Miracle-dz/UniFAR-FTUs huggingface dataset:
TIN2 facilitates TRF1-mediated trans- and cis-interactions on physiologically relevant long telomeric DNA

The shelterin complex consisting of TRF1, TRF2, RAP1, TIN2, TPP1, and POT1, functions to prevent false recognition of telomeres as double-strand DNA breaks, and to regulate telomerase and DNA repair protein access. TIN2 is a core component linking double-stranded telomeric DNA binding proteins (TRF1 and TRF2) and proteins at the 3’ overhang (TPP1-POT1). Since knockdown of TIN2 also removes TRF1 and TRF2 from telomeres, determining TIN2’s unique mechanistic function has been elusive. Here, we investigated DNA molecular structures promoted by TRF1-TIN2 using complementary single-molecule imaging platforms, including atomic force microscopy (AFM), total internal reflection fluorescence microscopy (TIRFM), and the DNA tightrope assay. We demonstrate that TIN2S and TIN2L isoforms facilitate TRF1-mediated DNA compaction (cis-interactions) and DNA-DNA bridging (trans-interactions) in a telomeric sequence- and length-dependent manner. On the short telomeric DNA substrate (6 TTAGGG repeats), the majority of TRF1 mediated telomeric DNA-DNA bridging events are transient with a lifetime of ~1.95 s. On longer DNA substrates (270 TTAGGG), TIN2 forms multi-protein complexes with TRF1 and stabilizes TRF1-mediated DNA-DNA bridging events that last for at least minutes. Preincubation of TRF1 with its regulator protein Tankyrase 1 significantly reduces TRF1-TIN2 mediated DNA-DNA bridging, whereas TIN2 protects the disassembly of TRF1-TIN2 mediated DNA-DNA bridging upon Tankyrase 1 addition. Our study provides evidence that TIN2 functions to promote TRF1 mediated trans-interactions of telomeric DNA, leading to new mechanistic insight into sister telomere cohesion.
New Holistic Conceptual Framework for the Assessment of the Performance of Photocatalytic Pavement

Despite serious health and environmental burdens associated with air pollution by NOx, the emission ceilings have been systematically exceeded in big European cities for several years. Photocatalytic technology can be an efficient solution for the removal of chemical air pollutants. Because diesel engine exhaust is the main source of NOx emissions, the application of a photocatalyst onto road pavement appears to be an effective NOx abatement method due to the large surface area, proximity to the emission source, and relatively good solar irradiance. Several laboratory-scale studies provided evidence demonstrating that most harmful contaminants can be readily mineralized. Furthermore, several projects were aiming to scale up this technology to pilot and real scales. Although the photocatalytic performances of selected materials in real urban environments were determined in some of these studies, the data are not conclusive for evaluating the overall performance because other material characteristics relevant to their functionality were not assessed. The lack of conformity criteria suitable for the evaluation of the overall performance of photocatalytic pavement under real operational conditions has generated skepticism and mistrust among public authorities and relevant stakeholders, which constrains the widespread implementation of this promising technology. In this context, the project LIFE–Photoscaling was focused on developing a new holistic conceptual framework to assess the photocatalytic pavement performance using the decision tool “Photoscaling Decision Maker” based on a set of quantitative indicators. For this purpose, a large volume of data obtained for 10 types of photocatalytic pavement materials was systemized on both the laboratory and pilot plant scales and three main indicators were defined: (1) photocatalytic performance effectiveness, (2) intrinsic performance, and (3) undesired secondary effects. Each top-level indicator includes several low-level subindicators associated with specific material characteristics. Finally, the ranges of the main indicators and subindicators and methods for their assessment were determined. These methods include standard, adopted, and original characterization techniques, which were selected based on the criteria such as simplicity, cost- and time-effectiveness, and relevance regarding the operational conditions.
Deciphering the evolution of the transcriptional and regulatory landscape in human placenta

In mammals, the placenta mediates maternal-fetal nutrient and waste exchange and provides immunomodulatory actions that facilitate maternal-fetal tolerance. The placenta is highly diversified among mammalian species, yet the molecular mechanisms that distinguish the placenta of human from other mammals are not fully understood. Using an interspecies transcriptomic comparison of human, macaque, and mouse term placentae, we identified hundreds of genes with lineage-specific expression – including dozens that are placentally-enriched and potentially related to pregnancy. We further annotated the enhancers for different human tissues using epigenomic data and demonstrate that the placenta and chorion are unique in that their enhancers display the least conservation. We identified numerous lineage-specific human placental enhancers, and found they are highly overlapped with specific families of endogenous retroviruses (ERVs), including MER21A, MER4A/B and MER39B that were previously linked to immune response and placental function. Among these ERV families, we further demonstrate that MER41 insertions create dozens of lineage-specific Serum Response Factor (SRF) binding loci in human, including one adjacent to FBN2, a placenta-specific gene with increased expression in humans that produces the peptide hormone placensin to stimulate glucose secretion and trophoblast invasion. Our results demonstrate the prevalence of lineage-specific human placental enhancers which are frequently associated with ERV insertions and likely facilitated the lineage-specific evolution of the mammalian placenta.
Response to Anonymous Referee # 1 : “ Interactive comment on A comparison of two Stokes ice sheet models applied to the Marine Ice Sheet Model Intercomparison Project for plan view models

I have several major concerns with the manuscript. First, I am questioning the novelty of this paper. The full-Stokes treatment of grounding lines has been investigated for almost 10 years, and a recent paper by Gagliardini et al. (2016) discusses the problem of numerical convergence due to the treatment of basal friction. The only new element introduced here is the development of grounding lines within FELIX-S, which I believe would be a better fit for Geoscientific Model Development.
Conceptual DFT-Based Computational Peptidology of Marine Natural Compounds: Discodermins A–H

A methodology based on the concepts that arise from Density Functional Theory named Conceptual Density Functional Theory (CDFT) was chosen for the calculation of some global and local reactivity descriptors of the Discodermins A–H family of marine peptides through the consideration of the KID (Koopmans in DFT) technique that was successfully used in previous studies of this kind of molecular systems. The determination of active sites of the studied molecules for different kinds of reactivities was achieved by resorting to some CDFT-based descriptors like the Fukui functions as well as the Parr functions derived from Molecular Electron Density Theory (MEDT). A few properties identified with their ability to behave as a drug and the bioactivity of the peptides considered in this examination were acquired by depending on a homology model by studying the correlation with the known bioactivity of related molecules in their interaction with various biological receptors. With the further object of analyzing their bioactivity, some parameters of usefulness for future QSAR studies, their predicted biological targets, and the ADME (Absorption, Distribution, Metabolism, and Excretion) parameters related to the Discodermins A–H pharmacokinetics are also reported.
Mid-Weight Image Super-Resolution with Bypass Connection Attention Network

Deeper networks have limited improvements for image super-resolution (SR), and are much more difﬁcult to train. The main reason is that these networks consist of many stacked building blocks which can produce many redundant features. Besides, most of SR methods neglect the fact that different features contain various types of information with varying degrees of contributions to image reconstruction, and thus lack sufﬁcient representational capability. Taking these issues into account, we propose a mid-weight bypass connection attention network (BCAN) with more powerful representational capability but fewer parameters. In detail, we design a novel bypass connection attention module (BCAM), which consists of several by-pass connection attention blocks (BCABs), enhancing high contribution information and suppressing redundant information. Further, we embed a mixed residual attention unit (MRAU) in each BCAB, which is composed of a channel attention unit and a spatial attention unit. After obtaining all hierarchical features, we propose an adaptive feature fusion module (AFFM), which can effectively combine hierarchical features based on different contributions of each BCAM. Experiments on benchmark datasets with various degradation models show that our BCAN can achieve better performance than existing state-of-the-art methods.
Intensity Modulated Radiotherapy (IMRT) of the Thorax, Abdomen, Pelvis, and Extremities

PLEASE NOTE: Contracts exclude from coverage, among other things, services or procedures that are considered investigational or cosmetic. Providers may bill members for services or procedures that are considered investigational or cosmetic. Providers are encouraged to inform members before rendering such services that the members are likely to be financially responsible for the cost of these services.
Hotspots and Regional Variation in Smoking Prevalence Among 514 Districts in Indonesia: Analysis of Basic Health Research 2018

BACKGROUND- The prevalence among adult men in Indonesia is among the highest in the world. Objective- Our study examines the hotspots and regional variation in smoking prevalence among 514 districts in Indonesia. METHODS- Taking advantage of the latest national health survey (Basic Health Research, Riskesdas 2018), which included smoking prevalence representative at the district level. We assessed the smoking prevalence among male and female adults (15+ years) and youth (13-14 years). We conducted geospatial analyses, using ArcMap 10.6, including quintile analysis (mapping the smoking prevalence by quintile for each district) and hotspot analysis (using Getis-Ord Gi* statistics to produce the hotspots, areas with a significantly higher density of advertisements). We also conducted quantitative analyses, using Stata 15.1, on geographic disparity, including region and urbanicity. RESULTS- We found huge disparity in smoking prevalence between districts, ranging from 9 to 81% for men, 0 to 50% for, 0 to 41% for women, and 0 to 50% for girls. We found up to 62 and 47 smoking hotspots among males and females, respectively. The poorest districts had significantly higher smoking prevalence among men but lower smoking prevalence among boys, and less educated districts had higher smoking prevalence among women. CONCLUSION- There were significant hotspots and regional variations among 514 districts in Indonesia.
The Multiplier Effect of Education Expenditure

This paper examines the short-run effects of federal education expenditures on local income. We exploit city-level variation in exposure to national changes in the $30-billion Federal Pell Grant Program, which is the largest program to help low-income students attend college in the U.S., to calculate fiscal multipliers of education expenditures. An increase in Pell grants by 1 percent of a city's income raises local income by 2.4 percent over the next two years. This multiplier effect is larger than estimates for military spending (1.5 on average). Multipliers are higher when grants are awarded to students at non-profit colleges, as for-profit colleges absorb most of the grant increases with raises in tuition. Multipliers are also higher during recessions than in expansions: Pell grants can be an effective tool for countercyclical policy that adds to already established benefits, such as, increasing the affordability of college and fostering long-run economic growth.
The Role of Establishment Size in the City-Size Earnings Premium in Spain

Both large establishments and large cities are known to offer workers an earnings premium. In this paper, we show that these two premia are closely linked by documenting a new fact: when workers move to a large city, they also move to larger establishments. We then ask how much of the city- size earnings premium can be attributed to transitions to larger and better-paying establishments. Using administrative data from Spain, we find that 38 percent of the city-size earnings premium can be explained by establishment-size composition. Most of the gains from the transition to larger establishments realize in the short-term upon moving to the large city. Establishment size explains 29 percent of the short-term gains, but only 5 percent of the medium-term gains that accrue as workers gain experience in the large city. The small contribution to the medium-term gains is due to two facts: first, within large cities workers transition to large establishments only slightly faster than in smaller cities; second, the relationship between earnings and establishment size is weaker in large cities.
Heritability of ethanol consumption and pharmacokinetics in a genetically diverse panel of Collaborative Cross mouse strains and their inbred founders

Background Inter-individual variation in voluntary ethanol consumption and ethanol response is partially influenced by genetic variation. Discovery of the genes and allelic variants that affect these phenotypes may clarify the etiology and pathophysiology of problematic alcohol use, including alcohol use disorder. Genetically diverse mouse populations also demonstrate heritable variation in ethanol consumption and can be utilized to discover the genes and gene networks that influence this trait. The Collaborative Cross (CC) recombinant inbred strains, Diversity Outbred (DO) population and their eight founder strains are complementary mouse resources that capture substantial genetic diversity and can demonstrate expansive phenotypic variation in heritable traits. These populations may be utilized to discover candidate genes and gene networks that moderate ethanol consumption and other ethanol-related traits. Methods We characterized ethanol consumption, preference and pharmacokinetics in the eight founder strains and ten CC strains in 12-hour drinking sessions during the dark phase of the circadian cycle. Results Ethanol consumption was found to be substantially heritable, both early in ethanol access and over a chronic intermittent access schedule. Ethanol pharmacokinetics were also found to be heritable; however, no association between strain-level ethanol consumption and pharmacokinetics was detected. The PWK/PhJ strain was found to be the highest drinking strain, with consumption substantially exceeding C57BL/6J, a strain commonly used as a model of “high” or “binge” drinking. Notably, we found strong evidence that sex moderated genetic effects on voluntary ethanol drinking. Conclusions Collectively, this research may serve as a foundation for expanded genetic study of ethanol consumption in the CC/DO and related populations; moreover, we have identified reference strains with extreme consumption phenotypes that effectively represent polygenic models of hazardous ethanol use.
Rank-ordering opera houses according to their sound quality parameters using PROMETHEE II method

Classifying sound quality in opera houses is a difficult task, as it depends on several subjective and objective parameters. The aim of this work is to create and evaluate a method for objective rank-ordering of Opera Houses and to compare it with the subjective rank-ordering procedure proposed in Hidaka and Beranek, J. Acoust. Soc. Am. 107, 368-383 (2000). This problem was solved using a multi criteria decision making method, called PROMETHEE II. This article describes its implementation and presents experimental results which are compared with subjective results presented in Hidaka and Beranek (2000). In addition, PROMETHEE II was used to classify 9 opera houses which had not been ranked in Hidaka and Beranek (2000). The results obtained show that the objective rank ordering created using PROMETHEE II which is based on objective parameters can successfully replace the subjectively based procedure of Hidaka and Beranek (2000). Four of the top six ranked opera houses were correctly classified and the performance can still be improved by means of optimization methods currently under investigation.
Agreement of Quantitative and Qualitative Antimicrobial Susceptibility Testing Methodologies: The Case of Enrofloxacin and Avian Pathogenic Escherichia coli

Avian pathogenic Escherichia coli (APEC) is the causal agent of colibacillosis, one of the most common bacterial infections in the poultry sector. Antimicrobial susceptibility testing (AST) is essential for rational and prudent antimicrobial therapy. Subsequently, uniformity in test results from the various testing methodologies used in diagnostic laboratories is pivotal. The aim of this study was therefore to evaluate the agreement between different AST methods in determining fluoroquinolone resistance in APEC. Twenty APEC isolates were selected and subjected to four different susceptibility tests: the quantitative microbroth dilution, agar dilution and gradient strip tests, and the qualitative disk diffusion method. The experiments were performed in triplicate. Categorical agreement, essential agreement and different errors were assessed. Moreover, agreement was also evaluated by calculating intraclass correlation coefficients (ICCs) for the quantitative tests and determining the Pearson correlation coefficients for the agreement between the disk diffusion method and the quantitative tests. Categorical agreement and essential agreement when compared with the microbroth technique ranged from 85–95% and 85–100%, respectively. No very major errors (false susceptible) and only one major error (false resistant) and minor errors (results involving an intermediary category) were detected. The calculated ICC values of the three quantitative tests fluctuated around 0.970 (range 0.940–0.988). There was a high negative correlation between the disk diffusion method and the other tests (correlation coefficients ranging from −0.979 to −0.940), indicating a clear inverse relationship between the minimum inhibitory concentration value and the zone diameter of growth inhibition. In conclusion, the overall agreement between the four different testing methodologies was very high. These results confirm the reliability of the disk diffusion and gradient strip test methods as substantiated alternatives, next to the gold standard agar and microbroth dilution, for fluoroquinolone susceptibility testing of APEC isolates.
Initial Experience of Challenge-Free MRI-Based Oxygen Extraction Fraction Mapping of Ischemic Stroke at Various Stages: Comparison With Perfusion and Diffusion Mapping

MRI-based oxygen extraction fraction imaging has a great potential benefit in the selection of clinical strategies for ischemic stroke patients. This study aimed to evaluate the performance of a challenge-free oxygen extraction fraction (OEF) mapping in a cohort of acute and subacute ischemic stroke patients. Consecutive ischemic stroke patients (a total of 30 with 5 in the acute stage, 19 in the early subacute stage, and 6 in the late subacute stage) were recruited. All subjects underwent MRI including multi-echo gradient echo (mGRE), diffusion weighted imaging (DWI), and 3D-arterial spin labeling (ASL). OEF maps were generated from mGRE phase + magnitude data, which were processed using quantitative susceptibility mapping (QSM) + quantitative blood oxygen level-dependent (qBOLD) imaging with cluster analysis of time evolution. Cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were reconstructed from 3D-ASL and DWI, respectively. Further, cerebral metabolic rate of oxygen (CMRO2) was calculated as the product of CBF and OEF. OEF, CMRO2, CBF, and ADC values in the ischemic cores (absolute values) and their contrasts to the contralateral regions (relative values) were evaluated. One-way analysis of variance (ANOVA) was used to compare OEF, CMRO2, CBF, and ADC values and their relative values among different stroke stages. The OEF value of infarct core showed a trend of decrease from acute, to early subacute, and to late subacute stages of ischemic stroke. Significant differences among the three stroke stages were only observed in the absolute OEF (F = 6.046, p = 0.005) and relative OEF (F = 5.699, p = 0.009) values of the ischemic core, but not in other measurements (absolute and relative CMRO2, CBF, ADC values, all values of p > 0.05). In conclusion, the challenge-free QSM + qBOLD-generated OEF mapping can be performed on stroke patients. It can provide more information on tissue viability that was not available with CBF and ADC and, thus, may help to better manage ischemic stroke patients.
Mutagenesis of Puccinia graminis f. sp. tritici and Selection of Gain-of-Virulence Mutants

Wheat stem rust caused by the fungus Puccinia graminis f. sp. tritici (Pgt), is regaining prominence due to the recent emergence of virulent isolates and epidemics in Africa, Europe and Central Asia. The development and deployment of wheat cultivars with multiple stem rust resistance (Sr) genes stacked together will provide durable resistance. However, certain disease resistance genes can suppress each other or fail in particular genetic backgrounds. Therefore, the function of each Sr gene must be confirmed after incorporation into an Sr-gene stack. This is difficult when using pathogen disease assays due to epistasis from recognition of multiple avirulence (Avr) effectors. Heterologous delivery of single Avr effectors can circumvent this limitation, but this strategy is currently limited by the paucity of cloned Pgt Avrs. To accelerate Avr gene cloning, we outline a procedure to develop a mutant population of Pgt spores and select for gain-of-virulence mutants. We used ethyl methanesulphonate (EMS) to mutagenize urediniospores and create a library of > 10,000 independent mutant isolates that were combined into 16 bulks of ~658 pustules each. We sequenced random mutants and determined the average mutation density to be 1 single nucleotide variant (SNV) per 258 kb. From this, we calculated that a minimum of three independently derived gain-of-virulence mutants is required to identify a given Avr gene. We inoculated the mutant library onto plants containing Sr43, Sr44, or Sr45 and obtained 9, 4, and 14 mutants with virulence toward Sr43, Sr44, or Sr45, respectively. However, only mutants identified on Sr43 and Sr45 maintained their virulence when reinolculated onto the lines from which they were identified. We further characterized 8 mutants with virulence toward Sr43. These also maintained their virulence profile on the stem rust international differential set containing 20 Sr genes, indicating that they were most likely not accidental contaminants. In conclusion, our method allows selecting for virulent mutants toward targeted resistance (R) genes. The development of a mutant library from as little as 320 mg spores creates a resource that enables screening against several R genes without the need for multiple rounds of spore multiplication and mutagenesis.