Voltammetry plays a crucial role in modern scientific research by offering valuable insights into the electrochemical properties of materials, with wide-ranging applications in fields such as... Show moreVoltammetry plays a crucial role in modern scientific research by offering valuable insights into the electrochemical properties of materials, with wide-ranging applications in fields such as materials science, energy storage, corrosion studies, and sensor development.Gold, known for its exceptional inertness, provides a unique platform for studying intricate electrochemical processes due to its stability and slow electrochemical behavior. However, certain questions regarding gold voltammetry have remained unresolved throughout history. To address these gaps, our research employed a combination of electrochemical cyclic voltammetry and advanced in situ techniques like surface-enhanced Raman spectroscopy (SERS), Rotating ring-disk electrode (RRDE), and Electrochemical quartz crystal microbalance (EQCM).Through our investigations, we not only redefined the mechanism of gold oxide formation but also uncovered the reasons behind the structural reconstruction of gold oxide. Additionally, we elucidated the electrochemical interfacial structure on gold from a novel perspective focusing on charge distribution.The significance of these findings lies in their fundamental nature, with the potential to inspire researcher to reconsider interpretations of voltammetry behaviors across various materials and research fields. We anticipate that our work will stimulate further exploration and innovation in the realm of electrochemistry, paving the way for new discoveries and advancements. Show less
Developing countries are growing apart on environmental issues. International environ- mental negotiations are no longer characterized merely by the North–South conflict. Rising powers have come to... Show moreDeveloping countries are growing apart on environmental issues. International environ- mental negotiations are no longer characterized merely by the North–South conflict. Rising powers have come to divide the Global South and redefine the Common-But- Differentiated Responsibilities principle. This article explains the divergence of China and India at the Kigali Amendment to the Montreal Protocol, one of the first global envi- ronmental agreements to differentiate obligations between developing countries. China and India, the world’s two largest hydrofluorocarbon producers, ended decades of collaboration and split the rest of the developing world behind them. I argue that devel- opmental strategy and political institutions shape the preferences and influences of industrial, governmental, and social stakeholders, thereby explaining their negotiation behavior and outcome. This article explains why China moved faster and further than India on negotiations for hydrofluorocarbon regulation. It has important implications for the two rising powers’ implementation of the Kigali Amendment and for their posi- tion formulations on other environmental issues. Show less
Pasham, D.R.; Lucchini, M.; Laskar, T.; Gompertz, B.P.; Srivastav, S.; Nicholl, M.; ... ; Yang, S. 2023
Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could... Show moreNeurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures. Show less
Kim, M.; Lee, S.P.; Kwak, S.; Yang, S.; Kim, Y.J.; Andreini, D.; ... ; Chang, H.J. 2021
Background: The association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).Methods: From a multinational registry of patients who... Show moreBackground: The association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).Methods: From a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 +/- 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression.Results: With a 3.3-years' median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm(3)/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm(3)/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and < 0.001, respectively). However, this tendency was not observed in any other plaque components. The annual volume changes of total plaque and dense calcification were also significantly different in the propensity score-matched lowest age quartile group versus the other age groups as was the composite clinical event (log-rank p = 0.003). In random forest analysis, age had comparable importance in the total plaque volume progression as other traditional factors.Conclusions: The rate of whole-heart plaque progression and dense calcification increases depending on age. Age is a significant factor in plaque growth, the importance of which is comparable to other traditional risk factors. Show less
Chopra, M.; McEntagart, M.; Clayton-Smith, J.; Platzer, K.; Shukla, A.; Girisha, K.M.; ... ; Genomics England Res Consortium 2021
ANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a co-factor of Yorkie. Here, we... Show moreANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a co-factor of Yorkie. Here, we delineate a neurodevelopmental disorder caused by de novo heterozygous ANKRD17 variants. The mutational spectrum of this cohort of 34 individuals from 32 families is highly suggestive of haploinsufficiency as the underlying mechanism of disease, with 21 truncating or essential splice site variants, 9 missense variants, 1 in-frame insertion-deletion, and 1 microdeletion (1.16 Mb). Consequently, our data indicate that loss of ANKRD17 is likely the main cause of phenotypes previously associated with large multi-gene chromosomal aberrations of the 4q13.3 region. Protein modeling suggests that most of the missense variants disrupt the stability of the ankyrin repeats through alteration of core structural residues. The major phenotypic characteristic of our cohort is a variable degree of developmental delay/intellectual disability, particularly affecting speech, while additional features include growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy and/or abnormal EEG, predisposition to recurrent infections (mostly bacterial), ophthalmological abnormalities, gait/balance disturbance, and joint hypermobility. Moreover, many individuals shared similar dysmorphic facial features. Analysis of single-cell RNA-seq data from the developing human telencephalon indicated ANKRD17 expression at multiple stages of neurogenesis, adding further evidence to the assertion that damaging ANKRD17 variants cause a neurodevelopmental disorder. Show less
Kara, E.; Mehdipour, M.; Kriss, G.A.; Cackett, E.M.; Arav, N.; Barth, A.J.; ... ; Zu, Y. 2021
Accurately identifying the active species of catalytic materials and understanding how they catalyze the oxygen evolution reaction (OER) are critical for the development of energy storage... Show moreAccurately identifying the active species of catalytic materials and understanding how they catalyze the oxygen evolution reaction (OER) are critical for the development of energy storage technologies. In this contribution, we identify two pH-dependent active oxides by mapping the reduction behavior of gold oxide and by in situ surface-enhanced Raman spectroscopy. It was found that α-oxide is preferentially formed in an acidic solution, whereas β-oxide, Au(OH)3, is preferably formed in an alkaline solution. In line with the presence of two different surface structures on gold, there are two OER mechanisms: one mechanism wherein water splitting occurs via proton-coupled electron-transfer steps mediated by α-oxide and the other mechanism wherein electron transfer and proton transfer are decoupled and mediated by a deprotonated form of Au(OH)3. This identification of pH-dependent oxides offers a different perspective in our understanding of the OER mechanism on metal oxides in a full pH scale range. Show less
Haan, N. de; Yang, S.; Cipollo, J.; Wuhrer, M. 2020
Sialic acids are a heterogeneous group of monosaccharides that play key roles in human glycobiology. This Review describes derivatization strategies that allow the straightforward analysis of... Show moreSialic acids are a heterogeneous group of monosaccharides that play key roles in human glycobiology. This Review describes derivatization strategies that allow the straightforward analysis of sialic acid linkage isomers by mass spectrometry and exemplifies their use for biological samples.Proteins can undergo glycosylation during and/or after translation to afford glycoconjugates, which are often secreted by a cell or populate cell surfaces. Changes in the glycan portion can have a strong influence on a glycoconjugate and are associated with a multitude of human pathologies. Of particular interest are sialylated glycoconjugates, which exist as constitutional isomers that differ in their linkages (alpha 2,3, alpha 2,6, alpha 2,8 or alpha 2,9) between sialic acids and their neighbouring monosaccharides. In general, mass spectrometry enables the rapid and sensitive characterization of glycosylation, but there are challenges specific to identifying and (relatively) quantifying sialic acid isomers. These challenges can be addressed using linkage-specific methodologies for sialic acid derivatization, after which mass spectrometry can enable product identification. This Review is concerned with the new and important derivatization approaches reported in the past decade, which have been implemented in various mass-spectrometry-glycomics workflows and have found clinical glycomics applications. The convenience and wide applicability of the approaches make them attractive for studies of sialylation in different types of glycoconjugate. Show less
MN1 encodes a transcriptional co-regulator without homology to other proteins, previously implicated in acute myeloid leukaemia and development of the palate. Large deletions cricoinp:wiing, MN1... Show moreMN1 encodes a transcriptional co-regulator without homology to other proteins, previously implicated in acute myeloid leukaemia and development of the palate. Large deletions cricoinp:wiing, MN1 have here reported in individuals with variable neurodevclop-mental anomalies and non-specific facial features. We identified a cluster of de novo truncating mutations in MN1 in a cohort of 23 individuals with strikingly similar dysmorphic facial features, especially midface hypoplasia, and intellectual disability with severe expressive language delay. Imaging revealed an atypical form of rhombencephalosynapsis, a distinctive brain malformation characterized by partial or complete loss of the cerebellar vermis with fusion of the cerebellar hemispheres, in 8/21 individuals. rhombencephalosynapsis has no previously known definitive genetic or environmental causes. Other frequent features included perisylvian polymicrogyria, abnormal posterior clinoid processes and persistent trigeminal artery, MN1 is encoded by only two exons. All mutations, including the recurrent variant p.Arg1295* observed in 8/21 probands, fall in the terminal exon or the extreme 3' region of eNon 1, and are therefore predicted to result in escape from nonsense-mediated mRNA decay. This was confirmed in fibroblasts from three individuals. we propose that the condition described here, MN1 C-termirim truncation (MCTT) syndrome, is not due to MN1 haploinsufficiency but rather is the result of dominandy acting C-terminally MN1 protein. Our data show that MN1 plays a critical role in human craniofacial and brain development, and opens the door t understanding the biological mechanisms underlying rhombencephalosynapsis. Show less
A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories.Glycosylation is a topic of intense current... Show moreA broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories.Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods. Show less
International institutions are important regulators of the trade–environment relationship. Many of them deploy trade measures for environmental purposes, with mixed results. The Basel Convention is... Show moreInternational institutions are important regulators of the trade–environment relationship. Many of them deploy trade measures for environmental purposes, with mixed results. The Basel Convention is one case where trade restrictions have not succeeded in curbing movements of hazardous waste or protecting vulner- able countries from waste dumping. Current literature emphasizes North–South conflict under the Basel Convention as a main reason for these shortcomings. This paper returns to the fundamental question as to why countries engage in this trade. It contends that hazardous wastes are not only characterized by their environmental impacts, but are also distinct in the ways they are generated, distributed, and managed. I argue that global economic integration has commodified these wastes, and countries are increasingly diverg- ing on their views of hazardous materials. This paper draws from the under-utilized Basel Convention Database and other sources to piece together a holistic picture of the global hazardous waste movements. It identifies three types of countries with distinct trade orientations: industrialized countries trading the larg- est amounts of hazardous wastes and with considerable specialization; newly industrializing countries as influential players in hazardous waste generation and management; and least developed countries, which oppose waste trade yet suffer from waste dumping. As globalization deepens, management of hazardous wastes may require extensive trade of hazardous materials between countries of varying capabilities and interests. Contrary to its current trade minimization approach based on a crude North–South dichotomy, the Basel Convention may benefit from an approach that motivates capable countries to import wastes and one that builds capacity for intended waste importers. Show less
The original version of this Article contained an error in the spelling of the author Shuxin Yang, which was incorrectly given as Shuxing Yang. This has now been corrected in both the PDF and HTML... Show moreThe original version of this Article contained an error in the spelling of the author Shuxin Yang, which was incorrectly given as Shuxing Yang. This has now been corrected in both the PDF and HTML versions of the Article.Correction to: Nature Communications; https://doi.org/10.1038/s41467-018-06658-4; published online 05 October 2018. Show less
If fiscal decentralization promotes growth, why do some regions decentralize more than others? This article identifies the growing divergence of fiscal centralization among Chinese cities and... Show moreIf fiscal decentralization promotes growth, why do some regions decentralize more than others? This article identifies the growing divergence of fiscal centralization among Chinese cities and explains it in a public finance framework. It argues that fiscal decentralization and its economy-liberalizing effect entail significant short-term fiscal risk. The more a locality relies on uncompetitive business ownership for fiscal revenue, the less likely fiscal decentralization is to occur. This article compiles a dataset of 20 provincial capitals between 1999 and 2016 to test for the connection between a city’s tax base and its fiscal centralization level. It then pairs two “most similar” cities to trace how fiscal security concerns drove their fiscal and economic policies apart. This article adds a micro-level perspective to the literature on fiscal federalism. By pointing out the fiscal constraints confronting local governments, it offers a new angle to understand the different growth paths of Chinese cities. Show less
