Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of ubiquitin‐mediated pathways in regulating synaptic development, axonal degeneration and regeneration: insights from fly and worm

Abstract The covalent attachment of the 76 amino acid peptide ubiquitin to target proteins is a rapid and reversible modification that regulates protein stability, activity and localization. As such, it is a potent mechanism for sculpting the synapse. Recent studies from two genetic model organisms, Caenorhabditis elegans and Drosophila, have provided mounting evidence that ubiquitin‐mediated pathways play important roles in controlling the presynaptic size, synaptic elimination and stabilization, synaptic transmission, postsynaptic receptor abundance, axonal degeneration and regeneration. While the data supporting the requirement of ubiquitination/deubiquitination for normal synaptic development and repair are compelling, detailed analyses of signalling events up‐ and downstream of these ubiquitin modifications are often challenging. This article summarizes the related research conducted in worms and flies and provides insight into the fundamental questions facing this field.
Neutrophil degranulation inhibits potential hydroxyl-radical formation. Relative impact of myeloperoxidase and lactoferrin release on hydroxyl-radical production by iron-supplemented neutrophils assessed by spin-trapping techniques.

Hydroxyl radical (.OH) formation by neutrophils in vitro requires exogenous iron. Two recent studies [Britigan, Rosen, Thompson, Chai & Cohen (1986) J. Biol. Chem. 261, 17026-17032; Winterbourn (1987) J. Clin. Invest. 78, 545-550] both reported that neutrophil degranulation could potentially inhibit the formation of . OH, but differed in their conclusions as to the responsible factor, myeloperoxidase (MPO) or lactoferrin (LF). By using a previously developed spin-trapping system which allows specific on-line detection of superoxide anion (O2-) and . OH production, the impact of MPO and LF release on neutrophil . OH production was compared. When iron-diethylenetriaminepenta-acetic acid-supplemented neutrophils were stimulated with phorbol myristate acetate or opsonized zymosan, . OH formation occurred, but terminated prematurely in spite of continued O2- generation. Inhibition of MPO by azide increased the magnitude, but not the duration, of . OH formation. No azide effect was noted when MPO-deficient neutrophils were used. Anti-LF antibody increased both the magnitude and duration of . OH generation. Pretreatment of neutrophils with cytochalasin B to prevent phagosome formation did not alter the relative impact of azide or anti-LF on neutrophil . OH production. An effect of azide or anti-LF on spin-trapped-adduct stability was eliminated as a confounding factor. These data indicate that neutrophils possess two mechanisms for limiting . OH production. Implications for neutrophil-derived oxidant damage are discussed.
Behavioral/systems/cognitive Selective Neuronal Entrainment to the Beat and Meter Embedded in a Musical Rhythm

Fundamental to the experience of music, beat and meter perception refers to the perception of periodicities while listening to music occurring within the frequency range of musical tempo. Here, we explored the spontaneous building of beat and meter hypothesized to emerge from the selective entrainment of neuronal populations at beat and meter frequencies. The electroencephalogram (EEG) was recorded while human participants listened to rhythms consisting of short sounds alternating with silences to induce a spontaneous perception of beat and meter. We found that the rhythmic stimuli elicited multiple steady state-evoked potentials (SS-EPs) observed in the EEG spectrum at frequencies corresponding to the rhythmic pattern envelope. Most importantly, the amplitude of the SS-EPs obtained at beat and meter frequencies were selectively enhanced even though the acoustic energy was not necessarily predominant at these frequencies. Furthermore, accelerating the tempo of the rhythmic stimuli so as to move away from the range of frequencies at which beats are usually perceived impaired the selective enhancement of SS-EPs at these frequencies. The observation that beat-and meter-related SS-EPs are selectively enhanced at frequencies compatible with beat and meter perception indicates that these responses do not merely reflect the physical structure of the sound envelope but, instead, reflect the spontaneous emergence of an internal representation of beat, possibly through a mechanism of selective neuronal entrainment within a resonance frequency range. Taken together, these results suggest that musical rhythms constitute a unique context to gain insight on general mechanisms of entrainment, from the neuronal level to individual level.
A Comparison of Re-ranking Methods in Digital Libraries Using User Profiles

In this paper we present a comparative study of re-ranking methods using user profiles in digital libraries which contain scientific articles. While most of present personalized search systems only use content-based methods to re-rank search results, in our work we use many different content-based and citation-based methods for this purpose. We also study many functions to combine scores computed by these methods. We conducted experiments on the test collection used in the INEX 2005 campaign to evaluate our strategies and received interesting results.
Inflammation Meets Metabolic Disease: Gut Feeling Mediated by GLP-1

Chronic diseases, such as obesity and diabetes, cardiovascular, and inflammatory bowel diseases (IBD) share common features in their pathology. Metabolic disorders exhibit strong inflammatory underpinnings and vice versa, inflammation is associated with metabolic alterations. Next to cytokines and cellular stress pathways, such as the unfolded protein response (UPR), alterations in the enteroendocrine system are intersections of various pathologies. Enteroendocrine cells (EEC) have been studied extensively for their ability to regulate gastrointestinal motility, secretion, and insulin release by release of peptide hormones. In particular, the L-cell-derived incretin hormone glucagon-like peptide 1 (GLP-1) has gained enormous attention due to its insulinotropic action and relevance in the treatment of type 2 diabetes (T2D). Yet, accumulating data indicate a critical role for EEC and in particular for GLP-1 in metabolic adaptation and in orchestrating immune responses beyond blood glucose control. EEC sense the lamina propria and luminal environment, including the microbiota via receptors and transporters. Subsequently, mediating signals by secreting hormones and cytokines, EEC can be considered as integrators of metabolic and inflammatory signaling. This review focuses on L cell and GLP-1 functions in the context of metabolic and inflammatory diseases. The effects of incretin-based therapies on metabolism and immune system are discussed and the interrelation and common features of metabolic and immune-mediated disorders are highlighted. Moreover, it presents data on the impact of inflammation, in particular of IBD on EEC and discusses the potential role of the microbiota as link between nutrients, metabolism, immunity, and disease.
Adaptive frequency sampling for radiation patterns and S-parameters of antennas

We present a fully automated method to predict the full radiation patterns and S-parameters of antennas over a large frequency bandwidth using the knowledge of the simulated results at a few frequency points. The frequency points are adaptively selected in regions of fast variations of radiation pattern and S-parameters, as well as in large unsampled regions. The method has a built-in absolute error control measure and is guaranteed to converge to an accurate model in a modest number of iterations. The proposed method is validated through pertinent examples.
Inhibitory effect of morphine on yawning induced by cholinoceptor and dopamine D2 receptor activation in rats

1 Bromocriptine (2, 4 and 8 mg kg−1, i.p.), physostigmine (0.05, 0.1 and 0.2 mg kg−1, i.p.) and pilocarpine (1, 3 and 5 mg kg−1, i.p.) induced dose‐dependent yawning in rats. 2 These responses were reduced in a dose‐dependent manner by pretreatment with morphine. 3 The inhibitory effect of morphine was reversed by naloxone. 4 Naloxone alone induced slight but significant yawning. 5 The present results suggest that morphine inhibits yawning in rats at an opiate receptor downstream from the sites at which cholinoceptor and dopamine D2 activation induce yawning. The anatomical location of these sites remains to be established.
Use of direct numerical simulation (DNS) data to investigate spatial resolution issues in measurements of wall-bounded turbulence

The effect of limited spatial resolution for hot-wire anemometry (HWA) is investigated by analysing the two-dimensional energy spectra from direct numerical simulation (DNS) of turbulent channel flow at Reτ ≈ 950. Various spanwise filter lengths are applied to the streamwise velocity components in order to mimic the limited spatial resolution of a single-normal hot-wire experiment. Clear attenuation of the small-scale DNS energy is observed as the filter length is increased and good agreement is noted between the missing energy from filtered DNS and that from hot-wire experiments over a range of sensing lengths. The missing energy in the near-wall region is shown to be highly anisotropic in nature, thus bringing into question existing correction schemes that rely on small-scale isotropic flow assumptions. An empirical model of the missing streamwise component energy spectra is formulated, as a function of wire length, and is shown to be useful as a new correction function for the missing energy and streamwise turbulence intensity at the near-wall energetic peak.
VOICES FROM THE FIELD Preschool Programs: Early Learning and Child Care

Child care is known by a number of terms, including Early Childhood Education and Care; Early Learning and Care, and Early Childhood Development. The Child Care Advocacy Association of Canada (CCAAC) defines child care as a non-compulsory program that supports the optimal development and learning of children aged 0-12 years. At the same time, it enables parents to work, study and care for other family members and participate in their community; it provides supports and resources to help parents become active participants in their children’s early learning, and promotes women’s equality.
Cache Performance Study of Portfolio-Based Parallel CDCL SAT Solvers

Parallel SAT solvers are becoming mainstream. Their performance has made them win the past two SAT competitions consecutively and are in the limelight of research and industry. The problem is that it is not known exactly what is needed to make them perform even better; that is, how to make them solve more problems in less time. Also, it is also not know how well they scale in massive multi-core environments which, predictably, is the scenario of comming new hardware. In this paper we show that cache contention is a main culprit of a slowing down in scalability, and provide empirical results that for some type of searches, physically sharing the clause Database between threads is beneficial.
Anti‐Toll‐like receptor 2 and 4 antibodies suppress inflammatory response in mice

Toll‐like receptors (TLRs) 2 and 4 recognize different endogenous and exogenous agonists and play a distinct role in infection and inflammation. However, their ultimate effect in a given infectious and inflammatory disease is less understood. We produced polyclonal anti‐murine TLR2 and TLR4 antibodies and investigated their effect on cutaneous leishmaniasis and inflammatory arthritis. Administration of these antibodies to susceptible BALB/c mice, infected in the footpad with Leishmania major, reduced footpad swelling but not the parasite load compared with mice treated with control IgG. The antibodies synergistically reduced leishmanial‐specific T‐cell proliferation, T helper type 1 and type 2 cytokine production, specific IgG1 and IgG2a antibody synthesis, and T‐cell receptor and co‐stimulatory molecule expression on dendritic cells in infected mice. We then tested the effect of these antibodies on collagen‐induced arthritis (CIA) in DBA/1 mice, a classic model of chronic inflammation. Both antibodies markedly suppressed the development of clinical parameters with concomitant reduction of pro‐inflammatory cytokine production. These data therefore suggest that anti‐TLR2 and 4 antibodies may have a synergistic therapeutic effect on inflammatory disease in vivo.
A threat-model for building and home automation

Security and privacy are very important assets within building and home automation because the System Control Unit (SCU) stores and processes a huge amount of data about the inhabitants or employees of the building. This data is necessary for managing the building and increasing the convenience of persons within. But this data can also be used to create a movement profile, monitor working times, and draw conclusions about people's health situation. Modern smart home implementations also control many actuators within the building including doors, windows, locks, and fire extinguisher. These increase security and safety, but unauthorized control can reduce the security and can even be harmful to persons. Therefore, identifying the different security and privacy threats is very important and helps system engineers and system managers to develop and deploy secure systems. This work presents an abstract model of a building automation system and some attack trees which simplify threat identification. Attack trees are common in secure software development and secure system deployment. An example smart home deployment is evaluated using the proposed model and attack trees to show the feasibility.
Chapter 1 Recognizing Textual Entailment

Since 2005, researchers have worked on a broad task called Recognizing Textual Entailment (RTE), which is designed to focus efforts on general textual inference capabilities, but without constraining participants to use a specific representation or reasoning approach. There have been promising developments in this sub-field of Natural Language Processing (NLP), with systems showing steady improvement, and investigations of a range of approaches to the problem. A number of researchers appear to have converged on some defining characteristics of the problem, and on characteristics of practical approaches to solving it. RTE solutions have been shown to be of practical use in other NLP applications, and other grand Natural Language Understanding (NLU) challenges, such as Learning by Reading [27] and Machine Reading [43] have emerged that will require similar problems to be solved. It is an exciting time to be working in this area. Textual Inference is a key capability for improving performance in a wide range of NLP tasks, particularly those which can benefit from integrating background knowledge. Performance of Question-Answering systems, which can be thought of as potentially the next generation of search engines, is limited, especially outside the class of factoid questions; and the task of extracting facts of interest (such as “People who have worked for Company X”) from a collection of plain text documents (such as newspaper articles) may require significant abstraction, synthesis, and application of world knowledge on the part of a human reader – and therefore
High-throughput sequencing offers insight into mechanisms of resource partitioning in cryptic bat species

Sympatric cryptic species, characterized by low morphological differentiation, pose a challenge to understanding the role of interspecific competition in structuring ecological communities. We used traditional (morphological) and novel molecular methods of diet analysis to study the diet of two cryptic bat species that are sympatric in southern England (Plecotus austriacus and P. auritus) (Fig. 1). Using Roche FLX 454 (Roche, Basel, CH) high-throughput sequencing (HTS) and uniquely tagged generic arthropod primers, we identified 142 prey Molecular Operational Taxonomic Units (MOTUs) in the diet of the cryptic bats, 60% of which were assigned to a likely species or genus. The findings from the molecular study supported the results of microscopic analyses in showing that the diets of both species were dominated by lepidopterans. However, HTS provided a sufficiently high resolution of prey identification to determine fine-scale differences in resource use. Although both bat species appeared to have a generalist diet, eared-moths from the family Noctuidae were the main prey consumed. Interspecific niche overlap was greater than expected by chance (Ojk = 0.72, P < 0.001) due to overlap in the consumption of the more common prey species. Yet, habitat associations of nongeneralist prey species found in the diets corresponded to those of their respective bat predator (grasslands for P. austriacus, and woodland for P. auritus). Overlap in common dietary resource use combined with differential specialist prey habitat associations suggests that habitat partitioning is the primary mechanism of coexistence. The performance of HTS is discussed in relation to previous methods of molecular and morphological diet analysis. By enabling species-level identification of dietary components, the application of DNA sequencing to diet analysis allows a more comprehensive comparison of the diet of sympatric cryptic species, and therefore can be an important tool for determining fine-scale mechanisms of coexistence.
Synthetic miR-34a Mimics as a Novel Therapeutic Agent for Multiple Myeloma: In Vitro and In Vivo Evidence

Purpose: Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a. Experimental Design: Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo. Results: Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown in vivo in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-synth-hu mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity. Conclusions: Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a–based treatment strategies in MM patients. Clin Cancer Res; 18(22); 6260–70. ©2012 AACR.
Identification and Characterization of New Molecular Partners for the Protein Arginine Methyltransferase 6 (PRMT6)

PRMT6 is a protein arginine methyltransferase that has been implicated in transcriptional regulation, DNA repair, and human immunodeficiency virus pathogenesis. Only few substrates of this enzyme are known and therefore its cellular role is not well understood. To identify in an unbiased manner substrates and potential regulators of PRMT6 we have used a yeast two-hybrid approach. We identified 36 new putative partners for PRMT6 and we validated the interaction in vivo for 7 of them. In addition, using in vitro methylation assay we identified 4 new substrates for PRMT6, extending the involvement of this enzyme to other cellular processes beyond its well-established role in gene expression regulation. Holistic approaches create molecular connections that allow to test functional hypotheses. The assembly of PRMT6 protein network allowed us to formulate functional hypotheses which led to the discovery of new molecular partners for the architectural transcription factor HMGA1a, a known substrate for PRMT6, and to provide evidences for a modulatory role of HMGA1a on the methyltransferase activity of PRMT6.
Deterministic and Stochastic Simulations of Simple Genetic Circuits

We analyze three simple genetic circuits which involve transcriptional regulation and feedback: the autorepressor, the switch and the repressilator, that consist of one, two and three genes, respectively. Such systems are commonly simulated using rate equations, that account for the concentrations of the mRNAs and proteins produced by these genes. Rate equations are suitable when the concentrations of the relevant molecules in a cell are large and fluctuations are negligible. However, when some of the proteins in the circuit appear in low copy numbers, fluctuations become important and the rate equations fail. In this case stochastic methods, such as direct numerical integration of the master equation or Monte Carlo simulations are required. Here we present deterministic and stochastic simulations of the autorepressor, the switch and the repressilator. We show that fluctuations give rise to quantitative and qualitative changes in the dynamics of these systems. In particular, we demonstrate a fluctuations-induced bistability in a variant of the genetic switch and and noisy oscillations obtained in the repressilator circuit.
A rare cause of hypocalcemia

Background: Many factors influence serum calcium concentration, but the major determinants of calcium homeostatsis are parathyroid hormone (PTH), vitamin D, the ionized calcium, and phosphate [1]. Therefore, deranged calcium metabolism is often seen in the presence of disordered parathyroid hormone (PTH) and/or vitamin D actions. Among these causes is end-organ resistance to the biological effect of parathyroid hormone. Case Report: In this paper, we report a case of a patient who presented with flu like symptoms and incidental finding of hypocalcemia that is consistent with parathyroid hormone resistance. Conclusions: Familial causes of hypocalcemia, although rare, should be thought about after ruling out the other common causes of hypocalcemia.
Image Feature Learning for Cold Start Problem in Display Advertising

In online display advertising, state-of-the-art Click Through Rate(CTR) prediction algorithms rely heavily on historical information, and they work poorly on growing number of new ads without any historical information. This is known as the the cold start problem. For image ads, current state-of-the-art systems use handcrafted image features such as multimedia features and SIFT features to capture the attractiveness of ads. However, these handcrafted features are task dependent, inflexible and heuristic. In order to tackle the cold start problem in image display ads, we propose a new feature learning architecture to learn the most discriminative image features directly from raw pixels and user feedback in the target task. The proposed method is flexible and does not depend on human heuristic. Extensive experiments on a real world dataset with 47 billion records show that our feature learning method outperforms existing handcrafted features significantly, and it can extract discriminative and meaningful features.