Titanium alloys are used due to their high specific strength and remarkable corrosion resistance. Their wear resistance however is poor, which in this paper is counteracted by laser surface ...texturing. Linear textures were created by the use of a nanosecond-pulsed laser, accompanied by melt bulges of resolidified material on the sides. Packing density, finishing procedure and atmosphere during laser texturing were varied between the experiments. Melt bulges lasered in air turned out to be tribologically beneficial in grease-lubricated sliding contact, reducing wear volume on Ti6Al4V significantly by up to a factor of 160, if a packing density of 5% or more was chosen. Further investigations of melt bulges with energy dispersive X-ray spectroscopy (EDX) and scanning transmission electron microscopy (STEM) revealed an increased content in interstitial oxygen and nitrogen and a purely martensitic α’-phase microstructure. Critical limitation of plastic deformation and a saturation of electronic bonds of the titanium atoms by interstitial elements is thought to be responsible for the reduction in adhesive tendency and therefore the pronounced decrease in wear.
•Laser surface texturing was used to improve the tribological performance of Ti6Al4V.•Laser-induced melt generation proved to be tribologically beneficial.•Interstitial elements (O, N) seem to be a major cause for increased wear resistance.•Wear volume was reduced by up to a factor of 160.
In the present study, several mixed quantum-classical (MQC) methods are applied to on-the-fly nonadiabatic molecular dynamics simulations of hole transport in molecular organic semiconductors (OSCs). ...The tested MQC methods contain the mean-field Ehrenfest (MFE), trajectory surface hopping (TSH) approaches based on Tully’s fewest switches surface hopping (FSSH) and the global flux surface hopping (GFSH), the latter in the diabatic/adiabatic representation, and a Landau–Zener type trajectory surface hopping (LZSH). We also tested several correction schemes which were proposed to identify trivial crossings and to remove unphysical long-range charge transfers due to decoherence corrections. In addition, several cost-effective approaches for the nuclear velocity adjustment after an energy-allowed/energy-forbidden hop are investigated with respect to detailed balance and internal consistency conditions. To model a broad spectrum of OSCs with different charge transport characteristics, we derived from the anthracene structural model the construction of two additional models by uniformly scaling down the electronic couplings by the factors of 0.1 and 0.5. Anthracene shows a bandlike charge transport mechanism, characterized by slightly delocalized charge carriers ‘diffusing’ through the crystal. For smaller couplings, the mechanism changes to a hopping type, characteristically differing in the charge delocalization and temperature dependence. The MFE and corrected adiabatic TSH approaches are able to quantitatively reproduce the expected behavior, while the diabatic LZSH method fails for large couplings, as do approaches which are based on the hopping of localized charge between neighboring sites. Moreover, we find that while the hole mobility of the anthracene crystal simulated using the celebrated Marcus theory is in good agreement with the experimental value, its agreement has to be regarded as an accident due to the overestimation of the prefactor in the Marcus rate equation.
Inhibition of O-GlcNAcase (OGA) has emerged as a promising therapeutic approach to treat tau pathology in neurodegenerative diseases such as Alzheimer’s disease and progressive supranuclear palsy. ...Beginning with carbohydrate-based lead molecules, we pursued an optimization strategy of reducing polar surface area to align the desired drug-like properties of potency, selectivity, high central nervous system (CNS) exposure, metabolic stability, favorable pharmacokinetics, and robust in vivo pharmacodynamic response. Herein, we describe the medicinal chemistry and pharmacological studies that led to the identification of (3aR,5S,6S,7R,7aR)-5-(difluoromethyl)-2-(ethylamino)-3a,6,7,7a-tetrahydro-5H-pyrano3,2-dthiazole-6,7-diol 42 (MK-8719), a highly potent and selective OGA inhibitor with excellent CNS penetration that has been advanced to first-in-human phase I clinical trials.
Secondary sclerosing cholangitis (SSC) is a rare disease with poor prognosis. Cases of SSC have been reported following coronavirus disease 2019 (COVID-SSC). The aim of this study was to compare ...COVID-SSC to SSC in critically ill patients (SSC-CIP) and to assess factors influencing transplant-free survival.
In this retrospective, multicenter study involving 127 patients with SSC from 9 tertiary care centers in Germany, COVID-SSC was compared to SSC-CIP and logistic regression analyses were performed investigating factors impacting transplant-free survival.
Twenty-four patients had COVID-SSC, 77 patients SSC-CIP, and 26 patients other forms of SSC. COVID-SSC developed after a median of 91 days following COVID-19 diagnosis. All patients had received extensive intensive care treatment (median days of mechanical ventilation, 48). Patients with COVID-SSC and SSC-CIP were comparable in most of the clinical parameters and transplant-free survival was not different from other forms of SSC (P = .443, log-rank test). In the overall cohort, the use of ursodeoxycholic acid (UDCA) (odds ratio OR, 0.36 95% confidence interval {CI}, .16-.80, P = .013; log-rank P < .001) and high serum albumin levels (OR, 0.40 95% CI, .17-.96, P = .040) were independently associated with an increased transplant-free survival, while the presence of liver cirrhosis (OR, 2.52 95% CI, 1.01-6.25, P = .047) was associated with worse outcome. Multidrug-resistant organism (MDRO) colonization or infection did not impact patients' survival.
COVID-SSC and CIP-SSC share the same clinical phenotype, course of the disease, and risk factors for its development. UDCA may be a promising therapeutic option in SSC, though future prospective trials are needed to confirm our findings.
We investigate the confinement-induced formation and stability of helix morphologies in lamella-forming AB diblock copolymers via large-scale, particle-based, single-chain-in-mean-field simulations. ...Such helix structures are rarely observed in bulk or thin films. Structure formation is induced by quenching incompatibility, χN, from a disordered morphology. If the surfaces of the cylindrical confinement do not prefer one component over the other, we observe that stacked lamellae, with their normals along the cylinder axis, are the preferred morphology. Kinetically, this morphology initially forms close to the cylinder surface, whereas the spontaneous, spinodal microphase separation in the cylinder’s interior gives rise to a microemulsion-like morphology, riddled with defects and no directional order. Subsequently, the ordered morphology on the cylinder surface progresses inward, pervading the entire volume. In case that the cylindrical pore is only partially filled, the additional confinement along the cylinder axis generally gives rise to incommensurability between the equilibrium spacing of stacked lamellae and the cylinder height. To accommodate this mismatch, the lamella normals will tilt away from the cylinder axis and generate helices of lamellae on the surface of the cylinder. Again, this order progresses from the cylinder surface inward, generating a chiral morphology. Because the spacing between the internal AB interfaces decreases upon approaching the helix center, the concomitant stress results in a decrease in the number of lamellae and the formation of unique dislocation defects. This type of chiral defect morphology is reproducibly formed by the kinetics of structure formation in partly filled cylindrical pores with nonpreferential surfaces and may find applications in photonic applications.
Acute kidney injury (AKI) is morphologically characterized by a synchronized plasma membrane rupture of cells in a specific section of a nephron, referred to as acute tubular necrosis (ATN). Whereas ...the involvement of necroptosis is well characterized, genetic evidence supporting the contribution of ferroptosis is lacking. Here, we demonstrate that the loss of ferroptosis suppressor protein 1 (Fsp1) or the targeted manipulation of the active center of the selenoprotein glutathione peroxidase 4 (Gpx4
) sensitize kidneys to tubular ferroptosis, resulting in a unique morphological pattern of tubular necrosis. Given the unmet medical need to clinically inhibit AKI, we generated a combined small molecule inhibitor (Nec-1f) that simultaneously targets receptor interacting protein kinase 1 (RIPK1) and ferroptosis in cell lines, in freshly isolated primary kidney tubules and in mouse models of cardiac transplantation and of AKI and improved survival in models of ischemia-reperfusion injury. Based on genetic and pharmacological evidence, we conclude that GPX4 dysfunction hypersensitizes mice to ATN during AKI. Additionally, we introduce Nec-1f, a solid inhibitor of RIPK1 and weak inhibitor of ferroptosis.
This study demonstrates that GPT-4V outperforms GPT-4 across radiology subspecialties in analyzing 207 cases with 1312 images from the Radiological Society of North America Case Collection.
Private high schools are often viewed as bastions of scholastic and social opportunities, but the cost of tuition has rendered these sites predominantly white and more segregated than public schools. ...However, with the ability to recruit, Black boys have become prime targets of predominantly white private Catholic high schools seeking promising student-athletes. As a result, the population of Black boys at these schools are composed almost entirely of students recruited to play a sport. Drawing from qualitative interview data, the purpose of this paper is to illustrate the racialized experiences of six Black boys who attended a predominantly white Catholic high school in which the entire Black population was composed of student-athletes. Findings indicate that participants initially saw the private Catholic school as an escape from their respective public schools but realized that mere attendance did not result in total inclusion. All six participants encountered forms of antiblackness via frequent structural and cultural assaults that made their daily attendance at the school difficult.
Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine ...CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13
follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients.
In North America, white‐nose syndrome (WNS) has caused precipitous declines in hibernating bat populations, raising the question of whether the rapid loss of arthropodivorous bats may affect the ...abundance of their prey. During the summers of 2015–2018 (1 year after the arrival of WNS in Wisconsin, USA), we performed intensive arthropod black‐light trapping, ultrasonic acoustic monitoring, and emergence counts at 10 little brown (Myotis lucifugus) and big brown (Eptesicus fuscus) bat maternity roosts with paired control sites. For little brown bats, which are severely affected by WNS, roost counts declined by 95% over the four‐year period, compared to a 38% decline in big brown bat roost counts. Total arthropod abundance decreased by 49%, although decreases among common little brown bat prey were less severe. Our natural predator exclusion experiment supports existing evidence that bats can have measurable trophic impacts on arthropod communities, primarily via top‐down effects on common prey.
In North America, white‐nose syndrome (WNS) has caused precipitous declines in hibernating bat populations, raising the question of whether the rapid loss of arthropodivorous bats may affect the abundance of their prey. During the summers of 2015–2018 (1 year after the arrival of WNS in Wisconsin, USA), we performed intensive arthropod black‐light trapping, ultrasonic acoustic monitoring, and emergence counts at 10 little brown (Myotis lucifugus) and big brown (Eptesicus fuscus) bat maternity roosts with paired control sites. For little brown bats, which are severely affected by WNS, roost counts declined by 95% over the four‐year period, compared to a 38% decline in big brown bat roost counts. Total arthropod abundance decreased by 49%, although decreases among common little brown bat prey were less severe. Our natural predator exclusion experiment supports existing evidence that bats can have measurable trophic impacts on arthropod communities, primarily via top‐down effects on common prey.
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