Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA methylation and transcriptome aberrations mediated by ERα in mouse seminal vesicles following developmental DES exposure

Significance Early developmental exposure to endocrine active compounds causes late-stage effects and alterations in the reproductive tract of adult mice. Unexpectedly, estrogen receptor alpha (ERα) plays a pivotal role in mediating these developmental effects. As a model outcome from these developmental effects, we present transcriptome and DNA methylation profiling of the seminal vesicles (SVs) following neonatal diethylstilbestrol (DES) exposure. ERα mediates transcriptome aberrations in SVs of adult mice that impact developmental reprogramming at adulthood. DNA methylation dynamically changes during development, and methylation is greater in ERα knockout mice compared with wild type. Expression levels of DES-altered genes are associated with their DNA methylation status. These findings provide unique evidence for understanding the developmental actions and mechanisms of endocrine-disrupting chemicals in human health. Early transient developmental exposure to an endocrine active compound, diethylstilbestrol (DES), a synthetic estrogen, causes late-stage effects in the reproductive tract of adult mice. Estrogen receptor alpha (ERα) plays a role in mediating these developmental effects. However, the developmental mechanism is not well known in male tissues. Here, we present genome-wide transcriptome and DNA methylation profiling of the seminal vesicles (SVs) during normal development and after DES exposure. ERα mediates aberrations of the mRNA transcriptome in SVs of adult mice following neonatal DES exposure. This developmental exposure impacts differential diseases between male (SVs) and female (uterus) tissues when mice reach adulthood due to most DES-altered genes that appear to be tissue specific during mouse development. Certain estrogen-responsive gene changes in SVs are cell-type specific. DNA methylation dynamically changes during development in the SVs of wild-type (WT) and ERα-knockout (αERKO) mice, which increases both the loss and gain of differentially methylated regions (DMRs). There are more gains of DMRs in αERKO compared with WT. Interestingly, the methylation changes between the two genotypes are in different genomic loci. Additionally, the expression levels of a subset of DES-altered genes are associated with their DNA methylation status following developmental DES exposure. Taken together, these findings provide an important basis for understanding the molecular and cellular mechanism of endocrine-disrupting chemicals (EDCs), such as DES, during development in the male mouse tissues. This unique evidence contributes to our understanding of developmental actions of EDCs in human health.
Quantitative nondestructive testing of wire rope based on pseudo-color image enhancement technology

ABSTRACT Detection of magnetic flux leakage (MFL) is widely used in nondestructive testing (NDT) of wire rope. We built and tested an MFL measuring device based on unsaturated magnetic excitation to address the problems of large volume, low accuracy and inconvenience of the traditional MFL instruments for locating and quantifying broken wires in wire ropes. We employed a pseudo-color imaging protocol to convert the MFL information to a pictorial representation. Localization of the breaks in the wire utilized the maximum modulus method. The color moment, statistical texture features, and spectral texture features were extracted from the image, revealing a network of broken wires, which could be localized and quantified. Testing showed that the device has high-detection accuracy and could detect small broken wires. Compared with traditional wire inspection devices, it has the advantages of small size, light weight and portability. We showed that pseudo-color image enhancement can effectively improve the recognition rate of broken wires and reduce the recognition error.
Multi-instance multi-label learning of natural scene images: via sparse coding and multi-layer neural network

The classification of natural scene images is multi-instance multi-label (MIML) for many labels that exist in a natural scene image. The traditional method of solving MIML is to degenerate it into single-instance single-label learning (SISL). However, the precision of the method could decrease due to information loss during the degeneration process. How to reasonably solve the MIML problem is key to obtaining high accuracy in this research area. An MIML algorithm based on instances via combining sparse coding with a deep neural network is proposed. First, an instance-based sparse representation with dictionary learning is adopted. Second, an MIML description model based on a deep network is proposed, which can realise parameter self-learning in combination with sparse representations. Third, the residuals of the sparse representation are introduced to the deep neural network. The results of the experiments show that the method outperforms a number of state-of-the-art approaches.
Peak visual gamma frequency is modified across the healthy menstrual cycle

Fluctuations in gonadal hormones over the course of the menstrual cycle are known to cause functional brain changes and are thought to modulate changes in the balance of cortical excitation and inhibition. Animal research has shown this occurs primarily via the major metabolite of progesterone, allopregnanolone, and its action as a positive allosteric modulator of the GABAA receptor. Our study used EEG to record gamma oscillations induced in the visual cortex using stationary and moving gratings. Recordings took place during twenty females’ mid‐luteal phase when progesterone and estradiol are highest, and early follicular phase when progesterone and estradiol are lowest. Significantly higher (∼5 Hz) gamma frequency was recorded during the luteal compared to the follicular phase for both stimuli types. Using dynamic causal modeling, these changes were linked to stronger self‐inhibition of superficial pyramidal cells in the luteal compared to the follicular phase. In addition, the connection from inhibitory interneurons to deep pyramidal cells was found to be stronger in the follicular compared to the luteal phase. These findings show that complex functional changes in synaptic microcircuitry occur across the menstrual cycle and that menstrual cycle phase should be taken into consideration when including female participants in research into gamma‐band oscillations.
In Situ Activity of Suspended and Immobilized Microbial Communities as Measured by Fluorescence Lifetime Imaging

ABSTRACT In this study, the feasibility of fluorescence lifetime imaging (FLIM) for measurement of RNA:DNA ratios in microorganisms was assessed. The fluorescence lifetime of a nucleic acid-specific probe (SYTO 13) was used to directly measure the RNA:DNA ratio inside living bacterial cells. In vitro, SYTO 13 showed shorter fluorescence lifetimes in DNA solutions than in RNA solutions. Growth experiments with bacterial monocultures were performed in liquid media. The results demonstrated the suitability of SYTO 13 for measuring the growth-phase-dependent RNA:DNA ratio in Escherichia coli cells. The fluorescence lifetime of SYTO 13 reflected the known changes of the RNA:DNA ratio in microbial cells during different growth phases. As a result, the growth rate of E. coli cells strongly correlated with the fluorescence lifetime. Finally, the fluorescence lifetimes of SYTO 13 in slow- and fast-growing biofilms were compared. For this purpose, biofilms developed from activated sludge were grown as autotrophic and heterotrophic communities. The FLIM data clearly showed a longer fluorescence lifetime for the fast-growing heterotrophic biofilms and a shorter fluorescence lifetime for the slow-growing autotrophic biofilms. Furthermore, starved biofilms showed shorter lifetimes than biofilms supplied with glucose, indicating a lower RNA:DNA ratio in starved biofilms. It is suggested that FLIM in combination with SYTO 13 represents a useful tool for the in situ differentiation of active and inactive bacteria. The technique does not require radioactive chemicals and may be applied to a broad range of sample types, including suspended and immobilized microorganisms.
The nucleosomal acidic patch relieves auto-inhibition by the ISWI remodeler SNF2h

ISWI family chromatin remodeling motors use sophisticated autoinhibition mechanisms to control nucleosome sliding. Yet how the different autoinhibitory domains are regulated is not well understood. Here we show that an acidic patch formed by histones H2A and H2B of the nucleosome relieves the autoinhibition imposed by the AutoN and the NegC regions of the human ISWI remodeler SNF2h. Further, by single molecule FRET we show that the acidic patch helps control the distance travelled per translocation event. We propose a model in which the acidic patch activates SNF2h by providing a landing pad for the NegC and AutoN auto-inhibitory domains. Interestingly, the INO80 complex is also strongly dependent on the acidic patch for nucleosome sliding, indicating that this substrate feature can regulate remodeling enzymes with substantially different mechanisms. We therefore hypothesize that regulating access to the acidic patch of the nucleosome plays a key role in coordinating the activities of different remodelers in the cell.
MicroRNA-126 is a prospective target for vascular disease

MicroRNA-126 was involved in angiogenesis during physiological and pathological process. It was mainly expressed in endothelial cells, and defined as a pivotal biological molecule associated with vascular disease. Increased microRNA-126 in endothelial cells promotes angiogenesis in ischemic stroke, repairs impaired endothelial cells in atherosclerosis, and attenuates vascular dysfunction in diabetics. By contrast, microRNA-126 transferred from endothelial cell to smooth muscle cells could lead to proliferation that induced intimal hyperplasia. Additionally, microRNA-126 could be a tumor suppressor or an oncogene, which was depended on the cancer type. In this review, we summarized the function of microRNA-126 in ischemic stroke, atherosclerosis, diabetics, tumor, and discussed the underlying mechanisms.
Nitric Oxide Synthase Inhibition as a Neuroprotective Strategy Following Hypoxic–Ischemic Encephalopathy: Evidence From Animal Studies

Background Hypoxic–ischemic encephalopathy following perinatal asphyxia is a leading cause of neonatal death and disability worldwide. Treatment with therapeutic hypothermia reduced adverse outcomes from 60 to 45%. Additional strategies are urgently needed to further improve the outcome for these neonates. Inhibition of nitric oxide synthase (NOS) is a potential neuroprotective target. This article reviews the evidence of neuroprotection by nitric oxide (NO) synthesis inhibition in animal models. Methods Literature search using the EMBASE, Medline, Cochrane, and PubMed databases. Studies comparing NOS inhibition to placebo, with neuroprotective outcome measures, in relevant animal models were included. Methodologic quality of the included studies was assessed. Results 26 studies were included using non-selective or selective NOS inhibition in rat, piglet, sheep, or rabbit animal models. A large variety in outcome measures was reported. Outcome measures were grouped as histological, biological, or neurobehavioral. Both non-selective and selective inhibitors show neuroprotective properties in one or more outcome measures. Methodologic quality was either low or moderate for all studies. Conclusion Inhibition of NO synthesis is a promising strategy for additional neuroprotection. In humans, intervention can only take place after the onset of the hypoxic–ischemic event. Therefore, combined inhibition of neuronal and inducible NOS seems the most likely candidate for human clinical trials. Future studies should determine its safety and effectiveness in neonates, as well as a potential sex-specific neuroprotective effect. Researchers should strive to improve methodologic quality of animal intervention studies by using a systematic approach in conducting and reporting of these studies.
Current view on the functional regulation of the neuronal K+-Cl− cotransporter KCC2

In the mammalian central nervous system (CNS), the inhibitory strength of chloride (Cl−)-permeable GABAA and glycine receptors (GABAAR and GlyR) depends on the intracellular Cl− concentration ([Cl−]i). Lowering [Cl−]i enhances inhibition, whereas raising [Cl−]i facilitates neuronal activity. A neuron's basal level of [Cl−]i, as well as its Cl− extrusion capacity, is critically dependent on the activity of the electroneutral K+-Cl− cotransporter KCC2, a member of the SLC12 cation-Cl− cotransporter (CCC) family. KCC2 deficiency compromises neuronal migration, formation and the maturation of GABAergic and glutamatergic synaptic connections, and results in network hyperexcitability and seizure activity. Several neurological disorders including multiple epilepsy subtypes, neuropathic pain, and schizophrenia, as well as various insults such as trauma and ischemia, are associated with significant decreases in the Cl− extrusion capacity of KCC2 that result in increases of [Cl−]i and the subsequent hyperexcitability of neuronal networks. Accordingly, identifying the key upstream molecular mediators governing the functional regulation of KCC2, and modifying these signaling pathways with small molecules, might constitute a novel neurotherapeutic strategy for multiple diseases. Here, we discuss recent advances in the understanding of the mechanisms regulating KCC2 activity, and of the role these mechanisms play in neuronal Cl− homeostasis and GABAergic neurotransmission. As KCC2 mediates electroneutral transport, the experimental recording of its activity constitutes an important research challenge; we therefore also, provide an overview of the different methodological approaches utilized to monitor function of KCC2 in both physiological and pathological conditions.
Dichotomies in Ontology-Mediated Querying with the Guarded Fragment

We study the complexity of ontology-mediated querying when ontologies are formulated in the guarded fragment of first-order logic (GF). Our general aim is to classify the data complexity on the level of ontologies where query evaluation w.r. t. an ontology O is considered to be in PTime if all (unions of conjunctive) queries can be evaluated in PTime w.r. t. O and coNP-hard if at least one query is coNP-hard w.r. t. O. We identify several large and relevant fragments of GF that enjoy a dichotomy between PTime and coNP, some of them additionally admitting a form of counting. In fact, almost all ontologies in the BioPortal repository fall into these fragments or can easily be rewritten to do so. We then establish a variation of Ladner's Theorem on the existence of NP-intermediate problems and use this result to show that for other fragments, there is provably no such dichotomy. Again for other fragments (such as full GF), establishing a dichotomy implies the Feder-Vardi conjecture on the complexity of constraint satisfaction problems. We also link these results to Datalog-rewritability and study the decidability of whether a given ontology enjoys PTime query evaluation, presenting both positive and negative results.
Mortar modified with sulfonated polystyrene produced from waste plastic cups

In this work, we studied the addition of sulfonated polystyrene produced from waste plastic cups as an admixture for mortars. Mortars were analyzed with polystyrene content of 0.0; 0.2; 0.6; 1.0 and 1.4% in relation to the cement mass. The influence of polystyrene on the mortars' properties was evaluated by the consistency index, water retention, water absorption, porosity, elasticity modulus, compressive strength, flexural strength, bond tensile strength and microscopy. The increase in the sulfonated polystyrene content decreased the elasticity modulus of the mortar and, despite higher porosity, there was a reduction of water absorption by capillarity. In relation to mortar without admixture, the modified mortar showed an increase in water retention and consistency index, and a large increase in flexural strength and bond tensile strength. The significant increase of bond tensile strength (214% with admixture 1%) highlights the potential of the produced material as an adhesive mortar.
A scalable ordering primitive for multicore machines

Timestamping is an essential building block for designing concurrency control mechanisms and concurrent data structures. Various algorithms either employ physical timestamping, assuming that they have access to synchronized clocks, or maintain a logical clock with the help of atomic instructions. Unfortunately, these approaches have two problems. First, hardware developers do not guarantee that the available hardware clocks are exactly synchronized, which they find difficult to achieve in practice. Second, the atomic instructions are a deterrent to scalability resulting from cache-line contention. This paper addresses these problems by proposing and designing a scalable ordering primitive, called Ordo, that relies on invariant hardware clocks. Ordo not only enables the correct use of these clocks, by providing a notion of a global hardware clock, but also frees various logical timestamp-based algorithms from the burden of the software logical clock, while trying to simplify their design. We use the Ordo primitive to redesign 1) a concurrent data structure library that we apply on the Linux kernel; 2) a synchronization mechanism for concurrent programming; 3) two database concurrency control mechanisms; and 4) a clock-based software transactional memory algorithm. Our evaluation shows that there is a possibility that the clocks are not synchronized on two architectures (Intel and ARM) and that Ordo generally improves the efficiency of several algorithms by 1.2--39.7X on various architectures.
Asymmetric Modulation of FRN by the Probability and Value of Outcomes in Auditory Mid Task

Reward prediction error (RPE) reflects the discrepancy between received and predicted outcomes and therefore plays an important role in learning in a dynamic environment. Using electroencephalographic measures of response to obtained and expected outcomes, previous studies have suggested that feedback-related negativity (FRN) could code RPE. It has further been hypothesized that FRN should be sensitive to both the likelihood and magnitude of behavioral outcomes. Previous studies consistently demonstrated that FRN is sensitive to the probability of outcomes, while the evidence of its sensitivity to the magnitude of outcomes is less consistent. In neuroimaging studies, a monetary incentive delay (MID) task is often used to evaluate the dependence of feedback processing on the RPE’s sign and size. In this article, for the first time, we studied FRN’s sensitivity to the valence, likelihood, and magnitude of outcomes during a novel auditory version of an MID task. FRN demonstrated sensitivity to both the valence of an outcome (gain vs. omission of a gain) and its probability (high vs. low). However, we did not observe a modulation of FRN amplitude by the magnitude of the outcomes. We also found that subjects’ behavior was more susceptible to changes in the probability than to the magnitude of the outcomes. Overall, FRN seems to be a promising tool to study the learning mechanisms of decision making
Risk Factors for Pneumocystis jirovecii Pneumonia in Patients With Rheumatoid Arthritis and a Prophylactic Indication of Trimethoprim/Sulfamethoxazole

Background/Objectives Immunosuppressant medications (ISPs) increase the occurrence of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients. The prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) for PCP is effective but has serious adverse effects and so should be selectively used for patients at high risk. The aims of this study were to clarify the risk factors for PCP in RA patients and to establish the indications for administering TMP/SMX. Methods This retrospective cohort study analyzed data from 2640 patients (2010–2014) diagnosed as having RA who had not received a prophylactic administration of TMP/SMX. The risk factors for PCP were evaluated by comparing the clinical parameters between patients with PCP (PCP group, n = 19) and those without (non-PCP group, n = 2621). Results The PCP group was older (70 vs. 64 years), received higher doses of prednisolone (6.2 vs. 2.4 mg/d) and methotrexate (7.7 vs. 5.2 mg/wk), and had a greater number of ISPs (1.3 vs. 0.8) (p < 0.05). We stratified the PCP risk using a scoring system based on odds ratios (ORs) calculated for these parameters (methotrexate ≥6 mg/wk OR = 4.5, 1 point; age ≥65 years, OR = 3.7, 1 point; ≥2 ISPs, OR = 3.7, 1 point; prednisolone ≥5 mg/d, OR = 12.4, 3 points). The incidence of PCP among patients scoring 0 to 2 points was 0.04%; 3 to 4 points, 2.3%; and 5 points or more, 5.8%. Conclusions The prophylactic administration of TMP/SMX for PCP is recommended for RA patients who score at least 5 points with our system.
Scalable human-in-the-loop decision support

A scalable human-in-the-loop decision support system has been built around an active learning algorithm operating on aircraft engine time series data. The system integrates hierarchical clustering and active learning algorithms backed by a big data analytics ecosystem with a browser-based user interface. This combination enables multiple expert users to efficiently train a model to classify aircraft engine behavior by prioritizing the segments of flight for human analysis. This system lowers the time required from human experts by eliminating unnecessary labelling effort and supporting the aircraft maintenance industry's service technicians.
Web enabled performance measurement systems

In order to respond proactively to the new emerging challenges, management requires up‐to‐date and accurate information on performance. Such performance measurement systems are still not common because there is not sufficient research focused on management implications of IT enabled performance measurement systems. This paper presents an empirical case study where a fully integrated IT enabled performance measurement system was implemented and its management implications studied. The paper concludes, based on a single case study, that if properly implemented, such systems would promote a proactive management style and greater confidence in management decisions.
Modeling and verification of evolving cyber-physical spaces

We increasingly live in cyber-physical spaces -- spaces that are both physical and digital, and where the two aspects are intertwined. Such spaces are highly dynamic and typically undergo continuous change. Software engineering can have a profound impact in this domain, by defining suitable modeling and specification notations as well as supporting design-time formal verification. In this paper, we present a methodology and a technical framework which support modeling of evolving cyber-physical spaces and reasoning about their spatio-temporal properties. We utilize a discrete, graph-based formalism for modeling cyber-physical spaces as well as primitives of change, giving rise to a reactive system consisting of rewriting rules with both local and global application conditions. Formal reasoning facilities are implemented adopting logic-based specification of properties and according model checking procedures, in both spatial and temporal fragments. We evaluate our approach using a case study of a disaster scenario in a smart city.