Miracle-dz/UniFAR-FTUs huggingface dataset:
Downregulation of miR-92a Is Associated with Aggressive Breast Cancer Features and Increased Tumour Macrophage Infiltration

Background MicroRNAs are small non-coding RNAs involved in the regulation of gene expression on a posttranscriptional level. These regulatory RNAs have been implicated in numerous cellular processes and are further deregulated in different cancer types, including breast cancer. MiR-92a is part of the miR-17∼92 cluster, which was first reported to be linked to tumourigenesis. However, little is known about the expression of miR-92a in breast cancer and potential associations to tumour properties. The expression of miR-92a was therefore characterized in 144 invasive breast cancer samples using in situ hybridization and related to clinico-pathological data as well as to selected key properties of the tumour stroma, including the presence of macrophages (CD68) and cancer activated fibroblasts (alpha-SMA). Methodology/Principal Findings To measure miR-92a levels, an in situ hybridisation protocol was developed and validated using cell lines and miR-92a inhibitors. The expression in the tumour samples was objectively evaluated using digital image analysis program subtracting background activities. We found that the miR-92a expression varied between tumours and was inversely correlated to tumour grade (r = −0.276, p = 0.003) and recurrence-free survival (p = 0.008) and provided independent prognostic information in multivariate Cox analysis (HR: 0.375, CI: 0.145–0.972, p = 0.043). MiR-92a was moreover inversely correlated to the number of infiltrating macrophages in the tumour stroma (r = −0.357, p<0.001), and downregulation of miR-92a promoted cell migration (p<0.01). Conclusions/Significance This study demonstrates that downregulation of miR-92a in breast cancer is linked to key epithelial and stromal properties as well as clinical outcome.
A chloroplast retrograde signal, 3’-phosphoadenosine 5’-phosphate, acts as a secondary messenger in abscisic acid signaling in stomatal closure and germination

Organelle-nuclear retrograde signaling regulates gene expression, but its roles in specialized cells and integration with hormonal signaling remain enigmatic. Here we show that the SAL1-PAP (3′-phosphoadenosine 5′- phosphate) retrograde pathway interacts with abscisic acid (ABA) signaling to regulate stomatal closure and seed germination in Arabidopsis. Genetically or exogenously manipulating PAP bypasses the canonical signaling components ABA Insensitive 1 (ABI1) and Open Stomata 1 (OST1); priming an alternative pathway that restores ABA-responsive gene expression, ROS bursts, ion channel function, stomatal closure and drought tolerance in ost1-2. PAP also inhibits wild type and abi1-1 seed germination by enhancing ABA sensitivity. PAP-XRN signaling interacts with ABA, ROS and Ca2+; up-regulating multiple ABA signaling components, including lowly-expressed Calcium Dependent Protein Kinases (CDPKs) capable of activating the anion channel SLAC1. Thus, PAP exhibits many secondary messenger attributes and exemplifies how retrograde signals can have broader roles in hormone signaling, allowing chloroplasts to fine-tune physiological responses. DOI: http://dx.doi. org/10.7554/eLife.23361. 001
Representation of Accumulating Evidence for a Decision in Two Parietal Areas

Decisions are often made by accumulating evidence for and against the alternatives. The momentary evidence represented by sensory neurons is accumulated by downstream structures to form a decision variable, linking the evolving decision to the formation of a motor plan. When decisions are communicated by eye movements, neurons in the lateral intraparietal area (LIP) represent the accumulation of evidence bearing on the potential targets for saccades. We now show that reach-related neurons from the medial intraparietal area (MIP) exhibit a gradual modulation of their firing rates consistent with the representation of an evolving decision variable. When decisions were communicated by saccades instead of reaches, decision-related activity was attenuated in MIP, whereas LIP neurons were active while monkeys communicated decisions by saccades or reaches. Thus, for decisions communicated by a hand movement, a parallel flow of sensory information is directed to parietal areas MIP and LIP during decision formation.
Does a Dollar Get You a Dollar’s Worth of Merchandise? The Impact of Power Distance Belief on Price-Quality Judgments

The role of cultural factors in influencing price perceptions is not understood well in the literature. The present research seeks to fill this gap by examining the link between power distance belief—the acceptance and endorsement of power disparities in society—and the tendency to use the price of a product to judge its quality, the underlying processes, and boundary conditions. Three studies show that consumers high (vs. low) in power distance belief have a greater tendency to use price to judge quality because they have a greater need for structure, which makes them more likely to discriminate between brands and rank them based on price. The relationships held regardless of whether the price-to-quality relation was assessed using a standard self-report scale or via actual product judgments, and whether power distance belief was measured or manipulated. The effect was found to be independent of self-construal, holistic thinking, and risk aversion, was mediated by a need for structure, and disappeared when the tendency to order was facilitated (impeded) by making price more (less) salient. Theoretical implications are discussed.
Filtering sensory information with XCSF: improving learning robustness and control performance

It was previously shown that the control of a robot arm can be efficiently learned using the XCSF classifier system. So far, however, the predictive knowledge about how actual motor activity changes the state of the arm system has not been exploited. In this paper, we exploit the forward velocity kinematics knowledge of XCSF to alleviate the negative effect of noisy sensors for successful learning and control. We incorporate Kalman filtering for estimating successive arm positions iteratively combining sensory readings with XCSF-based predictions of hand position changes over time. The filtered arm position is used to improve both trajectory planning and further learning of the forward velocity kinematics. We test the approach on a simulated, kinematic robot arm model. The results show that the combination can improve learning and control performance significantly. However, it also shows that variance estimates of XCSF predictions maybe underestimated, in which case self-delusional spiraling effects hinder effective learning. Thus, we introduce a heuristic parameter, which limits the influence of XCSF's predictions on its own further learning input. As a result, we obtain drastic improvements in noise tolerance coping with more than ten times higher noise levels.
Microbial Ecology of Four Coral Atolls in the Northern Line Islands

Microbes are key players in both healthy and degraded coral reefs. A combination of metagenomics, microscopy, culturing, and water chemistry were used to characterize microbial communities on four coral atolls in the Northern Line Islands, central Pacific. Kingman, a small uninhabited atoll which lies most northerly in the chain, had microbial and water chemistry characteristic of an open ocean ecosystem. On this atoll the microbial community was equally divided between autotrophs (mostly Prochlorococcus spp.) and heterotrophs. In contrast, Kiritimati, a large and populated (∼5500 people) atoll, which is most southerly in the chain, had microbial and water chemistry characteristic of a near-shore environment. On Kiritimati, there were 10 times more microbial cells and virus-like particles in the water column and these microbes were dominated by heterotrophs, including a large percentage of potential pathogens. Culturable Vibrios were common only on Kiritimati. The benthic community on Kiritimati had the highest prevalence of coral disease and lowest coral cover. The middle atolls, Palmyra and Tabuaeran, had intermediate densities of microbes and viruses and higher percentages of autotrophic microbes than either Kingman or Kiritimati. The differences in microbial communities across atolls could reflect variation in 1) oceaonographic and/or hydrographic conditions or 2) human impacts associated with land-use and fishing. The fact that historically Kingman and Kiritimati did not differ strongly in their fish or benthic communities (both had large numbers of sharks and high coral cover) suggest an anthropogenic component in the differences in the microbial communities. Kingman is one of the world's most pristine coral reefs, and this dataset should serve as a baseline for future studies of coral reef microbes. Obtaining the microbial data set, from atolls is particularly important given the association of microbes in the ongoing degradation of coral reef ecosystems worldwide.
Neurite outgrowth on immobilized axonin-1 is mediated by a heterophilic interaction with L1(G4)

Axonin-1 is an axon-associated cell adhesion molecule with dualistic expression, one form being glycophosphatidylinositol-anchored to the axonal membrane, the other secreted from axons in a soluble form. When presented as a substratum for neuronal cultures it strongly promotes neurite outgrowth from chicken embryonic dorsal root ganglia neurons. In this study, the axon-associated cell adhesion molecule G4, which is identical with Ng-CAM and 8D9, and homologous or closely related to L1 of the mouse and NILE of the rat, was investigated with respect to a receptor function for axonin-1. Using fluorescent microspheres with covalently coupled axonin-1 or L1(G4) at their surface we showed that these proteins bind to each other. Within the sensitivity of this microsphere assay, no interaction of axonin-1 with itself could be detected. Axonin-1-coated microspheres also bound to the neurites of cultured dorsal root ganglia neurons. This interaction was exclusively mediated by L1(G4), as indicated by complete binding suppression by monovalent anti-L1(G4) antibodies. The interaction between neuritic L1(G4) and immobilized axonin-1 was found to mediate the promotion of neurite growth on axonin-1, as evidenced by the virtually complete arrest of neurite outgrowth in the presence of anti-L1(G4) antibodies. Convincing evidence has recently been presented that neurite growth on L1(8D9) is mediated by the homophilic binding of neuritic L1(G4) (1989. Neuron. 2: 1597-1603). Thus, both L1(G4)- and axonin-1-expressing axons may serve as "substrate pathways" for the guidance of following axons expressing L1(G4) into their target area. Conceivably, differences in the concentration of axonin-1 and L1(G4), and/or modulatory influences on their specific binding parameters in leading pathways and following axons could represent elements in the control of axonal pathway selection.
Incentives vs. Control: An Analysis of U.S. Dual-Class Companies

Dual-class common stock allows for the separation of voting rights and cash flow rights across the different classes of equity. We construct a large sample of dual-class firms in the United States and analyze the relationships of insider's cash flow rights and voting rights with firm value, performance, and investment behavior. We find that relationship of firm value to cash flow rights is positive and concave and the relationship to voting rights is negative and convex. Identical quadratic relationships are found for the respective ownership variables with sales growth, capital expenditures, and the combination of R&D and advertising. Our evidence is consistent with an entrenchment effect of voting control that leads managers to underinvest and an incentive effect of cash flow ownership that induces managers to pursue more aggressive strategies.
Biophysical Characterization of a Vaccine Candidate against HIV-1: The Transmembrane and Membrane Proximal Domains of HIV-1 gp41 as a Maltose Binding Protein Fusion

The membrane proximal region (MPR, residues 649–683) and transmembrane domain (TMD, residues 684–705) of the gp41 subunit of HIV-1’s envelope protein are highly conserved and are important in viral mucosal transmission, virus attachment and membrane fusion with target cells. Several structures of the trimeric membrane proximal external region (residues 662–683) of MPR have been reported at the atomic level; however, the atomic structure of the TMD still remains unknown. To elucidate the structure of both MPR and TMD, we expressed the region spanning both domains, MPR-TM (residues 649–705), in Escherichia coli as a fusion protein with maltose binding protein (MBP). MPR-TM was initially fused to the C-terminus of MBP via a 42 aa-long linker containing a TEV protease recognition site (MBP-linker-MPR-TM). Biophysical characterization indicated that the purified MBP-linker-MPR-TM protein was a monodisperse and stable candidate for crystallization. However, crystals of the MBP-linker-MPR-TM protein could not be obtained in extensive crystallization screens. It is possible that the 42 residue-long linker between MBP and MPR-TM was interfering with crystal formation. To test this hypothesis, the 42 residue-long linker was replaced with three alanine residues. The fusion protein, MBP-AAA-MPR-TM, was similarly purified and characterized. Significantly, both the MBP-linker-MPR-TM and MBP-AAA-MPR-TM proteins strongly interacted with broadly neutralizing monoclonal antibodies 2F5 and 4E10. With epitopes accessible to the broadly neutralizing antibodies, these MBP/MPR-TM recombinant proteins may be in immunologically relevant conformations that mimic a pre-hairpin intermediate of gp41.
Delayed feedback stabilization of unstable equilibria

Abstract Analytical results of stabilizing of unstable equilibria of two- and three-dimensional linear systems are presented. The stabilization method is based on time-delayed feedback. Effective necessary and/or sufficient conditions for stabilizing the considered systems in terms of its parameters are obtained. The potential of delayed state and output feedback controls is shown. The theorems proved show that such a delayed feedback approach allows one to extend the possibilities available with static time-invariant state and output feedbacks for stabilizability of unstable linear time-invariant controllable systems. It is used two types of time-delayed feedback: conventional and by Pyragas' ones. A comparison of the stabilizability domains via both types of feedback is given.
Two Allelic Variants of Aldo-Keto Reductase 1A1 Exhibit Reduced in Vitro Metabolism of Daunorubicin

Aldo-keto reductases (AKRs) are a class of NADPH-dependent oxidoreductases that have been linked to metabolism of the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN). Although widely used, cardiotoxicity continues to be a serious side effect that may be linked to metabolites or reactive intermediates generated in their metabolism. In this study we examine the little known effects of nonsynonymous single nucleotide polymorphisms of human AKR1A1 on the metabolism of these drugs to their alcohol metabolites. Expressed and purified from bacteria using affinity chromatography, the AKR1A1 protein with a single histidine (6x-His) tag exhibited the greatest activity using two test substrates: p-nitrobenzaldehyde (5.09 ± 0.16 μmol/min/mg of purified protein) and dl-glyceraldehyde (1.24 ± 0.17 μmol/min/mg). These activities are in agreement with published literature values of nontagged human AKR1A1. The 6x-His-tagged AKR1A1 wild type and allelic variants, E55D and N52S, were subsequently examined for metabolic activity using DAUN and DOX. The tagged variants showed significantly reduced activities (1.10 ± 0.42 and 0.72 ± 0.47 nmol of daunorubicinol (DAUNol) formed/min/mg of purified protein for E55D and N52S, respectively) compared with the wild type (2.34 ± 0.71 nmol/min/mg). The wild type and E55D variant metabolized DOX to doxorubicinol (DOXol); however, the levels fell below the limit of quantitation (25 nM). The N52S variant yielded no detectable DOXol. A kinetic analysis of the DAUN reductase activities revealed that both amino acid substitutions lead to reduced substrate affinity, measured as significant increases in the measured Km for the reduction reaction by AKR1A1. Hence, it is possible that these allelic variants can act as genetic biomarkers for the clinical development of DAUN-induced cardiotoxicity.
The Pleasure of the Playable Text: Towards an Aesthetic Theory of Computer Games

This paper argues that the dominant study of the form and structure of games ‐ their poetics ‐ should be complemented by the analysis of their aesthetics (as understood by modern cultural theory): how gamers use their games, what aspects they enjoy and what kinds of pleasures they experience by playing them. The paper outlines a possible aesthetic theory of games based on different aspects of pleasure: the psychoanalytical, the social and the physical form of pleasure.
Situated Research Design and Methodological Choices in Formative Program Evaluation

Design-based implementation research offers the opportunity to rethink the relationships between intervention, research, and situation to better attune research and evaluation to the program development process. Using a heuristic called the intervention development curve, I describe the rough trajectory that programs typically follow as they evolve, and argue that research design considerations and methodological choices are best made in consideration of where interventions are along this curve. Further, I contend that, as programs develop, situational influences play a major role in their evolution and consequently require increased attention to design and methodological considerations. By viewing research as an integral part of a program's development, by making design and methodological choices in consideration of where programs are in their development, and by considering that the situation in which programs evolve as a potential source of change in the nature of the program itself, we alter fundamental perspectives on how research can best contribute to the steady work of building robust programs for educational improvement.
Primitives for Dynamic Big Model Parallelism

When training large machine learning models with many variables or parameters, a single machine is often inadequate since the model may be too large to fit in memory, while training can take a long time even with stochastic updates. A natural recourse is to turn to distributed cluster computing, in order to harness additional memory and processors. However, naive, unstructured parallelization of ML algorithms can make inefficient use of distributed memory, while failing to obtain proportional convergence speedups — or can even result in divergence. We develop a framework of primitives for dynamic model-parallelism, STRADS, in order to explore partitioning and update scheduling of model variables in distributed ML algorithms — thus improving their memory efficiency while presenting new opportunities to speed up convergence without compromising inference correctness. We demonstrate the efficacy of model-parallel algorithms implemented in STRADS versus popular implementations for Topic Modeling, Matrix Factorization and Lasso.
A Digital PCR-Based Method for Efficient and Highly Specific Screening of Genome Edited Cells

The rapid adoption of gene editing tools such as CRISPRs and TALENs for research and eventually therapeutics necessitates assays that can rapidly detect and quantitate the desired alterations. Currently, the most commonly used assay employs “mismatch nucleases” T7E1 or “Surveyor” that recognize and cleave heteroduplexed DNA amplicons containing mismatched base-pairs. However, this assay is prone to false positives due to cancer-associated mutations and/or SNPs and requires large amounts of starting material. Here we describe a powerful alternative wherein droplet digital PCR (ddPCR) can be used to decipher homozygous from heterozygous mutations with superior levels of both precision and sensitivity. We use this assay to detect knockout inducing alterations to stem cell associated proteins, NODAL and SFRP1, generated using either TALENs or an “all-in-one” CRISPR/Cas plasmid that we have modified for one-step cloning and blue/white screening of transformants. Moreover, we highlight how ddPCR can be used to assess the efficiency of varying TALEN-based strategies. Collectively, this work highlights how ddPCR-based screening can be paired with CRISPR and TALEN technologies to enable sensitive, specific, and streamlined approaches to gene editing and validation.
Attidudes of Secondary Level of Primary School Students Towards Music Lessons

The objective of this study is to examine the musical attitude of the 6 th , 7 th and 8 th grade students SUMMARY Purpose and significance: The objective of this study is to examine the musical attitude of the 6 th , 7 th and 8 th classes students of second level of primari education in relation with their genders, classes, the type of school and the school that they currently attend, the music kind they most listened, whether they make lesson in classroom that is specified for music lesson, whether they have had special music lesson out of the school, whether they have had music lesson from teacher that his or her branch is the music at 4 th and 5 th grade variables. Methods: The universe of the research consists of the state schools and the private schools that are situated in the European side of Istanbul. A total of 390 students, from 4 different school participated in the study.In order to find answers to the questions, the Musical Attitude Inventory, which was developed and its validity and reliability proved by Ayfer Kocabas, has been used. Indipendent t-test, One-way ANOVA were used to analyze the data. Results: According to the research results: There is a significant difference in music attitudes among students that attend the state school and the private school (t=2,05; p .05); Discussion and Conclusions:It can be thought that the fact of differentiation of musical attitudes among genders is that while male students pair music with the sentimentalism, they do not pair sentimentalism with the sexuality which they have already started to discover. Our expectation of positive effect of taking extra-scholastic music courses affect students attitudes is obvious. Teachers should lead and encourage students intended to take extra-scholastic music courses and their families and direct them to qualified centers; and if needed they track mentioned students achievements and should guide them. As the level of the class increases, the level of improvement on musical behavior of students acts in opposite direction. It is thought that, especially the reasons why students think that music courses are useless and unnecessary and precautions to prevent this belief are needed to be explored. Opportunities of the school and the importance given to music courses are one of the factors that have a possibility to affect student's attitudes positively or negatively.
A semantic occlusion model for human pose estimation from a single depth image

Human pose estimation from depth data has made significant progress in recent years and commercial sensors estimate human poses in real-time. However, state-of-the-art methods fail in many situations when the humans are partially occluded by objects. In this work, we introduce a semantic occlusion model that is incorporated into a regression forest approach for human pose estimation from depth data. The approach exploits the context information of occluding objects like a table to predict the locations of occluded joints. In our experiments on synthetic and real data, we show that our occlusion model increases the joint estimation accuracy and outperforms the commercial Kinect 2 SDK for occluded joints.