Miracle-dz/UniFAR-FTUs huggingface dataset:
Re-evaluation of the correction factors for the GROVEX

The GROVEX (GROssVolumige EXtrapolationskammer, large-volume extrapolation chamber) is the primary standard for the dosimetry of low-dose-rate interstitial brachytherapy at the Physikalisch-Technische Bundesanstalt (PTB). In the course of setup modifications and re-measuring of several dimensions, the correction factors have been re-evaluated in this work. The correction factors for scatter and attenuation have been recalculated using the Monte Carlo software package EGSnrc, and a new expression has been found for the divergence correction. The obtained results decrease the measured reference air kerma rate by approximately 0.9% for the representative example of a seed of type Bebig I25.S16C. This lies within the expanded uncertainty (k = 2).
Drivers of Dry Day Sensitivity to Increased CO2

Persistent precipitation deficits are among the most impactful consequences of global warming. Here we focus on changes in the annual number of dry days (NDD) and in the annual maximum length of dry spells due to a quadrupling of atmospheric CO2. We use atmosphere‐only simulations to decompose the projected changes into additive contributions. A fast adjustment leads to a global increase in NDD despite notable regional exceptions (e.g., South Asia and Sahel). The effect of the uniform component of the surface ocean warming is model‐dependent but shapes the regional distribution of the NDD response in each model. Finally, the ocean warming pattern also contributes to large uncertainties, likely through contrasting changes in large‐scale circulation. Our results thus highlight the complexity of the NDD response, with policy‐relevant practical implications for mitigation and adaptation strategies.
Monomeric amyloid-β inhibits microglial inflammatory activity in the brain via an APP/heterotrimeric G protein-mediated pathway

Microglia, the resident immune cell of the brain, play critical roles in brain development, function, and disease. However, how microglial activity is regulated in this process remains to be elucidated. Here we report an amyloid precursor protein (APP) and heterotrimeric G protein-mediated pathway that negatively regulates microglial inflammatory activation during cerebral cortex development. Disruption of this pathway results in dysregulated microglial activity, excessive extracellular matrix proteinase production, cortical basement membrane breach, and laminar assembly disruption. We further show that this pathway is activated by amyloid β (Aβ), the cleavage product of APP that accumulates in large quantities as plaques in the Alzheimer’s disease brain. Specifically, we find Aβ monomers potently suppress inflammatory cytokine transcription and secretion by brain microglia, in an APP and heterotrimeric G protein-dependent manner. These results discover a previously unknown activity of Aβ as a negative regulator of brain microglia as well as a new pathway that mediates the signal transduction. They shed new light on the cell-cell communication mechanisms that regulate brain immune homeostasis and may facilitate further insight into Alzheimer’s disease pathogenesis.
The spatial extent of anatomical connections within the thalamus varies across the cortical hierarchy in humans and macaques

Each cortical area has a distinct pattern of anatomical connections within the thalamus, a central subcortical structure composed of functionally and structurally distinct nuclei. Previous studies have suggested that certain cortical areas may have more extensive anatomical connections that target multiple thalamic nuclei, which potentially allows them to modulate distributed information flow. However, there is a lack of quantitative investigations into anatomical connectivity patterns within the thalamus. Consequently, it remains unknown if cortical areas exhibit systematic differences in the extent of their anatomical connections within the thalamus. To address this knowledge gap, we used diffusion magnetic resonance imaging (dMRI) to perform brain-wide probabilistic tractography for 828 healthy adults from the Human Connectome Project. We then developed a framework to quantify the spatial extent of each cortical area’s anatomical connections within the thalamus. Additionally, we leveraged resting-state functional MRI, cortical myelin, and human neural gene expression data to test if the extent of anatomical connections within the thalamus varied along the cortical hierarchy. Our results revealed two distinct cortico-thalamic tractography motifs: 1) a sensorimotor cortical motif characterized by focal thalamic connections targeting posterolateral thalamus, associated with fast, feed-forward information flow; and 2) an associative cortical motif characterized by diffuse thalamic connections targeting anteromedial thalamus, associated with slow, feed-back information flow. These findings were consistent across human subjects and were also observed in macaques, indicating cross-species generalizability. Overall, our study demonstrates that sensorimotor and association cortical areas exhibit differences in the spatial extent of their anatomical connections within the thalamus, which may support functionally-distinct cortico-thalamic information flow.
Consistent decrease in conifer embolism resistance from the stem apex to base resulting from axial trends in tracheid and pit traits

Drought-induced embolism formation in conifers is associated with several tracheid and pit traits, which vary in parallel from stem apex to base. We tested whether this axial anatomical variability is associated with a progressive variation in embolism vulnerability along the stem from apex to base. We assessed the xylem pressure at 50% loss of conductivity (P50), the tracheid hydraulic diameter (Dh) and mean pit membrane area (PMA) on longitudinal stem segments extracted at different distances from the stem apex (DFA) in a Picea abies and an Abies alba tree. In both trees, Dh and PMA scaled with DFA0.2. P50 varied for more than 3 MPa from the treetop to the stem base, according to a scaling of -P50 with DFA-0.2. The largest Dh, PMA and P50 variation occurred for DFA<1.5 m. PMA and Dh scaled isometrically (exponent b=1). Pit traits vary proportionally with tracheid lumen diameter. Apex-to-base trends in tracheid and pit traits determine a large DFA-dependent P50 variability. Such a DFA effect on P50 did not receive sufficient attention so far, although analysing the relationships P50 vs. DFA is fundamental for the assessment of embolism vulnerability at the individual level. Highlights Conifer embolism vulnerability depends on pit properties, in agreement with published data. Pit dimensions increase with tracheid lumen diameter, in agreement with published data Tracheid lumen diameter and pit dimensions increase progressively from the stem apex to base, in agreement with published data. Xylem vulnerability to embolism formation (P50) varies for > 3 MPa from the stem apex to base, with the largest variation occurring within 1.5 m from the stem apex. Axial anatomical patterns should be accounted for when analyzing hydraulic properties at individual, intra- and inter-specific scales.
Neural mechanism underlying preview effects and masked priming effects in visual word processing

Two classic experimental paradigms – masked repetition priming and the boundary paradigm – have played a pivotal role in understanding the process of visual word recognition. Traditionally, these paradigms have often been employed by different communities of researchers, with their own long-standing research traditions. Nevertheless, a review of the literature suggests that the brain-electric correlates of word processing established with both paradigms may show interesting similarities, in particular with regard to the location, timing, and direction of N1 and N250 effects. However, as of yet, no direct comparison has been undertaken between both paradigms. In the current study, we used combined eye-tracking/EEG to perform such a within-subject comparison using the same materials (single Chinese characters) as stimuli. Our results show the typical early repetition effects of N1 and N250 for both paradigms. However, repetition effects in N250 (i.e., a reduced negativity following identical-word primes/previews as compared to different-word primes/previews) were larger in the boundary paradigm than with masked priming. For N1 effects, repetition effects were similar across the two paradigms showing a larger N1 after repetitions as compared to alternations. Therefore, the results indicate that at the neural level, a briefly presented and masked foveal prime produces qualitatively similar facilitatory effects on visual word recognition as a parafoveal preview before a saccade, although such effects appear to be stronger in the latter case.
Noncanonical usage of stop codons in ciliates expands proteins with structurally flexible Q-rich motifs

Serine(S)/threonine(T)-glutamine(Q) cluster domains (SCDs), polyglutamine (polyQ) tracts and polyglutamine/asparagine (polyQ/N) tracts are Q-rich motifs found in many proteins. SCDs often are intrinsically disordered regions that mediate protein phosphorylation and protein-protein interactions. PolyQ and polyQ/N tracts are structurally flexible sequences that trigger protein aggregation. We report that due to their high percentages of STQ or STQN amino acid content, four SCDs and three prion-causing Q/N-rich motifs of yeast proteins possess autonomous protein expression-enhancing activities. Since these Q-rich motifs can endow proteins with structural and functional plasticity, we suggest that they represent useful toolkits for evolutionary novelty. Comparative Gene Ontology (GO) analyses of the near-complete proteomes of 26 representative model eukaryotes reveal that Q-rich motifs prevail in proteins involved in specialized biological processes, including Saccharomyces cerevisiae RNA-mediated transposition and pseudohyphal growth, Candida albicans filamentous growth, ciliate peptidyl-glutamic acid modification and microtubule-based movement, Tetrahymena thermophila xylan catabolism and meiosis, Dictyostelium discoideum development and sexual cycles, Plasmodium falciparum infection, and the nervous systems of Drosophila melanogaster, Mus musculus and Homo sapiens. We also show that Q-rich-motif proteins are expanded massively in 10 ciliates with reassigned TAAQ and TAGQ codons. Notably, the usage frequency of CAGQ is much lower in ciliates with reassigned TAAQ and TAGQ codons than in organisms with expanded and unstable Q runs (e.g. D. melanogaster and H. sapiens), indicating that the use of noncanonical stop codons in ciliates may have coevolved with codon usage biases to avoid triplet repeat disorders mediated by CAG/GTC replication slippage.
Exploring the Role of MMP9 and its Association with TGFβ Signalling in Patients with Mesial Temporal Lobe Epilepsy-Hippocampal Sclerosis

Inflammation and blood brain barrier (BBB) damage are associated with epileptogenesis in Mesial Temporal lobe epilepsy with Hippocampal sclerosis (MTLE-HS). Animal studies have predicted the role of Matrix metalloproteinase 9 (MMP9) in extracellular matrix (ECM) modulation, BBB leakage and neuro-inflammation, while Transforming growth factor beta (TGFβ) signalling in astrocytes potentiates hyper-excitability leading to seizure generation. We hypothesize whether changes in activity and expression of MMP9, and the ratio of MMP9 and its inhibitor, Tissue inhibitor of metalloproteinase 1 (TIMP1), have a role in epileptogenesis in the patients with MTLE-HS through zona occludens 1 (ZO1) modulation. We also proposed the role of astrocytic TGFβ signalling in these patients. mRNA expression of MMP9 and TIMP1 was significantly up-regulated. The ratio of MMP9 to its inhibitor TIMP1 was greater than one, suggesting activation of MMP9, further confirmed by gelatin zymography. MMP9 activity as well as immunoreactivity was higher in patients with MTLE-HS as compared to non-seizure controls, whereas the immunoreactivity of ZO1 was significantly lower in the patients. The downstream TGFβ signalling effector molecules, SMAD3 and pSMAD3 immunoreactivity were also significantly higher in MTLE-HS patients and both molecules showed co-localisation with astrocytes in the hippocampal region. Further, we showed preliminary data about interaction of MMP9 and TGFβ1 in these patients as evidenced by a co-immunoprecipitation assay. This study highlighted the MMP9 and astrocytic TGFβ signalling mediated potential mechanism of epileptogenesis in MTLE-HS patients.
Integrating Path-Dependent Functionals on Yeh-Wiener Space

Let C0[0, T ] denote one-parameter Wiener space (named after Norbert Wiener who did some of the earliest work in this area); that is the space of all continuous realvalued functions x on [0, T ] with x(0) = 0. During the past 75 years many people have made substantial contributions in studying this space with important applications to both physics and mathematics. In particular there is a considerable body of work relating to what we now call generalized Wiener spaces. Earlier discussions of these spaces can be found in [8, 22] and more recent developments can be found in [5, 6, 7, 9, 10]; the references listed in these papers led to a very large collection of other results. The space which we will refer to as Yeh-Wiener space was introduced in [25] with further results in [23, 24]. In these papers, Yeh explored the structure and behavior of a Gaussian measure analogous to the classical Weiner measure but defined on the space of continuous functions of two variables. The associated stochastic process is often called the Brownian sheet. See [3, 12, 13, 14, 15, 16, 17, 18] for more information and examples. The setting for this paper involves what we term a generalized Yeh-Wiener space. This function space extends the ordinary Yeh-Wiener space in a similar manner to
Genomic characterization and gene bank curation of Aegilops: the wild relatives of wheat

Genetic diversity found in crop wild relatives is critical to preserve and utilize for crop improvement to achieve sustainable food production amid climate change and increased demand. We genetically characterized a large collection of 1,041 Aegilops accessions distributed among 23 different species using more than 45K single nucleotide polymorphisms identified by genotyping-by-sequencing (GBS). The Wheat Genetics Resource Center (WGRC) Aegilops germplasm collection was curated through the identification of misclassified and redundant accessions. There were 49 misclassified and 28 sets of redundant accessions within the four diploid species. The curated germplasm sets now have improved utility for genetic studies and wheat improvement. We constructed a phylogenetic tree and PCA cluster for all Aegilops species together, giving one of the most comprehensive views of Aegilops. The Sitopsis section and the U genome Aegilops clade were further scrutinized with in-depth population analysis. The genetic relatedness among the pair of Aegilops species provided strong evidence for the species evolution, speciation and diversification. We inferred genome symbols for two species Ae. neglecta and Ae. columnaris based on the sequence read mapping and the presence of segregating loci on the pertinent genomes as well as genetic clustering. The high genetic diversity observed among Aegilops species indicated that the genus could play an even greater role in providing the critical need for untapped genetic diversity for future wheat breeding and improvement. To fully characterize these Aegilops species, there is an urgent need to generate reference assemblies for these wild wheats, especially for the polyploid Aegilops. One-sentence summary Genotyping Aegilops species, the wild relatives of wheat, has revealed high genetic diversity and unique evolutionary relationships among the Aegilops and with wheat, giving insight into the effective use of these germplasms for bread wheat improvement.
An integrative proteomics approach identifies tyrosine kinase KIT as a novel therapeutic target for SPINK1-positive prostate cancer

Elevated Serine Peptidase Inhibitor, Kazal type 1 (SPINK1) levels in ∼10-25% of prostate cancer (PCa) patients associate with aggressive phenotype, for which there are limited treatment choices and dismal clinical outcomes. Using an integrative proteomics approach involving label-free phosphoproteome and proteome profiling, we delineated the downstream signaling pathways involved in SPINK1-mediated tumorigenesis in PCa, and identified tyrosine kinase KIT as a highly enriched kinase. Furthermore, high to moderate levels of KIT expression was detected in ∼85% of SPINK1-positive PCa specimens. KIT signaling regulates SPINK1-associated oncogenesis, and treatment with KIT inhibitor reduces tumor growth and distant metastases in preclinical mice models. Mechanistically, KIT signaling modulates WNT/β-catenin pathway and confers stemness-related features in PCa. Notably, inhibiting KIT signaling restores AR/REST levels, forming a feedback loop enabling SPINK1 repression. Overall, we uncover the role of KIT signaling downstream of SPINK1 in maintaining lineage plasticity and provide new treatment modalities for advanced-stage SPINK1-positive subtype.
Freshwater Contributions to Decadal Variability of the Indonesian Throughflow

The Makassar Strait, the main passageway of the Indonesian Throughflow (ITF), is an important component of Indo‐Pacific climate through its inter‐basin redistribution of heat and freshwater. Observational studies suggest that wind‐driven freshwater advection from the marginal seas into the Makassar Strait modulates the strait's surface transport. However, direct observations are too short (<15 years) to resolve variability on decadal timescales. Here we use a series of global ocean simulations to assess the advected freshwater contributions to ITF transport across a range of timescales. The simulated seasonal and interannual freshwater dynamics are consistent with previous studies. On decadal timescales, we find that wind‐driven advection of South China Sea (SCS) waters into the Makassar Strait modulates upper‐ocean ITF transport. Atmospheric circulation changes associated with Pacific decadal variability appear to drive this mechanism via Pacific lower‐latitude western boundary current interactions that affect the SCS circulation.
Investigating Adaptive Nonresponse Follow-up Strategies for Small Businesses through Embedded Experiments

Abstract The U.S. Census Bureau is investigating adaptive Nonresponse Follow-Up (NRFU) strategies for single unit businesses in the 2017 Economic Census. These collection protocols require a suite of viable alternative procedures that can be implemented. With business surveys, the majority of cognitive research and nonresponse follow-up procedures focus on collection methods that obtain valid response data from the larger businesses, and there is relatively little quantitative or qualitative research for small businesses. Moreover, the contact methods for small businesses are often constrained by budget limitations. Business programs at the U.S. Census Bureau rely on mailed reminder letters and supplemental promotional materials, with options for certified and bulk mailings. To explore the benefits and disadvantages of the proposed alternative nonresponse follow-up procedures for small businesses, we conducted a field experiment embedded in the 2014 Annual Survey of Manufactures, an annual program that has similar data collection procedures and sampling units as the Economic Census. This article describes the study and presents the results, then discusses how the recommended nonresponse follow-up procedures are implemented in an adaptive collection design test presently being conducted in the 2015 Annual Survey of Manufactures.
RNA and FUS act in concert to prevent TDP-43 spatial segregation

FUS and TDP-43 are two self-adhesive aggregation-prone mRNA-binding proteins whose pathological mutations have been linked to neurodegeneration. While TDP-43 and FUS form reversible mRNA-rich compartments in the nucleus, pathological mutations promote their respective cytoplasmic aggregation in neurons with no apparent link between the two proteins except their intertwined function in mRNA processing. By combining analyzes in cellular context and at high-resolution in vitro, we unraveled that TDP-43 is specifically recruited in FUS assemblies to form TDP-43 rich sub-compartments but without reciprocity. The presence of mRNA provides an additional scaffold to promote the mixing between TDP-43 and FUS. Accordingly, we also found that the pathological truncated form of TDP-43, TDP-25, which has an impaired RNA binding ability, no longer mixes with FUS. Together, these results suggest that the binding of FUS along nascent mRNAs enables TDP-43, which is highly aggregation-prone, to mix with FUS phase in order to form mRNA-rich sub-compartments. A functional link between FUS and TDP-43 may explain their common implication in Amyotrophic Lateral Sclerosis (ALS).
SharePro: an accurate and efficient genetic colocalization method accounting for multiple causal signals

Motivation Colocalization analysis is commonly used to assess whether two or more traits share the same genetic signals identified in genome-wide association studies (GWAS), and is important for prioritizing targets for functional follow-up of GWAS results. Existing colocalization methods can have suboptimal performance when there are multiple causal variants in one genomic locus. Results We propose SharePro to extend the COLOC framework for colocalization analysis. Share-Pro integrates linkage disequilibrium (LD) modelling and colocalization assessment by grouping correlated variants into effect groups. With an efficient variational inference algorithm, posterior colocalization probabilities can be accurately estimated. In simulation studies, SharePro demonstrated increased power with a well-controlled false positive rate at a low computational cost. Through a challenging case of the colocalization analysis of the circulating abundance of R-spondin 3 (RSPO3) GWAS and estimated bone mineral density GWAS, we demonstrated the utility of SharePro in identifying biologically plausible colocalized signals. Availability and Implementation The SharePro software for colocalization analysis is openly available at https://github.com/zhwm/SharePro_coloc and the analysis conducted in this study is available at https://github.com/zhwm/SharePro_coloc_analysis.