Photophysics and light induced photobiology of antiviral and antitumor agents, hypericin and hypocrellin

The dissertation mainly focuses on the excited-state photophysics and the light-induced biological activity of hypericin and its analogs.;Femtosecond laser technology has provided the opportunity to investigate the rapid dynamics of these molecules. Fluorescence upconversion measurements, which monitor only emission from the fluorescent singlet state, demonstrate that hexamethoxy hypericin, which possesses no labile protons, has an instantaneous rise time for its transient response. On the other hand, hypericin shows a clear 10-ps rise time. This confirms excited-state H-atom transfer as the primary photophysical process in hypericin.;Femtosecond transient absorption spectroscopy technique is used to determine if excited state H-atom transfer is concerted. Previous studies using human serum albumin (HSA) and hypericin suggested that excited state H-atom transfer is concerted, but the results from the hypericin in reverse micelles show no evidence for a concerted hydrogen atom transfer mechanism. We are, however, unable to conclude if only one hydrogen atom is transferred or if two are transferred in a stepwise fashion.;By means of time-resolved infrared spectroscopy, ab initio quantum mechanical calculations, and synthetic organic chemistry, a region in the infrared spectrum, between 1400 and 1500 cm-1, of triplet hypericin has been found corresponding to translocation of the hydrogen atom between the enol and the keto oxygens, O &cdots; H &cdots; O. This result is discussed in the context of the photophysics of hypericin and of eventual measurements to observe directly the excited-state H-atom transfer.;Light-induced antiviral activity of hypericin and hypocrellin is compared in normoxic and hypoxic conditions. Although both molecules require oxygen to show full virucidal effects, hypericin is still effective at low oxygen level where hypocrellin is not. Since the singlet oxygen yield of hypericin is about half of that of hypocrellin, this result cannot be explained by a traditional Type II mechanism. We propose that the ejected proton upon illumination might enhance the activity of activated oxygen species.;A series of hypericin analogs were found to differ in their cytotoxic activity induced by ambient light levels. These analogs vary in their ability to partition into cells, to generate singlet oxygen as well as in other photophysical properties. The percent distribution of hypericin and its analogs in cells are measured using a steady state absorption technique. We attempt to find a relationship between those results and the exact localization of the drug at subcellular level

Quantitative agreement of Dzyaloshinskii-Moriya interactions for domain-wall motion and spin-wave propagation

The magnetic exchange interaction is the one of the key factors governing the basic characteristics of magnetic systems. Unlike the symmetric nature of the Heisenberg exchange interaction, the interfacial Dzyaloshinskii-Moriya interaction (DMI) generates an antisymmetric exchange interaction which offers challenging opportunities in spintronics with intriguing antisymmetric phenomena. The role of the DMI, however, is still being debated, largely because distinct strengths of DMI have been measured for different magnetic objects, particularly chiral magnetic domain walls (DWs) and non-reciprocal spin waves (SWs). In this paper, we show that, after careful data analysis, both the DWs and SWs experience the same strength of DMI. This was confirmed by spin-torque efficiency measurement for the DWs, and Brillouin light scattering measurement for the SWs. This observation, therefore, indicates the unique role of the DMI on the magnetic DW and SW dynamics and also guarantees the compatibility of several DMI-measurement schemes recently proposed.Comment: 24 pages, 5 figure

Computed tomography-based imaging biomarker identifies coal workers’ pneumoconiosis

Rationale: The increase in the incidence and the diagnostic limitations of pneumoconiosis have emerged as a public health concern. This study aimed to conduct a computed tomography (CT)- based quantitative analysis to understand differences in imaging results of pneumoconiosis according to disease severity.Methods: According to the International Labor Organization (ILO) guidelines, coal workers’ pneumoconiosis (CWP) are classified into five categories. CT images were obtained only at full inspiration and were quantitatively evaluated for airway structural variables such as bifurcation angle (θ), hydraulic diameter (Dh), wall thickness (WT), and circularity (Cr). Parenchymal functional variables include abnormal regions (emphysema, ground–glass opacities, consolidation, semi consolidation, and fibrosis) and blood vessel volume. Through the propensity score matching method, the confounding effects were decreased.Results: Category 4 demonstrated a reduced θ in TriLUL, a thicker airway wall in both the Trachea and Bronint compared to Category 0, and a decreased Cr in Bronint. Category 4 presented with higher abnormal regions except for ground–glass opacity and a narrower pulmonary blood vessel volume. A negative correlation was found between abnormal areas with lower Hounsfield units (HU) than the normal lung and the ratio of forced expiratory volume in 1 s/forced vital capacity, with narrowed pulmonary blood vessel volume which is positively correlated with abnormal areas with upper HU than the normal lung.Conclusion: This study provided valuable insight into pneumoconiosis progression through a comparison of quantitative CT images based on severity. Furthermore, as there has been paucity of studies on the pulmonary blood vessel volume of the CWP, in this study, a correlation between reduced pulmonary blood vessel volume and regions with low HU values holds significant importance

Singular Hall response from a correlated ferromagnetic flat nodal-line semimetal

Topological quantum phases have been largely understood in weakly correlated systems, which have identified various quantum phenomena such as spin Hall effect, protected transport of helical fermions, and topological superconductivity. Robust ferromagnetic order in correlated topological materials particularly attracts attention, as it can provide a versatile platform for novel quantum devices. Here, we report singular Hall response arising from a unique band structure of flat topological nodal lines in combination with electron correlation in an itinerant, van der Waals ferromagnetic semimetal, Fe3GaTe2, with a high Curie temperature of Tc=360 K. High anomalous Hall conductivity violating the conventional scaling, resistivity upturn at low temperature, and a large Sommerfeld coefficient are observed in Fe3GaTe2, which implies heavy fermion features in this ferromagnetic topological material. Our circular dichroism in angle-resolved photoemission spectroscopy and theoretical calculations support the original electronic features in the material. Thus, low-dimensional Fe3GaTe2 with electronic correlation, topology, and room-temperature ferromagnetic order appears to be a promising candidate for robust quantum devices

Abstract P-4: Robust Method for Background Subtraction in Serial X-ray Diffraction Data

Background: Membrane receptors play an important role in signal transduction across the cell membrane in all living organisms. Their structural studies have been enabled by multiple technological breakthroughs in their heterologous expression, stabilization, crystallization, and crystallographic data collection as well as in cryogenic electron microscopy (cryoEM). During the last decade, serial femtosecond crystallography (SFX) using X-ray free electron lasers (XFELs) has enabled structure determination of previously inaccessible proteins, including several G-protein-coupled receptors (GPCR), that produce only micrometer-sized crystals, thus paving the way towards understanding their activation mechanism and rational drug discovery. In addition to experimental difficulties, membrane protein structure determination is also often accompanied by data processing challenges. In particular, the lipidic cubic phase that serves as a carrier for membrane protein microcrystals, as well as various XFEL beam-shaping devices may generate substantial background scattering that could complicate the structure factor extraction from the diffraction images. Methods: In this work, we tested an adaptation of the denoising algorithm via matrix decomposition to XFEL-SFX data. We benchmarked its performance using high-background data from PAL-XFEL and established its applicability to serial crystallography image denoising, as well as compared it to the CrystFEL-based image denoising algorithm. Results: We find that, although the decomposition-based image denoising does not outperform CrystFEL median subtraction, it performs better than the integration without any additional subtraction. We find the non-negative matrix factorization performing better than more traditional singular-value decomposition methods, both in terms of visual interpretability and final data quality. Conclusion: We hope that this work will draw attention to background subtraction methods in structural biology, and will pave the way towards processing of most challenging datasets in structural biology, in particularly, those collected from membrane proteins

Universal field-tunable terahertz emission by ultrafast photoinduced demagnetization in Fe, Ni, and Co ferromagnetic films

We report a universal terahertz (THz) emission behavior from simple Ni, Fe, and Co metallic ferromagnetic films, triggered by the femtosecond laser pulse and subsequent photoinduced demagnetization on an ultrafast time scale. THz emission behavior in ferromagnetic films is found to be consistent with initial magnetization states controlled by external fields, where the hysteresis of the maximal THz emission signal is observed to be well-matched with the magnetic hysteresis curve. It is experimentally demonstrated that the ultrafast THz emission by the photoinduced demagnetization is controllable in a simple way by external fields as well as pump fluences. © 2020, The Author(s).1

Photophysics and light induced photobiology of antiviral and antitumor agents, hypericin and hypocrellin

The dissertation mainly focuses on the excited-state photophysics and the light-induced biological activity of hypericin and its analogs.;Femtosecond laser technology has provided the opportunity to investigate the rapid dynamics of these molecules. Fluorescence upconversion measurements, which monitor only emission from the fluorescent singlet state, demonstrate that hexamethoxy hypericin, which possesses no labile protons, has an instantaneous rise time for its transient response. On the other hand, hypericin shows a clear 10-ps rise time. This confirms excited-state H-atom transfer as the primary photophysical process in hypericin.;Femtosecond transient absorption spectroscopy technique is used to determine if excited state H-atom transfer is concerted. Previous studies using human serum albumin (HSA) and hypericin suggested that excited state H-atom transfer is concerted, but the results from the hypericin in reverse micelles show no evidence for a concerted hydrogen atom transfer mechanism. We are, however, unable to conclude if only one hydrogen atom is transferred or if two are transferred in a stepwise fashion.;By means of time-resolved infrared spectroscopy, ab initio quantum mechanical calculations, and synthetic organic chemistry, a region in the infrared spectrum, between 1400 and 1500 cm-1, of triplet hypericin has been found corresponding to translocation of the hydrogen atom between the enol and the keto oxygens, O &cdots; H &cdots; O. This result is discussed in the context of the photophysics of hypericin and of eventual measurements to observe directly the excited-state H-atom transfer.;Light-induced antiviral activity of hypericin and hypocrellin is compared in normoxic and hypoxic conditions. Although both molecules require oxygen to show full virucidal effects, hypericin is still effective at low oxygen level where hypocrellin is not. Since the singlet oxygen yield of hypericin is about half of that of hypocrellin, this result cannot be explained by a traditional Type II mechanism. We propose that the ejected proton upon illumination might enhance the activity of activated oxygen species.;A series of hypericin analogs were found to differ in their cytotoxic activity induced by ambient light levels. These analogs vary in their ability to partition into cells, to generate singlet oxygen as well as in other photophysical properties. The percent distribution of hypericin and its analogs in cells are measured using a steady state absorption technique. We attempt to find a relationship between those results and the exact localization of the drug at subcellular level.</p