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Modulated magnetically altered reaction yield (ModMARY) spectroscopy is a derivative variant of fluorescence detected magnetic field effect measurement, where the applied magnetic field has both a constant and a modulated component. As in many derivative spectroscopy techniques, the signal to noise ratio scales with the magnitude of the modulation. High modulation amplitudes, however, distort the signal and can obscure small features of the measured spectrum. In order to detect weak magnetic field effects (including the low field effect) a balance of the two has to be found. In this work we look in depth at the origin of the distortion of the MARY signal by field modulation. We then present an overtone detection scheme, as well as a data analysis method which allows for correct fitting of both harmonic and overtone signals of the modulation broadened MARY data. This allows us to robustly reconstruct the underlying MARY curve at different modulation depths. To illustrate the usefulness of the technique, we show measurements and analysis of a well known magnetosensitive system of pyrene/1,3-dicyanobenzene (Py/DCB). The measurements of first (h1) and second (h2) harmonic spectra are performed at different modulation depths for both natural isotopic abundance (PyH10), and perdeuterated (PyD10) pyrene samples.
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a stand-off Raman spectrometer has been developed to make observations of liquid samples within a gas pipeline. The instrument is based on a static Fourier Transform spectrometer. The high etendue offered by the instrument enabled four liquid samples to be measured from a distance of 2.4 m within a gas pipeline. Liquids were identified with depths less than 5 mm demonstrating that the concept is viable for active pipeline measurement.
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Magnetic field effect studies have been conducted on a variety of flavin-based radical pair systems chosen to model the magnetosensitivity of the photoinduced radical pairs found in cryptochrome flavoproteins. Cryptochromes are blue-light photoreceptor proteins which are thought to mediate avian magnetoreception, an hypothesis supported by recent in vitro observations of magnetic field-dependent reaction kinetics for a light-induced radical pair in a cryptochrome from the plant Arabidopsis thaliana. Many cryptochromes are difficult to express in large quantities or high concentrations and are easily photodegraded. Magnetic field effects are typically measured by spectroscopic detection of the transient radical (pair) concentrations. Due to its low sensitivity, single-pass transient absorption spectroscopy can be of limited use in such experiments and much recent work has involved development of other methodologies offering improved sensitivity. Here we explore the use of flavin fluorescence as the magnetosensitive probe and demonstrate the exceptional sensitivity of this technique which allows the detection of magnetic field effects in flavin samples at sub-nanomolar concentrations and in cryptochromes.
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Flavinas/química , Arabidopsis/química , Arabidopsis/metabolismo , Criptocromos/química , Campos Magnéticos , Espectrometría de FluorescenciaRESUMEN
We present a study of a carotenoid-porphyrin-fullerene triad previously shown to function as a chemical compass: the photogenerated carotenoid-fullerene radical pair recombines at a rate sensitive to the orientation of an applied magnetic field. To characterize the system we develop a time-resolved Low-Frequency Reaction Yield Detected Magnetic Resonance (tr-LF-RYDMR) technique; the effect of varying the relative orientation of applied static and 36 MHz oscillating magnetic fields is shown to be strongly dependent on the strength of the oscillating magnetic field. RYDMR is a diagnostic test for involvement of the radical pair mechanism in the magnetic field sensitivity of reaction rates or yields, and has previously been applied in animal behavioural experiments to verify the involvement of radical-pair-based intermediates in the magnetic compass sense of migratory birds. The spectroscopic selection rules governing RYDMR are well understood at microwave frequencies for which the so-called 'high-field approximation' is valid, but at lower frequencies different models are required. For example, the breakdown of the rotating frame approximation has recently been investigated, but less attention has so far been given to orientation effects. Here we gain physical insights into the interplay of the different magnetic interactions affecting low-frequency RYDMR experiments performed in the challenging regime in which static and oscillating applied magnetic fields as well as internal electron-nuclear hyperfine interactions are of comparable magnitude. Our observations aid the interpretation of existing RYDMR-based animal behavioural studies and will inform future applications of the technique to verify and characterize further the biological receptors involved in avian magnetoreception.
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Carotenoides/química , Fulerenos/química , Espectroscopía de Resonancia Magnética , Porfirinas/química , Espectroscopía de Resonancia por Spin del Electrón , Furanos/química , Campos Magnéticos , TermodinámicaRESUMEN
This publication presents an annotated accident dataset which fuses traffic data from radar detection sensors, weather condition data, and light condition data with traffic accident data (as illustrated in Fig. 1) in a format that is easy to process using machine learning tools, databases, or data workflows. The purpose of this data is to analyze, predict, and detect traffic patterns when accidents occur. Each file contains a timeseries of traffic speeds, flows, and occupancies at the sensor nearest to the accident, as well as 5 neighboring sensors upstream and downstream. It also contains information about the accident type, date, and time. In addition to the accident data, we provide baseline data for typical traffic patterns during a given time of day. Overall, the dataset contains 6 months of annotated traffic data from November 2020 to April 2021. During this timeframe, and 361 accidents occurred in the monitored area around Chattanooga, Tennessee. This dataset served as the basis for a study on topology-aware automated accident detection for a companion publication [1].
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The fact that many animals, including migratory birds, use the Earth's magnetic field for orientation and compass-navigation is fascinating and puzzling in equal measure. The physical origin of these phenomena has not yet been fully understood, but arguably the most likely hypothesis is based on the radical pair mechanism (RPM). Whilst the theoretical framework of the RPM is well-established, most experimental investigations have been conducted at fields several orders of magnitude stronger than the Earth's. Here we use transient absorption spectroscopy to demonstrate a pronounced orientation-dependence of the magnetic field response of a molecular triad system in the field region relevant to avian magnetoreception. The chemical compass response exhibits the properties of an inclination compass as found in migratory birds. The results underline the feasibility of a radical pair based avian compass and also provide further guidelines for the design and operation of exploitable chemical compass systems.
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Migración Animal , Aves , Criptocromos , Campos Magnéticos , Orientación Espacial , Animales , Carotenoides/efectos de la radiación , Química Física , Fulerenos/efectos de la radiación , Láseres de Estado Sólido , Fotoquímica , Porfirinas/efectos de la radiación , Análisis EspectralRESUMEN
Drosophila have been used as model organisms to explore both the biophysical mechanisms of animal magnetoreception and the possibility that weak, low-frequency anthropogenic electromagnetic fields may have biological consequences. In both cases, the presumed receptor is cryptochrome, a protein thought to be responsible for magnetic compass sensing in migratory birds and a variety of magnetic behavioural responses in insects. Here, we demonstrate that photo-induced electron transfer reactions in Drosophila melanogaster cryptochrome are indeed influenced by magnetic fields of a few millitesla. The form of the protein containing flavin and tryptophan radicals shows kinetics that differ markedly from those of closely related members of the cryptochrome-photolyase family. These differences and the magnetic sensitivity of Drosophila cryptochrome are interpreted in terms of the radical pair mechanism and a photocycle involving the recently discovered fourth tryptophan electron donor.
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Criptocromos/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas del Ojo/metabolismo , Campos Magnéticos , Fotoperiodo , Absorción de Radiación , Animales , Análisis EspectralRESUMEN
Broadband cavity-enhanced absorption spectroscopy (BBCEAS) is shown to be a sensitive method for the detection of magnetic field effects (MFEs) in two flavin-based chemical reactions which are simple models for cryptochrome magnetoreceptors. The advantages of optical cavity-based detection and (pseudo-white-light) supercontinuum radiation have been combined to provide full spectral coverage across the whole of the visible spectrum (425 < λ < 700 nm). This region covers the absorbance spectra of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) as well as their photogenerated radicals. To illustrate the power of this technique, BBCEAS has been used to record the spectral dependence of MFEs for photoinduced radical pairs formed in the intermolecular reaction of FMN with lysozyme and the intramolecular photochemistry of FAD. These reactions have been chosen for their photochemical similarities to cryptochrome proteins which have been proposed as key to the magnetic compass sense of many animals including birds. In experiments performed using low protein concentrations (10 µM) and 1 mm optical path-lengths, absorbance changes as small as 1 × 10(-7) (representing <0.1% MFEs) have been detected with good signal-to-noise offering the prospect of sensitive MFE detection in cryptochrome.
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Criptocromos/química , Modelos Químicos , Receptores de Superficie Celular/química , Animales , Flavinas/química , Campos Magnéticos , Análisis EspectralRESUMEN
We determine the spin-selective kinetics of a carotenoid-porphyrin-fullerene triad that has previously been used to establish the principle that a photochemical reaction could form the basis of the magnetic compass sensor of migratory birds and show that its magnetic sensitivity can be understood without invoking quantum Zeno effects.
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Magnetismo , Modelos Químicos , Marcadores de Spin , Carotenoides/química , Espectroscopía de Resonancia por Spin del Electrón , Fulerenos/química , Cinética , Porfirinas/química , Teoría CuánticaRESUMEN
Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. Additionally, recent research describes novel functions of ferritin independent of iron storage.
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Ferritinas/sangre , Ferritinas/metabolismo , Trastornos del Metabolismo del Hierro/metabolismo , Hierro/metabolismo , Quininógenos/metabolismo , Neoplasias/metabolismo , Apoferritinas/sangre , Apoferritinas/química , Apoferritinas/metabolismo , Ferritinas/química , Homeostasis/fisiología , Humanos , Hierro/sangre , Trastornos del Metabolismo del Hierro/terapiaRESUMEN
Recent studies have suggested that the presence of iron overload prior to stem cell transplantation is associated with decreased survival. Within these studies, the criteria used to define iron overload have varied considerably. Given the lack of consensus regarding the definition of iron overload in the transplant setting, we sought to methodically examine iron status among transplant patients. We studied 78 consecutive patients at risk for transfusion-related iron overload (diagnoses included AML, ALL, MDS, and aplastic anemia) who received either autologous or allogeneic stem cell transplant. Multiple measures of iron status were collected prior to transplantation and examined for their association with survival. Using this data, three potentially prognostic iron measures were identified and incorporated into a rational and unified scoring system. The resulting Transplant Iron Score assigns a point for each of the following variables: (1) greater than 25 red cell units transfused prior to transplantation; (2) serum ferritin > 1000 ng/ml; and (3) a semi-quantitative bone marrow iron stain of 6+. In our cohort, the score (range 0 to 3) was more closely associated with survival than any available single iron parameter. In multivariate analysis, we observed an independent effect of iron overload on transplant survival (p = 0.01) primarily attributable to an increase in early treatment-related deaths (p = 0.02) and lethal infections. In subgroup analysis, the predictive power of the iron score was most pronounced among allogeneic transplant patients, where a high score (> or = 2) was associated with a 50% absolute decrease in survival at one year. In summary, our results lend further credence to the notion that iron overload prior to transplant is detrimental and suggest iron overload may predispose to a higher rate of lethal infections.
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Sobrecarga de Hierro/mortalidad , Hierro/sangre , Leucemia/diagnóstico , Leucemia/terapia , Trasplante de Células Madre/mortalidad , Adulto , Anemia Aplásica/sangre , Anemia Aplásica/diagnóstico , Anemia Aplásica/mortalidad , Anemia Aplásica/terapia , Femenino , Humanos , Hierro/análisis , Sobrecarga de Hierro/etiología , Leucemia/sangre , Leucemia/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Pronóstico , Proyectos de Investigación , Trasplante de Células Madre/efectos adversos , Análisis de SupervivenciaRESUMEN
PURPOSE OF REVIEW: New therapies are needed for hormone refractory prostate cancer. Promising new treatments specifically target metastatic disease in the bone, the predominant site of spread in prostate cancer. Recent advances in the understanding of the biology of the tumor-bone microenvironment are leading to the development of new bone-targeted therapies. In this article, we review current and developing clinical strategies designed to control prostate-cancer bone metastases. RECENT FINDINGS: Newly developed biologic therapies that target prostate-cancer bone metastases have shown promising results in animal models and clinical trials. Additionally, currently established drugs such as bisphosphonates and bone-seeking radiopharmaceuticals are being applied in novel ways in an effort to improve patient care. SUMMARY: Therapies targeting bone in advanced prostate cancer have demonstrated improvements in morbidity, and more recently, in overall survival. The continuing development and use of these targeted therapies have the potential to alter the course of this currently fatal disease.