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Fluxgate magnetometers provide sensitive and stable measurements of the static and low frequency vector magnetic field. Fluxgates form a magnetic field measurement by periodically saturating a ferromagnetic core and the intrinsic magnetic noise of this material can determine the noise floor of the instrument. We present the results of an empirical experiment to understand the physical parameters that influence the intrinsic magnetic noise of fluxgate cores. We compare two permalloy alloys – the historical standard 6 % molybdenum alloy and a new 28 % copper alloy. We examine the influence of geometry using the historical standard 1” diameter spiral wound ring-core and a new stacked washer racetrack design. We evaluate the influence of material thickness by comparing 100 µm and 50 µm foils. Finally, we investigate heat treatments in terms of temperature and ramp rate and their role in both grain size and magnetic noise. The results of these experiments suggest that thinner foils, potentially comprising the copper alloy, manufactured into continuous racetrack geometry washers may provide excellent performance in fluxgate sensors.

IMPORTANCE: Pediatric sepsis definitions have evolved, and some have proposed using the measure used in adults to quantify organ dysfunction, a Sequential Organ Failure Assessment (SOFA) score of 2 or more in the setting of suspected infection. A pediatric adaptation of SOFA (pSOFA) showed excellent discrimination for mortality in critically ill children but has not been evaluated in an emergency department (ED) population. OBJECTIVE: To delineate test characteristics of the pSOFA score for predicting in-hospital mortality among (1) all patients and (2) patients with suspected infection treated in pediatric EDs. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study took place from January 1, 2012, to January 31, 2020 in 9 US children’s hospitals included in the Pediatric Emergency Care Applied Research Network (PECARN) Registry. The data was analyzed from February 1, 2020, to April 18, 2022. All ED visits for patients younger than 18 years were included. EXPOSURES: ED pSOFA score was assigned by summing maximum pSOFA organ dysfunction components during ED stay (each 0-4 points). In the subset with suspected infection, visit meeting criteria for sepsis (suspected infection with a pSOFA score of 2 or more) and septic shock (suspected infection with vasoactive infusion and serum lactate level >18.0 mg/dL) were identified. MAIN OUTCOMES AND MEASURES: Test characteristics of pSOFA scores of 2 or more during the ED stay for hospital mortality. RESULTS: A total of 3 999 528 (female, 47.3%) ED visits were included. pSOFA scores ranged from 0 to 16, with 126 250 visits (3.2%) having a pSOFA score of 2 or more. pSOFA scores of 2 or more had sensitivity of 0.65 (95% CI, 0.62-0.67) and specificity of 0.97 (95% CI, 0.97-0.97), with negative predictive value of 1.0 (95% CI, 1.00-1.00) in predicting hospital mortality. Of 642 868 patients with suspected infection (16.1%), 42 992 (6.7%) met criteria for sepsis, and 374 (0.1%) met criteria for septic shock. Hospital mortality rates for suspected infection (599 502), sepsis (42 992), and septic shock (374) were 0.0%, 0.9%, and 8.0%, respectively. The pSOFA score had similar discrimination for hospital mortality in all ED visits (area under receiver operating characteristic curve, 0.81; 95% CI, 0.79-0.82) and the subset with suspected infection (area under receiver operating characteristic curve, 0.82; 95% CI, 0.80-0.84). CONCLUSIONS AND RELEVANCE: In a large, multicenter study of pediatric ED visits, a pSOFA score of 2 or more was uncommon and associated with increased hospital mortality yet had poor sensitivity as a screening tool for hospital mortality. Conversely, children with a pSOFA score of 2 or less were at very low risk of death, with high specificity and negative predictive value. Among patients with suspected infection, patients with pSOFA-defined septic shock demonstrated the highest mortality.

Single-chain nanoparticles are intriguing materials inspired by proteins that consist of a single precursor polymer chain that has collapsed into a stable structure. In many prospective applications, such as catalysis, the utility of a single-chain nanoparticle will intricately depend on the formation of a mostly specific structure or morphology. However, it is not generally well understood how to reliably control the morphology of single-chain nanoparticles. To address this knowledge gap, we simulate the formation of 7,680 distinct single-chain nanoparticles from precursor chains that span a wide range of, in principle, tunable patterning characteristics of cross-linking moieties. Using a combination of molecular simulation and machine learning analyses, we show how the overall fraction of functionalization and blockiness of cross-linking moieties biases the formation of certain local and global morphological characteristics. Importantly, using the total volume of simulation data, we illustrate and quantify the dispersity of morphologies that arise due to both the stochastic nature of collapse from a well-defined sequence as well as from the ensemble of sequences that correspond to a given specification of precursor parameters. Moreover, we also examine the efficacy of precise sequence control in achieving morphological outcomes in different regimes of precursor parameters. Overall, this work critically assesses how precursor chains might be feasibly tailored to achieve given SCNP morphologies and provides a platform to pursue future sequence-based design.

Divalent metal transporter 1 (DMT1) cotransports ferrous iron and protons and is the primary mechanism for uptake of non-heme iron by enterocytes. Inhibitors are potentially useful as therapeutic agents to treat iron overload disorders such as hereditary hemochromatosis or β-thalassemia intermedia, provided that inhibition can be restricted to the duodenum. We used a calcein quench assay to identify human DMT1 (hDMT1) inhibitors. Dimeric constructs were made to generate more potent compounds with low systemic exposure. Direct block of DMT1 was confirmed by voltage clamp measurements. The lead compound, XEN602, strongly inhibits dietary iron uptake in both rats and pigs, yet has negligible systemic exposure. Efficacy is maintained for >2 weeks in a rat subchronic dosing assay. Doses that lowered iron content in the spleen and liver by >50% had no effect on the tissue content of other divalent cations except for cobalt. XEN602 represents a powerful pharmacological tool for understanding the physiological function of DMT1.SIGNIFICANCE STATEMENTThis report introduces methodology to develop potent, gut-restricted inhibitors of DMT1 and identifies XEN602 as a suitable compound for in vivo studies. We also report novel animal models to quantify the inhibition of dietary uptake of iron in both rodents and pigs. This research shows that inhibition of DMT1 is a promising means to treat iron overload disorders.

Site-specific protein modification is a widely-used biochemical tool. However, there are many challenges associated with the development of protein modification techniques, in particular, achieving site-specificity, reaction efficiency and versatility. The engineering of peptide ligases and their substrates has been used to address these challenges. This review will focus on sortase, peptidyl asparaginyl ligases (PALs) and variants of subtilisin; detailing how their inherent specificity has been utilised for site-specific protein modification. The review will explore how the engineering of these enzymes and substrates has led to increased reaction efficiency mainly due to enhanced catalytic activity and reduction of reversibility. It will also describe how engineering peptide ligases to broaden their substrate scope is opening up new opportunities to expand the biochemical toolkit, particularly through the development of techniques to conjugate multiple substrates site-specifically onto a protein using orthogonal peptide ligases.

We examine the impacts of potential artificial intelligence (AI) regulations on managers’ perceptions on ethical issues related to AI and their intentions to adopt AI technologies. We conduct a randomized online survey experiment on more than a thousand managers in the United States. We randomly present managers with different proposed AI regulations, and ask about ethical issues related to AI and their intentions related to AI adoption. We find that information about AI regulation increases manager perception of the importance of safety, privacy, bias/discrimination, and transparency issues related to AI. However, there is a tradeoff; regulation information reduces manager intent to adopt AI technologies. Moreover, information about regulation increases manager intent to spend on developing AI strategy including ethical issues at the cost of investing in AI adoption, such as providing AI training to current employees or purchasing AI software packages. (JEL: K24, L21, L51, O33, O38)

To address the tradeoff between mechanical strength and Li+ conductivity in Poly(Ethylene Oxide) (PEO)-based electrolytes, a rigid nonconductive polymer is frequently added to the electrolyte via blending or copolymerization. The ionic conductivity of mixed PEO electrolytes is generally lower than that of unmixed PEO electrolytes. The suppressed ionic conductivity is attributed to the reduced segmental mobility and connectivity of the conductive PEO cites. Most experimental systems make it difficult to decouple the two mechanisms and accurately examine their impact on conductivity. We compare two symmetric polymer mixtures (50:50 wt%): a miscible polymer blend PEO/PMMA and a disordered block copolymer (BCP) PEO-b-PMMA, both with the same amount of Li salt. Because their chemical and physical properties are the same, changes in ionic conductivity can be attributed solely to local changes in PEO network connectivity. We discover that the mixtures' immediate Li+ solvation sites (+ transport within and across PEO clusters at the appropriate length scales. This new understanding of network connectivity in polymer electrolyte mixtures is critical for the design of future multiphase polymer electrolyte systems.