Aquatic Ferrous Solutions of Prebiotic Mineral Salts as Strong UV Protectants and Possible Loci of Life Origin.

Liposomes are lipid-bilayer vesicles that spontaneously self-assemble from fatty acids (or other amphiphiles) in water by encapsulating surrounding aqueous media. After British scientist Alec Bangham described this phenomenon in the early 1960s, they became a prominent participant in the hypotheses on life origin, particularly in the Lipid World model. A novel scenario of self-sustained Darwinian liposome evolution is based on ever-present natural phenomena of cyclic day/night solar UV radiation and gravitational submersion of liposomes in the Archean aqueous media. One of the assumptions of the hypothesis is the UV-shielding ability of the Archean waters that could protect the submerged liposomes from the damaging solar UV radiation. To corroborate the idea, we measured UV absorption in aquatic solutions of several ferrous mineral salts assumed to be present in Archean pools. Single-agent solutions of simple salts such as FeCl2-iron dichloride, FeCl3-iron trichoride, Fe(NO3)3-ferric nitride, NH4Fe(SO4)2-ferric ammonium sulfate, and (NH4)5[Fe(C6H4O7)2]-ferric ammonium citrate were tested. These direct measurements of UV light absorption supplement and reinforce the proposed hypothesis.

Exploring the Lipid World Hypothesis: A Novel Scenario of Self-Sustained Darwinian Evolution of the Liposomes.

According to the Lipid World hypothesis, life on Earth originated with the emergence of amphiphilic assemblies in the form of lipid micelles and vesicles (liposomes). However, the mechanism of appearance of the information molecules (ribozymes/RNA) accompanying that process, considered obligatory for Darwinian evolution, is unclear. We propose a novel scenario of self-sustained Darwinian evolution of the liposomes driven by ever-present natural phenomena: solar UV radiation, day/night cycle, gravity, and the formation of liposomes in an aqueous media. The central tenet of this scenario is the liposomes' encapsulation of the heavy solutes, followed by their gravitational submerging in the water. The submerged liposomes, being protected from the damaging UV radiation, acquire the longevity necessary for autocatalytic replication of amphiphiles, their mutation, and the selection of those amphiphilic assemblies that provide the greatest membrane stability. These two sets of adaptive compositional information (heavy content and amphiphilic assemblies design) generate a population of liposomes with self-replication/reproduction properties, which are amendable to mutation, inheritance, and selection, thereby establishing Darwinian progression. Temporary and spatial expansion of this liposomal population will provide the basis for the next evolutionary step-a transition of accidentally entrapped RNA precursor molecules into complex functional molecules, such as ribozymes/RNA.

Design of proton deflectometry with in situ x-ray fiducial for magnetized high-energy-density systems.

We report a design and implementation of proton deflectometry with an in situ reference x-ray image of a mesh to precisely measure non-uniform magnetic fields in expanding plasmas at the OMEGA and OMEGA EP laser facilities. The technique has been developed with proton and x-ray sources generated from both directly driven capsule implosions and short pulse laser-solid interactions. The accuracy of the measurement depends on the contrast of both the proton and x-ray images. We present numerical and analytic studies to optimize the image contrast using a variety of mesh materials and grid spacings. Our results show clear enhancement of the image contrast by factors of four to six using a high Z mesh with large grid spacing. This leads to further improvement in the accuracy of the magnetic field measurement using this technique in comparison with its first demonstration at the OMEGA laser facility [Rev. Sci. Instrum.93, 023502 (2022)RSINAK0034-674810.1063/5.0064263].

Dispersion calibration for the National Ignition Facility electron-positron-proton spectrometers for intense laser matter interactions.

Electron-positron pairs, produced in intense laser-solid interactions, are diagnosed using magnetic spectrometers with image plates, such as the National Ignition Facility Electron-Positron-Proton Spectrometers (EPPSs). Although modeling can help infer the quantitative value, the accuracy of the models needs to be verified to ensure measurement quality. The dispersion of low-energy electrons and positrons may be affected by fringe magnetic fields near the entrance of the EPPS. We have calibrated the EPPS with six electron beams from a Siemens Oncor linear accelerator (linac) ranging in energy from 2.7 MeV to 15.2 MeV as they enter the spectrometer. A Geant4 traveling-wave optical parametric amplifier of superfluorescence Monte Carlo simulation was set up to match depth dose curves and lateral profiles measured in water at 100 cm source-surface distance. An accurate relationship was established between the bending magnet current setting and the energy of the electron beam at the exit window. The simulations and measurements were used to determine the energy distributions of the six electron beams at the EPPS slit. Analysis of the scanned image plates together with the determined energy distribution arriving in the spectrometer provides improved dispersion curves for the EPPS.

Modeling multi-needle injection into solid tumor.

The discovery of mechanisms by which the cancer cells avoid the host immune attack (immune checkpoints) as well the capability of the monoclonal antibodies (mAbs) to blockade the checkpoint proteins on cancer and tumor-infiltrating cells (CTLA-4, PD-1, and PD-L1) promised new breakthroughs in the cure of cancer. After these mechanisms of cancer escaping the host immunity were undoubtedly confirmed in numerous experimental and clinical studies, the FDA approval of CTLA-4 and PD-1/PD-L1 mAbs for systemic treatment thought to revolutionize the outcome of cancer treatment. However, as of today, the anticipated curative effect of anti-CTLA-4 and PD-1/PD-L1 mAb treatments has been observed only in a small population of patients. In addition, systemic administration of mAbs in clinics has been found associated with new toxicity profiles, sometimes very severe. The main obstacle that hinders the mAbs therapy appears to be the inability of delivering mAbs to a sufficient number of cancer cells and tumor infiltrating cells. As an alternative to the systemic administration (or as a complement to it), local intratumoral delivery of mAbs has been anticipated to resolve that issue. However, unlike the systemic mAbs administration, for which formidable but surmountable obstacles (big size of mAbs ~150 kD, high interstitial fluid pressure in solid tumors, etc.) have been known to hamper mAbs delivery to cancer and tumor-infiltrating cells, the lack of effects of intratumoral mAbs administration remains completely incomprehensible and needs a new theoretical reconsideration that we have attempted in our analysis. It can be suggested that the limited benefits of the intratumoral mAbs administration appeared to be rooted in the same problem that hindered the effects of systemic mAbs administration: the inability to reach a sufficient number of cancer cells and tumor-infiltrating cells. We hypothesize that the core of the problem stems from the fact that the single-needle intratumoral injection forms a very localized, jet-like distribution of the drug (mAbs) that constitutes only a small fraction of the total volume of the tumor. In this light we are re-evaluating the theoretical reasonableness of the single-needle intratumoral injection approach. We propose that multi-needle injection will circumvent this limitation and for that we analyze the behavior of an injectant in tissues using different configurations of the injection needles. To accomplish this goal, we created a model of injectant distribution in a solid tissue based on the traditional technique of single-needle injection and then extended that model to a case of simultaneous multi-needle injection. To develop the model of drug delivery and transport in biological tissues, we followed a frequently used approach of modeling the diffusive transport of liquid through a porous media using the Darcy's law that relates the flow velocity, the pressure gradient, and the tissue permeability. The analysis demonstrates that a multi-needle injection setup provides a significantly more widespread and homogeneous injectant distribution within a solid tumor than that for a single needle injection for the same tumor size. Adding separate draining needles can further improve the delivery of injectant to cancer and tumor-infiltrating cells.

A multi-channel capacitive probe for electrostatic fluctuation measurement in the Madison Symmetric Torus reversed field pinch.

A 40-channel capacitive probe has been developed to measure the electrostatic fluctuations associated with the tearing modes deep into Madison Symmetric Torus (MST) reversed field pinch plasma. The capacitive probe measures the ac component of the plasma potential via the voltage induced on stainless steel electrodes capacitively coupled with the plasma through a thin annular layer of boron nitride (BN) dielectric (also serves as the particle shield). When bombarded by the plasma electrons, BN provides a sufficiently large secondary electron emission for the induced voltage to be very close to the plasma potential. The probe consists of four stalks each with ten cylindrical capacitors that are radially separated by 1.5 cm. The four stalks are arranged on a 1.3 cm square grid so that at each radial position, there are four electrodes forming a square grid. Every two adjacent radial sets of four electrodes form a cube. The fluctuating electric field can be calculated by the gradient of the plasma potential fluctuations at the eight corners of the cube. The probe can be inserted up to 15 cm (r/a = 0.7) into the plasma. The capacitive probe has a frequency bandwidth from 13 Hz to 100 kHz, amplifier-circuit limit, sufficient for studying the tearing modes (5-30 kHz) in the MST reversed-field pinch.