Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules

Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulators on synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide “when” to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators.
Genome‐wide methylation screen in low‐grade breast cancer identifies novel epigenetically altered genes as potential biomarkers for tumor diagnosis

Aberrant DNA methylation constitutes a well‐established epigenetic marker for breast cancer. Changes in methylation early in cancer development may be clinically relevant for cancer detection and prognosis‐based therapeutic decisions. In the present study, a combination of methyl‐CpG immunoprecipitation (MCIp) and human CpG island (CGI) arrays was applied to compare genome‐wide DNA methylation profiles in 10 low‐grade in situ and invasive breast cancers against 10 normal breast samples. In total, 214 CGIs were found to be hypermethylated in ≥6 of 10 tumors. Functional term enrichment analyses revealed an overrepresentation of homeobox genes and genes involved in transcription and regulation of transcription. Significant hypermethylation of 11 selected genes in tumor vs. normal tissue was validated in two independent sample sets (45 tumors and 11 controls, 43 tumors and 8 controls) using quantitative EpiTyper technology. In tumors, median methylation levels of BCAN, HOXD1, KCTD8, KLF11, NXPH1, POU4F1, SIM1, and TCF7L1 were ≥30% higher than in normal samples, representing potential biomarkers for tumor diagnosis. Using the 90th percentile of methylation levels in normal tissue as cutoff value, 62–92% of in situ samples (n=13), 72–97% of invasive samples from the first validation set (n=32), and 86–100% of invasive samples from the second validation set (n=43) were classified as hypermethylated. Hypermethylation of KLF11 and SIM1 might also be associated with increased risk of developing metastases. In summary, early methylation changes are frequent in the low‐grade pathway of breast cancer and may be useful in the development of differential diagnostic and possibly also prognostic markers. —Faryna, M. , Konermann, C. , Aulmann, S. , Bermejo, J. L. , Brugger, M. , Diederichs, S. , Rom, J., Weichenhan, D. , Claus, R. , Rehli, M. , Schirmacher, P., Sinn, H. ‐P., Plass, C. , Gerhauser, C. Genome‐wide methylation screen in low‐grade breast cancer identifies novel epigenetically altered genes as potential biomarkers for tumor diagnosis. FASEB J. 26, 4937–4950 (2012). www.fasebj. org
GM-CSF facilitates the development of inflammation-associated colorectal carcinoma

The granulocyte macrophage colony-stimulating factor (GM-CSF) is known to play a protective role in intestinal inflammation. However, the effects of GM-CSF on the progression of colitis to colorectal carcinoma have long remained unclear. We have recently demonstrated that GM-CSF produced by colonic epithelial cells promotes colorectal tumorigenesis by stimulating the secretion of vascular endothelial growth factor.
Cross-lingual Coreference Resolution of Pronouns

This work is, to our knowledge, a first attempt at a machine learning approach to cross-lingual coreference resolution, i.e. coreference resolution (CR) performed on a bitext. Focusing on CR of English pronouns, we leverage language differences and enrich the feature set of a standard monolingual CR system for English with features extracted from the Czech side of the bitext. Our work also includes a supervised pronoun aligner that outperforms a GIZA++ baseline in terms of both intrinsic evaluation and evaluation on CR. The final cross-lingual CR system has successfully outperformed both a monolingual CR and a cross-lingual projection system.
Sexual Differentiation of the Brain Requires Perinatal Kisspeptin-GnRH Neuron Signaling

Sex differences in brain function underlie robust differences between males and females in both normal and disease states. Although alternative mechanisms exist, sexual differentiation of the male mammalian brain is initiated predominantly by testosterone secreted by the testes during the perinatal period. Despite considerable advances in understanding how testosterone and its metabolite estradiol sexually differentiate the brain, little is known about the mechanism that generates the male-specific perinatal testosterone surge. In mice, we show that a male-specific activation of GnRH neurons occurs 0–2 h following birth and that this correlates with the male-specific surge of testosterone occurring up to 5 h after birth. The necessity of GnRH signaling for the sexually differentiating effects of the perinatal testosterone surge was demonstrated by the persistence of female-like brain characteristics in adult male, GnRH receptor knock-out mice. Kisspeptin neurons have recently been identified to be potent, direct activators of GnRH neurons. We demonstrate that a population of kisspeptin neurons appears in the preoptic area of only the male between E19 and P1. The importance of kisspeptin inputs to GnRH neurons for the process of sexual differentiation was demonstrated by the lack of a normal neonatal testosterone surge, and disordered brain sexual differentiation of male mice in which the kisspeptin receptor was deleted selectively from GnRH neurons. These observations demonstrate the necessity of perinatal GnRH signaling for driving brain sexual differentiation and indicate that kisspeptin inputs to GnRH neurons are essential for this process to occur.
Polychronization: Computation with Spikes

We present a minimal spiking network that can polychronize, that is, exhibit reproducible time-locked but not synchronous firing patterns with millisecond precision, as in synfire braids. The network consists of cortical spiking neurons with axonal conduction delays and spike-timing-dependent plasticity (STDP); a ready-to-use MATLAB code is included. It exhibits sleeplike oscillations, gamma (40 Hz) rhythms, conversion of firing rates to spike timings, and other interesting regimes. Due to the interplay between the delays and STDP, the spiking neurons spontaneously self-organize into groups and generate patterns of stereotypical polychronous activity. To our surprise, the number of coexisting polychronous groups far exceeds the number of neurons in the network, resulting in an unprecedented memory capacity of the system. We speculate on the significance of polychrony to the theory of neuronal group selection (TNGS, neural Darwinism), cognitive neural computations, binding and gamma rhythm, mechanisms of attention, and consciousness as attention to memories.
Fitness Distance Correlation Analysis: An Instructive Counterexample

Fitness distance correlation (FDC) has been offered as a summary statistic with apparent success in predicting the performance of genetic algorithms for global optimization. Here, a counterexample to Hamming-distance based FDC is examined for what it reveals about how GAs work. The counterexample is a fitness function that is ``GA-easy'' for global optimization, but which shows no relationship between fitness and Hamming distance from the global optimum. Fitness is a function that declines with the number of switches between 0 and 1 along the bitstring. The test function is ``GA-easy,'' in that a GA using only single-point crossover can find the global optimum with a sample on the order of $10^{-3}$ to $10^{-9}$ of the points in the search space, an efficiency which increases with the size of the search space. This result confirms the suspicion that predictors for genetic algorithm performance are vulnerable if they are based on arbitrary properties of the search space, and not the actual dynamics of the genetic algorithm. The test function's solvability by a GA is accurately predicted, however, by another property---its evolvability, the probability that the genetic operator produces offspring that are fitter than their parents. It is also accurately predicted by FDC that uses not Hamming distance, but a distance measure defined by the crossover operator itself. A comparison is made between Hamming-distance based FDC analysis, crossover-distance based FDC analysis, evolvability analysis, and other methods of predicting GA performance.
Epidermal growth factor receptor inhibitor induces Interleukin-6 via NADPH oxidase enzymes in head and neck cancer cells

ii ABSTRACT The epidermal growth factor receptor (EGFR) is a tyrosine kinase cell surface receptor, belonging to the ErbB family of receptors, which functions to initiate downstream signaling pathways resulting in cellular proliferation, differentiation, migration, adhesion, and metastasis. EGFR is over expressed in numerous types of cancers including head and neck, breast, colon, lung, renal, and ovarian, and this overexpression of EGFR has been correlated with poor prognosis and survival rates specifically in head and neck squamous cell carcinoma (HNSCC). Due to the pro-oncogenic activity of EGFR (e.g. cell growth, angiogenesis, and metastasis), ameliorating the function of EGFR makes it an attractive target for chemotherapy. While clinical therapy with Erlotinib is quite successful, resistance to the chemotherapy agent is highly prevalent. To date, the molecular mechanism by which cancers become resistant to Erlotinib remains unclear. These studies identify a novel pathway in head and neck carcinoma cell lines involving the up-regulation of NADPH oxidase enzymes (NOX), specifically NOX4 and DUOX2, after Erlotinib treatment, which leads to an increased production of hydrogen peroxide and finally increased IL-6 production. The IL-6 axis has been proposed to play a definitive role in the long-term proliferation and survival of various cancers, and perturbation of this axis by Erlotinib may initiate pro-survival signals which render the cancers resistant to Erlotinib. Therefore, we put forth a model of multidrug therapy targeting NOX enzymes and/or IL-6 in combination with Erlotinib to counteract the potential drug-resistance mechanisms often observed in malignancy.
An investigation of dependencies between frequency components and speaker characteristics based on phoneme mean F-ratio contribution

This paper proposes a new speaker feature extraction method, which is based on the non-uniformly distributed speaker information in frequency bands. In order to emphasize individual differences effectively, in this study, we first examine the differences of the distribution of individual information in the frequency region when a speaker utters different phonemes. Then we adopt an improved F-ratio, a phoneme mean F-ratio, to measure the dependences between frequency components and individual characteristics. According to the result of the analysis, we adopt an adaptive frequency filter to extract more discriminative feature. The new feature was combined with GMM speaker models and applied to the speaker recognition database which includes 50 persons. The experiment shows that the error rate using the proposed feature is reduced by 28.5% compared with the F-ratio feature, and reduced by 68.02% compared with the MFCC feature.
Diazoxide-Induced Cardioprotection Requires Signaling Through a Redox-Sensitive Mechanism

Diazoxide, a selective opener of the mitochondrial ATP-sensitive potassium channel, has been shown to elicit tolerance to ischemia in cardiac myocytes and in perfused heart. However, the mechanism of this cardioprotection is poorly understood. Because reactive oxygen species (ROS) are recognized as important intracellular signaling molecules and have been implicated in ischemic preconditioning, we examined diazoxide-induced ROS production in adult cardiomyocytes. Cells treated with 50 &mgr;mol/L diazoxide showed a 173% increase in ROS production relative to baseline. 5-Hydroxydecanoate was found to attenuate the diazoxide-induced increase in ROS generation. The diazoxide-induced increase in ROS also was abrogated by the addition of either the antioxidant N-acetylcysteine (NAC) or N-mercaptopropionylglycine. We also examined the ability of NAC to block the protective effects of diazoxide in the perfused rat heart. After 20 minutes of global ischemia and 20 minutes of reflow, hearts perfused with 100 &mgr;mol/L diazoxide before ischemia showed significantly improved postischemic contractile function relative to untreated hearts (84% versus 29% of initial left ventricular developed pressure, respectively). Hearts treated with diazoxide in the presence of 4 mmol/L NAC recovered 53% of initial left ventricular developed pressure, whereas hearts treated with NAC alone recovered 46% of preischemic function. Using 31P NMR spectroscopy, we found that, similar to preconditioning, diazoxide significantly attenuated ischemia-induced intracellular acidification and enhanced post-ischemic recovery of phosphocreatine levels, both of which were blocked by cotreatment with NAC. These data suggest that the cardioprotective actions of diazoxide are mediated by generation of a pro-oxidant environment.
User association in massive MIMO and mmWave enabled HetNets powered by renewable energy

This paper considers a hybrid heterogeneous network (HetNet), where macro cells adopt massive multiple-input multiple-output (MIMO), and small cells adopt millimeter wave (mmWave) transmissions. We assume that all base stations (BSs) are solely powered by the renewable energy. The implementation of these emerging techniques has a substantial effect on the user association (UA). Motivated by this, we formulate a user association problem to maximize the network utility while the power cost of each BS does not exceed the harvested energy. To solve it, a low complexity distributed UA algorithm is proposed. The results demonstrate that the proposed algorithm achieves higher throughput than the max reference signal received power (RSRP) and max signal-to-interference-plus-noise ratio (SINR) UAs. It also shows that increasing the number of antennas at the macro cell BS with more power consumption, the throughput continues to increase by using the proposed algorithm, compared to the decrease in throughput by using the existing ones. Increasing the number of mmWave BSs, mmWave BS antennas or mmWave bandwidths can significantly improve the throughput. Compared with massive MIMO macro cells, mmWave small cells play a dominant role in enhancing the throughput of the networks due to the larger bandwidths.
Potassium and the K+/H+ Exchanger Kha1p Promote Binding of Copper to ApoFet3p Multi-copper Ferroxidase*

Acquisition and distribution of metal ions support a number of biological processes. Here we show that respiratory growth of and iron acquisition by the yeast Saccharomyces cerevisiae relies on potassium (K+) compartmentalization to the trans-Golgi network via Kha1p, a K+/H+ exchanger. K+ in the trans-Golgi network facilitates binding of copper to the Fet3p multi-copper ferroxidase. The effect of K+ is not dependent on stable binding with Fet3p or alteration of the characteristics of the secretory pathway. The data suggest that K+ acts as a chemical factor in Fet3p maturation, a role similar to that of cations in folding of nucleic acids. Up-regulation of KHA1 gene in response to iron limitation via iron-specific transcription factors indicates that K+ compartmentalization is linked to cellular iron homeostasis. Our study reveals a novel functional role of K+ in the binding of copper to apoFet3p and identifies a K+/H+ exchanger at the secretory pathway as a new molecular factor associated with iron uptake in yeast.
Predictions for masses of Ξ b baryons

The recent observation by CDF of Σ±b (uud and ddb) baryons within 2 MeV of the predicted Σb−Λb splitting has provided strong confirmation for the theoretical approach based on modeling the color hyperfine interaction. We now apply this approach to predict the masses of the Ξb family of baryons with quark content usb and dsb – the ground state Ξb at 5790 to 5800 MeV, and the excited states Ξ′b and Ξ ∗ b . The main source of uncertainty is the method used to estimate the mass difference mb −mc from known hadrons. We verify that corrections due to the details of the interquark potential and to Ξb–Ξ ′ b mixing are small.
ℓ1-Based Construction of Polycube Maps from Complex Shapes

Polycube maps of triangle meshes have proved useful in a wide range of applications, including texture mapping and hexahedral mesh generation. However, constructing either fully automatically or with limited user control a low-distortion polycube from a detailed surface remains challenging in practice. We propose a variational method for deforming an input triangle mesh into a polycube shape through minimization of the ℓ1-norm of the mesh normals, regularized via an as-rigid-as-possible volumetric distortion energy. Unlike previous work, our approach makes no assumption on the orientation, or on the presence of features in the input model. User-guided control over the resulting polycube map is also offered to increase design flexibility. We demonstrate the robustness, efficiency, and controllability of our method on a variety of examples, and explore applications in hexahedral remeshing and quadrangulation.
Marketing in Hypermedia Computer-Mediated Environments: Conceptual Foundations

The authors address the role of marketing in hypermedia computer-mediated environments (CMEs). Their approach considers hypermedia CMEs to be large-scale (i.e., national or global) networked environments, of which the World Wide Web on the Internet is the first and current global implementation. They introduce marketers to this revolutionary new medium, propose a structural model of consumer navigation behavior in a CME that incorporates the notion of flow, and examine a series of research issues and marketing implications that follow from the model.
Self Identity's New Model:Dual-Cycle Model

Self identity has been a crucial phenomenon in the study field of developmental psychology since Erikson first proposed the concept.Empirical study concerning self identity has been largely based on Marcia's identity status model.Further researchers like Luyckx try to integrate identity status model with its criticism and modification,thus propose the theory of self identity's dual-cycle model.According to dual-cycle model,self identity is a construct comprised of five dimensions:exploration in breadth,exploration in depth,ruminative exploration,commitment making and identification with commitment.The dimensions constitute two cycles:"commitment-formation cycle" and "commitment-evaluation cycle",and the dynamic interaction of the two cycles prompts the process of identity formation and development,thus results in six identity statuses:identity achievement,identity foreclosure,ruminative moratorium,carefree diffusion,diffused diffusion and undifferentiated.
DOT1L promotes angiogenesis through cooperative regulation of VEGFR2 with ETS-1

Histone methyltransferase DOT1L is implicated in various biological processes including cell proliferation, differentiation and embryogenesis. Gene ablation of Dot1l results in embryonic lethality and cardiovascular defects including decreased vasculature. However, how DOT1L might contribute to the development of vasculature is not clear. Here, we report that DOT1L is required for angiogenesis. We demonstrated that silencing of DOT1L in human umbilical vein endothelial cells (HUVECs) leads to decreased cell viability, migration, tube formation, and capillary sprout formation in vitro, as well as reduced formation of functional vascular networks in matrigel plugs in vivo. Genome-wide analysis of DOT1L targets via H3K79me2 ChIP-seq annotation in HUVECs identified a number of genes including VEGFR2 that are critically involved in angiogenesis. We showed that DOT1L cooperates with transcription factor ETS-1 to stimulate the expression of VEGFR2, thereby activating ERK1/2 and AKT signaling pathways and promoting angiogenesis. Our study revealed a mechanistic role for DOT1L in the promotion of angiogenesis, adding to the understanding of the biological function of this histone methyltransferase.
Planar and Nonplanar Konishi Anomalies and Effective Superpotential for Noncommutative N=1 Supersymmetric U(1)

The Konishi anomalies for noncommutative N=1 supersymmetric U(1) gauge theory arising from planar and nonplanar diagrams are calculated. Whereas planar Konishi anomaly is the expected \star-deformation of the commutative anomaly, nonplanar anomaly reflects the important features of nonplanar diagrams of noncommutative gauge theories, such as UV/IR mixing and the appearance of nonlocal open Wilson lines. We use the planar and nonplanar Konishi anomalies to calculate the effective superpotential of the theory. In the limit of vanishing |\Theta p|, with \Theta the noncommutativity parameter, the noncommutative effective superpotential depends on a gauge invariant superfield, which includes supersymmetric Wilson lines, and has nontrivial dependence on the gauge field supermultiplet.
What Matters for Team Cohesion Measurement? A Synthesis

Abstract Cohesion is a key contributor to team effectiveness, leading to great interest in understanding how to diagnose, monitor, and enhance it in practice. However, there is great inconsistency in how cohesion is conceptualized and measured, making it difficult to compare findings across studies, and therefore limiting the ability to advance science and practice. To begin addressing these issues, we draw from qualitative and quantitative analyses and extract themes indicating what matters most for effective cohesion measurement. Such themes are presented around six major questions – who, what, when, where, why, and how – as they pertain to each major component of the cohesion measurement process. Emerging approaches to cohesion measurement and corresponding avenues for future research are also discussed.
Association of macrophage activation with antitumor effect on rat syngeneic fibrosarcoma by Nocardia rubra cell wall skeleton.

The antitumor activities of the cell wall skeleton (CWS) of Nocardia rubra were demonstrated for syngeneic fibrosarcoma (AMC-60) in ACI/N rats in regard to macrophage activation. In the 24-hr cytolytic test, activated macrophages which were fractionated from peritoneal exudate cells induced by i.p. injection of Nocardia CWS showed significant cytolytic activity for [125I]iododeoxyuridine-labeled tumor cells. Activated macrophages also strongly inhibited [3H]thymidine incorporation into the tumor cells during the 24-hr cytostatic test. When tumor cells were inoculated s.c. with activated macrophages in the Winn-type transfer assay, subsequent tumor growth was significantly inhibited. Repeated i.p. injection of the CWS seemed to enhance these antitumor activities of macrophages. The therapeutic effect of Nocardia CWS was assessed with the ascites tumor and with the solid tumor inoculated i.m. into the hind leg. In the former treatment, repeated i.p. injections completely prevented the accumulation of ascites fluid and resulted in prolongation of the survival period. The peritoneal macrophages harvested from these survivors had a strong cytolytic activity for tumor cells in the cytolytic test. In the latter treatment, repeated intratumoral injections inhibited the growth of primary tumor and prevented metastasis. Furthermore, peritoneal resident macrophages from these tumor-bearing rats treated intratumorally with the CWS were found to be cytolytic for tumor cells in the cytolytic test.