Non‐oxidative, regioselective, and convergent access to densely functionalized oxazoles is realized in a functional‐group tolerant manner using alkynyl thioethers. Sulfur‐terminated alkynes provide ...access to reactivity previously requiring strong donor‐substituted alkynes such as ynamides. Sulfur does not act in an analogous donor fashion in this gold‐catalyzed reaction, thus leading to complementary regioselective outcomes and addressing the limitations of using ynamides.
Taking a different path: The first gold‐catalyzed annulations with alkynyl thioethers are reported. This transformation provides ready and convergent access into densely functionalized 1,3‐oxazole motifs. The sulfur substituent is integral to accessing the desired reactivity and provides a useful synthetic handle for later elaboration. In contrast with recent reports, the reaction does not follow a ketenethionium pathway.
This article examines the different ways that lesbian, gay, bisexual, transgender, and intersex (LGBTI) police liaison officers in three states of Australia conceptualized and problematized the ...public visibility of LGBTI police liaison services. In a climate where LGBTI police liaison services are a prominent model for building relationships between police and LGBTI people, this article considers, through interview data with LGBTI police liaison officers, these officers’ perceptions of the role that the visibility of these programs played in their success. Specifically, it explores the tensions and difficulties for officers and LGBTI communities resulting from the general invisibility of liaison officers themselves (and, by extension, these programs), as well as the problems that increased visibility of these programs might bring to officers, to LGBTI communities, and to policing work itself. Although enhancing the visibility of liaison services may be an important goal, this research suggests that careful consideration is required regarding how this visibility is produced and maintained, particularly given the concerns that officers reported about the potential risks posed by adopting new forms of visibility, including the risk of hypervisibility. This article questions the conventional view that increased visibility is unproblematic and is the key to the success of such programs.
A range of functionalized heteroaromatic boronic acid derivatives are readily accessed by a diboration/6π‐electrocyclization sequence. This study revealed the surprising observation that there is a ...direct relationship between oxime ether stereochemistry and reactivity towards electrocyclization. Specifically, E‐oxime ethers are found to be significantly more reactive than their Z‐counterparts (stereochemistry relative to azatriene scaffold). In contrast, the configuration at the azatriene alkene terminus has little impact on reaction rates. Computational analysis offers a rationale for this observation; a Nlone pair→C=C π* orbital interaction lowers the energy of the transition state in the electrocyclization of E‐oxime ethers. Finally, unreactive Z‐oxime ethers can be converted to the corresponding heterocyclic products by a photolytically promoted E→Z isomerization and electrocyclization sequence.
It's not all E/Z! E‐oxime ethers are found to be significantly more reactive in electrocyclizations than their Z‐counterparts because of an available transition state stabilizing orbital interaction in the former case. The scope of this chemistry to deliver useful heterocyclic products is also described.
Infection by soil transmitted parasitic helminths, such as Trichuris spp, are ubiquitous in humans and animals but the mechanisms determining persistence of chronic infections are poorly understood. ...Here we show that p43, the single most abundant protein in T. muris excretions/secretions, is non-immunogenic during infection and has an unusual sequence and structure containing subdomain homology to thrombospondin type 1 and interleukin (IL)-13 receptor (R) α2. Binding of p43 to IL-13, the key effector cytokine responsible for T. muris expulsion, inhibits IL-13 function both in vitro and in vivo. Tethering of p43 to matrix proteoglycans presents a bound source of p43 to facilitate interaction with IL-13, which may underpin chronic intestinal infection. Our results suggest that exploiting the biology of p43 may open up new approaches to modulating IL-13 function and control of Trichuris infections.
Pituitary adenoma is one of the most common primary intracranial neoplasms. Most of these tumors are soft, but up to 17% may have a firmer consistency. Therefore, knowing the tumor consistency in the ...preoperative setting could be helpful. Multiple imaging methods have been proposed to predict tumor consistency, but the results are controversial. This study aimed to evaluate the efficacy of MR elastography (MRE) in predicting tumor consistency and its potential use in a series of patients with pituitary adenomas.
Thirty-eight patients with pituitary adenomas (≥ 2.5 cm) were prospectively evaluated with MRI and MRE before surgery. Absolute MRE stiffness values and relative MRE stiffness ratios, as well as the relative ratio of T1 signal, T2 signal, and diffusion-weighted imaging apparent diffusion coefficient (ADC) values were determined prospectively by calculating the ratio of those values in the tumor to adjacent left temporal white matter. Tumors were classified into three groups according to surgical consistency (soft, intermediate, and firm). Statistical analysis was used to identify the predictive value of the different radiological parameters in determining pituitary adenoma consistency.
The authors included 32 (84.21%) nonfunctional and 6 (15.79%) functional adenomas. The mean maximum tumor diameter was 3.7 cm, and the mean preoperative tumor volume was 16.4 cm3. Cavernous sinus invasion was present in 20 patients (52.63%). A gross-total resection was possible in 9 (23.68%) patients. The entire cohort's mean absolute tumor stiffness value was 1.8 kPa (range 1.1-3.7 kPa), whereas the mean tumor stiffness ratio was 0.66 (range 0.37-1.6). Intraoperative tumor consistency was significantly correlated with absolute and relative tumor stiffness (p = 0.0087 and 0.007, respectively). Tumor consistency alone was not a significant factor for predicting gross-total resection. Patients with intermediate and firm tumors had more complications compared to patients with soft tumors (50.00% vs 12.50%, p = 0.02) and also had longer operative times (p = 0.0002).
Whereas other MRI sequences have proven to be unreliable in determining tumor consistency, MRE has been shown to be a reliable tool for predicting adenoma consistency. Preoperative knowledge of tumor consistency could be potentially useful for surgical planning, counseling about potential surgical risks, and estimating the length of operative time.
Alzheimer's disease (AD) alters astrocytes, but the effect of Aß and Tau pathology is poorly understood. TRAP-seq translatome analysis of astrocytes in APP/PS1 ß-amyloidopathy and MAPT
tauopathy mice ...revealed that only Aß influenced expression of AD risk genes, but both pathologies precociously induced age-dependent changes, and had distinct but overlapping signatures found in human post-mortem AD astrocytes. Both Aß and Tau pathology induced an astrocyte signature involving repression of bioenergetic and translation machinery, and induction of inflammation pathways plus protein degradation/proteostasis genes, the latter enriched in targets of inflammatory mediator Spi1 and stress-activated cytoprotective Nrf2. Astrocyte-specific Nrf2 expression induced a reactive phenotype which recapitulated elements of this proteostasis signature, reduced Aß deposition and phospho-tau accumulation in their respective models, and rescued brain-wide transcriptional deregulation, cellular pathology, neurodegeneration and behavioural/cognitive deficits. Thus, Aß and Tau induce overlapping astrocyte profiles associated with both deleterious and adaptive-protective signals, the latter of which can slow patho-progression.
A wide variety of Earth and planetary materials are very good recorders of paleomagnetic information. However, most magnetic grains in these materials are not in the stable single domain grain size ...range but are larger and in nonuniform vortex magnetization states. We provide a detailed account of vortex phenomena in geologic materials by simulating first‐order reversal curves (FORCs) via finite‐element micromagnetic modeling of magnetite nanoparticles with realistic morphologies. The particles have been reconstructed from focused ion beam nanotomography of magnetite‐bearing obsidian and accommodate single and multiple vortex structures. Single vortex (SV) grains have fingerprints with contributions to both the transient and transient‐free zones of FORC diagrams. A fundamental feature of the SV fingerprint is a central ridge, representing a distribution of negative saturation vortex annihilation fields. SV irreversible events at multiple field values along different FORC branches determine the asymmetry in the upper and lower lobes of generic bulk FORC diagrams of natural materials with grains predominantly in the vortex state. Multivortex (MV) FORC signatures are modeled here for the first time. MV grains contribute mostly to the transient‐free zone of a FORC diagram, averaging out to create a broad central peak. The intensity of the central peak is higher than that of the lobes, implying that MV particles are more abundant than SV particles in geologic materials with vortex state fingerprints. The abundance of MV particles, as well as their single domain‐like properties point to MV grains being the main natural remanent magnetization carriers in geologic materials.
Key Points
Micromagnetic modeling of FORC diagrams are key to understanding vortex phenomena in geologic materials
Single vortex assemblages have both remanent (notably, a central ridge) and transient FORC fingerprints
Multivortex assemblages are important remanence carriers; their FORC fingerprint is a broad central peak
The transition of Army Combat Medic Specialists (Military Occupational Specialty Code: 68W) from military to civilian emergency medical services (EMS) is challenging, and the pathway is not clearly ...defined. Our objective was to evaluate the current military requirements for 68W and how they compare to the 2019 EMS National Scope of Practice Model (SoPM) for the civilian emergency medical technician (EMT) and advanced emergency medical technician (AEMT).
This was a cross-sectional evaluation of the 68W skill floor as defined by the Soldier's Manual and Trainer's Guide Healthcare Specialist and Medical Education and Demonstration of Individual Competence in comparison to the 2019 SoPM, which categorizes EMS tasks into seven skill categories. Military training documents were reviewed and extracted for specific information on military scope of practice and task-specific training requirements. Descriptive statistics were calculated.
Army 68Ws were noted to perform all (59/59) tasks that coincide with the EMT SoPM. Further, Army 68W practiced above scope in the following skill categories: airway/ventilation (3 tasks); medication administration route (7 tasks); medical director approved medication (6 tasks); intravenous initiation maintenance fluids (4 tasks); and miscellaneous (1 task). Army 68W perform 96% (74/77) of tasks aligned with the AEMT SoPM, excluding tracheobronchial suctioning of an intubated patient, end-tidal CO
2
monitoring or waveform capnography, and inhaled nitrous oxide monitoring. Additionally, the 68W scope included six tasks that were above the SoPM for AEMT; airway/ventilation (2 tasks); medication administration route (2 tasks); and medical director approved medication (2 tasks).
The scope of practice of U.S. Army 68W Combat Medics aligns well with the civilian 2019 Scope of Practice Model for EMTs and AEMTs. Based on the comparative scope of practice analysis, transitioning from Army 68W Combat Medic to civilian AEMT would require minimal additional training. This represents a promising potential workforce to assist with EMS workforce challenges. Although aligning the scope of practice is a promising first step, future research is needed to assess the relationship of Army 68Ws training with state licensure and certification equivalency to facilitate this transition.
Identification of unknown micro‐ and nano‐sized mineral phases is commonly achieved by analyzing chemical maps generated from hyperspectral imaging data sets, particularly scanning electron ...microscope—energy dispersive X‐ray spectroscopy (SEM‐EDS). However, the accuracy and reliability of mineral identification are often limited by subjective human interpretation, non‐ideal sample preparation, and the presence of mixed chemical signals generated within the electron‐beam interaction volume. Machine learning has emerged as a powerful tool to overcome these problems. Here, we propose a machine‐learning approach to identify unknown phases and unmix their overlapped chemical signals. This approach leverages the guidance of Gaussian mixture modeling clustering fitted on an informative latent space of pixel‐wise elemental data points modeled using a neural network autoencoder, and unmixes the overlapped chemical signals of phases using non‐negative matrix factorization. We evaluate the reliability and the accuracy of the new approach using two SEM‐EDS data sets: a synthetic mixture sample and a real‐world particulate matter sample. In the former, the proposed approach successfully identifies all major phases and extracts background‐subtracted single‐phase chemical signals. The unmixed chemical spectra show an average similarity of 83.0% with the ground truth spectra. In the second case, the approach demonstrates the ability to identify potentially magnetic Fe‐bearing particles and their background‐subtracted chemical signals. We demonstrate a flexible and adaptable approach that brings a significant improvement to mineralogical and chemical analysis in a fully automated manner. The proposed analysis process has been built into a user‐friendly Python code with a graphical user interface for ease of use by general users.
Key Points
We develop a machine‐learning approach to automatically identify unknown mineral phases and unmix their compositional spectra
The approach successfully identifies all phases in a synthetic mixture data set with an average spectrum similarity 83% to the ground truth
The approach demonstrates its ability to generalize by identifying unknown minerals and their background‐subtracted chemical signals
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