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Sustainable aviation fuels (SAF) are needed in large quantities to reduce the negative impact of flying on the climate. So-called power-to-liquid (PtL) plants can produce SAF from renewable electricity, water, and carbon dioxide. Reactors for these processes that are suitable for flexible operation are difficult to manufacture. Metal 3D printing, also known as additive manufacturing (AM), enables the fabrication of process equipment, such as chemical reactors, with highly optimized functions. In this publication, we present an AM reactor design and conduct experiments for Fischer-Tropsch synthesis (FTS) under challenging conditions. The design includes heating, cooling, and sensing, among others, and can be easily fabricated without welding. We confirm that our reactor has excellent temperature control and high productivity of FTS products up to 800 kgC5+ mcat−3 h−1 (mass flow rate of hydrocarbons, liquid or solid at ambient conditions, per catalyst volume). The typical space-time yield for conventional multi-tubular Fischer-Tropsch reactors is ~100 kgC5+ mcat−3 h−1. The increased productivity is achieved by designing reactor structures in which the channels for catalyst and cooling/heating fluid are in the millimeter range. With the effective control of heat release, we observe neither the formation of hot spots nor catalyst deactivation.

Ulnar collateral ligament reconstruction (UCLR) is frequently performed among injured overhead-throwing athletes. One of the most common graft choices when performing a UCLR is the ipsilateral palmaris longus tendon (PL). The purpose of this study was to investigate the material properties of aseptically processed cadaveric knee collateral ligaments (kMCL) as a potential graft source for UCLR and compare them to the gold standard PL autograft. Each PL and kMCL cadaveric sample was subjected to cyclic preconditioning, stress relaxation, and load-to-failure testing, and the mechanical properties were recorded. PL samples exhibited a greater average decrease in stress compared to the kMCL samples during the stress-relaxation test (p < 0.0001). PL samples also demonstrated a greater average Young’s modulus in the linear region of the stress–strain curve compared to the kMCL samples (p < 0.01). The average yield strain and maximum strain of kMCL samples were significantly greater than the PL, p = 0.03 and 0.02, respectively. Both graft materials had comparable maximum toughness and demonstrated a similar ability to deform plastically without rupture. The clinical significance of our result is that prepared knee medial collateral ligament allografts may provide a viable graft material for use in the reconstruction of elbow ligaments.

Burmese pythons ( Python bivittatus ) have demonstrated prolific spread and low detectability within their invasive range in Florida, USA. Consequently, programs exist which incentivize contractors to remove pythons. While surveying, contractors collect data on search effort and python captures. We examined data from South Florida Water Management District’s Python Elimination Program to determine the effect of operational and environmental covariates on two measures of survey outcome: success (i.e., probability of removing at least one python) and efficiency (i.e., the number of pythons removed per survey hour). Additionally, we assessed the spatial distribution of contractor search effort and removals. Warm temperatures (> 25 °C) improve survey outcomes, especially when surveys occur late at night and during the wet season (May–Oct). The most efficient interval for conducting surveys occurs from 20:00 to 02:00. The spatial distribution of python removals is concentrated in four regions and coincides with contractor search effort. Our results provide insights into optimizing removal efforts for invasive Burmese pythons in Florida, which may allow for increases in removal efficiency. Moreover, this study demonstrates that community science data can be used to synthesize recommendations for invasive species removal efforts.

Efavirenz's effects on cytochrome P450 2C9 (CYP2C9) activity have not been formally characterized in vivo. We conducted the first clinical drug–drug interaction (DDI) study to test the effect of chronic efavirenz dosing on CYP2C9 activity, using tolbutamide as a selective probe. Healthy participants received a single oral dose of tolbutamide (250 mg) with a single 600 mg dose of efavirenz (SD) before and after 600 mg daily efavirenz for 17 days (MD). Tolbutamide, efavirenz, and their metabolites were quantified in plasma and urine samples by LC–MS/MS method. Participants were genotyped for CYP2C9*2 and *3 and for CYP2B6*4, *9, and *18. Pharmacokinetic data were valid for 71 and 59 participants for SD‐ and MD groups, respectively. MD efavirenz caused more than 50% increase in median tolbutamide AUC0‐∞ and C24 in all subjects, and 1.42–1.46‐fold increase in the paired analysis (p < 0.0001); tolbutamide/metabolite ratios were also increased (p < 0.001), while tolbutamide's CL/F/kg, metabolite formation clearance, and metabolite Cmax were significantly reduced. CYP2C9 genetic variants were associated with reduced tolbutamide elimination compared to *1/*1 and *1/*2 (slowest, *3/*3; and intermediate, *1/*3, *2/*2, and *2/*3). The lowest percent change occurred in *2/*2 and *3/*3 genotypes, though small sample sizes limited reliable assessment of genotype‐specific DDI effects. In conclusion, chronic efavirenz use inhibits CYP2C9 activity in vivo. This inhibition may increase the risk of adverse effects from narrow‐therapeutic‐index CYP2C9 substrates (e.g., warfarin, phenytoin, and sulfonylureas). Therefore, therapeutic drug monitoring and dose adjustments are warranted when efavirenz is co‐administered with these medications. Study Highlights What is the current knowledge on the topic? ○Efavirenz is a cornerstone NNRTI in HIV treatment regimens, but its widespread use is challenged by drug–drug interactions (DDIs) mediated through the induction or inhibition of various cytochrome P450 enzymes (including CYP1A2, CYP2A6, CYP2B6, CYP2C19, and CYP3A4). However, its effects on CYP2C9 activity have not been previously characterized in vivo. What question did this study address? ○This study determines whether chronic efavirenz therapy inhibits or induces CYP2C9 activity in healthy participants, using tolbutamide, a well‐established selective CYP2C9 probe as the index substrate. What does this study add to our knowledge? ○This is the first formal clinical drug–drug interaction trial to show that 17 days of daily 600 mg efavirenz leads to over 50% increase in median tolbutamide exposure, consistent with modest in vivo inhibition of CYP2C9 activity. How might this change clinical pharmacology or translational science? ○Though efavirenz's inhibition of CYP2C9 is modest, it may be clinically meaningful for patients taking narrow therapeutic index CYP2C9 substrates such as warfarin, phenytoin, or sulfonylureas. These findings support the need for therapeutic monitoring and potential dose adjustment, especially in individuals with compromised CYP2C9 capacity.

Persistent developmental stuttering is associated with basal ganglia dysfunction or dopamine dysregulation. Here, we studied whole-brain functional connectivity to test how basal ganglia structures coordinate and reorganize sensorimotor brain networks in stuttering. To this end, adults who stutter and fluent speakers (control participants) performed a response anticipation paradigm in the MRI scanner. The preparation of a manual Go/No-Go response reliably produced activity in the basal ganglia and thalamus and particularly in the substantia nigra. Strikingly, in adults who stutter, substantia nigra activity correlated positively with stuttering severity. Furthermore, functional connectivity analyses yielded altered task-related network formations in adults who stutter compared to fluent speakers. Specifically, in adults who stutter, the globus pallidus and the thalamus showed increased network synchronization with the inferior frontal gyrus. This implies dynamic shifts in the response preparation-related network organization through the basal ganglia in the context of a non-speech motor task in stuttering. Here we discuss current findings in the traditional framework of how D1 and D2 receptor activity shapes focused movement selection, thereby suggesting a disproportional involvement of the direct and the indirect pathway in stuttering.

Equipment integrity is an essential aspect of process engineering. Design guidelines facilitate the design and production of safe-to-operate and economic devices. Thin-walled, slit-shaped modules form a subgroup of process engineering devices made via additive manufacturing (AM). Being subject to internal pressure, they have lacked design guidelines until now. We derived a user-centered calculation model for such modules with regular internal structures. It was validated with Finite Element Analysis (FEA) and practical pressure tests for which the modules were manufactured additively. The performance of the calculation could be confirmed, and a design graph was derived. Slit-shaped modules with appropriate internal structures can withstand high pressure at a minimum wall thickness, and they are efficiently fabricated. These structures, being pins, fins, lattice, or heat transfer enhancing fluid-guiding elements (FGEs), occupied approximately 10% of the modules’ internal volume.

Efavirenz induces and inhibits multiple drug‐metabolizing enzymes, contributing to significant drug–drug interactions. This study quantified the impact of multiple doses of efavirenz on CYP3A activity via midazolam metabolism using a population pharmacokinetic approach. Healthy volunteers received 1 mg midazolam orally in two sessions: first with a single 600 mg efavirenz dose and then after chronic efavirenz dosing (600 mg/day for 17 days). Midazolam and 1′‐hydroxymidazolam were quantified via LC–MS/MS, and CYP2B6, CYP3A4, and CYP3A5 genotypes were assessed using TaqMan assays. Seventy‐two volunteers (n = 72) completed sampling after the initial dose, and 58 completed both occasions. Non‐linear mixed effects modeling was performed using the stochastic approximation expectation maximization estimation method in NONMEM. The base pharmacokinetic model employed was a two‐compartment model with first‐order absorption and first‐order elimination, incorporating proportional error terms for midazolam and 1′‐hydroxymidazolam. Covariate analysis utilized a full model approach to assess the impact of CYP3A4 and CYP3A5 genotypes, self‐reported sex, and multiple doses of efavirenz as covariates affecting the formation clearance of 1‐OH midazolam. CYP3A5 expressors exhibited a 1.27‐fold increase in midazolam clearance compared to non‐expressors, while CYP3A4 intermediate metabolizers showed a 0.94‐fold decrease relative to normal metabolizers. Clearance was also 1.30‐fold higher in females compared to males. Multiple doses of efavirenz increased midazolam clearance by 1.92‐fold (95% CI 1.65–2.28) after accounting for inter‐individual variability caused by other covariates. Furthermore, Ka and bioavailability (F) increased with repeated efavirenz exposure. In conclusion, this population pharmacokinetic analysis effectively quantified the specific induction effect of multiple doses of efavirenz on CYP3A compared to a single dose of efavirenz. Trial Registration: ClinicalTrials.gov identifier: NCT00668395

Replacement of lost cranial bone (partly mesodermal and partly neural crest‐derived) is challenging and includes the use of nonviable allografts. To revitalize allografts, bone marrow‐derived mesenchymal stromal cells (mesoderm‐derived BM‐MSCs) have been used with limited success. We hypothesize that coating of allografts with induced neural crest cell‐mesenchymal progenitor cells (iNCC‐MPCs) improves implant‐to‐bone integration in mouse cranial defects. Human induced pluripotent stem cells were reprogramed from dermal fibroblasts, differentiated to iNCCs and then to iNCC‐MPCs. BM‐MSCs were used as reference. Cells were labeled with luciferase (Luc2) and characterized for MSC consensus markers expression, differentiation, and risk of cellular transformation. A calvarial defect was created in non‐obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and allografts were implanted, with or without cell coating. Bioluminescence imaging (BLI), microcomputed tomography (μCT), histology, immunofluorescence, and biomechanical tests were performed. Characterization of iNCC‐MPC‐Luc2 vs BM‐MSC‐Luc2 showed no difference in MSC markers expression and differentiation in vitro. In vivo, BLI indicated survival of both cell types for at least 8 weeks. At week 8, μCT analysis showed enhanced structural parameters in the iNCC‐MPC‐Luc2 group and increased bone volume in the BM‐MSC‐Luc2 group compared to controls. Histology demonstrated improved integration of iNCC‐MPC‐Luc2 allografts compared to BM‐MSC‐Luc2 group and controls. Human osteocalcin and collagen type 1 were detected at the allograft‐host interphase in cell‐seeded groups. The iNCC‐MPC‐Luc2 group also demonstrated improved biomechanical properties compared to BM‐MSC‐Luc2 implants and cell‐free controls. Our results show an improved integration of iNCC‐MPC‐Luc2‐coated allografts compared to BM‐MSC‐Luc2 and controls, suggesting the use of iNCC‐MPCs as potential cell source for cranial bone repair. Bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) were obtained from human bone marrow. Induced neural crest cell‐mesenchymal progenitor cells (iNCC‐MPCs) were generated from induced pluripotent stem cell‐derived iNCCs. Cells were luciferase transfected and seeded onto decellularized allografts, which were implanted into 5 mm circular calvarial defects in non‐obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Allograft only was used as controls. Mice were followed for a duration of 8 weeks. Cell survival, allograft integration, and tissue morphology and transplanted cell contribution were monitored via bioluminescence imaging (BLI), micro‐computed tomography (μCT), and histology and immunofluorescence (IF). Green arrow: BLI; yellow arrow: μCT; Orange arrow: histology and IF; Blue arrow: biomechanical test.

The AMBER-experiment [2, 1], located in the North Experimental Area at CERN, is the successor of the NA58/COMPASS [11] experiment which ran from 2002-2022. AMBER will start its data taking in 2023. The experiment is served by the M2 beamline, employing secondary and tertiary beams produced by 400 GeV c -1 protons from the CERN Super Proton Synchrotron (SPS) impacting the T6 target. For the second phase of their measurements, AMBER will require high-intensity kaon beams [6, 7]. This requirement for high-intensity beams implies a need for accurate particle identification allowing tagging particles of interest that would otherwise be lost for analysis. The beam particle identification is carried out using Cherenkov (CEDAR) detectors [5], whose tagging efficiency depends critically on the beam divergence. In this paper we investigate the beam parameters required, the performance achievable with the current layout of the beamline, as well as possible improvements.

Polymorphisms in the endothelial nitric oxide synthase ( eNOS ) gene have been associated with variations in nitric oxide (NO) formation and response to drugs in white subjects. We examined whether genetic polymorphisms (T-786C, b/a intron 4 and Glu298Asp) and haplotypes of the eNOS gene affect NO formation in 179 healthy black subjects. To assess NO formation, we measured the concentrations of nitrite in the plasma, red blood cells and whole blood. Although we found no effects of individual eNOS polymorphisms on NO formation, we found that the ‘C-4b-Glu’ haplotype is significantly more common in subjects with low circulating plasma and whole blood nitrite concentrations compared with subjects with high circulating nitrite concentrations (both P <0.0007). These findings reproduce previous findings in white subjects and are consistent with the idea that defining genetic markers is more important than ethnic classification, at least in terms of NO formation.