Total substitution and partial modification of the set of non-ribosomal peptide synthetases clusters lead to pyoverdine diversity in the Pseudomonas fluorescens complex.

Pyoverdines are high affinity siderophores produced by most Pseudomonas with a wide role in microbial interspecies interactions. They are primarily composed of a conserved chromophore moiety, an acyl side chain and a peptide backbone which may be highly variable among strains. Upon ferric iron sequestration, pyoverdines are internalized through specialized receptors. The peptide precursor of pyoverdine, termed ferribactin, is synthesized by a set of non-ribosomal peptide synthetase (NRPS) enzymes and further modified by tailoring enzymes. While PvdL, the NRPS responsible for the synthesis of the peptide moiety that derives into the chromophore is conserved, the NRPSs for the peptide backbone are different across fluorescent Pseudomonas. Although the variation of pyoverdine is a widely recognized characteristic within the genus, the evolutionary events associated with the diversity and distribution of this trait remain mostly unknown. This study analyzed the NRPSs clusters for the biosynthesis of the peptide backbone of ferribactin in the genomes of a representative subset of strains of the Pseudomonas fluorescens complex. Bioinformatic analysis of the specificity of adenylation domains of the NRPSs allowed the prediction of 30 different pyoverdine variants. Phylogenetic reconstruction and mapping of the NRPS clusters pinpointed two different general levels of modifications. In the first level, a complete replacement of the set of NRPRs by horizontal transfer occurs. In the second level, the original set of NRPSs is modified through different mechanisms, including partial substitution of the NRPS genes by horizontal transfer, adenylation domain specificity change or NRPS accessory domain gain/loss.

A Multimetal Approach for the Reticulation of Iridium into Metal-Organic Framework Building Units.

Noble metal elements are ubiquitous in our everyday life, from medical applications to electronic devices and synthetic chemistry. Iridium is one of the least abundant elements, and despite its scarcity, it remains essential for efficient and active catalytic processes. Consequently, the development of heterogeneous catalysts with the presence of active iridium sites is of enormous interest as it leads to the improvement of their recyclability and reusability. Here, we demonstrate a strategy to incorporate iridium atoms into metal-organic frameworks (MOFs), as part of their secondary building units (SBUs), resulting in robust and reusable materials with heterogeneous photocatalytic activity.

Converting Strain Release into Aromaticity Loss for Activation of Donor-Acceptor Cyclopropanes: Generation of Quinone Methide Traps for C-Nucleophiles.

Here, we present a new approach for the activation of donor-acceptor cyclopropanes in ring-opening reactions, which does not require the use of a Lewis or Brønsted acid as a catalyst. Donor-acceptor cyclopropanes containing a phenolic group as the donor undergo deprotonation and isomerization to form the corresponding quinone methides. This innovative strategy was applied to achieve (4 + 1)-annulation of cyclopropanes with sulfur ylides, affording functionalized dihydrobenzofurans. Additionally, the generated ortho- and para-(aza)quinone methides can be trapped by various CH-acids.

2023 IEEE Scientific Visualization Contest Winner: VisAnywhere: Developing Multi-platform Scientific Visualization Applications.

Scientists often explore and analyze large-scale scientific simulation data by leveraging two- and three-dimensional visualizations. The data and tasks can be complex and therefore best supported using myriad display technologies, from mobile devices to large high-resolution display walls to virtual reality headsets. Using a simulation of neuron connections in the human brain provided for the 2023 IEEE Scientific Visualization Contest, we present our work leveraging various web technologies to create a multi-platform scientific visualization application. Users can spread visualization and interaction across multiple devices to support flexible user interfaces and both co-located and remote collaboration. Drawing inspiration from responsive web design principles, this work demonstrates that a single codebase can be adapted to develop scientific visualization applications that operate everywhere.

Nuclear Receptor Corepressors NCOR1 and SMRT Regulate Metabolism via Intestinal Regulation of Carbohydrate Transport.

Nuclear receptor action is mediated in part by the nuclear receptor corepressor 1 (NCOR1) and the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT). NCOR1 and SMRT regulate metabolic pathways that govern body mass, insulin sensitivity, and energy expenditure, representing an understudied area in the realm of metabolic health and disease. Previously, we found that NCOR1 and SMRT are essential for maintaining metabolic homeostasis and their knockout (KO) leads to rapid weight loss and hypoglycemia, which is not survivable. Because of a potential defect in glucose absorption, we sought to determine the role of NCOR1 and SMRT specifically in intestinal epithelial cells (IECs). We used a postnatal strategy to disrupt NCOR1 and SMRT throughout IECs in adult mice. These mice were characterized metabolically and underwent metabolic phenotyping, body composition analysis, and glucose tolerance testing. Jejunal IECs were isolated and profiled by bulk RNA sequencing. We found that the postnatal KO of NCOR1 and SMRT from IECs leads to rapid weight loss and hypoglycemia with a significant reduction in survival. This was accompanied by alterations in glucose metabolism and activation of fatty acid oxidation in IECs. Metabolic phenotyping confirmed a reduction in body mass driven by a loss of body fat without altered food intake. This appeared to be mediated by a reduction of key intestinal carbohydrate transporters, including SGLT1, GLUT2, and GLUT5. Intestinal NCOR1 and SMRT act in tandem to regulate glucose levels and body weight. This in part may be mediated by regulation of intestinal carbohydrate transporters.

Origin of the Laurentian Great Lakes fish fauna through upward adaptive radiation cascade prior to the Last Glacial Maximum.

The evolutionary histories of adaptive radiations can be marked by dramatic demographic fluctuations. However, the demographic histories of ecologically-linked co-diversifying lineages remain understudied. The Laurentian Great Lakes provide a unique system of two such radiations that are dispersed across depth gradients with a predator-prey relationship. We show that the North American Coregonus species complex ("ciscoes") radiated rapidly prior to the Last Glacial Maximum (80-90 kya), a globally warm period, followed by rapid expansion in population size. Similar patterns of demographic expansion were observed in the predator species, Lake Charr (Salvelinus namaycush), following a brief time lag, which we hypothesize was driven by predator-prey dynamics. Diversification of prey into deep water created ecological opportunities for the predators, facilitating their demographic expansion, which is consistent with an upward adaptive radiation cascade. This study provides a new timeline and environmental context for the origin of the Laurentian Great Lakes fish fauna, and firmly establishes this system as drivers of ecological diversification and rapid speciation through cyclical glaciation.

Dry hydroclimates in the late Palaeocene-early Eocene hothouse world.

Extreme global warming can produce hydroclimate changes that remain poorly understood for sub-tropical latitudes. Late Palaeocene-early Eocene (LPEE; ~58-52 Ma) proto-Mediterranean zones of the western Tethys offer opportunities to assess hydroclimate responses to massive carbon cycle perturbations. Here, we reconstruct LPEE hydroclimate conditions of these regions and find that carbon cycle perturbations exerted controls on orbitally forced hydroclimate variability. Long-term (~6 Myr) carbon cycle changes induced a gradual precipitation/moisture reduction, which was exacerbated by some short-lived (<200 kyr) carbon cycle perturbations that caused rapid warming and exceptionally dry conditions in western Tethyan continental areas. Hydroclimate recovery following the greatest short-lived global warming events took ~24-27 kyr. These observations support the notion that anthropogenically driven warming can cause widespread aridification with impacts that may last tens of thousands of years.

Zanthoxylum zanthoxyloides (Lam.) B. Zepernick & Timler alkaloidal extract exerts hepatoprotective effects in rats with a CCl4/olive oil-induced hepatocellular carcinoma-like phenotype.

Objective: This study assessed the prophylactic anti-HCC effects of a combined stem and root alkaloidal extract of Zanthoxylum zanthoxyloides (Z. zanthoxyloides) (SRAEZZ) in rats with a CCl4/olive oil-induced HCC-like phenotype. Methods: SRAEZZ was prepared from dried stems and roots of Z. zanthoxyloides in a 1:1 proportion and chemically characterized. A total of 30 healthy male Wistar rats (weighing 210-280 g) were randomly assigned to six groups (control, model, capecitabine, and SRAEZZ [50, 100, or 200 mg/kg]). All groups except the control received CCl4/olive oil (3 mL/kg, po) in the morning, whereas in the afternoon of the same dosing day, the model group received normal saline (5 mL/kg, po), the capecitabine group received capecitabine (50 mg/kg, po), and the SRAEZZ groups received SRAEZZ (50, 100, or 200 mg/kg, po, respectively) once per week for 36 days. Survival rate, serum α-fetoprotein (AFP), and C-reactive protein (CRP) were monitored. Gross liver anatomy, liver histology, liver enzymes (ALP, AST, and ALT), bilirubin, creatinine, urea, albumin, globulins, and hematological parameters were assessed. Results: SRAEZZ yield was 0.58% from the initial stem and root sample (520 g). Quaternary phenanthridin alkaloids were detected in SRAEZZ. Control rats had a 100% survival rate compared with rats in the model group. SRAEZZ treatment improved the survival rate with respect to that in the model group. Serum AFP, CRP, and bilirubin levels were greater in the model group than the control group. SRAEZZ decreased serum AFP, CRP, and bilirubin below the levels observed in the model group. ALP, AST, and AST were higher in the model group, but lower in SRAEZZ-treated group, than the control group. Conclusion: SRAEZZ demonstrated prophylactic anti-HCC effects against CCl4/olive oil-induced HCC-like phenotypes in rats. These findings highlight the potential of crude alkaloids from Z. zanthoxyloides as natural templates for semi-synthesis of anti-HCC pharmacotherapeutics.

The clinical utility of a glaucoma polygenic risk score in four population-based European-ancestry cohorts.

OBJECTIVE: We used a polygenic risk score (PRS) to identify high-risk groups for primary open-angle glaucoma (POAG) within population-based cohorts. DESIGN: Secondary analysis of four prospective population-based studies. PARTICIPANTS: We included four European-ancestry cohorts: the United States (US) based Nurses' Health Study (NHS), NHS2, and the Health Professionals Follow-up Study, and the Rotterdam Study (RS) in the Netherlands. The US cohorts included female nurses and male health professionals aged 55+ years. The RS included residents aged 45 years or older living in Rotterdam, the Netherlands. METHODS: PRS weights were estimated by applying the Lassosum method on imputed genotype and phenotype data from the UK-Biobank. This resulted in 144,020 variants, single nucleotide polymorphism (SNPs) and indels, with non-zero betas that we used to calculate a PRS in the target populations. Using multivariable Cox proportional hazard models, we estimated the relationship between the standardized PRS and relative risk for POAG. Additionally, POAG prediction was tested by calculating these models' concordance (Harrell's C-statistic). Finally, we assessed the association between PRS tertiles and glaucoma-related traits. MAIN OUTCOME MEASURES: The relative risk for POAG and Harrell's C-statistic (the equivalent of an area-under-the-curve for longitudinal models). RESULTS: Among 1,046 cases and 38,809‬ controls, the relative risk (95% confidence interval) for POAG for participants in the highest PRS quintile was 3.99 (3.08, 5.18) in the US cohorts, and 4.89 (2.93, 8.17) in the Rotterdam Study, compared with participants with median genetic risk (3rd quintile). In restricted cubic spline analyses, the relation between continuous PRS and POAG risk increased exponentially in the US and Rotterdam cohorts (Pspline<0.05). Combining age, sex, intraocular pressure >25 mmHg, and family history resulted in a meta-analyzed concordance of 0.75 (0.73, 0.75). Adding the PRS to this model improved the concordance to 0.82 (0.80, 0.84). In a meta-analysis of all cohorts, cases in the highest tertile had a larger cup-disc ratio at diagnosis, by 0.11 (0.07, 0.15), and a 2.07-fold increased risk of requiring glaucoma surgery (1.19, 3.60). CONCLUSIONS: Incorporating a PRS into a POAG predictive model improves identification concordance from 0.75 up to 0.82, supporting its potential for guiding more cost-effective screening strategies.

Electrophysical Characteristics of Acrylonitrile Butadiene Styrene Composites Filled with Magnetite and Carbon Fiber Fillers.

With the rapid development of wireless communication technologies and the miniaturization trend in the electronics industry, the reduction of electromagnetic interference has become an important issue. To solve this problem, a lot of attention has been focused on polymer composites with combined functional fillers. In this paper, we report a method for creating an acrylonitrile butadiene styrene (ABS) plastic composite with a low amount of conductive carbon and magnetic fillers preparation. Also, we investigate the mechanical, thermophysical, and electrodynamic characteristics of the resulting composites. Increasing the combined filler amount in the ABS composite from 1 to 5 wt % leads to a composite conductivity growth of almost 50 times. It is necessary to underline the temperature decrease of 5 wt % mass loss and, accordingly, the composite heat resistance reduction with an increase in the combined filler from 1 to 5 wt %, while the thermal conductivity remains almost constant. It was established that electrodynamic and physical-mechanical characteristics depend on the agglomeration of fillers. This work is expected to reveal the potential of combining commercially available fillers to construct effective materials with good electromagnetic interference (EMI) protection using mass production methods (extrusion and injection molding).

B cell-based therapy produces antibodies that inhibit glioblastoma growth.

Glioblastoma (GBM) is a highly aggressive and malignant brain tumor with limited therapeutic options and a poor prognosis. Despite current treatments, the invasive nature of GBM often leads to recurrence. A promising alternative strategy is to harness the potential of the immune system against tumor cells. Our previous data showed that the Bvax (B-cell-based vaccine) can induce therapeutic responses in preclinical models of GBM. In this study, we aim to characterize the antigenic reactivity of BVax-derived antibodies and evaluate their therapeutic potential. We performed immunoproteomics and functional assays in murine models and human GBM patient samples. Our investigations revealed that BVax distributes throughout the GBM tumor microenvironment (TME) and then differentiates into antibody-producing plasmablasts. Proteomic analyses indicate that the antibodies produced by BVax display unique reactivity, predominantly targeting factors associated with cell motility and the extracellular matrix. Crucially, these antibodies inhibit critical processes such as GBM cell migration and invasion. These findings provide valuable insights into the therapeutic potential of BVax-derived antibodies for GBM patients, pointing towards a novel direction in GBM immunotherapy.

Tuning (Photo)Electronic Properties of an Electron Deficient Porous Polymer via n-Doping with Tetrathiafulvalene.

Charge-transfer complex formation within the pores of porous polymers is an efficient way to tune their electronical properties. Introduction of electron accepting guests to the electron donating hosts to conduct their p-doping is intensively studied in this context. However, the vice versa scenario, n-doping by treating the electron deficient (i.e., n-type) porous polymers with electron donating dopants, is rare. In this work, synthesis of an n-type phenazine based conjugated microporous polymer and its exposure to strong electron donating tetrathiafulvalene (TTF) dopants are presented. The fundamental physical characterizations (e.g., elemental analysis, gas sorption) showed that the vacuum impregnation technique is a good approach to load the guest molecules inside the pores. Moreover, the formation of charge-transfer complexes between the phenazine building blocks of the polymeric network and TTF dopants are confirmed via spectral techniques such Fourier transform infra-red, UV-vis, steady-state/time-resolved photoluminescence, and transient absorbance spectroscopies. Effect of the doping to the electronical properties is monitored by employing photoelectrochemical measurements, which showed lower charge-transfer resistivity and nearly doubled photocurrents after the doping. The study is, therefore, an important advancement for the applicability of (n-type) porous polymeric materials in the field of photo(electro)catalysis and organic electronics.

Raman Lasing and Transverse Mode Selection in a Multimode Graded-Index Fiber with a Thin-Film Mirror on Its End Face.

Multimode fibers are attractive for high-power lasers if transverse modes are efficiently controlled. Here, a dielectric thin-film mirror (R~20%) is micro-fabricated on the central area of the end face of a 1 km multimode 100/140 µm graded-index fiber and tested as the output mirror of a Raman laser with highly multimode (M2~34) 940 nm diode pumping. In the cavity with highly reflective input FBG, Raman lasing of the Stokes wave at 976 nm starts at the threshold pump power of ~80 W. Mode-selective properties of mirrors with various diameters were tested experimentally and compared with calculations in COMSOL, with the optimum diameter found to be around 12 µm. The measured Raman laser output beam at 976 nm has a quality factor of M2~2 near the threshold, which confirms a rather good selection of the fundamental transverse mode. The power scaling capabilities, together with a more detailed characterization of the output beam's spatial profile, spectrum, and their stability, are performed. An approximately 35 W output power with an approximately 60% slope efficiency and a narrow spectrum has been demonstrated at the expense of a slight worsening of beam quality to M2~3 without any sign of mirror degradation at the achieved intensity of >30 MW/cm2. Further power scaling of such lasers as well as the application of the proposed technique in high-power fiber lasers are discussed.

CCL28 modulates neutrophil responses during infection with mucosal pathogens.

The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here we show that CCL28 promotes neutrophil accumulation in the gut of mice infected with Salmonella and in the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency varied between the two infections: Ccl28-/- mice were highly susceptible to Salmonella gut infection but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.

A single domain antibody-based Luminex assay for the detection of SARS-CoV-2 in clinical samples.

Within the past decade, single domain antibodies (sdAbs) have been recognized as unique affinity binding reagents that can be tailored for performance in a variety of immunoassay formats. Luminex MagPlex color-coded magnetic microspheres provide a high-throughput platform that enables multiplexed immunoassays. We developed a MagPlex bead-based assay for the detection of SARS-CoV-2, using sdAbs against SARS-CoV-2 nucleocapsid (N) protein in which we engineered the sdAb capture reagents to orient them on the beads. The oriented sdAbs provided an increase in sensitivity over randomly oriented sdAbs for samples of N diluted in buffer, which also translated into better detection of SARS-CoV-2 in clinical samples. We assessed the specificity of the assay by examining seasonal coronavirus clinical samples. In summary, we provide a proof-of-concept that a bead-based assay using sdAbs to detect SARS-CoV-2 is feasible and future research combining it with other sdAb-coated beads that can detect other viruses may provide a useful diagnostic tool.

Au@AuPd Core-Alloyed Shell Nanoparticles for Enhanced Electrocatalytic Activity and Selectivity under Visible Light Excitation.

Plasmonic catalysis has been employed to enhance molecular transformations under visible light excitation, leveraging the localized surface plasmon resonance (LSPR) in plasmonic nanoparticles. While plasmonic catalysis has been employed for accelerating reaction rates, achieving control over the reaction selectivity has remained a challenge. In addition, the incorporation of catalytic components into traditional plasmonic-catalytic antenna-reactor nanoparticles often leads to a decrease in optical absorption. To address these issues, this study focuses on the synthesis of bimetallic core@shell Au@AuPd nanoparticles (NPs) with ultralow loadings of palladium (Pd) into gold (Au) NPs. The goal is to achieve NPs with an Au core and a dilute alloyed shell containing both Au and Pd, with a low Pd content of around 10 atom %. By employing the (photo)electrocatalytic nitrite reduction reaction (NO2RR) as a model transformation, experimental and theoretical analyses show that this design enables enhanced catalytic activity and selectivity under visible light illumination. We found that the optimized Pd distribution in the alloyed shell allowed for stronger interaction with key adsorbed species, leading to improved catalytic activity and selectivity, both under no illumination and under visible light excitation conditions. The findings provide valuable insights for the rational design of antenna-reactor plasmonic-catalytic NPs with controlled activities and selectivity under visible light irradiation, addressing critical challenges to enable sustainable molecular transformations.

Small molecules targeting GRP78 mitigate anti-GRP78 autoantibody-mediated tissue factor procoagulant activity in cultured endothelial cells.

BACKGROUND: The 78-kDa glucose-regulated protein (GRP78) expressed on the cell surface (csGRP78) has been reported to regulate tissue factor (TF) procoagulant activity (PCA) in lesion-resident endothelial cells (ECs), which is further enhanced by circulating anti-GRP78 autoantibodies that bind to the Leu98-Leu115 epitope in GRP78. OBJECTIVES: Determine the effects of the engagement of the anti-GRP78 autoantibody to csGRP78 on ECs and the underlying mechanisms that impact TF PCA. METHODS: Immunofluorescent staining was used to determine the presence of csGRP78 in tumor necrosis factor α-treated ECs. An established TF PCA assay was used to evaluate human ECs following treatment with anti-GRP78 autoantibodies. The Fura 2-AM assay (Abcam) was used to quantify changes in intracellular Ca2+ levels. Small molecules predicted to bind GRP78 were identified using artificial intelligence. Enzyme-linked immunosorbent assays were used to assess the ability of these GRP78 binders to mitigate TF activity and interfere with the autoantibody/csGRP78 complex. RESULTS: In tumor necrosis factor α-treated ECs, anti-GRP78 autoantibodies increased TF PCA. This observation was further enhanced by endoplasmic reticulum stress-induced elevation of csGRP78 levels. Anti-GRP78 autoantibody treatment increased intracellular Ca2+ levels. Sequestering the anti-GRP78 autoantibody with a conformational peptide or blocking with heparin attenuated anti-GRP78 autoantibody-induced TF PCA. We identified B07∗, as a GRP78 binder that diminished anti-GRP78 autoantibody-induced TF PCA on ECs. CONCLUSION: These findings show how anti-GRP78 autoantibodies enhance TF PCA that contributes to thrombosis and identify novel GRP78 binders that represent a potential novel therapeutic strategy for treating and managing atherothrombotic disease.

Synthesis and characterization of micro-sized polyisobutylene and evaluation of its toxicological effects on the development and homeostasis of zebrafish (Danio rerio).

Rampant industrialization has led to widespread reliance on hydrocarbon polymers for various commercial applications. While these synthetic polymers, commonly known as plastics, degrade in slowly in the environments, the toxic effects of their micro-sized particles remain underexplored. In this study, we synthesized polyisobutylene (PIB) microparticles in the lab and evaluated their toxicity and accumulation in a zebrafish model. Pristine and fluorescent PIB-microplastics (MPs), with particle sizes ranging from 2 to 10 µm, were synthesized using the solvent evaporation method. Fourier-transform infrared spectroscopy (FTIR) confirmed the stability of the suspensions. Zebrafish larvae exposed to various concentrations of PIB-MPs exhibited numerous morphological and molecular changes, including delayed hatching, impaired swimming behavior, increased reactive oxygen species levels, altered mRNA levels of genes encoding antioxidant proteins, and reduced survival rates. Dissections revealed PIB-MP accumulation in the guts of larvae and adult fish within 7-21 days, causing damage to the intestinal mucosa. These findings provide insights into how contaminants like PIB can induce pathophysiological defects in aquatic fauna and pose potential health hazards to humans.

Addressing sagittal plane imbalance in primary total knee arthroplasty.

Aims: Sagittal plane imbalance (SPI), or asymmetry between extension and flexion gaps, is an important issue in total knee arthroplasty (TKA). The purpose of this study was to compare SPI between kinematic alignment (KA), mechanical alignment (MA), and functional alignment (FA) strategies. Methods: In 137 robotic-assisted TKAs, extension and flexion stressed gap laxities and bone resections were measured. The primary outcome was the proportion and magnitude of medial and lateral SPI (gap differential > 2.0 mm) for KA, MA, and FA. Secondary outcomes were the proportion of knees with severe (> 4.0 mm) SPI, and resection thicknesses for each technique, with KA as reference. Results: FA showed significantly lower rates of medial and lateral SPI (2.9% and 2.2%) compared to KA (45.3%; p < 0.001, and 25.5%; p < 0.001) and compared to MA (52.6%; p < 0.001 and 29.9%; p < 0.001). There was no difference in medial and lateral SPI between KA and MA (p = 0.228 and p = 0.417, respectively). FA showed significantly lower rates of severe medial and lateral SPI (0 and 0%) compared to KA (8.0%; p < 0.001 and 7.3%; p = 0.001) and compared to MA (10.2%; p < 0.001 and 4.4%; p = 0.013). There was no difference in severe medial and lateral SPI between KA and MA (p = 0.527 and p = 0.307, respectively). MA resulted in thinner resections than KA in medial extension (mean difference (MD) 1.4 mm, SD 1.9; p < 0.001), medial flexion (MD 1.5 mm, SD 1.8; p < 0.001), and lateral extension (MD 1.1 mm, SD 1.9; p < 0.001). FA resulted in thinner resections than KA in medial extension (MD 1.6 mm, SD 1.4; p < 0.001) and lateral extension (MD 2.0 mm, SD 1.6; p < 0.001), but in thicker medial flexion resections (MD 0.8 mm, SD 1.4; p < 0.001). Conclusion: Mechanical and kinematic alignment (measured resection techniques) result in high rates of SPI. Pre-resection angular and translational adjustments with functional alignment, with typically smaller distal than posterior femoral resection, address this issue.

Distributed Neural Representation for Reactive In Situ Visualization.

Implicit neural representations (INRs) have emerged as a powerful tool for compressing large-scale volume data. This opens up new possibilities for in situ visualization. However, the efficient application of INRs to distributed data remains an underexplored area. In this work, we develop a distributed volumetric neural representation and optimize it for in situ visualization. Our technique eliminates data exchanges between processes, achieving state-of-the-art compression speed, quality and ratios. Our technique also enables the implementation of an efficient strategy for caching large-scale simulation data in high temporal frequencies, further facilitating the use of reactive in situ visualization in a wider range of scientific problems. We integrate this system with the Ascent infrastructure and evaluate its performance and usability using real-world simulations.