Miracle-dz/UniFAR-FTUs huggingface dataset:
Using LC3 to monitor autophagy flux in the retinal pigment epithelium

Autophagy is a highly conserved housekeeping pathway that plays a critical role in the removal of aged or damaged intracellular organelles and their delivery to lysosomes for degradation.1,2 Autophagy begins with the formation of membranes arising in part from the endoplasmic reticulum, that elongate and fuse engulfing cytoplasmic constituents into a classic double-membrane bound nascent autophagosome. These early autophagosomes undergo a stepwise maturation process to form the late autophagosome or amphisome that ultimately fuses with a lysosome. Efficient autophagy is dependent on an equilibrium between the formation and elimination of autophagosomes; thus, a deficit in any part of this pathway will cause autophagic dysfunction. Autophagy plays a role in aging and age-related diseases. 1,2,7 However, few studies of autophagy in retinal disease have been reported. Recent studies show that autophagy and changes in lysosomal activity are associated with both retinal aging and age-related macular degeneration (AMD). 3,4 This article describes methods which employ the target protein LC3 to monitor autophagic flux in retinal pigment epithelial cells. During autophagy, the cytosolic form of LC3 (LC3-I) is processed and recruited to the phagophore where it undergoes site specific proteolysis and lipidation near the C terminus to form LC3-II.5 Monitoring the formation of cellular autophagosome puncta containing LC3 and measuring the ratio of LC3-II to LC3-I provides the ability to monitor autophagy flux in the retina.
A reoptimized GROMOS force field for hexopyranose‐based carbohydrates accounting for the relative free energies of ring conformers, anomers, epimers, hydroxymethyl rotamers, and glycosidic linkage conformers

This article presents a reoptimization of the GROMOS 53A6 force field for hexopyranose‐based carbohydrates (nearly equivalent to 45A4 for pure carbohydrate systems) into a new version 56ACARBO (nearly equivalent to 53A6 for non‐carbohydrate systems). This reoptimization was found necessary to repair a number of shortcomings of the 53A6 (45A4) parameter set and to extend the scope of the force field to properties that had not been included previously into the parameterization procedure. The new 56ACARBO force field is characterized by: (i) the formulation of systematic build‐up rules for the automatic generation of force‐field topologies over a large class of compounds including (but not restricted to) unfunctionalized polyhexopyranoses with arbritrary connectivities; (ii) the systematic use of enhanced sampling methods for inclusion of experimental thermodynamic data concerning slow or unphysical processes into the parameterization procedure; and (iii) an extensive validation against available experimental data in solution and, to a limited extent, theoretical (quantum‐mechanical) data in the gas phase. At present, the 56ACARBO force field is restricted to compounds of the elements C, O, and H presenting single bonds only, no oxygen functions other than alcohol, ether, hemiacetal, or acetal, and no cyclic segments other than six‐membered rings (separated by at least one intermediate atom). After calibration, this force field is shown to reproduce well the relative free energies of ring conformers, anomers, epimers, hydroxymethyl rotamers, and glycosidic linkage conformers. As a result, the 56ACARBO force field should be suitable for: (i) the characterization of the dynamics of pyranose ring conformational transitions (in simulations on the microsecond timescale); (ii) the investigation of systems where alternative ring conformations become significantly populated; (iii) the investigation of anomerization or epimerization in terms of free‐energy differences; and (iv) the design of simulation approaches accelerating the anomerization process along an unphysical pathway. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011
A new rank correlation coefficient for information retrieval

In the field of information retrieval, one is often faced with the problem of computing the correlation between two ranked lists. The most commonly used statistic that quantifies this correlation is Kendall's Τ. Often times, in the information retrieval community, discrepancies among those items having high rankings are more important than those among items having low rankings. The Kendall's Τ statistic, however, does not make such distinctions and equally penalizes errors both at high and low rankings. In this paper, we propose a new rank correlation coefficient, AP correlation (Τap), that is based on average precision and has a probabilistic interpretation. We show that the proposed statistic gives more weight to the errors at high rankings and has nice mathematical properties which make it easy to interpret. We further validate the applicability of the statistic using experimental data.
Tolfenamic Acid Inhibits the Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma: Involvement of p38-Mediated Down-Regulation of Slug

Purpose Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to exhibit antitumor effects in various cancers apart from nasopharyngeal cancer (NPC). NPC exhibits high invasiveness, as well as metastatic potential, and patients continue to suffer from residual, recurrent, or metastatic disease even after chemoradiation therapy. Therefore, new treatment strategies are needed for NPC. In this study, we investigated the efficacy and molecular mechanisms of TA in NPC treatment. Materials and Methods TA-induced cell death was detected by cell viability assay in the NPC cell lines, HNE1 and HONE1. Wound healing assay, invasion assay, and Western blot analysis were used to evaluate the antitumor effects of TA in NPC cell lines. Results Treatment with TA suppressed the migration and invasion of HNE1 and HONE1 cells. Hepatocyte growth factor enhanced the proliferation, migration, and invasion abilities of NPC cells. This enhancement was successfully inhibited by TA treatment. Treatment with TA increased phosphorylation of p38, and the inhibition of p38 with SB203580 reversed the cytotoxic, anti-invasive, and anti-migratory effects of TA treatment in NPC cell lines. Moreover, inhibition of p38 also reversed the decrease in expression of Slug that was induced by TA treatment. Conclusion In conclusion, the activation of p38 plays a role in mediating TA-induced cytotoxicity and inhibition of invasion and migration via down-regulation of Slug.
Moderate-Temperature Clusters of Galaxies from the RDCS and the High-Redshift Luminosity-Temperature Relation

We present our discovery observations and analysis of RDCS 1317+2911, z = 0.805, and RDCS 1350+6007, z = 0.804, two clusters of galaxies identified through X-ray emission in the ROSAT Deep Cluster Survey (RDCS). RDCS 1317+2911 has an unusual morphology in our Chandra observations, with an asymmetric surface brightness profile and a bend in the distribution of X-ray emission. In contrast, RDCS 1350+6007 appears to be more like low-redshift clusters, with β = 0.49 ± 0.06 and rcore = 165 ± 5 kpc (Ωm = 0.3, ΩΛ = 0.7, H0 = 65 km s-1 Mpc-1), though it also has an elliptical, slightly asymmetric surface brightness profile. We find a temperature of 3.7 keV and a bolometric luminosity of 8.2 × 1043 ergs s-1 for RDCS 1317+2911, and a temperature of 4.9 keV and a bolometric luminosity of 4.1 × 1044 ergs s-1 for RDCS 1350+6007. Our weak-lensing analysis of RDCS 1350+6007 confirms the general shape of the inner density profile but predicts twice the mass of the model based on the X-ray profile. There are two possibilities for this discrepancy: either there is a significant amount of mass near the redshift of the cluster that has not yet fallen into the potential well and shock-heated the gas, or, as we only see the X-ray emission from the core of the cluster, our β model fails to describe the true shape of the underlying potential. We combine the X-ray luminosities and temperatures for RDCS clusters of galaxies with such measurements of other clusters at high redshift (z > 0.7) and fit the luminosity-temperature relation. We find no statistically significant evolution in the slope or zero point of this relation at zmedian = 0.83. This result is in agreement with models of intracluster medium evolution with significant preheating or high initial entropy values. Quantifying the bolometric luminosity-temperature relation as L = L6(1 + z)A(T/6 keV)α, we find α = 2.9 ± 0.4, L6 = 8.7 ± 0.9 × 1044 ergs s-1 and A = 0.3 ± 0.2, or A = 0.4 ± 0.2, depending on which low-redshift luminosity-temperature relation we compare with. With this result, we rule out at the 5 σ level the self-similar scaling model of intracluster medium evolution. We discuss how low-temperature, high-redshift clusters of galaxies will allow us to improve on this result, and we announce the discovery of two such objects, CXOU J0910.1+5419 and CXOU J1316.9+2914.
Parsing Universal Dependency Treebanks using Neural Networks and Search-Based Oracle Milan

We describe a transition-based, non-projective dependency parser which uses a neural network classiﬁer for prediction and requires no feature engineering. We propose a new, search-based oracle, which improves parsing accuracy similarly to a dynamic oracle, but is applicable to any transition system, such as the fully non-projective swap system, contrary to dynamic oracles, which are speciﬁc for each transition system and usually quite complex. The parser has excellent parsing speed, compact models, and achieves high accuracy without requiring any additional resources such as raw corpora. We tested it on all 37 treebanks of the Universal Dependencies project. The C++ implementation of the parser is being released as an open-source tool.
Hierarchical linear modeling: Applications to social work research

Summary Using examples and nomenclature familiar to social workers, this article provides a brief, nontechnical introduction to hierarchically structured data and multilevel modeling. Findings Data structured hierarchically consist of units clustered within higher-level groups, such as individuals nested within families and families nested within counties. Longitudinal observations can also be thought of as having a hierarchical structure, with repeated measures clustered within a given individual. Because lower-level units within a group tend to be systematically more similar to one another than to units from another group, there is often a need to make statistical adjustments for within-group dependence. Hierarchical or multilevel modeling provides a method for researchers to account for possible within-group correlations while also explicitly modeling group-level attributes and membership, acknowledging the potential importance of contextual effects on lower-level outcomes. Applications Although hierarchical or multilevel modeling has been discussed (and used) extensively by researchers in other disciplines and fields, it has been more recently adopted as a modeling tool by social work researchers. Because hierarchical modeling is now a commonly employed technique, it is important that those in the field have a basic understanding of these models so that they remain informed consumers of research. This article offers a conceptual overview of hierarchical linear models written for social work practitioners, policy-makers, and other consumers of social welfare research.
When directional selection reduces geographic variation in traits mediating species interactions

Although we often focus on the causes of geographic variation, understanding processes that act to reduce geographic variation is also important. Here, we consider a process whereby adaptive foraging across the landscape and directional selection exerted by a conifer seed predator, the common crossbill (Loxia curvirostra), potentially act to homogenize geographic variation in the defensive traits of its prey. We measured seed predation and phenotypic selection exerted by crossbills on black pine (Pinus nigra) at two sites in the Pindos Mountains, Greece. Seed predation by crossbills was over an order of magnitude higher at the site where cone scale thickness was significantly thinner, which was also the cone trait that was the target of selection at the high predation site. Additional comparisons of selection differentials demonstrate that crossbills exert selection on black pine that is consistent in form across space and time, and increases in strength with increasing seed predation. If predators distribute themselves in relation to the defensive traits of their prey and the strength of selection predators exert is proportional to the amount of predation, then predators may act to homogenize trait variation among populations of their prey in a process analogous to coevolutionary alternation with escalation.
The Semantic Representation of Actresses and Actors

The present study explores the structure of moviegoers knowledge about actors and actresses considered as categories of semantic knowledge. For this purpose, participants generated either names of actors or names of actresses and, in a second phase of the experiment, judged their responses in terms of aesthetic preference and frequency of instantiation. Both categories exhibited a graded structure in terms of typicality but while frequency of instantiation was the strongest response determinant for actresses, aesthetic preference was the strongest response determinant for actors. Moviegoing frequency was positively related to the number of names produced for actors but not for actresses. Main conclusions suggest that actresses and actors are relevant semantic categories for moviegoers. Possible factors for differences between the two categories are also discussed.
APEX: an adaptive path index for XML data

The emergence of the Web has increased interests in XML data. XML query languages such as XQuery and XPath use label paths to traverse the irregularly structured data. Without a structural summary and efficient indexes, query processing can be quite inefficient due to an exhaustive traversal on XML data. To overcome the inefficiency, several path indexes have been proposed in the research community. Traditional indexes generally record all label paths from the root element in XML data. Such path indexes may result in performance degradation due to large sizes and exhaustive navigations for partial matching path queries start with the self-or-descendent axis("//"). In this paper, we propose APEX, an adaptive path index for XML data. APEX does not keep all paths starting from the root and utilizes frequently used paths to improve the query performance. APEX also has a nice property that it can be updated incrementally according to the changes of query workloads. Experimental results with synthetic and real-life data sets clearly confirm that APEX improves query processing cost typically 2 to 54 times better than the existing indexes, with the performance gap increasing with the irregularity of XML data.
Chapter I Push and Pull Systems

Data broadcasting has emerged as an efficient way for the dissemination of information over asymmetric wireless environments where the needs of the various users of the data items are usually overlapping. In such environments, data broadcasting stands to be an efficient solution since the broadcast of a single information item is likely to satisfy a possibly large number of users. Communications asymmetry is due to a number of facts, the most important being equipment, network, and application asymmetry. This chapter starts with a discussion of preliminary issues and terminology for asymmetric environments for data broadcasting. The chapter then discusses broadcast schedule construction for systems employing a single broadcast channel, schedule construction for systems employing multiple broadcast channels, and schedule construction for systems that take into account the effect of reception errors. It then presents an 2 Nicopolitidis, Papadimitriou, & Pomportsis Copyright © 2005, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. is prohibited. algorithm that tries to provide better support for clients whose access patterns deviate a lot form the overall access pattern of the client population. It also presents algorithms for environments where item requests by clients are dropped if not served in a certain time period. Brief comments on issues that affect performance of the discussed data broadcasting methods are also made.
Multitask Visual Learning Using Genetic Programming

We propose a multitask learning method of visual concepts within the genetic programming (GP) framework. Each GP individual is composed of several trees that process visual primitives derived from input images. Two trees solve two different visual tasks and are allowed to share knowledge with each other by commonly calling the remaining GP trees (subfunctions) included in the same individual. The performance of a particular tree is measured by its ability to reproduce the shapes contained in the training images. We apply this method to visual learning tasks of recognizing simple shapes and compare it to a reference method. The experimental verification demonstrates that such multitask learning often leads to performance improvements in one or both solved tasks, without extra computational effort.
influenza virus vaccine induces broadly reactive antibody responses 1 against H 7 N 9 in humans 2

17 18 Emerging H7N9 influenza virus infections in Asia have once more spurred the development of effective 19 pre-pandemic H7 vaccines. However, many vaccines based on avian influenza viruses including H7 are 20 poorly immunogenic as measured by traditional correlates of protection. Here we re-evaluated sera 21 from an H7N1 human vaccine trial performed in 2006. We examined cross-reactive antibody responses 22 CVI Accepts, published online ahead of print on 18 June 2014 Clin. Vaccine Immunol. doi:10.1128/CVI.00272-14 Copyright © 2014, American Society for Microbiology. All Rights Reserved. on O cber 0, 2017 by gest httpcvi.asm . rg/ D ow nladed fom
Angiotensin II Type 1 Receptor Blockade Does Not Enhance Apoptotic Cell Death During Ischemia and Reperfusion in Humans In Vivo

Despite the theoretical benefits, angiotensin II type 1 receptor antagonists seem to enhance rather than reduce morbidity and mortality after myocardial infarction compared with angiotensin-converting enzyme inhibitors. This may result from unopposed angiotensin II type 2 receptor stimulation, which is associated with enhanced apoptotic cell death and increased infarct size. We studied whether the clinical effectiveness of irbesartan is hampered by enhanced apoptotic activity, detected by exposition of phosphatidylserines, during ischemia and reperfusion in humans in vivo. Twenty healthy male volunteers were randomized to a 1-week treatment with irbesartan (300 mg/d) or placebo in a double-blind fashion. After treatment, all participants underwent 10 minutes of ischemic exercise of the nondominant forearm. Upon reperfusion, Tc-99m-labeled Annexin A5 was administered, and 1 and 4 hours afterward, both hands were scanned using a gamma camera. Targeting of annexin A5, expressed as the percentage difference in radioactivity in the area of interest (thenar muscle) between experimental and control hand, did not differ between participants treated with irbesartan or placebo. Therefore, irbesartan does not enhance phosphatidylserine exposition in humans in vivo. The results of this study do not support enhanced apoptotic activity after treatment with irbesartan in a setting of ischemia and reperfusion.
Resolving cosmic structure formation with the Millennium-II simulation

We present the Millennium-II Simulation (MS-II), a very large N-body simulation of dark matter evolution in the concordance A cold dark matter (ACDM) cosmology. The MS-II assumes the same cosmological parameters and uses the same particle number and output data structure as the original Millennium Simulation (MS), but was carried out in a periodic cube one-fifth the size (100 h - 1 Mpc) with five times better spatial resolution (a Plummer equivalent softening of 1.0 h -1 kpc) and with 125 times better mass resolution (a particle mass of 6.9 x 10 6 h -1 M ⊙ ). By comparing results at MS and MS-II resolution, we demonstrate excellent convergence in dark matter statistics such as the halo mass function, the subhalo abundance distribution, the mass dependence of halo formation times, the linear and non-linear autocorrelations and power spectra, and halo assembly bias. Together, the two simulations provide precise results for such statistics over an unprecedented range of scales, from haloes similar to those hosting Local Group dwarf spheroidal galaxies to haloes corresponding to the richest galaxy clusters. The 'Milky Way' haloes of the Aquarius Project were selected from a lower resolution version of the MS-II and were then resimulated at much higher resolution. As a result, they are present in the MS-II along with thousands of other similar mass haloes. A comparison of their assembly histories in the MS-II and in resimulations of 1000 times better resolution shows detailed agreement over a factor of 100 in mass growth. We publicly release halo catalogues and assembly trees for the MS-II in the same format within the same archive as those already released for the MS.
Inhibition of Autophagic Flux by Salinomycin Results in Anti-Cancer Effect in Hepatocellular Carcinoma Cells

Salinomycin raised hope to be effective in anti-cancer therapies due to its capability to overcome apoptosis-resistance in several types of cancer cells. Recently, its effectiveness against human hepatocellular carcinoma (HCC) cells both in vitro and in vivo was demonstrated. However, the mechanism of action remained unclear. Latest studies implicated interference with the degradation pathway of autophagy. This study aimed to determine the impact of Salinomycin on HCC-autophagy and whether primary human hepatocytes (PHH) likewise are affected. Following exposure of HCC cell lines HepG2 and Huh7 to varying concentrations of Salinomycin (0–10 µM), comprehensive analysis of autophagic activity using western-blotting and flow-cytometry was performed. Drug effects were analyzed in the settings of autophagy stimulation by starvation or PP242-treatment and correlated with cell viability, proliferation, apoptosis induction, mitochondrial mass accumulation and reactive oxygen species (ROS) formation. Impact on apoptosis induction and cell function of PHH was analyzed. Constitutive and stimulated autophagic activities both were effectively suppressed in HCC by Salinomycin. This inhibition was associated with dysfunctional mitochondria accumulation, increased apoptosis and decreased proliferation and cell viability. Effects of Salinomycin were dose and time dependent and could readily be replicated by pharmacological and genetic inhibition of HCC-autophagy alone. Salinomycin exposure to PHH resulted in transient impairment of synthesis function and cell viability without apoptosis induction. In conclusion, our data suggest that Salinomycin suppresses late stages of HCC-autophagy, leading to impaired recycling and accumulation of dysfunctional mitochondria with increased ROS-production all of which are associated with induction of apoptosis.