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In this work, we use an extreme-ultraviolet (XUV) free-electron laser (FEL) to resonantly excite the I: 4d5/2-σ∗ transition of a gas-phase di-iodomethane (CH2I2) target. This site-specific excitation generates a 4d core hole located at an iodine site, which leaves the molecule in a well-defined excited state. We subsequently measure the time-dependent absorption change of the molecule with the FEL probe spectrum centered on the same I: 4d resonance. Using ab initio calculations of absorption spectra of a transient isomerization pathway observed in earlier studies, our time-resolved measurements allow us to assign the timescales of the previously reported direct and indirect dissociation pathways. The presented method is thus sensitive to excited-state molecular geometries in a time-resolved manner, following a core-resonant site-specific trigger.

Despite crucial roles of RNA-binding proteins (RBPs) in plant physiology and development, methods for determining their transcriptome-wide binding landscape are less developed than those used in other model organisms. Cross-linking and immunoprecipitation (CLIP) methods (based on UV-mediated generation of covalent bonds between RNAs and cognate RBPs in vivo, purification of the cross-linked complexes and identification of the co-purified RNAs by high-throughput sequencing) have been applied mainly in mammalian cells growing in monolayers or in translucent tissue. We have developed plant iCLIP2, an efficient protocol for performing individual-nucleotide-resolution CLIP (iCLIP) in plants, tailored to overcome the experimental hurdles posed by plant tissue. We optimized the UV dosage to efficiently cross-link RNA and proteins in plants and expressed epitope-tagged RBPs under the control of their native promoters in loss-of-function mutants. We select epitopes for which nanobodies are available, allowing stringent conditions for immunopurification of the RNA-protein complexes to be established. To overcome the inherently high RNase content of plant cells, RNase inhibitors are added and the limited RNA fragmentation step is modified. We combine the optimized isolation of RBP-bound RNAs with iCLIP2, a streamlined protocol that greatly enhances the efficiency of library preparation for high-throughput sequencing. Plant researchers with experience in molecular biology and handling of RNA can complete this iCLIP2 protocol in ~5 d. Finally, we describe a bioinformatics workflow to determine targets of Arabidopsis RBPs from iCLIP data, covering all steps from downloading sequencing reads to identifying cross-linking events ( https://github.com/malewins/Plant-iCLIPseq ), and present the R/Bioconductor package BindingSiteFinder to extract reproducible binding sites ( https://bioconductor.org/packages/release/bioc/html/BindingSiteFinder.html )., (© 2024. Springer Nature Limited.)

Sleep disturbances are common in individuals with posttraumatic stress disorder. Exercise interventions are a promising approach in the treatment of sleep disorders, but little is known about the efficacy of exercise interventions for sleep disturbances associated with posttraumatic stress disorder. A total of 40 individuals with posttraumatic stress disorder were randomized to six sessions of either high-intensity interval training or low-to-moderate-intensity training, administered within 12 days. Sleep quality was assessed over 24 days from baseline to post with the Pittsburgh Sleep Quality Index, a sleep log, and a waist-worn actigraphy. Analyses revealed that, regardless of group allocation, Pittsburgh Sleep Quality Index score improved significantly by 2.28 points for high-intensity interval training and 1.70 points for low-to-moderate-intensity training (d = 0.56 for high-intensity interval training; 0.49 for low-to-moderate-intensity training) over time, while there were no significant changes in any sleep log or actigraphy measure. Analysis of a subsample of those affected by clinically significant sleep disturbances (n = 24) revealed a significant time effect with no difference between exercise interventions: Pittsburgh Sleep Quality Index improved significantly by 2.65 points for high-intensity interval training and 2.89 points for low-to-moderate-intensity training (d = 0.53 for high-intensity interval training; 0.88 for low-to-moderate-intensity training), and actigraphy measure of wake after sleep onset was reduced significantly by 14.39 minutes for high-intensity interval training and 6.96 minutes for low-to-moderate-intensity training (d = 0.47 for high-intensity interval training; 0.11 for low-to-moderate-intensity training) from baseline to post. In our pilot study, we found an improvement in sleep quality from pre- to post-assessment. There were no significant differences between exercise groups. Further studies are needed to investigate whether the found time effects reflect the exercise intervention or unrelated factors., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

This paper presents an easy to operate time-dependent, two-dimensional vertical model for the simulation of sand and mud concentrations, transport, and morphodynamic bed evolution in conditions with combined currents and waves. The basic model equation is the advection–diffusion equation for sediments including flow velocities, sediment mixing coefficients, and the settling velocity. The vertical distribution of the sediment mixing coefficient is described by fairly simple and flexible expressions based on flow and wave parameters with user-specified coefficients for calibration of results. The settling velocity is constant or dependent on the sediment concentration to represent mud flocculation and hindered settling processes based on input parameters. The bed boundary condition is modeled by a bed concentration as a function of the bed-shear stress due to currents and waves. The model is valid for sand concentrations and for low and high mud concentrations including fluid mud concentrations. The numerical SUSTIM2DV model has been used to simulate sand and mud transport and bed level changes in dredged (shipping) channels. The model is valid for perpendicular and oblique flow across a dredged channel. The channel slopes should not be too steep (1V:7H or milder), because logarithmic velocity profiles are used. Results of various validation cases of channel deposition of sand, silt, and (fluid) mud in tidal conditions with and without waves are presented. The effect of channel geometry is specifically addressed. The numerical model has also been used to derive sediment trapping factors, which can be used in simpler channel deposition models. [ABSTRACT FROM AUTHOR]

Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries are efficient in triggering iron accumulation, which in turn can cause senescence and promote fibrosis. Notably, we find that senescent cells persistently accumulate iron, even when the surge of extracellular iron has subdued. Indeed, under normal conditions of extracellular iron, cells exposed to different types of senescence-inducing insults accumulate abundant ferritin-bound iron, mostly within lysosomes, and present high levels of labile iron, which fuels the generation of reactive oxygen species and the SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging might allow non-invasive assessment of fibrotic burden in the kidneys of mice and in patients with renal fibrosis. Our findings suggest that iron accumulation plays a central role in senescence and fibrosis, even when the initiating events may be independent of iron, and identify iron metabolism as a potential therapeutic target for senescence-associated diseases., (© 2023. The Author(s).)

In this paper, dry etched vertical nanowires (VNWs) are used in transmission line/transfer length analysis to study the contacts of gate-all-around devices for future technology nodes. VNW resistors with Mo and Pd based metal stack contacts to p-InGaAs show Schottky behavior, unlike the planar counterpart. The resistance for Mo contact is higher than Pd, however, Pd was found to form an alloy with InGaAs at temperatures as low as 190 °C, and the length of Pd diffusion into the InGaAs increased at smaller NW dimensions, hindering future scalability. The minimum extracted specific contact resistivity (ρC) values are 1.6 × 10−5 Ω cm2 (Mo) and 4.2 × 10−6 Ω cm2 (Pd) for a doping level of 1 × 1019 cm−3. An apparent dependence of ρC on the NW diameter was also observed. This has been attributed to the surface states under the un-gated region of NW devices and found to dominate at smaller diameters. An analytical model to account for such geometrical effects has also been developed and validated with technology computer-aided design simulations. The analysis presented in this paper effectively captures the 3D aspects of an NW contact at nanoscale dimensions and can be applied irrespective of the semiconductor and contact metal used. [ABSTRACT FROM AUTHOR]

Dispersal of propagules (seeds, spores) from a geographically isolated habitat into an uninhabitable matrix can play a decisive role in driving population dynamics. ODE and integrodifference models of these dynamics commonly feature a "dispersal success" parameter representing the average proportion of dispersing propagules that remain in viable habitat. While dispersal success can be estimated by empirical measurements or by integration of dispersal kernels, one may lack resources for fieldwork or details on dispersal kernels for numerical computation. Here we derive simple upper bounds on the proportion of propagule loss-the complement of dispersal success-that require only habitat area, habitat perimeter, and the mean dispersal distance of a propagule. Using vector calculus in a probabilistic framework, we rigorously prove bounds for the cases of both symmetric and asymmetric dispersal. We compare the bounds to simulations of integral models for the population of Asclepias syriaca (common milkweed) at McKnight Prairie-a 14 hectare reserve surrounded by agricultural fields in Goodhue County, Minnesota-and identify conditions under which the bounds closely estimate propagule loss., (© 2024. The Author(s).)

The qualities of antibody (Ab) responses provided by B lymphocytes and their plasma cell (PC) descendants are crucial facets of responses to vaccines and microbes. Metabolic processes and products regulate aspects of B cell proliferation and differentiation into germinal center (GC) and PC states as well as Ab diversification. However, there is little information about lymphoid cell-intrinsic functions of enzymes that mediate ether lipid biosynthesis, including a major class of membrane phospholipids. Imaging mass spectrometry (IMS) results had indicated that concentrations of a number of these phospholipids were substantially enhanced in GC compared to the background average in spleens. However, it was not clear if biosynthesis in B cells was a basis for this finding, or whether such cell-intrinsic biosynthesis contributes to B cell physiology or Ab responses. Ether lipid biosynthesis can involve the enzyme PexRAP, the product of the Dhrs7b gene. Using combinations of IMS and immunization experiments in mouse models with inducible Dhrs7b loss-of-function, we now show that B lineage-intrinsic expression of PexRAP promotes the magnitude and affinity maturation of a serological response. Moreover, the data revealed a Dhrs7b -dependent increase in ether phospholipids in primary follicles with a more prominent increase in GC. Mechanistically, PexRAP impacted B cell proliferation via enhanced survival associated with controlling levels of ROS and membrane peroxidation. These findings reveal a vital role of this peroxisomal enzyme in B cell homeostasis and the physiology of humoral immunity.

The diiron(II) complex, [(OCO)Fe(MeCN)] 2 ( 1 , MeCN = acetonitrile), supported by the bis-phenolate carbene pincer ligand, 1,3-bis(3,5-di- tert -butyl-2-hydroxyphenyl)benzimidazolin-2-ylidene (OCO), was synthesized and characterized by single-crystal X-ray diffraction, 1 H nuclear magnetic resonance, infrared (IR) vibrational, ultraviolet/visible/near-infrared (UV/vis/NIR) electronic absorption, 57 Fe Mössbauer, X-band electron paramagnetic resonance (EPR) and SQUID magnetization measurements. Complex 1 activates dioxygen to yield the diferric, μ-oxo-bridged complex [(OCO)Fe(py)(μ-O)Fe(O(C═O)O)(py)] ( 2 ) that was isolated and fully characterized. In 2 , one of the iron-carbene bonds was oxidized to give a urea motif, resulting in an O(C NHC ═O)O binding site, while the other Fe(OCO) unit remained unchanged. When the reaction is performed at -80 °C, an intensively colored, purple intermediate is observed ( INT , λ max = 570 nm; ε = 5600 mol L -1 cm -1 ). INT acts as a sluggish oxidant, reacting only with easily oxidizable substrates, such as PPh 3 or 2-phenylpropionic aldehyde (2-PPA). The identity of INT can be best described as a dinuclear complex containing a closed diamond core motif [(OCO)Fe IV (μ-O) 2 Fe IV (OCO)]. This proposal is based on extensive spectroscopic [UV/vis/NIR electronic absorption, 57 Fe Mössbauer, X-band EPR, resonance Raman (rRaman), X-ray absorption, and nuclear resonance vibrational (NRVS)] and computational studies. The conversion of the diiron(II) complex 1 to the oxo diiron(IV) intermediate INT is reminiscent of the O 2 activation process in soluble methane monooxygenases (sMMO). Most importantly, the low reactivity of INT supports the consensus that the [Fe IV (μ-O) 2 Fe IV ] diamond core in sMMO is kinetically inert and needs to open up to terminal Fe IV ═O cores to react with the strong C-H bonds of methane.

Trial Registration: This trial is registered at ClinicalTrials.gov (NCT05292248)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The objective is to demonstrate that omitting ureteral stent placement in robotic intracorporeal urinary diversion does not lead to increased risk of perioperative complications, namely ureteral strictures or anastomotic leaks. We retrospectively reviewed the records of 68 consecutive patients who underwent robotic radical cystectomy with ileal conduit creation or orthotopic neobladder by a single surgeon between January 2020 and September 2023. Chronologically, the first cohort of patients had ureteral stents placed to bridge the ureteroenteric anastomosis, and in the second cohort, stenting was omitted. Cohort 1 consisted of 28 patients with surgeries performed between January 2020 and April 2021, while cohort 2 had 40 patients who underwent surgery from April 2021 to September 2023. The cohorts were well matched with regard to patient age, gender, ASA score and rate of neoadjuvant chemotherapy. The choice of urinary diversion was left to surgeon and patient preference, and there was no significant difference in the proportion of ileal conduits versus orthotopic neobladders within each cohort. Estimated blood loss, total operative time, inpatient length of stay and pathologic T and N staging did not statistically differ between the cohorts. Overall, there was no difference in the rates of postoperative ileus, ureteral stricture, anastomotic leak, infectious complications, and 30-day readmission rates between the groups. Tubeless ureteroenteric anastomosis in patients undergoing robotic radical cystectomy with intracorporeal diversion does not appear to increase the risk of anastomotic strictures or postoperative complications. Further prospective evaluation is warranted., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Rare genetic variants can have strong effects on phenotypes, yet accounting for rare variants in genetic analyses is statistically challenging due to the limited number of allele carriers and the burden of multiple testing. While rich variant annotations promise to enable well-powered rare variant association tests, methods integrating variant annotations in a data-driven manner are lacking. Here we propose deep rare variant association testing (DeepRVAT), a model based on set neural networks that learns a trait-agnostic gene impairment score from rare variant annotations and phenotypes, enabling both gene discovery and trait prediction. On 34 quantitative and 63 binary traits, using whole-exome-sequencing data from UK Biobank, we find that DeepRVAT yields substantial gains in gene discoveries and improved detection of individuals at high genetic risk. Finally, we demonstrate how DeepRVAT enables calibrated and computationally efficient rare variant tests at biobank scale, aiding the discovery of genetic risk factors for human disease traits., (© 2024. The Author(s).)

Iron overload and cellular senescence have been implicated in liver fibrosis, but their possible mechanistic connection has not been explored. To address this, we have delved into the role of iron and senescence in an experimental model of chronic liver injury, analyzing whether an iron chelator would prevent liver fibrosis by decreasing hepatocyte senescence. The model of carbon tetrachloride (CCl 4 ) in mice was used as an experimental model of liver fibrosis. Results demonstrated that during the progression of liver fibrosis, accumulation of iron occurs, concomitant with the appearance of fibrotic areas and cells undergoing senescence. Isolated parenchymal hepatocytes from CCl 4 -treated mice present a gene transcriptomic signature compatible with iron accumulation and senescence, which correlates with induction of Reactive Oxygen Species (ROS)-related genes, activation of the Transforming Growth Factor-beta (TGF-β) pathway and inhibition of oxidative metabolism. Analysis of the iron-related gene signature in a published single-cell RNA-seq dataset from CCl 4 -treated livers showed iron accumulation correlating with senescence in other non-parenchymal liver cells. Treatment with deferiprone, an iron chelator, attenuated iron accumulation, fibrosis and senescence, concomitant with relevant changes in the senescent-associated secretome (SASP), which switched toward a more anti-inflammatory profile of cytokines. In vitro experiments in human hepatocyte HH4 cells demonstrated that iron accumulates in response to a senescence-inducing reagent, doxorubicin, being deferiprone able to prevent senescence and SASP, attenuating growth arrest and cell death. However, deferiprone did not significantly affect senescence induced by two different agents (doxorubicin and deoxycholic acid) or activation markers in human hepatic stellate LX-2 cells. Transcriptomic data from patients with different etiologies demonstrated the relevance of iron accumulation in the progression of liver chronic damage and fibrosis, correlating with a SASP-related gene signature and pivotal hallmarks of fibrotic changes. Altogether, our study establishes iron accumulation as a clinically exploitable driver to attenuate pathological senescence in hepatocytes., (© 2024. The Author(s).)

As glia mature, they undergo glial tiling to abut one another without invading each other's boundaries. Upon the loss of the secreted neurotrophin Spätzle3 (Spz3), Drosophila cortex glia transform morphologically and lose their intricate interactions with neurons and surrounding glial subtypes. Here, we reveal that all neighboring glial cell types (astrocytes, ensheathing glia, and subperineurial glia) react by extending processes into the previous cortex glial territory to compensate for lost cortex glial function and reduce the buildup of neuronal debris. However, the loss of Spz3 alone is not sufficient for glia to cross their natural borders, as blocking CNS growth via nutrient-restriction blocks the aberrant infiltration induced by the loss of Spz3. Surprisingly, even when these neighboring glia divert their cellular resources beyond their typical borders to take on new compensatory roles, they are able to multitask to continue to preserve their own normal functions to maintain CNS homeostasis., Competing Interests: Declaration of Interests The authors declare no competing interests.

An estimated 6.8 million people in the United States have an unruptured intracranial aneurysms, with approximately 30,000 people suffering from intracranial aneurysms rupture each year. Despite the development of population-based scores to evaluate the risk of rupture, retrospective analyses have suggested the limited usage of these scores in guiding clinical decision-making. With recent advancements in imaging technologies, artery wall motion has emerged as a promising biomarker for the general study of neurovascular mechanics and in assessing the risk of intracranial aneurysms. However, measuring arterial wall deformations in vivo itself poses several challenges, including how to image local wall motion and deriving the anisotropic wall strains over the cardiac cycle. To overcome these difficulties, we first developed a novel in vivo MRI-based imaging method to acquire cardiac gated images of the human basilar artery (BA) over the cardiac cycle. Next, complete BA endoluminal surfaces from each frame were segmented, producing high-resolution point clouds of the endoluminal surfaces. From these point clouds we developed a novel B-spline-based surface representation, then exploited the local support nature of B-splines to determine the local endoluminal surface strains. Results indicated distinct regional and temporal variations in BA wall deformation, highlighting the heterogeneous nature BA function. These included large circumferential strains (up to ∼ 20 % ), and small longitudinal strains, which were often contractile and out of phase with the circumferential strains patterns. Of particular interest was the temporal phase lag in the maximum circumferential perimeter length, which indicated that the BA deforms asynchronously over the cardiac cycle. In summary, the proposed method enabled local deformation analysis, allowing for the successful reproduction of local features of the BA, such as regional principal stretches, areal changes, and pulsatile motion. Integrating the proposed method into existing population-based scores has the potential to improve our understanding of mechanical properties of human BA and enhance clinical decision-making., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

An accurate measurement of the amount fraction of hydrogen in gas mixtures is mandatory for practical applications, requiring methods that are fast, continuous, robust, and cost-effective. This study compares the performance of Raman and benchtop NMR process spectroscopy for determining the hydrogen amount fraction in gas mixtures. A setup was designed to integrate both techniques, enabling measurements of the same sample. Tests were conducted with gravimetrically prepared gas mixtures of reference quality ranging from 1.20 cmol/mol to 85.83 cmol/mol of hydrogen. The results demonstrate that Raman spectroscopy provides superior performance, with a minimal root mean square error (RMSE) of 0.22 cmol/mol and excellent linearity. In contrast, benchtop NMR spectroscopy faced challenges, such as overlapping peaks and longer measurement times, resulting in a higher RMSE of 0.71 cmol/mol. Raman spectroscopy proves to be particularly well-suited for practical applications due to its high accuracy and linearity. Meanwhile, benchtop NMR spectroscopy holds potential for future enhancements through ongoing technological advances, such as higher magnetic field strengths. In summary, the results from our study indicate that Raman spectroscopy is already a serviceable method for precise hydrogen quantification, whereas benchtop NMR spectroscopy can be attributed potential for future applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

UV irradiation of yellow CH 2 Cl 2 solutions of trans -Fe(CO) 3 (P((CH 2 ) 10 ) 3 P) ( 2a ) and PMe 3 (10 equiv) gives, in addition to the previously reported dibridgehead diphosphine P((CH 2 ) 10 ) 3 P (46%), a green paramagnetic complex that crystallography shows to be the trigonal-bipyramidal iron(I) radical trans -[Fe(CO) 2 (Cl)(P((CH 2 ) 10 ) 3 P)] • ( 1a • ; 31% after workup). This is a rare example of an isolable species of the formula [Fe(CO) 4- n (L) n (X)] • ( n = 0-3, L = two-electron-donor ligand; X = one-electron-donor ligand). Analogous precursors with longer P(CH 2 ) n P segments ( n = 12, 14, 16, 18) give only the demetalated diphosphines, and a rationale is proposed. The magnetic susceptibility of 1a • , assayed by Evans' method and SQUID measurements, indicates a spin ( S ) of 1 / 2 . Cyclic voltammetry shows that 1a • undergoes a partially reversible one-electron oxidation, but no facile reduction. The UV-visible, EPR, and 57 Fe Mössbauer spectra are analyzed in detail. Complex 2a is similarly studied, and, despite the extra valence electron, exhibits a comparable oxidation potential (Δ E 1/2 ≤ 0.04 V). The crystal structure shows a cage conformation, solvation level, disorder motif, and unit cell parameters essentially identical to those of 1a • . DFT calculations provide much insight regarding the structural, redox, and spectroscopic properties.