rat heart: ex vivo animal studies

Fluorescence imaging of intrinsic fluorophores of tissue is a powerful method to assess metabolic changes at the cellular and intracellular levels. At the same time, exogenous phosphorescent probes can be used to accurately measure intravascular tissue oxygenation. Heart failure is the leading cause of death in America. A rat heart can potentially model the human heart to study failures or other abnormalities optically. We report simultaneous fluorescence and phosphorescence measurements performed on a rat heart. We have used two different optical systems to acquire fluorescence signals of flavoprotein and nicotinamide adenine dinucleotide—the two intrinsic fluorophores of mitochondria—and the phosphorescence signal of an intravascular oxygen probe to extract intracellular and intravascular metabolism loads, respectively

Workflow for real-time in-vivo Cherenkov-excited luminescence imaging during radiotherapy

Radiotherapy is a common method for treating tumors, however, radiosensitivity can vary between tumor types or within the tumor microenvironment. The ability to deliver oxygen is crucial for the generation of reactive oxygen species resulting in increased localized cytotoxic effects. Alternatively, hypoxic tumors are thought to indicate a poor prognosis and may benefit from more aggressive treatments, yet identifying tumor hypoxia early in the course of a multi-week fractionated dose regimen is currently impractical. Using a time-gated imaging system and oxygen-sensitive phosphorescent compound (PtG4) we are able to estimate in vivo pO2 distribution at a rate of 2.6 estimates per second, which corresponds to 50+ values during a common 2Gy dose fraction. While our previous work has reported using Cherenkov-excited luminescence to estimate in vivo pO2 during external beam radiotherapy, the dose required was often greater than a standard fraction and camera acquisition parameters required modification during treatments, resulting in interrupted workflows. The current method utilizes custom control software which cycles through camera timing parameters during acquisition. Python code using the web-based user interface JupyterLab allows for interactive analysis of the resulting image stack without the need to pay expensive licensing fees for scientific computing packages. Using open source libraries, the analysis code is able to split the image stack into respective Cherenkov excitation and phosphorescence images, which can then be further automatically segmented to find regions of interest including the subject and phosphorescent region. The intensity of the regions in the phosphorescence images are used to estimate the compound lifetime, which can then be used in the Stern-Volmer relationship to estimate pO2. This entire process does not compromise clinical workflow and is able to provide a pO2 estimate within minutes after delivering the fractionated dose, providing clinicians early feedback about trends in tumor hypoxia. The current method has been validated with both direct injection of 50mM PtG4 in Matrigel in a mouse flank, and 24hrs post IV injection of mouse with MDA-MB-231 tumor implanted in the flank. The mouse with the direct injection was imaged under anesthesia and while awake and mobile to test the ability of the automated segmentation algorithm (Figure below). While the signal from the IV injection was less intense, simultaneous imaging using the previously reported method and current method resulted in similar lifetime estimates. While oxygen-sensitive PtG4 exhibits a lifetime between 16ms under atmospheric oxygen and 47ms when deprived of oxygen, other compounds have also been investigated. Europium chelate nanoparticle (~600ms), Iridium-based small molecules (~5ms), Si nanoparticles (~60ms), and UV-sensitive tattoo inks (~15ms) have all been imaged using Cherenkov-excitation. Camera time-gating can be utilized to discriminate these compound when mixed in the same field, allowing for additional tools in the realm of contrast enhancement during radiotherapy imaging. Ongoing studies with PtG4 and other compounds are being conducted to further improve system sensitivity and refine imaging workflows so they are more clinically translatable. Please click Additional Files below to see the full abstract

Mesoscopic effective material parameters for thin layers modeled as single and double grids of interacting loaded wires

As an example of thin composite layers we consider single and double grids of periodically arranged interacting wires loaded with a certain distributed reactive impedance. Currents induced to the wires by a normally incident plane wave are rigorously calculated and the corresponding dipole moment densities are determined. Using this data and the averaged fields we assign mesoscopic material parameters for the proposed grid structures. These parameters depend on the number of grids, and measure the averaged induced polarizations. It is demonstrated that properly loaded double grids possess polarization response that over some frequency range can be described by assigning negative values for the mesoscopic parameters. Discussion is conducted on the physical meaningfulness to assign such material parameters for thin composite slabs. The results predicted by the proposed method for the double-grid structures are compared with the results obtained using the commonly adopted S-parameter retrieval procedure.Comment: 36 pages, 23 figure

Electromagnetic wave refraction at an interface of a double wire medium

Plane-wave reflection and refraction at an interface with a double wire medium is considered. The problem of additional boundary conditions (ABC) in application to wire media is discussed and an ABC-free approach, known in the solid state physics, is used. Expressions for the fields and Poynting vectors of the refracted waves are derived. Directions and values of the power density flow of the refracted waves are found and the conservation of the power flow through the interface is checked. The difference between the results, given by the conventional model of wire media and the model, properly taking into account spatial dispersion, is discussed.Comment: 17 pages, 11 figure