Bimetallic Two-Dimensional Metal–Organic Frameworks for the Chemiresistive Detection of Carbon Monoxide

This paper describes the demonstration of a series of heterobimetallic, isoreticular 2D conductive metal–organic frameworks (MOFs) with metallophthalocyanine (MPc, M=Co and Ni) units interconnected by Cu nodes towards low-power chemiresistive sensing of ppm levels of carbon monoxide (CO). Devices achieve a sub-part-per-million (ppm) limit of detection (LOD) of 0.53 ppm toward CO at a low driving voltage of 0.1 V. MPc-based Cu-linked MOFs can continuously detect CO at 50 ppm, the permissible exposure limit required by the Occupational Safety and Health Administration (OSHA), for multiple exposures, and realize CO detection in air and in humid environment. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), density functional theory (DFT) calculations, and comparison experiments suggest the contribution of Cu nodes to CO binding and the essential role of MPc units in tuning and amplifying the sensing response

DU Undergraduate Showcase: Research, Scholarship, and Creative Works: Abstracts

Abstracts from the DU Undergraduate Showcase

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge Cancer Centre and Medical Research Council Infrastructure Award. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain

Background: Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1) engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.). An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (H-1-MRS) was used to measure metabolite levels in seven voxels of interest (VOIs) (including hippocampus) before and after learning.Results: Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA/(Cr+Cho) ratio.Conclusion: Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training

Photometry of the Didymos System across the DART Impact Apparition

On 2022 September 26, the Double Asteroid Redirection Test (DART) spacecraft impacted Dimorphos, the satellite of binary near-Earth asteroid (65803) Didymos. This demonstrated the efficacy of a kinetic impactor for planetary defense by changing the orbital period of Dimorphos by 33 minutes. Measuring the period change relied heavily on a coordinated campaign of lightcurve photometry designed to detect mutual events (occultations and eclipses) as a direct probe of the satellite’s orbital period. A total of 28 telescopes contributed 224 individual lightcurves during the impact apparition from 2022 July to 2023 February. We focus here on decomposable lightcurves, i.e., those from which mutual events could be extracted. We describe our process of lightcurve decomposition and use that to release the full data set for future analysis. We leverage these data to place constraints on the postimpact evolution of ejecta. The measured depths of mutual events relative to models showed that the ejecta became optically thin within the first ∼1 day after impact and then faded with a decay time of about 25 days. The bulk magnitude of the system showed that ejecta no longer contributed measurable brightness enhancement after about 20 days postimpact. This bulk photometric behavior was not well represented by an HG photometric model. An HG 1 G 2 model did fit the data well across a wide range of phase angles. Lastly, we note the presence of an ejecta tail through at least 2023 March. Its persistence implied ongoing escape of ejecta from the system many months after DART impact

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Reducing Voltage Hysteresis in Li-rich Sulfide Cathodes by Tuning the Metal-ligand Covalency

Conventional intercalation-based cathode materials in Li-ion batteries are based on charge compensation of the redox active cation and can only intercalate one mole of electron per formula unit. Anion redox, which employs the anion sublattice to compensate charge, is a promising way to achieve multielectron cathode materials. Most anion redox materials still face the problems of slow kinetics and large voltage hysteresis. One potential solution to reduce voltage hysteresis is to increase the covalency of the metal-ligand bonds. By substituting Mn into the electrochemically inert Li1.33Ti0.67S2 (Li2TiS3), anion redox can be activated in the Li1.33–2y/3Ti0.67–y/3MnyS2 (y = 0 – 0.5) series. Not only do we observe substantial anion redox, but the voltage hysteresis is significantly reduced, and the rate capability is dramatically enhanced. The y = 0.3 phase exhibits excellent rate and cycling performance, maintaining 90% of the C/10 capacity at 1C, which indicates fast kinetics for anion redox. X-ray absorption spectroscopy (XAS) shows that both the cation and anion redox processes contribute to the charge compensation. We attribute the drop in hysteresis and increase in rate performance to the increased covalency between the metal and the anion. Electrochemical signatures suggest the anion redox mechanism resembles holes on the anion, but the S K-edge XAS data confirm persulfide formation. The mechanism of anion redox suggests that even if persulfides are formed, the hysteresis and rate performances can still be improved. This work provides insights on how to design cathode materials with anion redox to achieve fast kinetics and low voltage hysteresis