Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlated evolution of large DNA fragments in the 3D genome of Arabidopsis thaliana.

In eukaryotes, the three-dimensional (3D) conformation of the genome is far from random, and this nonrandom chromatin organization is strongly correlated with gene expression and protein function, which are two critical determinants of the selective constraints and evolutionary rates of genes. However, whether genes and other elements that are located close to each other in the 3D genome evolve in a coordinated way has not been investigated in any organism. To address this question, we constructed chromatin interaction networks (CINs) in Arabidopsis thaliana based on high-throughput chromosome conformation capture (Hi-C) data and demonstrated that adjacent large DNA fragments in the CIN indeed exhibit more similar levels of polymorphism and evolutionary rates than random fragment pairs. Using simulations that account for the linear distance between fragments, we proved that the 3D chromosomal organization plays a role in the observed correlated evolution. Spatially interacting fragments also exhibit more similar mutation rates and functional constraints in both coding and noncoding regions than the random expectations, indicating that the correlated evolution between 3D neighbors is a result of combined evolutionary forces. A collection of 39 genomic and epigenomic features can explain much of the variance in genetic diversity and evolutionary rates across the genome. Moreover, features that have a greater effect on the evolution of regional sequences tend to show higher similarity between neighboring fragments in the CIN, suggesting a pivotal role of epigenetic modifications and chromatin organization in determining the correlated evolution of large DNA fragments in the 3D genome.
Development of neural oscillatory activity in response to speech in children from 4 to 6 years old

Abstract Recent neurophysiological theories propose that the cerebral hemispheres collaborate to resolve the complex temporal nature of speech, such that left‐hemisphere (or bilateral) gamma‐band oscillatory activity would specialize in coding information at fast rates (phonemic information), whereas right‐hemisphere delta‐ and theta‐band activity would code for speech's slow temporal components (syllabic and prosodic information). Despite the relevance that neural entrainment to speech might have for reading acquisition and for core speech perception operations such as the perception of intelligible speech, no study had yet explored its development in young children. In the current study, speech‐brain entrainment was recorded via EEG in a cohort of children at three different time points since they were 4–5 to 6–7 years of age. Our results showed that speech‐brain entrainment occurred only at delta frequencies (0.5 Hz) at all testing times. The fact that, from the longitudinal perspective, coherence increased in bilateral temporal electrodes suggests that, contrary to previous hypotheses claiming for an innate right‐hemispheric bias for processing prosodic information, at 7 years of age the low‐frequency components of speech are processed in a bilateral manner. Lastly, delta speech‐brain entrainment in the right hemisphere was related to an indirect measure of intelligibility, providing preliminary evidence that the entrainment phenomenon might support core linguistic operations since early childhood.
Sulforaphane mitigates mast cell-mediated allergic inflammatory reactions in in silico simulation and in vitro models

Abstract Objectives: Sulforaphane, a major ingredient isolated from Brassica oleracea var. italica (broccoli), is known to exhibit anti-inflammatory, anti-cancer, and anti-diabetic effects. In this study, we employed an in vitro model of phorbol 12-myristate 13-acetate and a23187 (PMACI)-stimulated human mast cells (HMC-1 cells) to investigate the anti-allergic inflammatory effects and mechanisms of sulforaphane and Brassica oleracea var. italica extracts. Methods: Cytokine levels were measured by ELISA and quantitative real-time-PCR methods. Caspase-1 activity was determined by caspase-1 assay. Binding mode of sulforaphane within caspase-1 was determined by molecular docking simulation. Protein expression was determined by Western blotting. Results: Water extract of Brassica oleracea var. italica (WE) significantly reduced thymic stromal lymphopoietin (TSLP) secretion and caspase-1 activity on activated HMC-1 cells. In the molecular docking simulation and in vitro caspase-1 assays, sulforaphane regulated caspase-1 activity by docking with the identical binding site of caspase-1. Sulforaphane significantly inhibited the levels of inflammatory mediators including TSLP, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 in a dose-dependent manner. Immunoblotting experiments revealed that sulforaphane and WE reduced translocation of NF-κBp65 into the nucleus and phosphorylation of IκBα in the cytosol. Furthermore, phosphorylation of mitogen-activated protein kinases (MAPK) was down-regulated by treatment with sulforaphane or WE. Conclusion: Our findings suggest that sulforaphane and WE have anti-allergic inflammatory effects by intercepting caspase-1/NF-κB/MAPKs signaling pathways.
Increased membrane permeation and blood concentration of 6‐carboxyfluorescein associated with dysfunction of paracellular route barrier in the small intestine of ulcerative colitis model rats

In the colon of patients with ulcerative colitis (UC), decreased function of the paracellular barrier, especially hypofunction of the tight junction, is associated with pathological conditions. However, there has been no report to date on the function of tight junctions in the small intestine. Here, we focused on the barrier function of the small intestine, especially in tight junctions, and compared it with that of the colon. Dextran sulfate sodium (DSS) was used to induce ulcerative colitis in rats in order to evaluate the function of the paracellular barrier in the jejunum, ileum, and colon. An in vitro diffusion chamber method was used to evaluate membrane resistance, which is an index of tight junction function and mucosal permeability, using 6‐carboxyfluorescein (6‐CF), a paracellular marker. In the jejunum and colon, with decrease of membrane resistance in the DSS group, mucosal permeability increased, whereas no marked difference was observed in the ileum. In the in situ closed‐loop method, absorption of 6‐CF from the jejunum was higher than that from the ileum. Immunohistochemical staining of claudin‐4 showed heterogeneous attenuation of claudin‐4 in the jejunum. Pharmacokinetic parameters were calculated from the blood concentration after intravenous injection and oral administration of 6‐CF. In the DSS group, there was a delay in the elimination phase, suggesting a decrease in renal function, and an increase in maximum blood concentration, associated with an increased absorption rate constant. The increased absorption and decreased renal function due to decreased paracellular barrier function in the small intestine and colon may cause fluctuations in drug efficacy and side effects.
Microbiome swings with repeated insults

with real-time polymerase chain reaction. Transfusion and Apheresis Science, 27, 217– 223. Lun, F.M. , Chiu, R.W. , Chan, K.C. , Leung, T.Y. , Lau, T.K. & Lo, Y.M. (2008) Microfluidics digital PCR reveals a higher than expected fraction of fetal DNA in maternal plasma. Clinical Chemistry, 54, 1664–1672. Mackie, F.L. , Hemming, K. , Allen, S. , Morris, R.K. & Kilby, M.D. (2016) The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta-analysis. BJOG: An International Journal of Obstetrics & Gynaecology, 124, 32–46. Royal College of Obstetricians and Gynaecologists. (2014) The Management of Women with Red Cell Antibodies during Pregnancy, Green-top Guideline No.65. Scheffer, P.G. , van der Schoot, C.E. , Page-Christiaens, G.C. & de Haas, M. (2011) Noninvasive fetal blood group genotyping of rhesus D, c, E and of K in alloimmunised pregnant women: evaluation of a 7-year clinical experience. BJOG: An International Journal of Obstetrics & Gynaecology, 118, 1340–1348.
Improving HIV outreach testing yield at cross-border venues in East Africa.

OBJECTIVE To evaluate HIV testing yield under several candidate strategies for outreach testing at venues (i.e., places where people socialize and meet new sex partners) in East Africa cross-border areas. DESIGN Population-based cross-sectional biobehavioral survey of people who had not been previously diagnosed with HIV found in venues. METHODS We identified participants who would have been tested for HIV under each of 10 hypothetical outreach testing strategies and calculated the proportion who would have newly tested positive for HIV under each strategy. Based on this proportion, we calculated the "number needed to test" (NNT) to identify 1 new case of HIV under each strategy. All estimates were obtained by applying survey sampling weights to account for the complex sampling design. RESULTS If testing were performed at a random sample of venues, 35 people would need to be tested to identify 1 new case of HIV, but higher yield could be found by limiting testing to venues with specific characteristics. Strategies focusing on women had higher testing yield. Testing women employed by venues would result in highest yield of all strategies examined (NNT = 15), while testing men under age 24 would result in the lowest yield (NNT = 99). CONCLUSIONS Quantitatively evaluating HIV testing strategies prior to implementation using survey data presents a new opportunity to refine and prioritize outreach testing strategies for the people and places most likely to result in high HIV testing yield.
Anti-angiogenic and anti-proliferative effects of Benja-ummarit extract in rats with hepatocellular carcinoma

The herbal extract Benja-ummarit (BU) is a traditional Thai medicine with a putative cancer-suppressing effect. However, this effect has only been tested in vitro in human hepatocarcinoma cell lines. The present study determined the efficacy of a BU extract to treat hepatocellular carcinoma (HCC) in rats in vivo and established its anti-angiogenic and anti-proliferative properties. The BU extract was prepared in 95% ethanol and its composition determined using liquid chromatography-mass spectrometry. HCC was induced in Wistar rats by an injection of diethylnitrosamine (DEN), followed 2 weeks later by injections of thioacetamide (TAA) thrice weekly for 4 weeks. Following 2 months, the DEN-TAA-treated rats were divided into 6 groups that were treated orally for another 2 months with: i) No treatment; ii) vehicle; iii) 30 mg/kg sorafenib (SF); iv) 1 mg/kg BU; v) 10 mg/kg BU; or vi) 50 mg/kg BU. Liver samples were collected for gross morphological, histological, reverse transcription-quantitative PCR and western blot analyses, and serum samples were collected for liver function tests. The size and number of the cancer nodules were reduced ~10-fold in BU-treated HCC groups and ~14-fold in the SF-treated group compared with the HCC group. Furthermore, the serum parameters of liver damage were lower in BU-compared with SF-treated rats. These results indicate that while each of these formulations strongly reduce HCC expansion, BU extract results in less liver damage. Vascular endothelial growth factor expression was reduced significantly in the BU-and SF-treated HCC groups compared with the HCC group (P<0.05). BU extract antagonizes HCC growth in vivo potently through inhibiting tumor angiogenesis. BU, therefore, qualifies as a promising medical herb requiring further evaluation as a treatment of HCC.
QSAR studies on benzothiophene derivatives as Plasmodium falciparum N‐myristoyltransferase inhibitors: Molecular insights into affinity and selectivity

Malaria is an infectious disease caused by protozoan parasites of the genus Plasmodium and transmitted by Anopheles spp. mosquitos. Due to the emerging resistance to currently available drugs, great efforts must be invested in discovering new molecular targets and drugs. N‐myristoyltransferase (NMT) is an essential enzyme to parasites and has been validated as a chemically tractable target for the discovery of new drug candidates against malaria. In this work, 2D and 3D quantitative structure–activity relationship (QSAR) studies were conducted on a series of benzothiophene derivatives as P. falciparum NMT (PfNMT) and human NMT (HsNMT) inhibitors to shed light on the molecular requirements for inhibitor affinity and selectivity. A combination of Quantitative Structure–activity Relationship (QSAR) methods, including the hologram quantitative structure–activity relationship (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) models, were used, and the impacts of the molecular alignment strategies (maximum common substructure and flexible ligand alignment) and atomic partial charge methods (Gasteiger‐Hückel, MMFF94, AM1‐BCC, CHELPG, and Mulliken) on the quality and reliability of the models were assessed. The best models exhibited internal consistency and could reasonably predict the inhibitory activity against both PfNMT (HQSAR: q2/r2/r2pred = 0.83/0.98/0.81; CoMFA: q2/r2/r2pred = 0.78/0.97/0.86; CoMSIA: q2/r2/r2pred = 0.74/0.95/0.82) and HsNMT (HQSAR: q2/r2/r2pred = 0.79/0.93/0.74; CoMFA: q2/r2/r2pred = 0.82/0.98/0.60; CoMSIA: q2/r2/r2pred = 0.62/0.95/0.56). The results enabled the identification of the polar interactions (electrostatic and hydrogen‐bonding properties) as the major molecular features that affected the inhibitory activity and selectivity. These findings should be useful for the design of PfNMT inhibitors with high affinities and selectivities as antimalarial lead candidates.
Demystifying ritual abuse - insights by self-identified victims and health care professionals

ABSTRACT Empirical evidence on organized and ritual child sexual abuse (ORA), that is, organized child sexual abuse with an ideological framework, is rare and definitions of the term “ritual” are often vague or inhomogeneous. The aim of the current study is to analyze contents, purposes and acts of violence in ORA. In a project of the Independent Inquiry into Child Sexual Abuse in Germany, 165 adults who identified themselves as ORA victims as well as 174 health care professionals who supported ORA victims were recruited via various sources and completed anonymous online surveys. Both samples report experiences with ideological frameworks in organized child sexual abuse contexts at the same ratio (88%). Ideologies are mostly perceived as a means to facilitate violent acts (e.g. commercial sexual exploitation). Positive correlations between the manifestation of ideologies and all violent acts suggest that organized and ritual perpetrator groups use the same violent strategies, but ritual or ideological groups, in which perpetrators are more often family members, use them to a greater extent. A modified narrative of “ritual abuse” as a (pseudo-)ideological, domestic and more violent subtype of organized child sexual abuse could enhance the credibility and visibility of ORA in science as well as in society.
Prediction model of artificial neural network for the risk of hyperuricemia incorporating dietary risk factors in a Chinese adult study

Background Risk of hyperuricemia (HU) has been shown to be strongly associated with dietary factors. However, there is scarce evidence on prediction models incorporating dietary factors to estimate the risk of HU. Objective The aim of this study was to develop a prediction model to predict the risk of HU in Chinese adults based on dietary information. Design Our study was based on a cross-sectional survey, which recruited 1,488 community residents aged 18 to 60 years in Beijing from October 2010 to January 2011. The eligible participants were randomly divided into a training set (n1 = 992) and a validation set (n2 = 496) in the ratio of 2:1. We developed the prediction model in three stages. We first used a logistic regression model (LRM) based on the training set to select a set of dietary risk factors which were related to the risk of HU. Artificial neural network (ANN) was then used to construct the prediction model using the training set. Finally, we used receiver operating characteristic (ROC) curve analysis to assess the accuracy of the prediction model using training and validation sets. Results In the training set, the mean age of participants with and without HU was 39.3 (standard deviation [SD]: 9.65) and 38.2 (SD: 9.38) years, respectively. Patients with HU consisted of 101 males (77.7%) and 29 females (22.3%). The LRM found that food frequency (vegetables [odds ratio (OR) = 0.73], meat [0.72], eggs [0.80], plant oil [0.78], tea [0.51], eating habits (breakfast [OR = 1.28]), and the salty cooking style (OR = 1.33) were associated with risk of HU. In the ANN analysis, we selected a three-layer back propagation neural network (BPNN) model with 14, 3, and 1 neuron in the input, hidden, and output layers, respectively, as the best prediction model. The areas under the ROC of the training and validation sets were 0.827 and 0.814, respectively. HU would occur when the incidence probability is greater than 0.128. The indicators of accuracy, sensitivity, specificity, and Yuden Index suggested that the ANN model in our study is successful and valuable. Conclusions This study suggests that the ANN model could be used to predict the risk of HU in Chinese adults. Further prospective studies are needed to improve the accuracy and to generalize the use of model.
On Deterministic Linearizable Set Agreement Objects.

A recent work showed that, for all n and k , there is a linearizable ( n, k )-set agreement object O L that is equivalent to the ( n, k )-set agreement task [4]: given O L , it is possible to solve the ( n, k )-set agreement task, and given any algorithm that solves the ( n, k )-set agreement task (and registers), it is possible to implement O L . This linearizable object O L , however, is not deterministic. It turns out that there is also a deterministic ( n, k )-set agreement object O D that is equivalent to the ( n, k )-set agreement task, but this deterministic object O D is not linearizable. This raises the question whether there exists a deterministic and linearizable ( n, k )-set agreement object that is equivalent to the ( n, k )-set agreement task. Here we show that in general the answer is no: speciﬁcally, we prove that for all n ≥ 4, every deterministic linearizable ( n, 2)-set agreement object is strictly stronger than the ( n, 2)-set agreement task. We prove this by showing that, for all n ≥ 4, every deterministic and linearizable ( n, 2)-set agreement object (together with registers) can be used to solve 2-consensus, whereas it is known that the ( n, 2)-set agreement task cannot do so. For a natural subset of ( n, 2)-set agreement objects, we prove that this result holds even for n = 3.
A Generic Undo Support for State-Based CRDTs

CRDTs (Conflict-free Replicated Data Types) have properties desirable for large-scale distributed systems with variable network latency or transient partitions. With CRDT, data are always available for local updates and data states converge when the replicas have incorporated the same updates. Undo is useful for correcting human mistakes and for restoring system-wide invariant violated due to long delays or network partitions. There is currently no generally applicable undo support for CRDTs. There are at least two reasons for this. First, there is currently no abstraction that we can practically use to capture the relations between undo and normal operations with respect to concurrency and causality. Second, using inverse operations as the existing partial solutions, the CRDT designer has to hard-code certain rules and design a new CRDT for almost every operation that needs undo support. In this paper, we present an approach to generic support of undo for CRDTs. The approach consists of two major parts. We first work out an abstraction that captures the semantics of concurrent undo and redo operations through equivalence classes. The abstraction is a natural extension of undo and redo in sequential applications and is straightforward to implement in practice. By using this abstraction, we then device a mechanism to augment existing CRDTs. The mechanism provides an "out of the box" support for undo without the involvement of the CRDT designers. We also present a practical application of the approach in collaborative editing.
Byzantine-Tolerant Set-Constrained Delivery Broadcast

Set-Constrained Delivery Broadcast (SCD-broadcast), recently introduced at ICDCN 2018, is a high-level communication abstraction that captures ordering properties not between individual messages but between sets of messages. More precisely, it allows processes to broadcast messages and deliver sets of messages, under the constraint that if a process delivers a set containing a message m before a set containing a message m 0 , then no other process delivers ﬁrst a set containing m 0 and later a set containing m . It has been shown that SCD-broadcast and read/write registers are computationally equivalent, and an algorithm implementing SCD-broadcast is known in the context of asynchronous message passing systems prone to crash failures. This paper introduces a Byzantine-tolerant SCD-broadcast algorithm, which we call BSCD-broadcast. Our proposed algorithm assumes an underlying basic Byzantine-tolerant reliable broadcast abstraction. We ﬁrst introduce an intermediary communication primitive, Byzantine FIFO broadcast (BFIFO-broadcast), which we then use as a primitive in our ﬁnal BSCD-broadcast algorithm. Unlike the original SCD-broadcast algorithm that is tolerant to up to t < n/ 2 crashing processes, and unlike the underlying Byzantine reliable broadcast primitive that is tolerant to up to t < n/ 3 Byzantine processes, our BSCD-broadcast algorithm is tolerant to up to t < n/ 4 Byzantine processes. As an illustration of the high abstraction power provided by the BSCD-broadcast primitive, we show that it can be used to implement a Byzantine-tolerant read/write snapshot object in an extremely simple way.
Bucket-Sorted Hash Join ∗

HYUNKWANG SHIN , BYUNG-WON ON , INGYU LEE 3 AND GYU SANG CHOI 1 Department of Information and Communication Engineering Yeungnam University 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea E-mail: shg3786@naver.com, castchoi@ynu.ac. kr Department of Software Convergence Engineering Kunsan National University 558 Daehak-ro, Gunsan-si, Jeollabuk-do E-mail: bwon@kunsan.ac. kr Sorrell College of Business Troy University 231F Bibb Graves, Troy, Alabama, USA, 36082 E-mail: inlee@troy.edu