Harnessing Sulfinyl Nitrenes: A Unified One-Pot Synthesis of Sulfoximines and Sulfonimidamides.

Sulfoximines and sulfonimidamides are promising compounds for medicinal and agrochemistry. As monoaza analogues of sulfones and sulfonamides, respectively, they combine good physicochemical properties, high stability, and the ability to build complexity from a three-dimensional core. However, a lack of quick and efficient methods to prepare these compounds has hindered their uptake in molecule discovery programmes. Herein, we describe a unified, one-pot approach to both sulfoximines and sulfonimidamides, which exploits the high electrophilicity of sulfinyl nitrenes. We generate these rare reactive intermediates from a novel sulfinylhydroxylamine (R-O-N=S=O) reagent through an N-O bond fragmentation process. Combining sulfinyl nitrenes with carbon and nitrogen nucleophiles enables the synthesis of sulfoximines and sulfonimidamides in a reaction time of just 15 min. Alkyl, (hetero)aryl, and alkenyl organometallic reagents can all be used as the first or second component in the reaction, while primary and secondary amines, and anilines, all react with high efficiency as the second nucleophile. The tolerance of the reaction to steric and electronic factors has allowed for the synthesis of the most diverse set of sulfoximines and sulfonimidamides yet described. Experimental and computational investigations support the intermediacy of sulfinyl nitrenes, with nitrene formation proceeding via a transient triplet intermediate before reaching a planar singlet species.

Economic uncertainty before and during the COVID-19 pandemic.

We consider several economic uncertainty indicators for the US and UK before and during the COVID-19 pandemic: implied stock market volatility, newspaper-based policy uncertainty, Twitter chatter about economic uncertainty, subjective uncertainty about business growth, forecaster disagreement about future GDP growth, and a model-based measure of macro uncertainty. Four results emerge. First, all indicators show huge uncertainty jumps in reaction to the pandemic and its economic fallout. Indeed, most indicators reach their highest values on record. Second, peak amplitudes differ greatly - from a 35% rise for the model-based measure of US economic uncertainty (relative to January 2020) to a 20-fold rise in forecaster disagreement about UK growth. Third, time paths also differ: Implied volatility rose rapidly from late February, peaked in mid-March, and fell back by late March as stock prices began to recover. In contrast, broader measures of uncertainty peaked later and then plateaued, as job losses mounted, highlighting differences between Wall Street and Main Street uncertainty measures. Fourth, in Cholesky-identified VAR models fit to monthly U.S. data, a COVID-size uncertainty shock foreshadows peak drops in industrial production of 12-19%.

Visible Light Photocatalysis of 6π Heterocyclization.

Photo-mediated 6π cyclization is a valuable method for the formation of fused heterocyclic systems. Here we demonstrate that irradiation of cyclic 2-aryloxyketones with blue LED light in the presence of an IrIII complex leads to efficient and high yielding arylation across a panoply of substrates by energy transfer. 2-Arylthioketones and 2-arylaminoketones also cyclize effectively under these conditions. Quantum calculation demonstrates that the reaction proceeds via conrotatory ring closure in the triplet excited state. Subsequent suprafacial 1,4-hydrogen shift and epimerization leads to the observed cis-fused products.

Recent applications in natural product synthesis of dihydrofuran and -pyran formation by ring-closing alkene metathesis.

In the past two decades, alkene metathesis has risen in prominence to become a significant synthetic strategy for alkene formation. Many total syntheses of natural products have used this transformation. We review the use, from 2003 to 2015, of ring-closing alkene metathesis (RCM) for the generation of dihydrofurans or -pyrans in natural product synthesis. The strategies used to assemble the RCM precursors and the subsequent use of the newly formed unsaturation will also be highlighted and placed in context.

Clotting activity of polyphosphate-functionalized silica nanoparticles.

We present a silica nanoparticle (SNP) functionalized with polyphosphate (polyP) that accelerates the natural clotting process of the body. SNPs initiate the contact pathway of the blood-clotting system; short-chain polyP accelerates the common pathway by the rapid formation of thrombin, which enhances the overall blood-clotting system, both by accelerating fibrin generation and by facilitating the regulatory anticoagulation mechanisms essential for hemostasis. Analysis of the clotting properties of bare SNPs, bare polyP, and polyP-functionalized SNPs in plasma demonstrated that the attachment of polyP to SNPs to form polyP-SNPs creates a substantially enhanced synergistic effect that lowers clotting time and increases thrombin production at low concentrations. PolyP-SNP even retains its clotting function at ambient temperature. The polyP-SNP system has the potential to significantly improve trauma-treatment protocols and outcomes in hospital and prehospital settings.

The Impact of Standard vs Early Apical Release Holmium Laser Enucleation of the Prostate Technique on Postoperative Incontinence and Quality of Life.

OBJECTIVE: To investigate the difference in postoperative incontinence and quality of life comparing standard vs early apical release (EAR) Holmium Laser Enucleation of the Prostate (HoLEP). METHODS: A retrospective review was performed to identify patients who underwent HoLEP from December 2021 to December 2022 at a single tertiary referral center with two participating consultant urologists. Patients were assessed with questionnaires and evaluated clinically. We performed propensity score matching with a logistic regression and a 1:1 matching method. A propensity score-adjusted logistic regression (PSRM) was performed to compare the pads per day between surgical techniques controlling for age, prostate size, preoperative survey data, uroflow, and postvoid residual. RESULTS: One hundred fourteen patients underwent HoLEP, of which 60 patients were treated with EAR and 54 patients with standard technique. EAR technique demonstrated shorter operative times (P = .046). The EAR cohort demonstrated improved AUASS (P = .034, P = .001), QOL (P = .001, P <.001), and continence rates (P <.001, P <.001) at 6 and 12weeks postoperatively. PSRM showed that the standard HoLEP increased the risk of requiring ≥2 pads per day 4.2x (P = .031, HR 95%, CI=1.16, 15.35) and 8.3x (P <.001, HR 95% CI 3.17, 21.6) at 6 and 12weeks postoperatively. CONCLUSION: EAR technique promoted earlier return of continence and improved quality of life within 6weeks of surgery.

Excision of recurrent penile schwannoma with neurovascular bundle sparing: A novel surgical approach.

Penile schwannomas are rare, often painless lesions usually growing on the dorsum of the penis. A young and otherwise healthy male with recurrent painful penile schwannomas and decreased libido was successfully treated with surgical excision. Through fine dissection of the nerve fascicles leading to the primary schwannoma, the lesion was successfully removed without compromising erectile or ejaculatory function. This novel approach allowed for significant symptomatic relief and improved quality of life.

Remote epitaxial interaction through graphene.

The concept of remote epitaxy involves a two-dimensional van der Waals layer covering the substrate surface, which still enable adatoms to follow the atomic motif of the underlying substrate. The mode of growth must be carefully defined as defects, e.g., pinholes, in two-dimensional materials can allow direct epitaxy from the substrate, which, in combination with lateral epitaxial overgrowth, could also form an epilayer. Here, we show several unique cases that can only be observed for remote epitaxy, distinguishable from other two-dimensional material-based epitaxy mechanisms. We first grow BaTiO3 on patterned graphene to establish a condition for minimizing epitaxial lateral overgrowth. By observing entire nanometer-scale nuclei grown aligned to the substrate on pinhole-free graphene confirmed by high-resolution scanning transmission electron microscopy, we visually confirm that remote epitaxy is operative at the atomic scale. Macroscopically, we also show variations in the density of GaN microcrystal arrays that depend on the ionicity of substrates and the number of graphene layers.

Inference for epidemic models with time-varying infection rates: Tracking the dynamics of oak processionary moth in the UK.

Invasive pests pose a great threat to forest, woodland, and urban tree ecosystems. The oak processionary moth (OPM) is a destructive pest of oak trees, first reported in the UK in 2006. Despite great efforts to contain the outbreak within the original infested area of South-East England, OPM continues to spread.Here, we analyze data consisting of the numbers of OPM nests removed each year from two parks in London between 2013 and 2020. Using a state-of-the-art Bayesian inference scheme, we estimate the parameters for a stochastic compartmental SIR (susceptible, infested, and removed) model with a time-varying infestation rate to describe the spread of OPM.We find that the infestation rate and subsequent basic reproduction number have remained constant since 2013 (with R 0 between one and two). This shows further controls must be taken to reduce R 0 below one and stop the advance of OPM into other areas of England. Synthesis. Our findings demonstrate the applicability of the SIR model to describing OPM spread and show that further controls are needed to reduce the infestation rate. The proposed statistical methodology is a powerful tool to explore the nature of a time-varying infestation rate, applicable to other partially observed time series epidemic data.

Demographic effects of a megafire on a declining prairie grouse in the mixed-grass prairie.

Recent studies have documented benefits of small, prescribed fire and wildfire for grassland-dependent wildlife, such as lesser prairie-chickens (Tympanuchus pallidicintus), but wildlife demographic response to the scale and intensity of megafire (wildfire >40,000 ha) in modern, fragmented grasslands remains unknown. Limited available grassland habitat makes it imperative to understand if increasing frequency of megafires could further reduce already declining lesser prairie-chicken populations, or if historical evolutionary interactions with fire make lesser prairie-chickens resilient. To evaluate lesser prairie-chicken demographic response to megafires, we compared lek counts, nest density, and survival rates of adults, nests, and chicks before (2014-2016) and after (2018-2020) a 2017 megafire in the mixed-grass prairie of Kansas, USA (Starbuck fire ~254,000 ha). There was a 67% decline in attending males on leks post-fire and a 57% decline in occupied leks post-fire. Despite population declines as indicated by lek counts, adult female breeding season survival ( S ^ ) was similar pre- ( S ^  = 0.65 ± 0.08 [SE]) and post-fire (0.61 ± 0.08), as was chick survival (pre-fire: 0.23 ± 0.07; post-fire: 0.27 ± 0.11). Nest survival appeared lower post-fire (pre-fire: 0.38 ± 0.06; post-fire: 0.20 ± 0.06), but did not differ at the 95% confidence interval. Nest density of marked females declined 73% in areas burned by megafire. Although lesser prairie-chickens persisted in the study area and we documented minimal effects on most demographic rates, reduced lesser prairie-chicken abundance and reproductive output suggests full recovery may take >3 years. Increased propensity for megafire resulting from suppression of smaller fires, compounded by climate change and woody encroachment, may impose a short-term (3-5 year) threat to already declining lesser prairie-chicken populations.

Estimating the asphaltene critical nanoaggregation concentration region using ultrasonic measurements and Bayesian inference.

Bayesian inference and ultrasonic velocity have been used to estimate the self-association concentration of the asphaltenes in toluene using a changepoint regression model. The estimated values agree with the literature information and indicate that a lower abundance of the longer side-chains can cause an earlier onset of asphaltene self-association. Asphaltenes constitute the heaviest and most complicated fraction of crude petroleum and include a surface-active sub-fraction. When present above a critical concentration in pure solvent, asphaltene "monomers" self-associate and form nanoaggregates. Asphaltene nanoaggregates are thought to play a significant role during the remediation of petroleum spills and seeps. When mixed with water, petroleum becomes expensive to remove from the water column by conventional methods. The main reason of this difficulty is the presence of highly surface-active asphaltenes in petroleum. The nanoaggregates are thought to surround the water droplets, making the water-in-oil emulsions extremely stable. Due to their molecular complexity, modelling the self-association of the asphaltenes can be a very computationally-intensive task and has mostly been approached by molecular dynamic simulations. Our approach allows the use of literature and experimental data to estimate the nanoaggregation and its credible intervals. It has a low computational cost and can also be used for other analytical/experimental methods probing a changepoint in the molecular association behaviour.

Management of patients with hepatocellular adenoma: a single-institution experience.

BACKGROUND: Hepatocellular adenoma (HCA) is a rare benign liver tumour that may cause diagnostic and management dilemmas. This study describes the clinical and histopathological characteristics of patients who were treated for HCA in a tertiary referral hospital over a 17-year period. METHODS: A retrospective review was performed of prospectively collected data of all patients treated for HCA within the Northern Upper GI Surgical unit between 2002 and 2018. Immunohistochemical ß-catenin expression was evaluated. RESULTS: Thirty-two patients had histological or radiologically confirmed HCA. Twenty-eight patients underwent 30 operations and four patients were treated conservatively. The median age of the operative group was 43 years (range 19-83) and most patients were female (95%). The median body mass index was 28.7 (range 20-51), and nine patients (33%) were obese. Seven patients (25%) had multifocal HCA. Evidence of prior bleed or rupture or a perceived risk of either a bleed or malignant change (i.e. tumours ≥50 mm) were the most common indications for resection. There were no perioperative mortalities. Nuclear expression of ß-catenin by immunohistochemical staining was negative in all cases and there was no malignancy identified in any of the resected lesions. Two patients required transarterial embolization and two patients required a second liver resection for residual HCA. CONCLUSION: HCA is a rare lesion predominantly affecting females. Haemorrhage is seen frequently on imaging studies, occasionally requiring urgent angioembolization and/or surgical intervention. Malignant transformation and immunohistochemical ß-catenin expression are uncommon. HCA may be multifocal and residual tumours usually require ongoing surveillance and occasionally further intervention.

Quantification of the morphological characteristics of hESC colonies.

The maintenance of the undifferentiated state in human embryonic stem cells (hESCs) is critical for further application in regenerative medicine, drug testing and studies of fundamental biology. Currently, the selection of the best quality cells and colonies for propagation is typically performed by eye, in terms of the displayed morphological features, such as prominent/abundant nucleoli and a colony with a tightly packed appearance and a well-defined edge. Using image analysis and computational tools, we precisely quantify these properties using phase-contrast images of hESC colonies of different sizes (0.1-1.1 [Formula: see text]) during days 2, 3 and 4 after plating. Our analyses reveal noticeable differences in their structure influenced directly by the colony area [Formula: see text]. Large colonies (A > 0.6 mm2) have cells with smaller nuclei and a short intercellular distance when compared with small colonies (A < 0.2 mm2). The gaps between the cells, which are present in small and medium sized colonies with A ≤ 0.6 mm2, disappear in large colonies (A > 0.6 mm2) due to the proliferation of the cells in the bulk. This increases the colony density and the number of nearest neighbours. We also detect the self-organisation of cells in the colonies where newly divided (smallest) cells cluster together in patches, separated from larger cells at the final stages of the cell cycle. This might influence directly cell-to-cell interactions and the community effects within the colonies since the segregation induced by size differences allows the interchange of neighbours as the cells proliferate and the colony grows. Our findings are relevant to efforts to determine the quality of hESC colonies and establish colony characteristics database.

MI-Sim: A MATLAB package for the numerical analysis of microbial ecological interactions.

Food-webs and other classes of ecological network motifs, are a means of describing feeding relationships between consumers and producers in an ecosystem. They have application across scales where they differ only in the underlying characteristics of the organisms and substrates describing the system. Mathematical modelling, using mechanistic approaches to describe the dynamic behaviour and properties of the system through sets of ordinary differential equations, has been used extensively in ecology. Models allow simulation of the dynamics of the various motifs and their numerical analysis provides a greater understanding of the interplay between the system components and their intrinsic properties. We have developed the MI-Sim software for use with MATLAB to allow a rigorous and rapid numerical analysis of several common ecological motifs. MI-Sim contains a series of the most commonly used motifs such as cooperation, competition and predation. It does not require detailed knowledge of mathematical analytical techniques and is offered as a single graphical user interface containing all input and output options. The tools available in the current version of MI-Sim include model simulation, steady-state existence and stability analysis, and basin of attraction analysis. The software includes seven ecological interaction motifs and seven growth function models. Unlike other system analysis tools, MI-Sim is designed as a simple and user-friendly tool specific to ecological population type models, allowing for rapid assessment of their dynamical and behavioural properties.

Determination of Asphaltene Critical Nanoaggregate Concentration Region Using Ultrasound Velocity Measurements.

Asphaltenes constitute the heaviest, most polar and aromatic fraction of petroleum crucial to the formation of highly-stable water-in-crude oil emulsions. The latter occur during crude oil production as well as spills and cause difficulties to efficient remediation practice. It is thought that in nanoaggregate form, asphaltenes create elastic layers around water droplets enhancing stability of the emulsion matrix. Ultrasonic characterisation is a high-resolution non-invasive tool in colloidal analysis shown to successfully identify asphaltene nanoaggregation in toluene. The high sensitivity of acoustic velocity to molecular rearrangements and ease in implementation renders it an attractive method to study asphaltene phase properties. Currently, aggregation is thought to correspond to an intersection of two concentration-ultrasonic velocity regressions. Our measurements indicate a variation in the proximity of nanoaggregation which is not accounted for by present models. We attribute this uncertainty to physico-chemical heterogeneity of the asphaltene fraction driven by variation in molecular size and propose a critical nanoaggregation region. We treated asphaltenes from North and South American crude oils with ruthenium ion catalysed oxidation to characterize their n-alkyl appendages attached to aromatic cores. Principal component analysis was performed to investigate the coupling between asphaltene structures and velocity measurements and their impact on aggregation.

Application of a maximum likelihood algorithm to ultrasound modulated optical tomography.

In pulsed ultrasound modulated optical tomography (USMOT), an ultrasound (US) pulse performs as a scanning probe within the sample as it propagates, modulating the scattered light spatially distributed along its propagation axis. Detecting and processing the modulated signal can provide a 1-dimensional image along the US axis. A simple model is developed wherein the detected signal is modelled as a convolution of the US pulse and the properties (ultrasonic/optical) of the medium along the US axis. Based upon this model, a maximum likelihood (ML) method for image reconstruction is established. For the first time to our knowledge, the ML technique for an USMOT signal is investigated both theoretically and experimentally. The ML method inverts the data to retrieve the spatially varying properties of the sample along the US axis, and a signal proportional to the optical properties can be acquired. Simulated results show that the ML method can serve as a useful reconstruction tool for a pulsed USMOT signal even when the signal-to-noise ratio (SNR) is close to unity. Experimental data using 5 cm thick tissue phantoms (scattering coefficient µ(s) = 6.5 cm(-1), anisotropy factor g=0.93) demonstrate that the axial resolution is 160 µm and the lateral resolution is 600 µm using a 10 MHz transducer.