Miracle-dz/UniFAR-FTUs huggingface dataset:
Tropical forcing of increased Southern Ocean climate variability revealed by a 140-year subantarctic temperature reconstruction

Abstract. Occupying about 14 % of the world's surface, the Southern Ocean plays a fundamental role in ocean and atmosphere circulation, carbon cycling and Antarctic ice-sheet dynamics. Unfortunately, high interannual variability and a dearth of instrumental observations before the 1950s limits our understanding of how marine–atmosphere–ice domains interact on multi-decadal timescales and the impact of anthropogenic forcing. Here we integrate climate-sensitive tree growth with ocean and atmospheric observations on southwest Pacific subantarctic islands that lie at the boundary of polar and subtropical climates (52–54° S). Our annually resolved temperature reconstruction captures regional change since the 1870s and demonstrates a significant increase in variability from the 1940s, a phenomenon predating the observational record. Climate reanalysis and modelling show a parallel change in tropical Pacific sea surface temperatures that generate an atmospheric Rossby wave train which propagates across a large part of the Southern Hemisphere during the austral spring and summer. Our results suggest that modern observed high interannual variability was established across the mid-twentieth century, and that the influence of contemporary equatorial Pacific temperatures may now be a permanent feature across the mid- to high latitudes.
Using the electrocorticographic speech network to control a brain–computer interface in humans

Electrocorticography (ECoG) has emerged as a new signal platform for brain–computer interface (BCI) systems. Classically, the cortical physiology that has been commonly investigated and utilized for device control in humans has been brain signals from the sensorimotor cortex. Hence, it was unknown whether other neurophysiological substrates, such as the speech network, could be used to further improve on or complement existing motor-based control paradigms. We demonstrate here for the first time that ECoG signals associated with different overt and imagined phoneme articulation can enable invasively monitored human patients to control a one-dimensional computer cursor rapidly and accurately. This phonetic content was distinguishable within higher gamma frequency oscillations and enabled users to achieve final target accuracies between 68% and 91% within 15 min. Additionally, one of the patients achieved robust control using recordings from a microarray consisting of 1 mm spaced microwires. These findings suggest that the cortical network associated with speech could provide an additional cognitive and physiologic substrate for BCI operation and that these signals can be acquired from a cortical array that is small and minimally invasive.
When tenure ends: the short-run effects of the elimination of Louisiana's teacher employment protections on teacher exit and retirement

ABSTRACT Most teachers have tenure protections that constrain dismissal. Some argue that tenure improves recruitment and retention by mitigating the risk of monopsony employment and substituting job security for lower salaries. Others argue that tenure reduces performance incentives making it difficult to dismiss ineffective teachers. We examine supply-side responses of teachers after the elimination of tenure before administrators could use performance to dismiss teachers. Voluntary teacher attrition increased after tenure elimination with effects concentrated in groups that are theoretically most likely to value job protections. Specifically, tenure removal increased exit of teachers with bottom decile value-added measures and retirement eligible teachers.
Do potential past and future events activate the Lateral Mental Timeline?

Current evidence provides support for the idea that time is mentally represented by spatial means, as a lateral mental time line. However, available studies have tested only factual events, i.e., those which have occurred in the past or will occur in the future. In the present study we tested whether past and future potential events are also represented along the lateral mental timeline. In Experiment 1 participants categorized the temporal reference (past or future) of either factual or potential events and responded by means of a lateralized (left or right) keypress. Factual events showed a space-time congruency effect that replicated prior findings: participants were faster to categorize past events with the left hand and future events with the right hand than when using the opposite mapping. More importantly, this also ocurred for potential events. Experiment 2 replicated this finding using blocks comprising only potential events. In order to assess the degree of automaticity of the activation of the mental timeline in these two kinds of events, Experiment 3 asked participants to judge whether the expressions referred to factual or potential events. In this case, there was no space-time congruency effect, showing that the lateral timeline is active only when relevant to the task. Moreover, participants were faster to categorize potential events with the left hand and factual events with the right hand than when using the opposite mapping, suggesting for the first time a link between the mental representations of space and potentiality.
Chronostratigraphy of Alluvia and Age of Fluvial Landforms in the Carpathian Foreland During the Vistulian

Abstract A development of opinions on stratigraphy of alluvia and age of the Vistulian terraces in the valleys of the Carpathian foreland is presented, based mainly on publications of Professor Leszck Starkel. Studies of age of fluvial landforms and sediments of the Last Cold Stage in the Carpathian foreland have been started more than 100 years ago. Before the modern sedimentological methods and radiocarbon dating were introduced, pioneer studies of Pleistocene river terraces and sediments in the Carpathians were performed by Mieczysław Klimaszewski, and subsequently, by his student Leszek Starkel who mapped in 1950s a margin of the Carpathian Foothills as well as alluvial fans of Wistoka, Wistok and San rivers in the Carpathian foreland. In that time a stratigraphy of alluvial infillings in the marginal mountain zone was elaborated for the Late Vistulian and the Holocene. Starting from 1970s and basing on studies in key sites in the Wisioka valley near Dębica, focused on palynological analyses and radiocarbon dating, general strati- graphical schemes of alluvial fills within the Vistulian terrace 15 m high and within the Holocene terrace 8-10 m high have been constructed. A comparison with the valleys in a periglacial area prowed that the Vistulian terrace 15 m high was incised before the maximum extension of the last Scandinavian ice sheet (i.e. before 20 ka BP) and the terrace 11-12 m high (with relics of braided river channels) was formed at the decline of the Plenivistulian. A final incision below the present river bed and aggradation occurred during the Late Vistulian (13-10 ka BP). The rivers changed their regime and their channel pattern from braided to large meanders-type as an effect of forest development and lower sediment load. The Younger Dryas cooling resulted in increased bedload and braiding.
Immunoglobulin E-Mediated Autoimmunity

The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP), and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.
A Discontinuous RNA Platform Mediates RNA Virus Replication: Building an Integrated Model for RNA–based Regulation of Viral Processes

Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA–RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA–RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA–based interaction spanning ∼3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes.
Ionized calcium in normal serum, ultrafiltrates, and whole blood determined by ion-exchange electrodes.

Ion-exchange calcium electrodes represent the first practical method for the direct measurement of ionized calcium [Ca(++)] in biologic fluids. Using both "static" and "flow-through" electrodes, serum [Ca(++)] was within a rather narrow range: 0.94-1.33 mmoles/liter (mean, 1.14 mmoles/liter). Within a given individual, [Ca(++)] varied only about 6% over a several month period. Consistent pH effects on [Ca(++)] were observed in serum and whole blood, [Ca(++)] varying inversely with pH. Less consistent pH effects were also noted in ultrafiltrates, believed to largely represent precipitation of certain calcium complexes from a supersaturated solution. Heparinized whole blood [Ca(++)] was significantly less than in corresponding serum at normal blood pH, related to the formation of a calcium-heparin complex. [Ca(++)] in ultrafiltrates represented a variable fraction (66.7-90.2%) of total diffusible calcium. There was no apparent correlation between serum ionized and total calcium concentrations. Thus, neither serum total calcium nor total ultrafiltrable calcium provided a reliable index of serum [Ca(++)]. Change in serum total calcium was almost totally accounted for by corresponding change in protein-bound calcium [CaProt]. About 81% of [CaProt] was estimated to be bound to albumin and about 19% to globulins. From observed pH, serum protein, and [CaProt] data, a nomogram was developed for estimating [CaProt] without ultrafiltration. Data presented elsewhere indicate that calcium binding by serum proteins obeys the mass-law equation for a monoligand association. This was indicated in the present studies by a close correspondence of observed serum [Ca(++)] values with those predicted by the McLean-Hastings nomogram. While these electrodes allow study of numerous problems not possible previously, they have not been perfected to the same degree of reliability obtainable with current pH electrodes. The commercial (Orion flow-through) electrode is: (a) expensive. (b) requires periodic replacement of membranes, and (c) has not yet been thermostated. As with blood pH measurements. (d) electrode response is logarithmic, i.e. small potential errors generate rather large [Ca(++)] errors. (e) loss of CO(2) should be prevented, and (f) errors due to other cations must be considered under certain conditions. Despite these limitations, we believe the electrode represents a major advance in calcium metabolism.
Opportunities to Apply the 3Rs in Safety Assessment Programs

Abstract Before a potential new medicine can be administered to humans it is essential that its safety is adequately assessed. Safety assessment in animals forms an integral part of this process, from early drug discovery and initial candidate selection to the program of recommended regulatory tests in animals. The 3Rs (replacement, reduction, and refinement of animals in research) are integrated in the current regulatory requirements and expectations and, in the EU, provide a legal and ethical framework for in vivo research to ensure the scientific objectives are met whilst minimizing animal use and maintaining high animal welfare standards. Though the regulations are designed to uncover potential risks, they are intended to be flexible, so that the most appropriate approach can be taken for an individual product. This article outlines current and future opportunities to apply the 3Rs in safety assessment programs for pharmaceuticals, and the potential (scientific, financial, and ethical) benefits to the industry, across the drug discovery and development process. For example, improvements to, or the development of, novel, early screens (e.g., in vitro, in silico, or nonmammalian screens) designed to identify compounds with undesirable characteristics earlier in development have the potential to reduce late-stage attrition by improving the selection of compounds that require regulatory testing in animals. Opportunities also exist within the current regulatory framework to simultaneously reduce and/or refine animal use and improve scientific outcomes through improvements to technical procedures and/or adjustments to study designs. It is important that approaches to safety assessment are continuously reviewed and challenged to ensure they are science-driven and predictive of relevant effects in humans.
Land use strategies to mitigate climate change in carbon dense temperate forests

Significance Regional quantification of feasibility and effectiveness of forest strategies to mitigate climate change should integrate observations and mechanistic ecosystem process models with future climate, CO2, disturbances from fire, and management. Here, we demonstrate this approach in a high biomass region, and found that reforestation, afforestation, lengthened harvest cycles on private lands, and restricting harvest on public lands increased net ecosystem carbon balance by 56% by 2100, with the latter two actions contributing the most. Forest sector emissions tracked with our life cycle assessment model decreased by 17%, partially meeting emissions reduction goals. Harvest residue bioenergy use did not reduce short-term emissions. Cobenefits include increased water availability and biodiversity of forest species. Our improved analysis framework can be used in other temperate regions. Strategies to mitigate carbon dioxide emissions through forestry activities have been proposed, but ecosystem process-based integration of climate change, enhanced CO2, disturbance from fire, and management actions at regional scales are extremely limited. Here, we examine the relative merits of afforestation, reforestation, management changes, and harvest residue bioenergy use in the Pacific Northwest. This region represents some of the highest carbon density forests in the world, which can store carbon in trees for 800 y or more. Oregon’s net ecosystem carbon balance (NECB) was equivalent to 72% of total emissions in 2011–2015. By 2100, simulations show increased net carbon uptake with little change in wildfires. Reforestation, afforestation, lengthened harvest cycles on private lands, and restricting harvest on public lands increase NECB 56% by 2100, with the latter two actions contributing the most. Resultant cobenefits included water availability and biodiversity, primarily from increased forest area, age, and species diversity. Converting 127,000 ha of irrigated grass crops to native forests could decrease irrigation demand by 233 billion m3⋅y−1. Utilizing harvest residues for bioenergy production instead of leaving them in forests to decompose increased emissions in the short-term (50 y), reducing mitigation effectiveness. Increasing forest carbon on public lands reduced emissions compared with storage in wood products because the residence time is more than twice that of wood products. Hence, temperate forests with high carbon densities and lower vulnerability to mortality have substantial potential for reducing forest sector emissions. Our analysis framework provides a template for assessments in other temperate regions.
The Association Between Metabolically Healthy Obesity and the Risk of Proteinuria: The Kansai Healthcare Study

Background Metabolically healthy obesity seems to be a unique phenotype for the risk of cardiometabolic diseases. However, it is not known whether this phenotype is associated with the risk of proteinuria. Methods Study subjects were 9,185 non-diabetic Japanese male workers aged 40–55 years who had no proteinuria, an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, no history of cancer, and no use of antihypertensive or lipid-lowering medications at baseline. Obesity was defined as body mass index ≥25.0 kg/m2. Metabolic health was defined as the presence of no Adult Treatment Panel III components of the metabolic syndrome criteria, excluding waist circumference, and metabolic unhealth was defined as the presence of one or more metabolic syndrome components, excluding waist circumference. “Consecutive proteinuria” was considered positive if proteinuria was detected twice consecutively as 1+ or higher on urine dipstick at annual examinations to exclude chance proteinuria as much as possible. Results During the 81,660 person-years follow-up period, we confirmed 390 cases of consecutive proteinuria. Compared with metabolically healthy non-obesity, metabolically healthy obesity was not associated with the risk of consecutive proteinuria (multiple-adjusted hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.37–1.99), but metabolically unhealthy non-obesity with ≥2 metabolic syndrome components (HR 1.77; 95% CI, 1.30–2.42), metabolically unhealthy obesity with one component (HR 1.71; 95% CI, 1.12–2.61), and metabolically unhealthy obesity with ≥2 metabolic syndrome components (HR 2.77; 95% CI, 2.01–3.82) were associated with an increased risk of consecutive proteinuria. Conclusions Metabolically healthy obesity did not increase the risk of consecutive proteinuria in Japanese middle-aged men.
Language Patterns Discriminate Mild Depression From Normal Sadness and Euthymic State

Objectives Deviations from typical word use have been previously reported in clinical depression, but language patterns of mild depression (MD), as distinct from normal sadness (NS) and euthymic state, are unknown. In this study, we aimed to apply the linguistic approach as an additional diagnostic key for understanding clinical variability along the continuum of affective states. Methods We studied 402 written reports from 124 Russian-speaking patients and 77 healthy controls (HC), including 35 cases of NS, using hand-coding procedures. The focus of our psycholinguistic methods was on lexico-semantic [e.g., rhetorical figures (metaphors, similes)], syntactic [e.g., predominant sentence type (single-clause and multi-clause)], and lexico-grammatical [e.g., pronouns (indefinite, personal)] variables. Statistical evaluations included Cohen’s kappa for inter-rater reliability measures, a non-parametric approach (Mann–Whitney U-test and Pearson chi-square test), one-way ANOVA for between-group differences, Spearman’s and point-biserial correlations to analyze relationships between linguistic and gender variables, discriminant analysis (Wilks’ λ) of linguistic variables in relation to the affective diagnostic types, all using SPSS-22 (significant, p < 0.05). Results In MD, as compared with healthy individuals, written responses were longer, demonstrated descriptive rather than analytic style, showed signs of spoken and figurative language, single-clause sentences domination over multi-clause, atypical word order, increased use of personal and indefinite pronouns, and verb use in continuous/imperfective and past tenses. In NS, as compared with HC, we found greater use of lexical repetitions, omission of words, and verbs in continuous and present tenses. MD was significantly differentiated from NS and euthymic state by linguistic variables [98.6%; Wilks’ λ(40) = 0.009; p < 0.001; r = 0.992]. The highest predictors in discrimination between MD, NS, and euthymic state groups were the variables of word order (typical/atypical) (r = −0.405), ellipses (omission of words) (r = 0.583), colloquialisms (informal words/phrases) (r = 0.534), verb tense (past/present/future) (r = −0.460), verbs form (continuous/perfect) (r = 0.345), amount of reflexive (e.g., myself)/personal (r = 0.344), and negative (e.g., nobody)/indefinite (r = 0.451) pronouns. The most significant between-group differences were observed in MD as compared with both NS and euthymic state. Conclusion MD is characterized by patterns of atypical language use distinguishing depression from NS and euthymic state, which points to a potential role of linguistic indicators in diagnosing affective states.
Meta-analysis based on control of false discovery rate: combining yeast ChIP-chip datasets

MOTIVATION High-throughput microarray technology can be used to examine thousands of features, such as all the genes of an organism, and measure their expression. Two important issues of microarray bioinformatics are first, how to combine the significance values for each feature across experiments with high statistical power, and second, how to control the proportion of false positives. Existing methods address these issues separately, in spite of their linked usage. RESULTS We present a novel method (ESP) to address the two requirements in an interdependent way. It generalizes the truncated product method of Zaykin et al. to combine only those significance values which clear their respective experiment-specific false discovery restrictive thresholds, thus allowing us to control the false discovery rate (FDR) for the final combined result. Further, we introduce several concepts that together offer FDR control, high power, quality control and speed-up in meta-analysis as done by our algorithm. Computational and statistical methods of research synthesis like the one described here will be increasingly important as additional genome-wide datasets accumulate in databases. We apply our method to combine three well-known ChIP-chip transcription factor binding datasets for budding yeast to identify significant intergenic regulatory sequences for nine cell cycle regulating transcription factors, both with high power and controlled FDR.