A mechanism for the Arctic sea ice spring predictability barrier

The decline of Arctic sea ice extent has created a pressing need for accurate seasonal predictions of regional summer sea ice. Recent work has shown evidence for an Arctic sea ice spring predictability barrier, which may impose a sharp limit on regional forecasts initialized prior to spring. However, the physical mechanism for this barrier has remained elusive. In this work, we perform a daily sea ice mass (SIM) budget analysis in large ensemble experiments from two global climate models to investigate the mechanisms that underpin the spring predictability barrier. We find that predictability is limited in winter months by synoptically driven SIM export and negative feedbacks from sea ice growth. The spring barrier results from a sharp increase in predictability at melt onset, when ice‐albedo feedbacks act to enhance and persist the preexisting export‐generated mass anomaly. These results imply that ice thickness observations collected after melt onset are particularly critical for summer Arctic sea ice predictions

A mechanism for the Arctic sea ice spring predictability barrier

The decline of Arctic sea ice extent has created a pressing need for accurate seasonal predictions of regional summer sea ice. Recent work has shown evidence for an Arctic sea ice spring predictability barrier, which may impose a sharp limit on regional forecasts initialized prior to spring. However, the physical mechanism for this barrier has remained elusive. In this work, we perform a daily sea ice mass (SIM) budget analysis in large ensemble experiments from two global climate models to investigate the mechanisms that underpin the spring predictability barrier. We find that predictability is limited in winter months by synoptically driven SIM export and negative feedbacks from sea ice growth. The spring barrier results from a sharp increase in predictability at melt onset, when ice‐albedo feedbacks act to enhance and persist the preexisting export‐generated mass anomaly. These results imply that ice thickness observations collected after melt onset are particularly critical for summer Arctic sea ice predictions

Development of novel methods for non-canonical myeloma protein analysis with an innovative adaptation of immunofixation electrophoresis, native top-down mass spectrometry, and middle-down de novo sequencing

OBJECTIVES: Multiple myeloma (MM) is a malignant plasma cell neoplasm, requiring the integration of clinical examination, laboratory and radiological investigations for diagnosis. Detection and isotypic identification of the monoclonal protein(s) and measurement of other relevant biomarkers in serum and urine are pivotal analyses. However, occasionally this approach fails to characterize complex protein signatures. Here we describe the development and application of next generation mass spectrometry (MS) techniques, and a novel adaptation of immunofixation, to interrogate non-canonical monoclonal immunoproteins. METHODS: Immunoprecipitation immunofixation (IP-IFE) was performed on a Sebia Hydrasys Scan2. Middle-down de novo sequencing and native MS were performed with multiple instruments (21T FT-ICR, Q Exactive HF, Orbitrap Fusion Lumos, and Orbitrap Eclipse). Post-acquisition data analysis was performed using Xcalibur Qual Browser, ProSight Lite, and TDValidator. RESULTS: We adapted a novel variation of immunofixation electrophoresis (IFE) with an antibody-specific immunosubtraction step, providing insight into the clonal signature of gamma-zone monoclonal immunoglobulin (M-protein) species. We developed and applied advanced mass spectrometric techniques such as middle-down de novo sequencing to attain in-depth characterization of the primary sequence of an M-protein. Quaternary structures of M-proteins were elucidated by native MS, revealing a previously unprecedented non-covalently associated hetero-tetrameric immunoglobulin. CONCLUSIONS: Next generation proteomic solutions offer great potential for characterizing complex protein structures and may eventually replace current electrophoretic approaches for the identification and quantification of M-proteins. They can also contribute to greater understanding of MM pathogenesis, enabling classification of patients into new subtypes, improved risk stratification and the potential to inform decisions on future personalized treatment modalities

Distinct Temporal and Anatomical Distributions of Amyloid-β and Tau Abnormalities following Controlled Cortical Impact in Transgenic Mice

Traumatic brain injury (TBI) is a major environmental risk factor for Alzheimer's disease. Intracellular accumulations of amyloid-β and tau proteins have been observed within hours following severe TBI in humans. Similar abnormalities have been recapitulated in young 3xTg-AD mice subjected to the controlled cortical impact model (CCI) of TBI and sacrificed at 24 h and 7 days post injury. This study investigated the temporal and anatomical distributions of amyloid-β and tau abnormalities from 1 h to 24 h post injury in the same model. Intra-axonal amyloid-β accumulation in the fimbria was detected as early as 1 hour and increased monotonically over 24 hours following injury. Tau immunoreactivity in the fimbria and amygdala had a biphasic time course with peaks at 1 hour and 24 hours, while tau immunoreactivity in the contralateral CA1 rose in a delayed fashion starting at 12 hours after injury. Furthermore, rapid intra-axonal amyloid-β accumulation was similarly observed post controlled cortical injury in APP/PS1 mice, another transgenic Alzheimer's disease mouse model. Acute increases in total and phospho-tau immunoreactivity were also evident in single transgenic TauP301L mice subjected to controlled cortical injury. These data provide further evidence for the causal effects of moderately severe contusional TBI on acceleration of acute Alzheimer-related abnormalities and the independent relationship between amyloid-β and tau in this setting

Abnormal Intracellular Accumulation and Extracellular Aβ Deposition in Idiopathic and Dup15q11.2-q13 Autism Spectrum Disorders

<div><h3>Background</h3><p>It has been shown that amyloid ß (Aβ), a product of proteolytic cleavage of the amyloid β precursor protein (APP), accumulates in neuronal cytoplasm in non-affected individuals in a cell type–specific amount.</p> <h3>Methodology/Principal Findings</h3><p>In the present study, we found that the percentage of amyloid-positive neurons increases in subjects diagnosed with idiopathic autism and subjects diagnosed with duplication 15q11.2-q13 (dup15) and autism spectrum disorder (ASD). In spite of interindividual differences within each examined group, levels of intraneuronal Aβ load were significantly greater in the dup(15) autism group than in either the control or the idiopathic autism group in 11 of 12 examined regions (p<0.0001 for all comparisons; Kruskall-Wallis test). In eight regions, intraneuronal Aβ load differed significantly between idiopathic autism and control groups (p<0.0001). The intraneuronal Aβ was mainly N-terminally truncated. Increased intraneuronal accumulation of Aβ_17–40/42 in children and adults suggests a life-long enhancement of APP processing with α-secretase in autistic subjects. Aβ accumulation in neuronal endosomes, autophagic vacuoles, Lamp1-positive lysosomes and lipofuscin, as revealed by confocal microscopy, indicates that products of enhanced α-secretase processing accumulate in organelles involved in proteolysis and storage of metabolic remnants. Diffuse plaques containing Aβ_1–40/42 detected in three subjects with ASD, 39 to 52 years of age, suggest that there is an age-associated risk of alterations of APP processing with an intraneuronal accumulation of a short form of Aβ and an extracellular deposition of full-length Aβ in nonfibrillar plaques.</p> <h3>Conclusions/Significance</h3><p>The higher prevalence of excessive Aβ accumulation in neurons in individuals with early onset of intractable seizures, and with a high risk of sudden unexpected death in epilepsy in autistic subjects with dup(15) compared to subjects with idiopathic ASD, supports the concept of mechanistic and functional links between autism, epilepsy and alterations of APP processing leading to neuronal and astrocytic Aβ accumulation and diffuse plaque formation.</p> </div

What Mechanism Design Theorists Had to Say About Laboratory Experimentation in the Mid-1980s

Thanks to the recent studies of the history and philosophy of experimental economics, it is well known that around the early 1980s, experimental economists made a case for the legitimacy of their laboratory work by emphasizing that it was a nice and indispensable complement to mechanism design theorists' mathematical study of institutions. The present paper examines what mechanism design theorists thought of laboratory experimentation, or whether they were willing to form a coalition with experimental economists circa the mid-1980s. By exploring several dimensions of the relationship between mechanism design theory and experimental economics, the present paper shows that a close rapport had been established by the early 1980s between the representative members of the two camps, and also that mechanism design theorists were among the strongest supporters of laboratory experimentation in the economics profession in the mid-1980s

An “Exceeding Faire” Baby in the King James Bible: A New Testament Greek Example of a Hebrew Elohim Superlative

Stephen, in his defense recorded in Acts 7, mentions the fact that Moses’ parents hid him against the direct command of Pharaoh to kill the baby because they saw that he was “exceeding faire” (Acts 7.20, KJV). This paper discusses the origins of this novel understanding of the Greek text ἀστεῖος τῷ θεῷ (beautiful to God), which follows neither the traditional translations which were previous to the English Bible nor the various English versions which paved the way for the KJV. Rather, the translation reflects the use of the Elohim superlative of the KJV Old Testament. It is a clear example of the influence the KJV has had on subsequent English Bible translations, both in the cases of Bibles which obviously follow the KJV’s reading as well as those traditional revisions or translations which normally follow the language and style of the KJV but in this specific case do not

Dominance of the Southern Ocean in Anthropogenic Carbon and Heat Uptake in CMIP5 Models

The authors assess the uptake, transport, and storage of oceanic anthropogenic carbon and heat over the period 1861-2005 in a new set of coupled carbon-climate Earth system models conducted for the fifth phase of the Coupled Model Intercomparison Project (CMIP5), with a particular focus on the Southern Ocean. Simulations show that the Southern Ocean south of 30 degrees S, occupying 30% of global surface ocean area, accounts for 43% 63% (42 + 5 PgC) of anthropogenic CO2 and 75% 622% (23 + 9 x 10(22) J) of heat uptake by the ocean over the historical period. Northward transport out of the Southern Ocean is vigorous, reducing the storage to 33 +/- 6 Pg anthropogenic carbon and 12 +/- 7 x 10(22) J heat in the region. The CMIP5 models, as a class, tend to underestimate the observation-based global anthropogenic carbon storage but simulate trends in global ocean heat storage over the last 50 years within uncertainties of observation-based estimates. CMIP5 models suggest global and Southern Ocean CO2 uptake have been largely unaffected by recent climate variability and change. Anthropogenic carbon and heat storage show a common broad-scale pattern of change, but ocean heat storage is more structured than ocean carbon storage. The results highlight the significance of the Southern Ocean for the global climate and as the region where models differ the most in representation of anthropogenic CO2 and, in particular, heat uptake