Miracle-dz/UniFAR-FTUs huggingface dataset:
Strawberry notch homolog 2 is a novel inflammatory response factor predominantly but not exclusively expressed by astrocytes in the central nervous system

Interleukin‐6 (IL‐6) participates in the host response to injury and infection in the central nervous system (CNS). We identified strawberry notch homolog 2 (Sbno2) as an IL‐6‐stimulated gene in murine astrocytes. Sbno2 is a mouse homolog of the sno gene in Drosophila but little is known about the regulation or function of the mammalian gene. Here we examined the regulation of the Sbno2 gene in astrocytes in vitro and in the murine CNS following systemic endotoxin administration. In murine and human cultured astrocytes, Sbno2 gene expression was significantly upregulated in a dose‐ and time‐dependent fashion by hyper‐IL‐6 (IL‐6 + soluble IL‐6 receptor). The level of Sbno2 mRNA was also upregulated significantly in murine astrocytes by other glycoprotein130 cytokine‐family members and the pro‐inflammatory cytokines interleukin‐1 beta and tumor necrosis factor alpha. These changes were reflected by corresponding alterations in the level of the SBNO2 protein. Inhibiting protein synthesis resulted in higher Sbno2 mRNA and did not abolish the upregulation of Sbno2 mRNA mediated by hyper‐IL‐6. Inhibition of transcription led to a rapid reduction in hyper‐IL‐6‐induced Sbno2 mRNA in astrocytes suggesting that the Sbno2 mRNA is quite unstable. Following intra‐peritoneal lipopolysaccharide injection in mice, Sbno2 mRNA levels in the brain were significantly increased. Cellular localization studies revealed that this increase in Sbno2 mRNA occurred predominantly in astrocytes and in the choroid plexus and in some microglia, endothelial cells, and neurons. These findings are consistent with SBNO2 functioning as an acute inflammatory response gene in astrocytes as well as other cells in the CNS. GLIA 2015;63:1738–1752
Influence of Pre-Freezing Temperature on the Corneal Endothelial Cytocompatibility and Cell Delivery Performance of Porous Hyaluronic Acid Hydrogel Carriers

The development of porous hyaluronic acid (HA) hydrogels for corneal endothelial tissue engineering is attractive because they can be used as functional cell delivery carriers to help in the reconstruction of damaged areas. The purpose of this study was to investigate the corneal endothelial cytocompatibility and cell delivery performance of porous HA hydrogel biomaterials fabricated at different pre-freezing temperatures. As compared to their counterparts prepared at −80 °C, the HA samples fabricated at higher pre-freezing temperature (i.e., 0 °C) exhibited a larger pore size and higher porosity, thereby leading to lower resistance to glucose permeation. Live/dead assays and gene expression analyses showed that the restricted porous structure of HA carriers decreases the viability and ionic pump function of cultured corneal endothelial cells (CECs). The results also indicated that the porous hydrogel biomaterials fabricated at high pre-freezing temperature seem to be more compatible with rabbit CECs. In an animal model of corneal endothelial dysfunction, the wounded rabbit corneas receiving bioengineered CEC sheets and restricted porous-structured HA carriers demonstrated poor tissue reconstruction. The therapeutic efficacy of cell sheet transplants can be improved by using carrier materials prepared at high pre-freezing temperature. Our findings suggest that the cryogenic operation temperature-mediated pore microstructure of HA carriers plays an important role in corneal endothelial cytocompatibility and cell delivery performance.
Outcomes Assessment following Treatment of Spasmodic Dysphonia with Botulinum Toxin

Spasmodic dysphonia (SD), a disabling focal dystonia involving the laryngeal musculature, is most commonly treated by the intramuscular injection of botulinum toxin (BTX). Although the treatment is well tolerated and generally produces clinical voice improvement, it has never been statistically shown to alter the patient's perception of voice quality or general health. Declining resources for medical care mandate that treatment outcomes be documented. A prospective analysis of the effects of BTX on the patient's perception of voice and general health was undertaken. The Voice Handicap Index (VHI) and Short Form 36 (SF-36) surveys were administered to patients before treatment and 1 month after. Pretreatment and posttreatment scores were analyzed with a Student's t-test. On the VHI, improvements in the patients' perception of their functional, physical, and emotional voice handicap reached statistical significance (p ≤ .0005). On the SF-36, patients had statistically significant improvements in mental health (p ≤ .03) and social functioning (p ≤ .04). Treatment of SD with BTX significantly lessened the patients' perception of dysphonia. In addition, it improved their social functioning and their perception of their mental health. These outcome measures justify the continued treatment of SD with BTX.
Endotoxin fever in granulocytopenic rats: evidence that brain cyclooxygenase‐2 is more important than circulating prostaglandin E2

PGE2 is a recognized mediator of many fevers, and cyclooxygenase (COX) is the major therapeutic target for antipyretic therapy. The source, as well as the site of action of PGE2, as an endogenous pyrogen, is widely accepted as being central, but PGE2 in the circulation, possibly from leukocytes, may also contribute to the development of fever. However, bacterial infections are important causes of high fever in patients receiving myelosuppressive chemotherapy, and such fevers persist despite the use of COX inhibitors. In the study reported here, the febrile response to bacterial LPS was measured in rats made leukopenic by cyclophosphamide. A striking increase in LPS fever occurred in these granulocytopenic rats when compared with febrile responses in normal animals. Unlike LPS fever in normal rats, fever in granulocytopenic rats was neither accompanied by an increase in blood PGE2 nor inhibited by ibuprofen. Both leukopenic and normal rats showed LPS‐induced COX‐2‐immunoreactivity in cells associated with brain blood vessels. Furthermore, LPS induced an increase of PGE2 in cerebrospinal fluid. Induction of COX‐2‐expression and PGE2 production was inhibited by ibuprofen in normal but not in leukopenic rats. Although the results presented are, in part, confirmatory, they add new information to this field and open a number of important questions as yet unresolved. Overall, the present results indicate that, in contrast to immunocompetent rats, leukocytes and/or other mechanisms other than PGE2 are implicated in the mechanisms restricting and reducing the enhanced febrile response to endotoxin in immunosuppressed hosts.
Comprehensive Characterization of Mouse UDP-Glucuronosyltransferase (Ugt) Belonging to the Ugt2b Subfamily: Identification of Ugt2b36 as the Predominant Isoform Involved in Morphine Glucuronidation

UDP-Glucuronosyltransferases (UGTs) are classified into three subfamilies in mice: Ugt1a, 2b, and 2a. In the Ugt1a subfamily, Ugt1a1 and 1a6 appear to correspond to human UGT1A1 and 1A6. The mouse is an important animal for its use in investigations, but the substrate specificities of Ugt isoforms belonging to the 2b subfamily in mice remain largely unknown. To address this issue, we characterized the substrate specificity of all isoforms of the Ugt2b subfamily expressed in the mouse liver. The cDNAs of Ugt1a1, Ugt2a3, and all the Ugt2b isoforms expressed in the liver were reverse-transcribed from the total RNA of male FVB-mouse livers and then amplified. A baculovirus-Sf9 cell system for expressing each Ugt was established. Of all the Ugts examined, Ugt2b34, 2b36, and 2b37 exhibited the ability to glucuronidate morphine with Ugt2b36, the most active in this regard. Ugt1a1, but also Ugt2b34, 2b36, and 2b37 to a lesser extent, preferentially catalyzed the glucuronidation of 17β-estradiol on the 3-hydroxyl group (E3G). With these isoforms, E3G formation by Ugt1a1 was efficient; however, Ugt2b5 exhibited a preference for the 17β-hydroxyl group (E17G). Ugt2b1 and Ugt2a3 formed comparable levels of E3G and E17G. Ugt2b1 and 2b5 were the only isoforms involved in chloramphenicol glucuronidation. As Ugt2b36 is highly expressed in the liver, it is most likely that Ugt2b36 is a major morphine Ugt in mouse liver. Regarding E3G formation, Ugt1a1, like the human homolog, seems to play an important role in the liver.
Constructing travel itineraries from tagged geo-temporal breadcrumbs

Vacation planning is a frequent laborious task which requires skilled interaction with a multitude of resources. This paper develops an end-to-end approach for constructing intra-city travel itineraries automatically by tapping a latent source reflecting geo-temporal breadcrumbs left by millions of tourists. In particular, the popular rich media sharing site, Flickr, allows photos to be stamped by the date and time of when they were taken, and be mapped to Points Of Interest (POIs) by latitude-longitude information as well as semantic metadata (e.g., tags) that describe them. Our extensive user study on a "crowd-sourcing" marketplace (Amazon Mechanical Turk), indicates that high quality itineraries can be automatically constructed from Flickr data, when compared against popular professionally generated bus tours.
Correlation between vocal tract length, body height, formant frequencies, and pitch frequency for the five Japanese vowels uttered by fifteen male speakers

We conducted quantitative analyses of a magnetic resonance imaging (MRI) database to examine the correlation between physical measures (vocal tract length and body height) and acoustic parameters (pitch and formant frequencies) of vowels. The vocal tract length was measured from MRI data for the five Japanese vowels produced by fifteen male Japanese speakers between the ages of 24 and 55. The acoustic features were computed from vowel sounds recorded during scan. The vocal tract length showed a weak positive correlation with the speakers’ age (correlation coefficient r = 0.51) but not with the speaker body height (r = 0.08). There were only weaker correlations between the vocal tract length and the first four formant frequencies except that F1 and F2 of the vowel /e/ show negative correlations with the vocal tract length (F1: r = -0.65, F2: r = -0.56). The result suggests that the vocal tract length is one of the dominant factors causing individual differences in the formant frequencies for the vowel /e/, produced by not forming a strong constriction. Furthermore, the pitch frequency was negatively correlated with the body height (r = -0.61).
University of Groningen Towards Metabolic Engineering of Podophyllotoxin Production

The pharmaceutically important anticancer drugs etoposide and teniposide are derived from podophyllotoxin, a natural product isolated from roots of Podophyllum hexandrum growing in the wild. The overexploitation of this endangered plant has led to the search for alternative sources. Metabolic engineering aimed at constructing the pathway in another host cell is very appealing, but for that approach, an in-depth knowledge of the pathway toward podophyllotoxin is necessary. In this chapter, we give an overview of the lignan pathway leading to podophyllotoxin. Subsequently, we will discuss the engineering possibilities to produce podophyllotoxin in a heterologous host. This will require detailed knowledge on the cellular localization of the enzymes of the lignan biosynthesis pathway. Due to the high number of enzymes involved and the scarce information on compartmentalization, the heterologous production of podophyllotoxin still remains a tremendous challenge. At the moment, research is focusing on the last step(s) in the conversion of deoxypodophyllotoxin to (epi)podophyllotoxin and 4′-demethyldesoxypodophyllotoxin by plant cytochromes.
Examining the Direct and Moderating Effects of Relational Exchange and Innovation Characteristics on New Product Adoption

The purposes of this paper are twofold: (1) to examine the probable positive, direct effect of relational exchange and innovation characteristics on new product adoption, and (2) to explore the moderating effects of relational exchange on the relation of innovation characteristics and new product adoption. This study was conducted in the B-to-B context. Data were collected through questionnaire survey. The respondents were 120 purchasing employees in various industries in Taiwan. PLS (Partial Least Squares), a component-based structural equation modeling (SEM) tool, was employed to validate measures and evaluate the hypothesized structural model. A product indicator approach in conjunction with PLS procedure was employed to assess the interaction effect. The results show that the supplier's relationship investments, relationship quality, and product relative advantages had significant positive impacts on new product adoption. Relationship investment interacts with relative advantage and compatibility, respectively, to influence new product adoption. These findings imply that implementing successful relational exchange could have an additional, important positive effect on new products to be adopted, which is beyond and above the mere effect generated by favorable characteristics of innovations.
Unpicking Tartan CIAO Plots: Understanding Irregular Coevolutionary Cycling

We report results from a series of studies coevolving players for simple Rock-Paper-Scissors games. These results demonstrate that Current Individual versus Ancestral Opponent (CIAO) plots, which have been proposed as a visualization technique for detecting both coevolutionary progress and coevolutionary cycling, suffer from ambiguity with regard to an important but rarely discussed class of cyclic behavior. While regular cycling manifests itself as a characteristic banded plot, irregular cycling produces an irregular tartan pattern that is also consistent with random drift through strategy space. Although this tartan pattern is often reported in the literature on coevolutionary algorithms, it has received little attention or analysis. Here we argue that irregular cycling will tend to be more prevalent than regular cycling, and that it corresponds to a class of coevolutionary scenario that is important both theoretically and in practice. As such, it is desirable that we improve our ability to distinguish its occurrence from that of random drift, and other forms of coevolutionary dynamic.
Stochastic theory for jerky deformation in small crystal volumes with pre-existing dislocations

A statistical theory is proposed to describe the jerky deformation of micron-sized crystal pillars. The probability for a specimen surviving the applied load without generating a strain burst of a given order is analytically expressed in terms of the nucleation rate of that burst. The survival probability can be measured from an ensemble of macroscopically similar deformation experiments to obtain the nucleation rate. From experiments on aluminium pillars, the nucleation rate is found to increase with the pillar size and to decrease with the burst order, indicating that more sources are present in a larger specimen and that the available nucleating sources are progressively exhausted by the occurrence of bursts. The activation volume measured is roughly independent of the pillar size and burst order, indicating a constant mechanism for burst nucleation.
Presence and engagement in an interactive drama

In this paper we present the results of a qualitative, empirical study exploring the impact of immersive technologies on presence and engagement, using the interactive drama Façade as the object of study. In this drama, players are situated in a married couple's apartment, and interact primarily through conversation with the characters and manipulation of objects in the space. We present participants' experiences across three different versions of Façade -- augmented reality (AR) and two desktop computing based implementations, one where players communicate using speech and the other using typed keyboard input. Through interviews and observations of players, we find that immersive AR can create an increased sense of presence, confirming generally held expectations. However, we demonstrate that increased presence does not necessarily lead to more engagement. Rather, mediation may be necessary for some players to fully engage with certain interactive media experiences.
The slowpoke gene is necessary for rapid ethanol tolerance in Drosophila.

BACKGROUND Ethanol is one of the most commonly used drugs in the world. We are interested in the compensatory mechanisms used by the nervous system to counter the effects of ethanol intoxication. Recently, the slowpoke BK-type calcium-activated potassium channel gene has been shown to be involved in ethanol sensitivity in Caenorhabditis elegans and in rapid tolerance to the anesthetic benzyl alcohol in Drosophila. METHODS We used Drosophila mutants to investigate the role of slowpoke in rapid tolerance to sedation with ethanol vapor. Rapid tolerance was defined as a reduction in the sedative phase caused by a single previous sedation. The ethanol and water contents of flies were measured to determine if pharmacodynamic changes could account for tolerance. RESULTS A saturated ethanol air stream caused sedation in <20 min and resulted in rapid tolerance that was apparent 4 hr after sedation. Two independently isolated null mutations in the slowpoke gene eliminated the capacity for tolerance. In addition, a third mutation that blocked expression specifically in the nervous system also blocked rapid tolerance. Water measurements showed that both ethanol and mock sedation caused equivalent dehydration. Furthermore, a single prior exposure to ethanol did not cause a change in the ethanol clearance rate. CONCLUSIONS Rapid tolerance, measured as a reduction in the duration of sedation, is a pharmacokinetic response to ethanol that does not occur without slowpoke expression in the nervous system in Drosophila. The slowpoke channel must be involved in triggering or producing a homeostatic mechanism that opposes the sedative effects of ethanol.
Attractor Dynamics and Semantic Neighborhood Density: Processing Is Slowed by near Neighbors and Speeded by Distant Neighbors We Thank Ann Kulikowski for Her Help with Data Collection And

The authors investigated semantic neighborhood density effects on visual word processing to examine the dynamics of activation and competition among semantic representations. Experiment 1 validated feature-based semantic representations as a basis for computing semantic neighborhood density and suggested that near and distant neighbors have opposite effects on word processing. Experiment 2 confirmed these results: Word processing was slower for dense near neighborhoods and faster for dense distant neighborhoods. Analysis of a computational model showed that attractor dynamics can produce this pattern of neighborhood effects. The authors argue for reconsideration of traditional models of neighborhood effects in terms of attractor dynamics, which allow both inhibitory and facilitative effects to emerge. Semantic processing is a crucial, yet poorly understood, aspect of language processing. For example, there is general agreement that as a word is processed, related words and/or words with similar meanings are partially accessed or activated. However, the term similar meanings refers to very different relationships in different theories of semantic representation. The similarity structure of semantic representations goes to the very heart of knowledge and meaning— how knowledge is organized determines which concepts are similar or related and which ones are not. There are at least five approaches to semantic representation that propose strikingly different bases for semantic representations and consequently for the similarity relations among concepts. define similarity in terms of category membership and location in a hierarchy. Embodied cognition approaches define similarity in terms of perceptual or action-based overlap. Association-based semantic network approaches define similarity in terms of connections defined by subject report (e. 2004) define similarity in terms of cross-correlations of word co-occurrence. Semantic microfeature-based representations define similarity in terms of empirically determined feature overlap. Despite concerted efforts over the last few decades, there is surprisingly little empirical basis for claiming that any one of these approaches captures the nature of human semantic representations. In part, this is because most studies of the structure of semantic knowledge have examined pairwise semantic similarity relations using paradigms such as priming, similarity ratings, and cued recall. This approach provides a measure of the similarity between any two concepts but risks missing the forest for the trees. An alternative, larger scope approach is to examine the effects of semantic neighborhood density (SND) or size—the number and/or proximity of neighboring representations— on word recognition. Analysis of neighborhood effects shifts the focus from the effect of a single related word on processing of …
Mice Deficient in Cellular Glutathione Peroxidase Develop Normally and Show No Increased Sensitivity to Hyperoxia*

Glutathione peroxidase, a selenium-containing enzyme, is believed to protect cells from the toxicity of hydroperoxides. The physiological role of this enzyme has previously been implicated mainly using animals fed with a selenium-deficient diet. Although selenium deficiency also affects the activity of several other cellular selenium-containing enzymes, a dramatic decrease of glutathione peroxidase activity has been postulated to play a role in the pathogenesis of a number of diseases, particularly those whose progression is associated with an overproduction of reactive oxygen species, found in selenium-deficient animals. To further clarify the physiological relevance of this enzyme, a model of mice deficient in cellular glutathione peroxidase (GSHPx-1), the major isoform of glutathione peroxidase ubiquitously expressed in all types of cells, was generated by gene-targeting technology. Mice deficient in this enzyme were apparently healthy and fertile and showed no increased sensitivity to hyperoxia. Their tissues exhibited neither a retarded rate in consuming extracellular hydrogen peroxide nor an increased content of protein carbonyl groups and lipid peroxidation compared with those of wild-type mice. However, platelets from GSHPx-1-deficient mice incubated with arachidonic acid generated less 12-hydroxyeicosatetraenoic acid and more polar products relative to control platelets at a higher concentration of arachidonic acid, presumably reflecting a decreased ability to reduce the 12-hydroperoxyeicosatetraenoic acid intermediate. These results suggest that the contribution of GSHPx-1 to the cellular antioxidant mechanism under normal animal development and physiological conditions and to the pulmonary defense against hyperoxic insult is very limited. Nevertheless, the potential antioxidant role of this enzyme in protecting cells and animals against the pathogenic effect of reactive oxygen species in other disorders remains to be defined. The knockout mouse model described in this report will also provide a new tool for future study to distinguish the physiological role of this enzyme from other selenium-containing proteins in mammals under normal and disease states.