Tuning Supported Catalyst Reactivity with Dendrimer-Templated Pt-Cu Nanoparticles

The effects of particle composition on heterogeneous catalysis were studied using dendrimer-encapsulated nanoparticles (DENs) as precursors to supported Pt-Cu catalysts. Bimetallic Pt-Cu DENs with varying Pt/Cu ratios were prepared in an anaerobic aqueous solution and deposited onto a high-purity commercial alumina support. The dendrimer template was then thermally removed to yield supported nanoparticle catalysts, which were studied with toluene hydrogenation and CO oxidation catalysis as well as infrared spectroscopy of adsorbed CO. Incorporating Cu into Pt nanoparticles had opposite effects on the two test reactions. Cu acted as a mild promoter for CO oxidation catalysis, and the promoting effect was independent of the amount of Cu present. Conversely, Cu acted as a strong poison for toluene hydrogenation catalysis, and the normalized rate tracked inversely with Cu content. Infrared spectroscopy of the supported nanoparticles indicated that electronic effects (electron donation from Cu to Pt) were minimal for these materials. Consequently, the catalysis results are interpreted in terms of potential structural differences as a function of Cu incorporation and reaction conditions

Homer2 deletion alters dendritic spine morphology but not alcohol-associated adaptations in GluN2B-containing N-methyl-D-aspartate receptors in the nucleus accumbens

Repeated exposure to ethanol followed by withdrawal leads to the alterations in glutamatergic signaling and impaired synaptic plasticity in the nucleus accumbens (NAc) in both clinical and preclinical models of ethanol exposure. Homer2 is a member of a family of postsynaptic density (PSD) scaffolding proteins that functions in part to cluster NMDA signaling complexes in the PSD, and has been shown to be critically important for plasticity in multiple models of drug and alcohol abuse. Here we used Homer2 KO mice and a chronic intermittent intraperitoneal (IP) ethanol injection model to investigate a potential role for the protein in ethanol-induced adaptations in dendritic spine morphology and PSD protein expression. While deletion of Homer2 was associated with increased density of long spines on medium spiny neurons of the NAc core of saline treated mice, ethanol exposure had no effect on dendritic spine morphology in either wild-type (WT) or Homer2 KO mice. Western blot analysis of tissue samples from the NAc enriched for PSD proteins revealed a main effect of ethanol treatment on the expression of GluN2B, but there was no effect of genotype or treatment on the expression other glutamate receptor subunits or PSD95. These data indicate that the global deletion of Homer2 leads to aberrant regulation of dendritic spine morphology in the NAc core that is associated with an increased density of long, thin spines. Unexpectedly, intermittent IP ethanol did not affect spine morphology in either WT or KO mice. Together these data implicate Homer2 in the formation of long, thin spines and further supports its role in neuronal structure

Lessons learnt from prenatal exome sequencing

BACKGROUND: Prenatal exome sequencing (ES) for monogenic disorders in fetuses with structural anomalies increases diagnostic yield. In England there is a national trio ES service delivered from two laboratories. To minimise incidental findings and reduce the number of variants investigated, analysis uses a panel of 1205 genes where pathogenic variants may cause abnormalities presenting prenatally. Here we review our laboratory's early experience developing and delivering ES to identify challenges in interpretation and reporting and inform service development. METHODS: A retrospective laboratory records review from 01.04.2020 to 31.05.2021. RESULTS: Twenty-four of 116 completed cases were identified as challenging including 13 resulting in difficulties in analysis and reporting, nine where trio inheritance filtering would have missed the diagnosis, and two with no prenatal diagnosis; one due to inadequate pipeline sensitivity, the other because the gene was not on the panel. Two cases with copy number variants identified were not detectable by microarray. CONCLUSIONS: Variant interpretation requires close communication between referring clinicians, with occasional additional examination of the fetus or parents and communication of evolving phenotypes. Inheritance filtering misses ∼5% of diagnoses. Panel analysis reduces but does not exclude incidental findings. Regular review of published literature is required to identify new reports that may aid classification

Tuning Supported Catalyst Reactivity with Dendrimer-Templated Pt-Cu Nanoparticles

The effects of particle composition on heterogeneous catalysis were studied using dendrimer-encapsulated nanoparticles (DENs) as precursors to supported Pt-Cu catalysts. Bimetallic Pt-Cu DENs with varying Pt/Cu ratios were prepared in an anaerobic aqueous solution and deposited onto a high-purity commercial alumina support. The dendrimer template was then thermally removed to yield supported nanoparticle catalysts, which were studied with toluene hydrogenation and CO oxidation catalysis as well as infrared spectroscopy of adsorbed CO. Incorporating Cu into Pt nanoparticles had opposite effects on the two test reactions. Cu acted as a mild promoter for CO oxidation catalysis, and the promoting effect was independent of the amount of Cu present. Conversely, Cu acted as a strong poison for toluene hydrogenation catalysis, and the normalized rate tracked inversely with Cu content. Infrared spectroscopy of the supported nanoparticles indicated that electronic effects (electron donation from Cu to Pt) were minimal for these materials. Consequently, the catalysis results are interpreted in terms of potential structural differences as a function of Cu incorporation and reaction conditions. Introduction Highly dispersed supported metal nanoparticle catalysts are an important class of industrial materials, as one-third of material U. S. gross national product involves a catalytic process somewhere in the production chain. 1 State of the art heterogeneous catalysts often contain dopant metals, which are incorporated to promote a desired reaction, prevent undesirable side reactions, or enhance catalyst longevity. Recent advances in computational methods are beginning to shed light onto the fundamental properties of bimetallic catalyst systems, and predictive models are beginning to emerge. To address these fundamental issues, preparation methods for new model catalysts and appropriate control materials are needed. Inorganic and organometallic cluster compounds have been used to successfully prepare novel bimetallic catalysts, 5 particularly for metal combinations that are thermodynamically unstable in the bulk. Background Polyamidoamine (PAMAM) dendrimer-encapsulated nanoparticles (DENs) are attractive potential precursors for model heterogeneous catalysts. PAMAM dendrimers are versatile synthetic hosts, as they have been used to template a variety of metal and semiconductor nanoparticles on the order of 1-3 nm. In this work, we extend this general preparative route for heterogeneous catalysts to the Pt-Cu system (Scheme 1) and report the first study varying heterogeneous catalyst composition using DENs as catalyst precursors. Coincident with these goals is the desire to begin learning how to tune nanoparticle properties and reactivity through the controlled addition of dopant metals. Additionally, we seek to begin developing methods of rationally and systematically testing theoretical models for bimetallic catalyst systems. The Pt-Cu system is a good choice for initial investigations into composition effects because the two metals are miscible through the entire composition range. 34 Additionally, the system has been well studied and characterized, and there is current interest in its reactivity for dehydrodehalogenation, 35,36 dehydrogenation, Metal Uptake by G5-OH Dendrimers. UV-vis spectra during dendrimer-metal complexation were collected using an Ocean Optics, Inc. high-resolution fiber optic spectrometer (HR2000CG UV-NIR). For Pt 2+ uptake by G5-OH PAMAM dendrimer, 10 mL of 0.01 mM dendrimer solution was mixed in a round-bottom flask with sufficient 5 mM K 2 PtCl 4 to prepare the following Pt/dendrimer ratios: 30:1, 23:1, and 15:1. A portion of the solution was transferred to a cuvette and analyzed at various time intervals using 0.01 mM G5-OH PAMAM dendrimer solution as a reference. After 4 days the pH was increased to 7. For Cu uptake by G5-OH, 10 mL of 0.01 mM dendrimer solution was mixed in a round-bottom flask with sufficient 5 mM Cu(NO 3 ) 2 to result in the following Cu/dendrimer ratios: 30:1, 23:1, and 15:1. An aliquot of the solution was immediately transferred to a cuvette for UV-vis spectroscopic analysis. A spectrum was obtained every 3 min for 30 min, and the pH was increased to 7. For Cu uptake by the Pt-dendrimer complex, 10 mL of 0.01 mM dendrimer solution was mixed in a round-bottom flask with sufficient 5 mM K 2 PtCl 4 to result in the following Pt/dendrimer ratios: 30:1, 23:1, and 15:1. The solutions were stirred for 2 days, and the Cu uptake procedure was followed using sufficient 5 mM Cu(NO 3 ) 2 to result in a metal/dendrimer ratio of 45:1 for all solutions. Preparation of Supported Nanoparticles. The DENs were prepared based on techniques detailed in the literature. NaBH 4 solution (0.045 M) was degassed, and 1 mL was added to the flask as N 2 was continually bubbled through the SCHEME 1 Dendrimer-Templated Pt-Cu Catalysts J. Phys. Chem. B, Vol. 110, No. 17, 2006 8607 solution. The solution turned a champagne color as the metals were reduced after stirring for 20 min. The pH of the solution was then adjusted to 8.5 with NaOH and HNO 3 . The alumina support was prepared by degassing 700 mg of 60-80 mesh alumina in a Schlenk flask for 1 h. The DEN solution was then added to the degassed support via cannula, and the mixture was stirred overnight under N 2 . The solid gray catalyst was isolated from a colorless solution by vacuum filtration over a medium grain frit, washed with 95% ethanol, and dried at 80°C in a vacuum oven overnight. The supported DENs were activated by exposing the dried catalyst to flowing O 2 for 16 h at 300°C , as described previously. 31 Pt and Cu Analysis with Atomic Absorption Spectroscopy. Pt and Cu loadings were determined with a Varian SpectrAA 220FS atomic absorption spectrometer using an acetylene/air flame, as described previously. 32 Briefly, the sample was treated with freshly prepared aqua regia. The pH of the resulting solution was adjusted to 6.0-7.0 with ammonium hydroxide, condensed, and transferred to a 10 mL volumetric flask containing sufficient La(NO 3 ) 3 to yield a final solution of 1% La. Atomic absorption (AA) standards were prepared from Aldrich AA standard solutions and Nanopure water. FT-IR Spectroscopy. Spectra were collected using a Thermo Nicolet Nexus 470 spectrometer equipped with a deuterated triglyceride sulfate (DTGS) detector using 2 cm -1 resolution. A water-cooled stainless steel IR flow cell with NaCl windows was used to hold the pressed catalyst wafer (18-20 mg). The optical bench and beam path (outside the flow cell) were continuously purged with N 2 . A heating element wrapped around the cell with a thermocouple placed in close proximity to the catalyst sample allowed for in situ heating of samples and collection spectra at different temperatures. All spectra were collected with gases flowing at 60 mL/min; the gas composition was manipulated using the external manifold. Previously oxidized catalyst samples underwent in situ reduction (20% H 2 balance He at 300°C for 3 h) followed by flushing with He for 1 h at 300°C. The samples were then cooled under He flow, and a background spectrum was collected at room temperature. A 5% CO/He mixture was then flowed over the sample for 15 min, followed by pure He. IR spectra of CO adsorbed on the surface were collected once the gas-phase CO had been removed from the cell. CO desorption was accomplished by heating the sample under He flow. CO Oxidation Catalysis. The feed and reactor effluent composition was monitored with an SRI 8610C gas chromatograph with a thermal conductivity detector. Toluene Hydrogenation Catalysis. The oxidized catalyst was diluted 20:1 by mass with R-Al 2 O 3 . Approximately 300 mg of the diluted catalyst was loaded into a glass U-tube and reduced in flowing H 2 . The temperature was ramped 5°C/min to 200°C and soaked for 1 h. The temperature was then ramped 5°C/min to 300°C and held at that temperature for an additional 1.5 h. The reactor was then cooled to 60°C under flowing H 2 . A 3.2% toluene in H 2 feed was prepared using a two-stage bubbler. The first stage was held at approximately 40°C, and the second stage was maintained at 23°C. . Peak areas were standardized against external calibration solutions of toluene in hexanes and methylcyclohexane in toluene. by monitoring conversion as a function of flow rate. Flow rates were measured with a bubble flow meter immediately prior to each injection. Plots of conversion versus inverse space velocity were linear and had y-intercepts of 0.02% or lower. Results and Discussion Nanoparticle and Catalyst Preparation. Because PtCl 4 2-uptake is slow (1-2 days) relative to Cu 2+ (seconds), we used sequential binding of PtCl 4 2-followed by Cu 2+ to load generation 5 PAMAM dendrimers (G5-OH) with metal precursors (Scheme 1). Most previous studies with these metaldendrimer systems used G4-OH dendrimers, so the use of G5-OH dendrimers in the present study may have moderate effects on the kinetics of metal uptake. Additionally, metal-dendrimer interactions with one precursor may affect the binding of the second when preparing bimetallic nanoparticles. Accordingly, the individual metal binding steps in Scheme 1 were monitored with UV-vis spectroscopy. PtCl 4 2-uptake by G5-OH, monitored by following the disappearance of the PtCl charge transfer band at 380 nm, was complete in approximately 24 h and did not change after adjusting the solution pH to 7 (spectra in the Supporting Information). Changes in the 380 nm band were concurrent with changes in a dendrimerbased UV band at 320 nm indicating uptake into the dendrimer interior. 8608 J. Phys. Chem. B, Vol. 110, No. 17, 2006 Hoover et al. The consistent relative excess of Cu in the final materials also indicates that complexation of Pt(II) species to the dendrimer interior may not be complete in 48 h or that Cu 2+ may displace some of the Pt(II) species within the dendrimer. Our study is consistent with studies from other labs in that UVvis spectra of mixtures of PtCl 4 2-and PAMAM dendrimers cease to change after approximately 2 days. Infrared Spectroscopy of Adsorbed CO. Infrared spectra of CO adsorbed on the activated catalysts, shown in Evaluations of structural and electronic effects and their potential impact on catalytic activity are of fundamental interest and importance. CO adsorption studies are an important tool in evaluating these effects, as both can impact observed CO stretching frequencies. The absence of Cu-CO stretching frequencies provides important indirect information regarding the state of Cu in the catalysts. CO is relatively unstable and easily removed from fully reduced Cu surfaces (i.e., during the He flush required to remove gas-phase CO) yet is stable at ambient temperatures when adsorbed on cationic Cu species. The shifts in Pt-CO stretching frequencies are attributable to a combination of electronic and dipole-dipole coupling effects. Electronic effects arise from a net (partial) electron donation from Cu to the more electronegative Pt. This enhances population of Pt d-bands (relative to a pure Pt material), increasing CO back-bonding and resulting in a lower CO stretching frequency. Dipole-dipole coupling, which is thoughspace interaction between adsorbed dipoles vibrating at the same frequency (Pt-CO adsorbates), also plays an important role in CO stretching frequencies on supported catalysts. Increased dipole coupling, which occurs when vibrating dipoles are close to one another, causes a blue shift in the observed CO stretching frequency. Consequently, as one metal dilutes another, dipole coupling effects are diminished, and a resulting red shift is observed in the CO stretching frequency. Dendrimer-Templated Pt-Cu Catalysts J. Phys. Chem. B, Vol. 110, No. 17, 2006 8609 To evaluate the relative importance of dipole coupling effects, low-coverage CO stretching frequencies Catalytic Test Reactions. Catalytic activity of the supported nanoparticles was evaluated with the toluene hydrogenation and CO oxidation test reactions. Toluene hydrogenation activities, collected in The data in CO oxidation activity data for the Pt-containing catalysts is shown in Structural and Electronic Effects on Catalytic Activity. It is appropriate and important to reconcile the divergent effects of Cu incorporation on the two test reactions, particularly since they are opposite in both direction and magnitude (mild promotion of CO oxidation that is independent of Cu content versus strong inhibition of toluene hydrogenation that is Cudependent). Structural and electronic factors can affect the catalytic activity for these oxidation-reduction reactions. Pt is 8610 J. Phys. Chem. B, Vol. 110, No. 17, 2006 Hoover et al. slightly more electronegative than Cu, so it is possible that the more active metal is enriched in electron density upon incorporation of Cu. However, the electronegativity difference is small (2.2 vs 1.9), and the IR spectroscopy data indicate that any electronic differences between the mono-and bimetallic catalysts are correspondingly mild. The low-coverage Pt-CO stretching frequencies show only a weak trend with Cu incorporation, but the shifts are fairly small and are in the range of singleton Pt-CO stretching frequencies for monometallic Pt catalysts. Although these small potential electronic effects might be a reasonable explanation for the copper's promotion of CO oxidation catalysis (vide infra), we do not believe that they are sufficient to explain the 100-fold decrease in Pt activity for toluene hydrogenation. The trend in hydrogenation activity tracks directly with the metal stoichiometry, which is set and controlled in the initial nanoparticle synthesis. This reduction in catalytic activity with increasing Cu content is likely due to surface enrichment in copper under a reducing atmosphere. Cu surface enrichment in this system been postulated for a number of traditionally prepared supported Pt-Cu catalysts, particularly under reducing atmospheres. The simplest structural explanation is that surface Cu atoms provide a new type of surface site that binds CO more weakly than monometallic Pt sites. The E app values for the bimetallic nanoparticles, which strongly depend on heats of adsorption, are 30% lower than that of the monometallic Pt catalyst. This explanation is also attractive in light of models for this reaction over Pt, which implicates desorption of a key weakly bound CO-based intermediate as the rate-determining step. Oxygen is also more competitive for binding on Cu than Pt (Cu-CO bonds are weak, vide supra), so Cu incorporation may simply increase the amount of surface oxygen available on the particle. Because CO binding appears to enrich the surface in Pt, the surface stoichiometry under the reaction conditions is unclear. It is also possible that, in the presence of CO, the bimetallic particles result in Pt-on-Cu subsurface alloys that have been predicted by some computational models. 6-9 These subsurface alloys can be activated through electronic influences or structurally through the epitaxial compression of surface Pt atoms. This explanation is consistent with a mild electronic effect on Pt observed in the infrared spectra. At the same time, correlations between IR spectra and catalytic activity must be drawn with extreme care, since there is no guarantee that the strongly bound Pt-CO species observed in the IR are the active species in CO oxidation catalysis. Additionally, the expected influence of the electronic effect (enhanced metal-ligand back-bonding inferred from a slightly weaker CO bond) would predict stronger Pt-C bonds and is inconsistent with a model involving desorption in the slow step. 47 Although we cannot rule out an electronic nature of the activity enhancement, we favor structural explanations

Monogenic conditions and central nervous system anomalies:A prospective study, systematic review and meta-analysis

Objectives: Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities.Methods: Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model. Results: Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%–36%; I2 = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%–34%; I2 = 74%]; (b) single CNS anomaly; 16% [95% CI 10%–23%; I2 = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%–40%; I2 = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%–57%; I2 = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus. Conclusions: Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.</p

Transcriptomic Approaches to Modelling Long Term Changes in Human Cardiac Electrophysiology

Slow changes in the activity of the heart occur with time scales from days through to decades, and may in part result from changes in cardiomyocyte properties. The cellular mechanisms of the cardiomyocyte action potential have time scales from < ms to hundreds of ms. Although the quantitative dynamic relations between mRNA transcription, protein synthesis, trafficking, recycling, and membrane protein activity are unclear, mRNA-Seq can be used to inform parameters in cell excitation equations. We use such transcriptomic data from a non-human primate to scale maximal conductances in the O’Hara-Rudy (2011) family of human ventricular cell models, and to predict diurnal changes in human ventricular action potential durations. These are related to circadian changes in the incidence of sudden cardiac deaths. Transcriptomic analysis of human fetal hearts between 9 and 16 weeks gestational age is beginning to be used to inform ventricular cell and tissue models of the electrophysiology of the developing fetal heart

Evaluation of the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in infantile epilepsy (Gene-STEPS): an international, multicentre, pilot cohort study

BACKGROUND: Most neonatal and infantile-onset epilepsies have presumed genetic aetiologies, and early genetic diagnoses have the potential to inform clinical management and improve outcomes. We therefore aimed to determine the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in this population. METHODS: We conducted an international, multicentre, cohort study (Gene-STEPS), which is a pilot study of the International Precision Child Health Partnership (IPCHiP). IPCHiP is a consortium of four paediatric centres with tertiary-level subspecialty services in Australia, Canada, the UK, and the USA. We recruited infants with new-onset epilepsy or complex febrile seizures from IPCHiP centres, who were younger than 12 months at seizure onset. We excluded infants with simple febrile seizures, acute provoked seizures, known acquired cause, or known genetic cause. Blood samples were collected from probands and available biological parents. Clinical data were collected from medical records, treating clinicians, and parents. Trio genome sequencing was done when both parents were available, and duo or singleton genome sequencing was done when one or neither parent was available. Site-specific protocols were used for DNA extraction and library preparation. Rapid genome sequencing and analysis was done at clinically accredited laboratories, and results were returned to families. We analysed summary statistics for cohort demographic and clinical characteristics and the timing, diagnostic yield, and clinical impact of rapid genome sequencing. FINDINGS: Between Sept 1, 2021, and Aug 31, 2022, we enrolled 100 infants with new-onset epilepsy, of whom 41 (41%) were girls and 59 (59%) were boys. Median age of seizure onset was 128 days (IQR 46-192). For 43 (43% [binomial distribution 95% CI 33-53]) of 100 infants, we identified genetic diagnoses, with a median time from seizure onset to rapid genome sequencing result of 37 days (IQR 25-59). Genetic diagnosis was associated with neonatal seizure onset versus infantile seizure onset (14 [74%] of 19 vs 29 [36%] of 81; p=0·0027), referral setting (12 [71%] of 17 for intensive care, 19 [44%] of 43 non-intensive care inpatient, and 12 [28%] of 40 outpatient; p=0·0178), and epilepsy syndrome (13 [87%] of 15 for self-limited epilepsies, 18 [35%] of 51 for developmental and epileptic encephalopathies, 12 [35%] of 34 for other syndromes; p=0·001). Rapid genome sequencing revealed genetic heterogeneity, with 34 unique genes or genomic regions implicated. Genetic diagnoses had immediate clinical utility, informing treatment (24 [56%] of 43), additional evaluation (28 [65%]), prognosis (37 [86%]), and recurrence risk counselling (all cases). INTERPRETATION: Our findings support the feasibility of implementation of rapid genome sequencing in the clinical care of infants with new-onset epilepsy. Longitudinal follow-up is needed to further assess the role of rapid genetic diagnosis in improving clinical, quality-of-life, and economic outcomes. FUNDING: American Academy of Pediatrics, Boston Children's Hospital Children's Rare Disease Cohorts Initiative, Canadian Institutes of Health Research, Epilepsy Canada, Feiga Bresver Academic Foundation, Great Ormond Street Hospital Charity, Medical Research Council, Murdoch Children's Research Institute, National Institute of Child Health and Human Development, National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, One8 Foundation, Ontario Brain Institute, Robinson Family Initiative for Transformational Research, The Royal Children's Hospital Foundation, University of Toronto McLaughlin Centre

Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2

Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilized pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID-19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in-house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterized samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries

Evaluating the large-scale hydrological cycle response within the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2) ensemble

The mid-Pliocene (∼3 Ma) is one of the most recent warm periods with high CO2 concentrations in the atmosphere and resulting high temperatures, and it is often cited as an analog for near-term future climate change. Here, we apply a moisture budget analysis to investigate the response of the large-scale hydrological cycle at low latitudes within a 13-model ensemble from the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2). The results show that increased atmospheric moisture content within the mid-Pliocene ensemble (due to the thermodynamic effect) results in wetter conditions over the deep tropics, i.e., the Pacific intertropical convergence zone (ITCZ) and the Maritime Continent, and drier conditions over the subtropics. Note that the dynamic effect plays a more important role than the thermodynamic effect in regional precipitation minus evaporation (PmE) changes (i.e., northward ITCZ shift and wetter northern Indian Ocean). The thermodynamic effect is offset to some extent by a dynamic effect involving a northward shift of the Hadley circulation that dries the deep tropics and moistens the subtropics in the Northern Hemisphere (i.e., the subtropical Pacific). From the perspective of Earth's energy budget, the enhanced southward cross-equatorial atmospheric transport (0.22 PW), induced by the hemispheric asymmetries of the atmospheric energy, favors an approximately 1∘ northward shift of the ITCZ. The shift of the ITCZ reorganizes atmospheric circulation, favoring a northward shift of the Hadley circulation. In addition, the Walker circulation consistently shifts westward within PlioMIP2 models, leading to wetter conditions over the northern Indian Ocean. The PlioMIP2 ensemble highlights that an imbalance of interhemispheric atmospheric energy during the mid-Pliocene could have led to changes in the dynamic effect, offsetting the thermodynamic effect and, hence, altering mid-Pliocene hydroclimate