Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of α5β1 integrin conformation and function by urokinase receptor binding

Urokinase-type plasminogen activator receptors (uPARs), up-regulated during tumor progression, associate with β1 integrins, localizing urokinase to sites of cell attachment. Binding of uPAR to the β-propeller of α3β1 empowers vitronectin adhesion by this integrin. How uPAR modifies other β1 integrins remains unknown. Using recombinant proteins, we found uPAR directly binds α5β1 and rather than blocking, renders fibronectin (Fn) binding by α5β1 Arg-Gly-Asp (RGD) resistant. This resulted from RGD-independent binding of α5β1–uPAR to Fn type III repeats 12–15 in addition to type III repeats 9–11 bound by α5β1. Suppression of endogenous uPAR by small interfering RNA in tumor cells promoted weaker, RGD-sensitive Fn adhesion and altered overall α5β1 conformation. A β1 peptide (res 224NLDSPEGGF232) that models near the known α-chain uPAR-binding region, or a β1-chain Ser227Ala point mutation, abrogated effects of uPAR on α5β1. Direct binding and regulation of α5β1 by uPAR implies a modified “bent” integrin conformation can function in an alternative activation state with this and possibly other cis-acting membrane ligands.
Free Fatty Acid-Induced PP2A Hyperactivity Selectively Impairs Hepatic Insulin Action on Glucose Metabolism

In type 2 Diabetes (T2D) free fatty acids (FFAs) in plasma are increased and hepatic insulin resistance is “selective”, in the sense that the insulin-mediated decrease of glucose production is blunted while insulin's effect on stimulating lipogenesis is maintained. We investigated the molecular mechanisms underlying this pathogenic paradox. Primary rat hepatocytes were exposed to palmitate for twenty hours. To establish the physiological relevance of the in vitro findings, we also studied insulin-resistant Zucker Diabetic Fatty (ZDF) rats. While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. In contrast, similar to findings in human T2D, the ability of insulin to induce triglyceride (TG) accumulation and transcription of the enzymes that catalyze de novo lipogenesis and TG assembly was unaffected. Insulin-induction of these genes could, however, be blocked by inhibition of the atypical PKCs (aPKCs). The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity.
Applying Harmonic Optical Microscopy for Spatial Alignment of Atrial Collagen Fibers

Background Atrial fibrosis creates a vulnerable tissue for atrial fibrillation (AF), but the spatial disarray of collagen fibers underlying atrial fibrosis is not fully elucidated. Objective This study hypothesizes that harmonics optical microscopy can illuminate the spatial mal-alignment of collagen fibers in AF via a layer-by-layer approach. Patients and Methods Atrial tissues taken from patients who underwent open-heart surgery were examined by harmonics optical microscopy. Using the two-dimensional Fourier transformation method, a spectral-energy description of image texture was constituted and its entropy was used to quantify the mal-alignment of collagen fibers. The amount of collagen fiber was derived from its area ratio to total atrial tissue in each image. Serum C-terminal pro-collagen pro-peptide (CICP), pro-matrix metalloproteinase-1 (pro-MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were also evaluated. Results 46 patients were evaluated, including 20 with normal sinus rhythm and 26 with AF. The entropy of spectral-energy distribution of collagen alignment was significantly higher in AF than that in sinus rhythm (3.97±0.33 vs. 2.80±0.18, p<0.005). This difference was more significant in the permanent AF group. The amount of collagen was also significantly higher in AF patients (0.39±0.13 vs. 0.18±0.06, p<0.005) but serum markers of cardiac fibrosis were not significantly different between the two groups. Conclusions Harmonics optical microscopy can quantify the spatial mal-alignment of collagen fibers in AF. The entropy of spectral-energy distribution of collagen alignment is a potential tool for research in atrial remodeling.
Discovery of new Milky Way star clusters candidates in the 2MASS point source catalog

A systematic search of the 2MASS point source catalog, covering 47% of the sky, was carried out aiming to reveal any hidden globular clusters in our Galaxy. Eight new star clusters were discovered by a search algorithm based on finding peaks in the apparent stellar surface density, and a visual inspection of their vicinities yielded additional two. They all are concentrated toward the Galactic plane and are hidden behind up to AV = 20 mag which accounts for their late discovery. The majority of new clusters are associated with H regions or unidentified IRAS sources suggesting that they are young, probably similar to Arches or open clusters. Only one candidate has morphology similar to a globular cluster and the verification of its nature will require deeper observations with higher angular resolution than the 2MASS data.
AN HST/COS OBSERVATION OF BROAD Lyα EMISSION AND ASSOCIATED ABSORPTION LINES OF THE BL LACERTAE OBJECT H 2356–309

Weak spectral features in BL Lacertae objects (BL Lacs) often provide a unique opportunity to probe the inner region of this rare type of active galactic nucleus. We present a Hubble Space Telescope/Cosmic Origins Spectrograph observation of the BL Lac H 2356–309. A weak Lyα emission line was detected. This is the fourth detection of a weak Lyα emission feature in the ultraviolet (UV) band in the so-called high-energy peaked BL Lacs, after Stocke et al. Assuming the line-emitting gas is located in the broad line region (BLR) and the ionizing source is the off-axis jet emission, we constrain the Lorentz factor (Γ) of the relativistic jet to be ⩾8.1 with a maximum viewing angle of 3. °6. The derived Γ is somewhat larger than previous measurements of Γ ≈ 3–5, implying a covering factor of ∼3% of the line-emitting gas. Alternatively, the BLR clouds could be optically thin, in which case we constrain the BLR warm gas to be ∼10−5 M☉. We also detected two H i and one O vi absorption lines that are within |Δv| < 150 km s−1 of the BL Lac object. The O vi and one of the H i absorbers likely coexist due to their nearly identical velocities. We discuss several ionization models and find a photoionization model where the ionizing photon source is the BL Lac object that can fit the observed ion column densities with reasonable physical parameters. This absorber can either be located in the interstellar medium of the host galaxy or in the BLR.
Speed and accuracy of dyslexic versus typical word recognition: an eye-movement investigation

Developmental dyslexia is often characterized by a dual deficit in both word recognition accuracy and general processing speed. While previous research into dyslexic word recognition may have suffered from speed-accuracy trade-off, the present study employed a novel eye-tracking task that is less prone to such confounds. Participants (10 dyslexics and 12 controls) were asked to look at real word stimuli, and to ignore simultaneously presented non-word stimuli, while their eye-movements were recorded. Improvements in word recognition accuracy over time were modeled in terms of a continuous non-linear function. The words' rhyme consistency and the non-words' lexicality (unpronounceable, pronounceable, pseudohomophone) were manipulated within-subjects. Speed-related measures derived from the model fits confirmed generally slower processing in dyslexics, and showed a rhyme consistency effect in both dyslexics and controls. In terms of overall error rate, dyslexics (but not controls) performed less accurately on rhyme-inconsistent words, suggesting a representational deficit for such words in dyslexics. Interestingly, neither group showed a pseudohomophone effect in speed or accuracy, which might call the task-independent pervasiveness of this effect into question. The present results illustrate the importance of distinguishing between speed- vs. accuracy-related effects for our understanding of dyslexic word recognition.
eCHASE: sustainable exploitation of electronic cultural heritage

Europe’s digital cultural heritage content has tremendous exploitation potential in applications such as Education, Publishing, e-Commerce, Public Access and Tourism. Value is hugely amplified if the content can be aggregated, repurposed and distributed at a European level. The eCHASE project seeks to demonstrate that public-private partnerships between content holders and commercial service providers can create new services and a sustainable business based on access and exploitation of digital cultural heritage content. This paper describes these issues and introduces the eCHASE architecture that is being developed to showcase the business models created for the project.
Cross‐cultural measurement invariance of the General Health Questionnaire‐12 in a German and a Colombian population sample

While the General Health Questionnaire, 12‐item version (GHQ‐12) has been widely used in cross‐cultural comparisons, rigorous tests of the measurement equivalence of different language versions are still lacking. Thus, our study aims at investigating configural, metric and scalar invariance across the German and the Spanish version of the GHQ‐12 in two population samples. The GHQ‐12 was applied in two large‐scale population‐based samples in Germany (N = 1,977) and Colombia (N = 1,500). To investigate measurement equivalence, confirmatory factor analyses were conducted in both samples. In the German sample mean GHQ‐12 total scores were higher than in the Colombian sample. A one‐factor model including response bias on the negatively worded items showed superior fit in the German and the Colombian sample; thus both versions of the GHQ‐12 showed configural invariance. Factor loadings and intercepts were not equal across both samples; thus GHQ‐12 showed no metric and scalar invariance. As both versions of the GHQ‐12 did not show measurement equivalence, it is not recommendable to compare both measures and to conclude that mental distress is higher in the German sample, although we do not know if the differences are attributable to measurement problems or represent a real difference in mental distress. The study underlines the importance of measurement equivalence in cross‐cultural comparisons.
The Relationship between the Production and Perception of L2 Spanish Stops.

A study explored the relationship between the second language (L2) production of the Spanish stop consonants /p/ and /b/. Subjects were native English-speaking students enrolled in an undergraduate Spanish phonetics course. Data were collected on their production of Spanish /p,b/ in sentence context, and on their perceptual boundary between the phonemes as reflected by changes in voice onset time (VOT). Mean production and perception VOTs were compared. Results do not reveal a strong correlation between learners' perceptual abilities and production of the L2 Spanish stops. In particular, while some learners' L2 productions approximated those of native Spanish speakers, their perceptual boundaries were similar to boundaries for monolingual English speakers, and vice versa. (MSE) ****************************************************** ***** ********************* * Reproductions supplied by EDRS are the best that can be made * * from the original document. * ******************************************************************************** The Relationship Between the Production and Perception of 12 Spanish Stops MARY L. ZAMPINL The University of Arizona ii PERMISSION TO REPRODUCE AND DISSEMINATE THIS MATERIAL HAS BEEN GRANTED BY
Pressure‐synchronized Cineangiography During Experimental Cardiopulmonary Resuscitation

Cardiopulmonary resuscitation (CPR) has been thought to produce blood flow by compression of the heart between the sternum and spine, termed “external cardiac massage,” but there has been-no direct experimental documentation of this proposed mechanism.Micromanometric pressure recordings were synchronized with cineangiograms during mechanical CPR in 17 dogs with induced ventricular fibrillation. Chest compression produced equivalent pressure increases in the aorta (Ao) and right atrium (RA) (Ao 32 + 14 mm Hg, RA 30 ± 14 mm Hg; NS), a linear relationship between aortic and intrapleural pressures (r = 0.87, p < 0.001) over a wide range of induced pressures, cineangiographic blood flow through both left-heart chambers, and a pressure gradient (21 ± 14 mm Hg) between all intrathoracic cardiovascular compartments and the jugular veins that resulted from closure of venous valves at the thoracic inlets. Simultaneous chest compression and lung inflation significantly increased all intrathoracic vascular pressures, the aortojugular venous gradient (42 ± 13 mm Hg, p < 0.05 vs chest compression alone), electromagnetically determined carotid arterial blood flow (1.75 ± 0.81 ml/min/kg vs 0.51 ± 0.27 mI/min/kg during chest compression alone, p < 0.005), and angiographic left-heart flow.We conclude that blood flow during CPR results principally from an increased intrathoracic pressure and that there is selective flow to the brachiocephalic vascular bed because of the arteriovepous gradient produced by venous valves at the thoracic inlets. Greater intrathoracic pressure resulting from simultaneous inflation and compression improves left-heart flow. The left heart is therefore a conduit, not a pump, during CPR.
Students' Experiences of Dance: a Hermeneutic Phenomenological Study

The dominance of instrumentalism and utilitarianism in education today tends to reduce the value of dance. Research on dance in education is very limited. Recent reviews of research on the arts in education propose that research has to move from exploring transfer effects of artistic activity towards exploring the meaningfulness of the arts themselves. New researches as well as new theoretical approaches are thus called for (Winner, Goldstein and VincentLancrin, 2013). Hence my research question is: what are students’ experiences of dance? Research on experiences in the arts is contested by the problem to verbalise lived experience. Therefore, in the thesis, a new method based on hermeneutic phenomenology (HP) and arts-based research (ABR) is developed. It includes artistic activity in three forms arts: dance, poetry, and visual art. An oral interview built on a circular structure gives the students a variety of opportunities to interpret and verbalise their experiences of dance. Twenty students, 18 years old, who regularly dance in school, participated. Answers were analysed following van Manen’s (1990) method of structural analysis of themes, including poetic interpretations. The findings reveal that dance is experienced as very important for personal exploration and transformation. Experiences of finding ‘my home’, security, freedom, authenticity, well-being, and happiness are most evident in research
Exercise, Aging and Health: Overcoming Barriers to an Active Old Age

Appropriate for professionals in gerontology, sports psychology, health psychology, physical education and social science programs that deal with older populations and community resources, this book first discusses the pros and cons of physical activity for older persons. It then explores the theoretical reasons for which older people do not pursue physical activity and how to overcome this reluctance. There is a model included, as well as implications for future social policy.
Tight Analysis for the 3-Majority Consensus Dynamics

We present a tight analysis for the well-studied randomized 3-majority dynamics of stabilizing consensus, hence answering the main open question of Becchetti et al. [SODA'16]. Consider a distributed system of n nodes, each initially holding an opinion in {1, 2, . , k}. The system should converge to a setting where all (non-corrupted) nodes hold the same opinion. This consensus opinion should be \emph{valid}, meaning that it should be among the initially supported opinions, and the (fast) convergence should happen even in the presence of a malicious adversary who can corrupt a bounded number of nodes per round and in particular modify their opinions. A well-studied distributed algorithm for this problem is the 3-majority dynamics, which works as follows: per round, each node gathers three opinions --- say by taking its own and two of other nodes sampled at random --- and then it sets its opinion equal to the majority of this set; ties are broken arbitrarily, e.g., towards the node's own opinion. Becchetti et al. [SODA'16] showed that the 3-majority dynamics converges to consensus in O((k^2\sqrt{\log n} + k\log n)(k+\log n)) rounds, even in the presence of a limited adversary. We prove that, even with a stronger adversary, the convergence happens within O(k\log n) rounds. This bound is known to be optimal.
Make-to-order, make-to-stock, or delay product differentiation? A common framework for modeling and analysis

Delaying product differentiation is a hybrid strategy that strives to reconcile the dual needs of high variety and quick response time. A common product platform is built to stock in the first stage of production (called the Make-To-Stock (MTS) stage) which is then differentiated into different products after demand is known in the second stage (known as the Make-To-Order (MTO) stage). In this article, we develop models to compute the costs and benefits of delaying differentiation in series production systems when the order lead times are load dependent. The models are then used to gain insights through analytical and numerical comparisons. For example, we observe the following patterns in a large number of numerical experiments. The effect of congestion in the MTS and MTO stages is asymmetric with tighter capacity at the MTO stage having a greater detrimental effect on the desirability of delaying differentiation. If there is flexibility in choosing the point of differentiation, higher loading is observed to favor later differentiation. Also, if the sequence in which work is performed can be affected, then placing workstations that have a tighter capacity in the MTS stage lowers costs.
Erythroid Cells Rendered Erythropoietin Independent by Infection with Friend Spleen Focus-Forming Virus Show Constitutive Activation of Phosphatidylinositol 3-Kinase and Akt Kinase: Involvement of Insulin Receptor Substrate-Related Adapter Proteins

ABSTRACT The erythroleukemia-inducing Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo). In an effort to understand how SFFV causes Epo independence, we have been examining erythroid cells rendered factor independent by SFFV infection for constitutive activation of signal-transducing molecules. Previous studies from our laboratory showed that various signal-transducing molecules known to be activated by Epo, including Stat proteins and components of the Raf-1/MAP kinase pathway, are constitutively activated in SFFV-infected erythroid cells in the absence of Epo. Since another signal transduction pathway involving activation of phosphatidylinositol 3-kinase (PI 3-kinase) after Epo stimulation plays an important role in erythroid cell proliferation and differentiation, we carried out studies to determine if this pathway was also activated in SFFV-infected cells in the absence of Epo. Our studies show that PI 3-kinase is constitutively activated in erythroid cells rendered factor independent by infection with SFFV and that PI 3-kinase activity, but not Epo receptor tyrosine phosphorylation, is required for the proliferation of these cells in the absence of Epo. We further show that in SFFV-infected erythroid cells grown in the absence of Epo, PI 3-kinase associates with the insulin receptor substrate (IRS)-related adapter molecules IRS-2, Gab1, and Gab2, which are constitutively tyrosine phosphorylated in SFFV-infected cells. Finally, Akt, a protein kinase that is one of the downstream effectors of PI 3-kinase, and SHIP, a lipid phosphatase that is important for Akt activation through PI 3-kinase, are both tyrosine phosphorylated in SFFV-infected cells grown in the absence of Epo. Our results indicate that induction of Epo independence by SFFV requires the activation of PI 3-kinase and suggest that constitutive activation of this kinase in SFFV-infected cells may occur primarily through interaction of PI 3-kinase with constitutively phosphorylated IRS-related adapter molecules.
Learning and Evaluation of Dialogue Strategies for New Applications: Empirical Methods for Optimization from Small Data Sets

We present a new data-driven methodology for simulation-based dialogue strategy learning, which allows us to address several problems in the field of automatic optimization of dialogue strategies: learning effective dialogue strategies when no initial data or system exists, and determining a data-driven reward function. In addition, we evaluate the result with real users, and explore how results transfer between simulated and real interactions. We use Reinforcement Learning (RL) to learn multimodal dialogue strategies by interaction with a simulated environment which is “bootstrapped” from small amounts of Wizard-of-Oz (WOZ) data. This use of WOZ data allows data-driven development of optimal strategies for domains where no working prototype is available. Using simulation-based RL allows us to find optimal policies which are not (necessarily) present in the original data. Our results show that simulation-based RL significantly outperforms the average (human wizard) strategy as learned from the data by using Supervised Learning. The bootstrapped RL-based policy gains on average 50 times more reward when tested in simulation, and almost 18 times more reward when interacting with real users. Users also subjectively rate the RL-based policy on average 10% higher. We also show that results from simulated interaction do transfer to interaction with real users, and we explicitly evaluate the stability of the data-driven reward function.