Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancer methylation dynamics contribute to cancer plasticity and patient mortality

During development, enhancers play pivotal roles in regulating gene expression programs; however, their involvement in cancer progression has not been fully characterized. We performed an integrative analysis of DNA methylation, RNA-seq, and small RNA-seq profiles from thousands of patients, including 25 diverse primary malignances and seven body sites of metastatic melanoma. We found that enhancers are consistently the most differentially methylated regions (DMR) as cancer progresses from normal to primary tumors and then to metastases, compared to other genomic features. Remarkably, identification of enhancer DMRs (eDMRs) enabled classification of primary tumors according to physiological organ systems, and in metastasis eDMRs are the most correlated with patient outcome. To further understand the eDMR role in cancer progression, we developed a model to predict genes and microRNAs that are regulated by enhancer and not promotor methylation, which shows high accuracy with chromatin architecture methods and was experimentally validated. Interestingly, among all metastatic melanoma eDMRs, the most correlated with patient survival were eDMRs that “switched” their methylation patterns back and forth between normal, primary, and metastases and target cancer drivers, e.g., KIT. We further demonstrated that eDMR target genes were modulated in melanoma by the bone metastasis microenvironment, suggesting that eDMRs respond to microenvironmental cues in metastatic niches. Our findings that aberrant methylation in cancer cells mostly affects enhancers, which contribute to tumor progression and cancer cell plasticity, will facilitate development of epigenetic anticancer approaches.
mRNA Decay Factor AUF1 Binds the Internal Ribosomal Entry Site of Enterovirus 71 and Inhibits Virus Replication

AU-rich element binding factor 1 (AUF1) has a role in the replication cycles of different viruses. Here we demonstrate that AUF1 binds the internal ribosome entry site (IRES) of enterovirus 71 (EV71) and negatively regulates IRES-dependent translation. During EV71 infection, AUF1 accumulates in the cytoplasm where viral replication occurs, whereas AUF1 localizes predominantly in the nucleus in mock-infected cells. AUF1 knockdown in infected cells increases IRES activity and synthesis of viral proteins. Taken together, the results suggest that AUF1 interacts with the EV71 IRES to negatively regulate viral translation and replication.
Parents and Siblings as Early Resources for Young Children's Learning in Mexican-Descent Families

This study explored the ways in which both parents and older siblings are important resources for young children 's learning in the home context. Parents from 50 Mexicandescent families were interviewed in their homes and were asked questions regarding the kinds of causal questions their children ask, and the different skills their children learn from one another. Parents reported that their children ask questions about complex phenomena in important domains such as biology, physics, and behavior; and parents generally feel good about, and encourage, these questions. Parents also indicated that their children learn different skills from one another; younger siblings learn mostly academic skills from older siblings, and older siblings learn mostly social skills from younger siblings. Both children are reported to learn mostly through observation and imitation of one another Findings are discussed in relation to the issues of "match" between homes and schools as complementary contexts for young children's learning.
Soldier Characteristics, Alcohol Abuse Risk, and Mental Health Risk as Treatment Predictors

Combat exposure and other factors associated with military service may place soldiers at increased risk of substance use and mental health issues. We examine the importance of soldier characteristics and risk for alcohol abuse and mental health issues in predicting entry into treatment for alcohol abuse and treatment for mental health issues among active duty soldiers (n = 43,342). Results indicated that soldiers were more likely to be referred for mental health issues than alcohol abuse issues and that marital status, race/ethnicity, and pay grade were predictive of the likelihood of entering treatment. We discuss the implications of our findings with regard to the referral and treatment of alcohol abuse and mental health issues within the military environment.
Mechanisms of resistance to rapamycins.

Rapamycins represent a novel family of anticancer agents, currently including rapamycin and its derivatives, CCI-779 and RAD001. Rapamycins inhibit the function of the mammalian target of rapamycin (mTOR), and potently suppress tumor cell growth by arresting cells in G1 phase or potentially inducing apoptosis of cells, in culture or in xenograft tumor models. However, recent data indicate that genetic mutations or compensatory changes in tumor cells influence the sensitivity of rapamycins. First, mutations of mTOR or FKBP12 prevent rapamycin from binding to mTOR, conferring rapamycin resistance. Second, mutations or defects of mTOR-regulated proteins, including S6K1, 4E-BP1, PP2A-related phosphatases, and p27(Kip1) also render rapamycin insensitivity. In addition, the status of ATM, p53, PTEN/Akt and 14-3-3 are also associated with rapamycin sensitivity. To better explore the role of rapamycins against tumors, this review will summarize the current knowledge of the mechanism of action of rapamycins, and progress in understanding mechanisms of acquired or intrinsic resistance.
A Testing Pattern for Automatic Control Software Addressing Different Degrees of Process Autonomy and Cooperation

Abstract This article considers different automatic control paradigms allowing for varying degrees of agent cooperation and autonomy. In order to support the automatic verification of safety-relevant software controllers, it proposes the use of a generic testing pattern which can be instantiated such as to allow to optimize automatic test data generation with respect to the specific targets of the application considered and of the testing phase involved. The article reports on successful case studies carried out in different real-world environments.
Design of Novel Overhang Structure for Separated Pole-Piece Type Ferrite Magnet Motor

A separated pole-piece type ferrite magnet motor (FMM) is a novel type of motor that can maximize reluctance torque and reduce leakage flux by separating the pole pieces and the web. However, when this type of motor has a short stack length and a large area of pole pieces, the leakage flux in the axial direction has significant influence on the motor's performance. A rotor overhang structure is one of the most crucial design parameters that compensate for the side effects of leakage flux. A conventional overhang structure increases magnetic torque but raises the level of induced voltage. This limits the operation speed range. To overcome such problems, this paper presents a novel multilevel overhang structure. Based on the unique structure of the separated pole-piece type FMM, the overhang length of the pole pieces was set to be shorter than the other parts of the rotor. It was observed that the operating speed range was widened, and more reluctance torque was generated, compared to motors with conventional overhang structures. The proposed overhang structure was optimized by 3-D finite element analysis, and the model was validated by comparing the actual experimental results with its predicted performance.
A nonlinear observer for integration of GNSS and IMU measurements with gyro bias estimation

We present an observer for estimating position, velocity, attitude, and gyro bias, by using inertial measurements of accelerations and angular velocities, magnetometer measurements, and satellite-based measurements of position and (optionally) velocity. The design proceeds in two stages: in Stage I, an attitude and gyro bias estimator is designed based on an unmeasured signal. In Stage II, that design is recovered using measured signals only, by combining it with a position and velocity estimator. We prove global exponential stability of the estimation error and test the design using realistic flight simulation.
Idea‐Generation Techniques: A Formulary of Active Ingredients

The profusion of creativity techniques that have been proposed and used is based on a much smaller set of active ingredients, devices that promote idea generation. This paper reports the results of a study that identified these active ingredients through an analysis of 172 idea-generation methods. Fifty idea-generation devices of three types — strategies, tactics, and enablers — were identified and organized in a formulary. Research results facilitate the evaluation of idea-generation methods and the selection of methods suited to particular idea-generation tasks.
Influences of Parental and Best Friends' Smoking and Drinking on Adolescent Use: A Longitudinal Study1

Many studies have dealt with the relative impact of parents and peers on adolescent substance use. However, only a few studies have explored the role of adolescents themselves in social relationships. Homogeneity in behavioral patterns within friendships can also be generated by selective association. Acknowledgment of selection processes might shed new light on the debate on the influences of parents and friends. This paper examines the impact of parental and best friends' smoking and drinking on adolescents' use, using data (N= 1,063) from a 3-wave, 5-year longitudinal study. The results show that friends' smoking did not affect adolescent smoking over time. Only in early adolescence did friends' drinking exert an influence on subjects' alcohol use. On the other hand, parental use had a small but significant impact on their offspring. Furthermore, support was found for processes of selective association.
Cellular Electrophysiologic Basis of Cardiac Arrhythmias

Initiation of the Cardiac Action Potential Impalement of cardiac cells with glass capillary microelectrodes makes it possible to measure the electrical events that occur during systole and diastole. The resting cardiac cell has an electronegative membrane potential of approximately -80 to -90 mV (Figure 1). This transmembrane potential is largely the result of a potassium ion cowcentration gradient maintained across the cell membrane by active transport1,2 involving the enzyme sodium-potassium activated ATPase.3 The ratio of intracellular to extracellular potassium concentration produced by active transport is approximately 30: 1. While at the level of resting potential, the cell is highly permeable to potassium ion. It is poorly permeable to sodium ion, which is in high concentration in the extracellular fluid and in low concentration in the cell/ This situation too is maintained by the enzyme sodium-potassium activated ATPase. When a depolarizing stimulus of appropriate magnitude and duration is delivered to the cell, resulting in a transiently decreased (i.e. less negative) membrane potential, sodium permeability in-
A Novel Markov Logic Rule Induction Strategy for Characterizing Sports Video Footage

The grounding of high-level semantic concepts is a key requirement of video annotation systems. Rule induction can thus constitute an invaluable intermediate step in characterizing protocol-governed domains, such as broadcast sports footage. The authors propose a clause grammar template approach to the problem of rule induction in video footage of court games that employs a second-order meta-grammar for Markov Logic Network construction. The aim is to build an adaptive system for sports video annotation capable, in principle, of both learning ab initio and adaptively transferring learning between distinct rule domains. The authors tested the method using a simulated game predicate generator as well as real data derived from tennis footage via computer-vision-based approaches including HOG3D-based player-action classification, Hough-transform-based court detection, and graph-theoretic ball tracking. Experiments demonstrate that the method exhibits both error resilience and learning transfer in the court domain context. Moreover, the clause template approach naturally generalizes to any suitably constrained, protocol-governed video domain characterized by feature noise or detector error.
Low cost LDPC decoder for DVB-S2

Because of its excellent bit-error-rate performance, the low-density parity-check (LDPC) algorithm is gaining increased attention in communication standards and literature. The new digital video broadcast via satellite standard (DVB-S2) is the first broadcast standard to include a LDPC-code, and the first implementations are available. In our investigation of generic LDPC-implementations we found that scalable sub-block parallelism enables efficient implementations for a wide range of applications. For the DVB-S2 case, using subblock parallelism we obtain half the chip-size of known solutions. For the required performance in the normative configurations for the broadcast service (90Mbps), the area is even 1/3 compared to the smallest published decoder
Efficient Attribute Based Access Control for RESTful Services

The popularity of REST grows more and more and so does the need for fine-grained access control for RESTful services. Attribute Based Access Control (ABAC) is a very generic concept that covers mul- tiple dierent access control mechanism. XACML is an implementation of ABAC based on XML and is established as a standard mechanism. Its flexibility opens the opportunity to specify detailed security policies. But on the other hand it has some drawbacks regarding maintenance and per- formance when the complexity of security policies grows. Long processing times for authorization requests are the consequence in environments that require fine-grained access control. We describe how to design a security policy in a resource oriented environment so that its drawbacks are minimized. The results are faster processing times for access requests and an easy to manage concept for security policies for RESTful services.
Implementation of a baby doll therapy protocol for people with dementia: Innovative practice

Dementia is exhibited by both emotional and physical states such as agitation. Chemical restraints, often used for agitated behaviors, are not always effective and produce untoward effects. Baby doll therapy is a nonpharmacologic therapy that can affect agitated behavior in dementia patients, yet a protocol for the therapy did not exist. An implementation protocol for doll therapy for those with dementia was developed and implemented with 16 residents in a dementia care center. Outcomes were measurements of the impact of the dolls on six areas of the resident’s behavior and their reactions to the doll. Participants had an increase in level of happiness, activity/liveliness, interaction with staff and others, and ease of giving care. There was also a reduction in the level of anxiety. The increase in happiness was a statistically significant outcome. Baby doll therapy is an effective nonpharmacological approach for improving the well-being of patients with moderate to severe dementia.
Three-year-olds' theories of mind are symbolic but of low complexity

Rhodes and Brandone (2014) have shown evidence of limited theory of mind in 3-year old children. The study was based on a false belief procedure in which an observer [E1] saw a toy hidden in location 1, then it was moved to location 2. E1 observed the move in the true belief (TB) test but not in the false belief (FB) test. Then the child was assessed for understanding of E1's belief about the toy. In the FB test E1 should falsely believe the toy was still at location 1, whereas in the TB test E1 would know the toy was at location 2. In the action condition the child was asked to open the door where E1 would enter to retrieve the toy, whereas in the verbal condition the child was asked where E1 thought the toy was. Participants performed above chance in both TB and FB tests in the action condition but in the verbal condition they performed above chance in the TB test only. Rhodes and Brandone (2014) interpret correct performance in the action condition as reflecting implicit theory of mind whereas in the verbal condition it is interpreted as explicit.
Cooperative object manipulation in immersive virtual environments: framework and techniques

Cooperative manipulation refers to the simultaneous manipulation of a virtual object by multiple users in an immersive virtual environment. This paper describes a framework supporting the development of collaborative manipulation techniques, and example techniques we have tested within this framework. We describe the modeling of cooperative interaction techniques, methods of combining simultaneous user actions, and the awareness tools used to provide the necessary knowledge of partner activities during the cooperative interaction process. Our framework is based on a Collaborative Metaphor concept that defines rules to combine user interaction techniques. The combination is based on the separation of degrees of freedom between two users. Finally, we present novel combinations of two interaction techniques (Simple Virtual Hand and Ray-casting).
Doubleness in Experience: Toward a Distributed Enactive Approach to Metaphoricity

A new concept of cognition also implies a novel approach to the study of metaphor. This insight is the starting point of this article presenting two innovations to comprehending and analyzing metaphor, one theoretical and one in terms of methodology. On a theoretical level we argue for a new orientation to metaphor and metaphoricity based on enactive cognition and distributed language and cognition. In recent years enactive and distributed cognition have been developing a new concept of cognition as an inter-bodily and ecologically afforded achievement, and in light of this theoretical development we propose an approach to metaphor as a multi-body, multi-party, and multi-timescale phenomenon. On a methodological level we demonstrate a new way of analyzing metaphoricity in multimodal social interaction based on in-depth video analyses of two real life examples in which we introduce metaphorical identification criteria focusing on doubleness in meaning, affordances for co-action, co-ordination, and co-experience. Here metaphoricity is explored as a distinct and emergent aspect of the coordination processes that constitute social interaction. In the final section we point to the general findings of the analyses and discuss the challenges that conceptual metaphor theory faces in the light of the new tendencies within cognitive science as well as a possible way forward.
Unexpected Hydrolytic Instability of N-Acylated Amino Acid Amides and Peptides

Remote amide bonds in simple N-acyl amino acid amide or peptide derivatives 1 can be surprisingly unstable hydrolytically, affording, in solution, variable amounts of 3 under mild acidic conditions, such as trifluoroacetic acid/water mixtures at room temperature. This observation has important implications for the synthesis of this class of compounds, which includes N-terminal-acylated peptides. We describe the factors contributing to this instability and how to predict and control it. The instability is a function of the remote acyl group, R2CO, four bonds away from the site of hydrolysis. Electron-rich acyl R2 groups accelerate this reaction. In the case of acyl groups derived from substituted aromatic carboxylic acids, the acceleration is predictable from the substituent’s Hammett σ value. N-Acyl dipeptides are also hydrolyzed under typical cleavage conditions. This suggests that unwanted peptide truncation may occur during synthesis or prolonged standing in solution when dipeptides or longer peptides are acylated on the N-terminus with electron-rich aromatic groups. When amide hydrolysis is an undesired secondary reaction, as can be the case in the trifluoroacetic acid-catalyzed cleavage of amino acid amide or peptide derivatives 1 from solid-phase resins, conditions are provided to minimize that hydrolysis.
Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo

Our data show that 1 X 10(7) to 1.5 X 10(7) lymphocytic choriomeningitis virus-specific, H-2-restricted cloned cytotoxic T lymphocytes (CTL) administered intravenously into acutely infected mice totally cleared virus from the spleens (10(4) to 10(5) PFU per spleen reduced to less than 50 PFU per spleen) by 24 h. This activity was genetically restricted in that cloned CTL could reduce titers of infectious virus in syngeneic C57BL/6 mice but not allogeneic BALB/c mice. Dose-response analysis indicated that at least 3 X 10(6) to 5 X 10(6) cloned CTL injected intravenously were needed to reduce significant amounts of infectious virus in the spleens. No infectious virus could be recovered from the spleens for at least 4 days after injection of cloned CTL. Hence, CTL play a major role in elimination of infectious virus from spleens during lymphocytic choriomeningitis virus infection. Our results also indicate that cloned CTL propagated in vitro for long periods of time can mediate a biologically relevant effect in vivo. These cells should be of considerable value in defining the precise manner in which CTL bring about control of viral infection, analyzing lymphocyte trafficking, and the potential use of cloned CTL in immunotherapy against viral disease.
Impact of Some Ecological Factors on Fecal Contamination of Drinking Water by Diarrheagenic Antibiotic-Resistant Escherichia coli in Zagazig City, Egypt

Fecal contamination of drinking water is a major health problem which accounts for many cases of diarrhea mainly in infants and foreigners. This contamination is a complex interaction of many parameters. Antibiotic resistance among bacterial isolates complicates the problem. The study was done to identify fecal contamination of drinking water by Diarrheagenic Antibiotic-Resistant Escherichia coli in Zagazig city and to trace reasons for such contamination, three hundred potable water samples were investigated for E. coli existence. Locations of E. coli positive samples were investigated in relation to population density, water source, and type of water pipe. Sixteen E. coli strains were isolated. Antibiotic sensitivity was done and enterotoxigenic, enteropathogenic, and enterohaemorrhagic virulence genes were investigated by PCR. Probability of fecal contamination correlated with higher population density, with increased distance from Zagazig water plant, and with asbestos cement water pipes. Resistance to at least one antimicrobial drug was found in all isolates. Virulence genes were detected in a rate of 26.27%, 13.13%, 20%, 6.67%, and 33.33% for LT, ST, stx1, stx2, and eae genes, respectively. This relatively high frequency of fecal contamination points towards the high risk of developing diarrhea by antibiotic resistant DEC in low socioeconomic communities particularly with old fashion distribution systems.