Exploring Geometrical, Electronic and Spectroscopic Properties of 2-Nitroimidazole-Based Radiopharmaceuticals via Computational Chemistry Methods.

Tumor hypoxia plays an important role in the clinical management and treatment planning of various cancers. The use of 2-nitroimidazole-based radiopharmaceuticals has been the most successful for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging probes, offering noninvasive means to assess tumor hypoxia. In this study we performed detailed computational investigations of the most used compounds for PET imaging, focusing on those derived from 2-nitroimidazole: fluoromisonidazole (FMISO), fluoroazomycin arabinoside (FAZA), fluoroetanidazole (FETA), fluoroerythronitroimidazole (FETNIM) and 2-(2-nitroimidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5). Conformational analysis, structural parameters, vibrational IR and Raman properties (within both harmonic and anharmonic approximations), as well as the NMR shielding tensors and spin-spin coupling constants were obtained by density functional theory (DFT) calculations and then correlated with experimental findings, where available. Furthermore, time-dependent DFT computations reveal insight into the excited states of the compounds. Our results predict a significant change in the conformational landscape of most of the investigated compounds when transitioning from the gas phase to aqueous solution. According to computational data, the 2-nitroimidazole moiety determines to a large extent the spectroscopic properties of its derivatives. Due to the limited structural information available in the current literature for the investigated compounds, the findings presented herein deepen the current understanding of the electronic structures of these five radiopharmaceuticals.

Trans-dimensional inversion for seafloor properties for three mud depocenters on the New England shelf under dynamical oceanographic conditionsa).

This paper presents inversion results for three datasets collected on three spatially separated mud depocenters (hereafter called mud ponds) during the 2022 Seabed Characterization Experiment (SBCEX). The data considered here represent modal time-frequency (TF) dispersion as estimated from a single hydrophone. Inversion is performed using a trans-dimensional (trans-D) Bayesian inference method that jointly estimates water-column and seabed properties along with associated uncertainties. This enables successful estimation of the seafloor properties, consistent with in situ acoustic core measurements, even when the water column is dynamical and mostly unknown. A quantitative analysis is performed to (1) compare results with previous modal TF trans-D studies for one mud pond but under different oceanographic condition, and (2) inter-compare the new SBCEX22 results for the three mud ponds. Overall, the estimated mud geoacoustic properties show no significant temporal variability. Further, no significant spatial variability is found between two of the mud ponds while the estimated geoacoustic properties of the third are different. Two hypotheses, considered to be equally likely, are explored to explain this apparent spatial variability: it may be the result of actual differences in the mud properties, or the mud properties may be similar but the inversion results are driven by difference in data information content.

Depth and frequency dependence of geoacoustic properties on the New England Mud Patch from reflection coefficient inversiona).

Muddy sediments cover significant portions of continental shelves, but their physical properties remain poorly understood compared to sandy sediments. This paper presents a generally applicable model for sediment-column structure and variability on the New England Mud Patch (NEMP), based on trans-dimensional Bayesian inversion of wide-angle, broadband reflection-coefficient data in this work and in two previously published reflection-coefficient inversions at different sites on the NEMP. The data considered here include higher frequencies and larger bandwidth and cover lower reflection grazing angles than the previous studies, hence, resulting in geoacoustic profiles with significantly better structural resolution and smaller uncertainties. The general sediment-column structure model includes an upper mud layer in which sediment properties change slightly with depth due to near-surface processes, an intermediate mud layer with nearly uniform properties, and a geoacoustic transition layer where properties change rapidly with depth (porosity decreases and sound speed, density, and attenuation increase) due to increasing sand content in the mud above a sand layer. Over the full frequency band considered in the new and two previous data sets (400-3125 Hz), there is no significant sound-speed dispersion in the mud, and attenuation follows an approximately linear frequency dependence.

"Three Decades of Research:" A New Sex Ed Agenda and the Veneer of Science.

The research review, "Three Decades of Research: The Case for Comprehensive Sex Education," by Goldfarb and Lieberman (2021), purports to show "strong support" for the effectiveness of school-based comprehensive sex education (CSE) at producing many benefits beyond its original goals of preventing teen pregnancy and STDs. We reviewed the evidence the study cites in support of these claims, item by item, and found that 1) 80% of the sources cited as supporting evidence for CSE are not studies of CSE programs and 2) of the few cited studies of actual CSE programs, roughly 90% do not meet recommended scientific standards for evidence of program effectiveness. Important to note, contrary to its claims, the study does not show scientific evidence that comprehensive sex education helps prevent child sex abuse, reduces dating/intimate partner violence or homophobic bullying, or that it should be taught to young children in the early grades. Rather than making "the case for CSE," Goldfarb and Lieberman's review gives the appearance of scientific support to a new CSE agenda that the authors articulate and endorse, which includes early sex education, gender ideology, and social justice theory. However, they do not present scientifically reliable confirmatory evidence for that agenda.

Direct Measurement of the Local Density of Optical States in the Time Domain.

One of the most fundamental and relevant properties of a photonic system is the local density of optical states (LDOS) as it defines the rate at which an excited emitter dissipates energy by coupling to its surrounding. However, the direct determination of the LDOS is challenging as it requires measurements of the complex electric field of a point dipole at its own position. We introduce here a near-field setup which can measure the terahertz electric field amplitude at the position of a point source in the time domain. From the measured amplitude, the frequency-dependent imaginary component of the electric field can be determined and the LDOS can be retrieved. As a proof of concept, this setup has been used to measure the partial LDOS (the LDOS for a defined dipole orientation) as a function of the distance to planar interfaces made of gold, InSb, and quartz. Furthermore, the spatially dependent partial LDOS of a resonant gold rod has been measured as well. These results have been compared with analytical results and simulations. The excellent agreement between measurements and theory demonstrates the applicability of this setup for the quantitative determination of the LDOS in complex photonic systems.

The intralaminar thalamus: a review of its role as a target in functional neurosurgery.

The intralaminar thalamus, in particular the centromedian-parafascicular complex, forms a strategic node between ascending information from the spinal cord and brainstem and forebrain circuitry that involves the cerebral cortex and basal ganglia. A large body of evidence shows that this functionally heterogeneous region regulates information transmission in different cortical circuits, and is involved in a variety of functions, including cognition, arousal, consciousness and processing of pain signals. Not surprisingly, the intralaminar thalamus has been a target area for (radio)surgical ablation and deep brain stimulation (DBS) in different neurological and psychiatric disorders. Historically, ablation and stimulation of the intralaminar thalamus have been explored in patients with pain, epilepsy and Tourette syndrome. Moreover, DBS has been used as an experimental treatment for disorders of consciousness and a variety of movement disorders. In this review, we provide a comprehensive analysis of the underlying mechanisms of stimulation and ablation of the intralaminar nuclei, historical clinical evidence, and more recent (experimental) studies in animals and humans to define the present and future role of the intralaminar thalamus as a target in the treatment of neurological and psychiatric disorders.

Joint trans-dimensional inversion for water-column sound speed and seabed geoacoustic models.

This letter considers joint estimation of the water-column sound-speed profile (SSP) and seabed geoacoustic model through Bayesian inversion of ocean-acoustic data. The inversion is formulated in terms of separate trans-dimensional models for the water column (as an unknown number of nodes of a piecewise-continuous SSP) and seabed (as an unknown number of uniform layers) to intrinsically parameterize each according to the information content of the data. The inversion estimates marginal posterior probability profiles, quantifying the resolution of water-column and seabed structure. To validate the proposed method, modal-dispersion data from the New England Mud Patch, collected using hand-deployable systems, are considered.

Thickness-dependent Auger scattering in a single WS2 microcrystal probed with time-resolved terahertz near-field microscopy.

Time-resolved terahertz (THz) spectroscopy has been shown as a powerful technique to non-invasively determine the charge carrier properties in photoexcited semiconductors. However, the long wavelengths of terahertz radiation reduce the applicability of this technique to large samples. Using THz near-field microscopy, we show THz measurements of the lifetime of 2D single exfoliated microcrystals of transition metal dichalcogenides (WS2). The increased spatial resolution of THz near-field microscopy allows spatial mapping of the evolution of the carrier lifetime, revealing Auger assisted surface defect recombination as the dominant recombination channel. THz near-field microscopy allows for the non-invasive and high-resolution investigation of material properties of 2D semiconductors relevant for nanoelectronic and optoelectronic applications.

High-Frequency Sheet Conductance of Nanolayered WS2 Crystals for Two-Dimensional Nanodevices.

Time-resolved terahertz (THz) spectroscopy is a powerful technique for the determination of charge transport properties in photoexcited semiconductors. However, the relatively long wavelengths of THz radiation and the diffraction limit imposed by optical imaging systems reduce the applicability of THz spectroscopy to large samples with dimensions in the millimeter to centimeter range. Exploiting THz near-field spectroscopy, we present the first time-resolved THz measurements on a single exfoliated 2D nanolayered crystal of a transition metal dichalcogenide (WS2). The high spatial resolution of THz near-field spectroscopy enables mapping of the sheet conductance for an increasing number of atomic layers. The single-crystalline structure of the nanolayered crystal allows for the direct observation of low-energy phonon modes, which are present in all thicknesses, coupling with free carriers. Density functional theory calculations show that the phonon mode corresponds to the breathing mode between atomic layers in the weakly bonded van der Waals layers, which can be strongly influenced by substrate-induced strain. The non-invasive and high-resolution mapping technique of carrier dynamics in nanolayered crystals by time-resolved THz time domain spectroscopy enables possibilities for the investigation of the relation between phonons and charge transport in nanoscale semiconductors for applications in two-dimensional nanodevices.

Hamilton's geoacoustic model.

The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.

Unveiling the Symmetry Protection of Bound States in the Continuum with Terahertz Near-Field Imaging.

Bound states in the continuum (BICs) represent a new paradigm in photonics due to the full suppression of radiation losses. However, this suppression has also hampered the direct observation of them. By using a double terahertz (THz) near-field technique that allows the local excitation and detection of the THz amplitude, we are able to map for the first time the electromagnetic field amplitude and phase of BICs over extended areas, unveiling the field-symmetry protection that suppresses the far-field radiation. This investigation, done for metasurfaces of dimer scatterers, reveals the in-plane extension and formation of BICs with antisymmetric phases, in agreement with coupled-dipole calculations. By displacing the scatterers, we show experimentally that a mirror symmetry is not a necessary condition for a BIC formation. Only π-rotation symmetry is required, making BICs exceptionally robust to structural changes. This work makes the local field of BICs experimentally accessible, which is crucial for the engineering of cavities with infinite lifetimes.

Fröhlich interaction dominated by a single phonon mode in CsPbBr3.

The excellent optoelectronic performance of lead halide perovskites has generated great interest in their fundamental properties. The polar nature of the perovskite lattice means that electron-lattice coupling is governed by the Fröhlich interaction. Still, considerable ambiguity exists regarding the phonon modes that participate in this crucial mechanism. Here, we use multiphonon Raman scattering and THz time-domain spectroscopy to investigate Fröhlich coupling in CsPbBr3. We identify a longitudinal optical phonon mode that dominates the interaction, and surmise that this mode effectively defines exciton-phonon scattering in CsPbBr3, and possibly similar materials. It is additionally revealed that the observed strength of the Fröhlich interaction is significantly higher than the expected intrinsic value for CsPbBr3, and is likely enhanced by carrier localization in the colloidal perovskite nanocrystals. Our experiments also unearthed a dipole-related dielectric relaxation mechanism which may impact transport properties.

On compressional wave attenuation in muddy marine sediments.

A method for measuring in situ compressional wave attenuation exploiting the spectral decay of reflection coefficient Bragg resonances is applied to fine-grained sediments in the New England Mud Patch. Measurements of layer-averaged attenuation in a 10.3 m mud layer yield 0.04 {0.03, 0.055} dB/m/kHz (braces indicate outer bounds); the attenuation is twice as large at a site with 3.2 m mud thickness. It is shown that both results are heavily influenced by a ∼1 m sand-mud transition interval created by geological and biological processes that mix sand (at the base of the mud) into the mud. Informed by the observations, it appears that the spatial dependence of mud layer attenuation across the New England Mud Patch can be predicted by accounting for the transition interval via simple scaling. Further, the ubiquity of the processes that form the transition interval suggests that the scaling may be applied to any muddy continental shelf. In principle, attenuation predictions in littoral environments could be substantively improved with a modest amount of geologic and biologic information.

Ship source level estimation and uncertainty quantification in shallow water via Bayesian marginalization.

This paper applies a non-linear Bayesian marginalization approach to ship spectral source level estimation in shallow water with unknown seabed properties and uncertain source depth. The algorithm integrates the posterior probability density over seabed models sampled via trans-dimensional Bayesian matched-field inversion and over depths/ranges of multiple point sources (representing different noise-generating components of a large ship) via Metropolis-Hastings sampling. Source levels and uncertainty are derived from marginal distributions for source strength. The approach is applied to radiated noise due to a container ship recorded on a bottom-moored horizontal array in shallow water. The average uncertainty is 3.8 dB/Hz for tonal frequencies.

GeoMx™ RNA Assay: High Multiplex, Digital, Spatial Analysis of RNA in FFPE Tissue.

RNA in situ hybridization (ISH) is a widely used technique for the localization of mRNA in tissues. Limitations to traditional ISH include the number of targets that can be analyzed concurrently and the ability for many of these assays to be used in formalin-fixed, paraffin-embedded tissues (FFPE). Here, we describe the GeoMx™ RNA assay that is capable of the highly multiplexed detection of mRNA targets in FFPE tissues. This assay utilizes ISH probes linked to indexing oligo barcodes via a photocleavable linker and the GeoMx Digital Spatial Profiler (DSP) Instrument to enable profiling of RNA targets in a region-of-interest-based method. In brief, 5 µm FFPE sections are dewaxed, target retrieved, digested with proteinase K, post-fixed, and then incubated overnight with GeoMx RNA detection probes. Stringent washes are performed followed by the addition of fluorescently labeled antibodies for use as morphology markers. User-defined regions of interest are then profiled on the GeoMx DSP through region-specific cleaving and collecting the photocleaved indexing oligos. Cleaved indices are then quantified using NanoString nCounter® Technology generating digital quantification of RNA expression with spatial context.

Geoacoustic inversion of the acoustic-pressure vertical phase gradient from a single vector sensor.

A vector sensor can provide measurements of ocean acoustic fields in terms of the acoustic pressure and three-dimensional particle velocity, providing potentially highly-informative data for applications such as geoacoustic inversion. This paper applies nonlinear Bayesian inversion to vector sensor data to estimate seabed geoacoustic properties and uncertainties in South China Sea. Linear-frequency-modulated source transmissions, recorded as acoustic pressure and vertical particle velocity, are processed to estimate the vertical phase gradient of acoustic pressure at multiple frequencies as the inversion data. An advantage of this type of data is that it can be modeled without knowledge of the source spectrum, allowing inversion with an unknown source and a single sensor. Geoacoustic inversion of phase-gradient data is carried out and compared to inversion of the vertical acoustic impedance, another type of vector-sensor data, independent of the source spectrum, which has been considered previously. Model selection for the optimal number of seabed sediment layers is carried out using Bayesian information criterion, and parameter estimates, uncertainties, and correlations are calculated using delayed-rejection adaptive Metropolis-Hastings sampling. Results indicate a three-layer seabed model (including the semi-infinite basement), with properties in agreement with independent measurements including a high-resolution seismic profile and surficial sediment type from a core.

Re-Examining the Evidence for School-Based Comprehensive Sex Education: A Global Research Review.

PURPOSE: To evaluate the global research on school-based comprehensive sex education (CSE) by applying rigorous and meaningful criteria to outcomes of credible studies in order to identify evidence of real program effectiveness. METHODS: We examined 120 studies of school-based sex education contained in the reviews of research sponsored by three authoritative agencies: the United Nations Educational, Scientific and Cultural Organization, the U.S. federal Teen Pregnancy Prevention Program, and the Centers for Disease Control and Prevention. Their reviews screened more than 600 hundred studies and accepted only those that reached a threshold of adequate scientific rigor. These included 60 U.S. studies and 43 non-U.S. studies of school-based CSE plus 17 U.S. studies of school-based abstinence education (AE). We evaluated these studies for evidence of effectiveness using criteria grounded in the science of prevention research: sustained positive impact (at least 12 months post-program), on a key protective indicator (abstinence, condom use-especially consistent use, pregnancy, or STDs), for the main (targeted) teenage population, and without negative/harmful program effects. RESULTS: Worldwide, six out of 103 school-based CSE studies (U.S. and non-U.S. combined) showed main effects on a key protective indicator, sustained at least 12 months post-program, excluding programs that also had negative effects. Sixteen studies found harmful CSE impacts. Looking just at the U.S., of the 60 school-based CSE studies, three found sustained main effects on a key protective indicator (excluding programs with negative effects) and seven studies found harmful impact. For the 17 AE studies in the U.S., seven showed sustained protective main effects and one study showed harmful effects. CONCLUSIONS: Some of the strongest, most current school-based CSE studies worldwide show very little evidence of real program effectiveness. In the U.S., the evidence, though limited, appeared somewhat better for abstinence education.

Cataloging fish sounds in the wild using combined acoustic and video recordings.

Although many fish are soniferous, few of their sounds have been identified, making passive acoustic monitoring (PAM) ineffective. To start addressing this issue, a portable 6-hydrophone array combined with a video camera was assembled to catalog fish sounds in the wild. Sounds are detected automatically in the acoustic recordings and localized in three dimensions using time-difference of arrivals and linearized inversion. Localizations are then combined with the video to identify the species producing the sounds. Uncertainty analyses show that fish are localized near the array with uncertainties < 50 cm. The proposed system was deployed off Cape Cod, MA and used to identify sounds produced by tautog (Tautoga onitis), demonstrating that the methodology can be used to build up a catalog of fish sounds that could be used for PAM and fisheries management.

Technical note: A 3D-printed phantom for routine accuracy check of Gamma Knife Icon HDMM system.

PURPOSE: To report a novel 3D-printed device ("SH phantom") that is designed for routine accuracy check of the Gamma Knife Icon High Definition Motion Management (HDMM) system. METHODS: SH phantom was designed using tinkerCAD software and printed on a commercial 3D printer. We evaluated the SH phantom on our Gamma Knife Icon unit regarding its usability and accuracy for routine HDMM QA. RESULTS: Single-axis and multiple-axis measurements validated the SH phantom design and implementation. An HDMM QA accuracy of 0.22 mm or better along single axis was found using SH phantom. CONCLUSIONS: The SH phantom proved to be a quick and simple tool to use to perform the HDMM system QA. The SH phantom was tested successfully and adopted by us as part of monthly QA for the Gamma Knife Icon.

Bowhead whale localization using time-difference-of-arrival data from asynchronous recorders.

This paper estimates bowhead whale locations and uncertainties using nonlinear Bayesian inversion of the time-difference-of-arrival (TDOA) of low-frequency whale calls recorded on onmi-directional asynchronous recorders in the shallow waters of the northeastern Chukchi Sea, Alaska. A Y-shaped cluster of seven autonomous ocean-bottom hydrophones, separated by 0.5-9.2 km, was deployed for several months over which time their clocks drifted out of synchronization. Hundreds of recorded whale calls are manually associated between recorders. The TDOA between hydrophone pairs are calculated from filtered waveform cross correlations and depend on the whale locations, hydrophone locations, relative recorder clock offsets, and effective waveguide sound speed. A nonlinear Bayesian inversion estimates all of these parameters and their uncertainties as well as data error statistics. The problem is highly nonlinear and a linearized inversion did not produce physically realistic results. Whale location uncertainties from nonlinear inversion can be low enough to allow accurate tracking of migrating whales that vocalize repeatedly over several minutes. Estimates of clock drift rates are obtained from inversions of TDOA data over two weeks and agree with corresponding estimates obtained from long-time averaged ambient noise cross correlations. The inversion is suitable for application to large data sets of manually or automatically detected whale calls.