Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomarkers of hypothalamic–pituitary–adrenal axis activity in mice lacking 11β-HSD1 and H6PDH

Glucocorticoid concentrations are a balance between production under the negative feedback control and diurnal rhythm of the hypothalamic–pituitary–adrenal (HPA) axis and peripheral metabolism, for example by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which catalyses the reduction of inactive cortisone (11-dehydrocorticosterone (11-DHC) in mice) to cortisol (corticosterone in mice). Reductase activity is conferred upon 11β-HSD1 by hexose-6-phosphate dehydrogenase (H6PDH). 11β-HSD1 is implicated in the development of obesity, and selective 11β-HSD1 inhibitors are currently under development. We sought to address the concern regarding potential up-regulation of the HPA axis associated with inhibition of 11β-HSD1. We assessed biomarkers for allele combinations of 11β-HSD1 and H6PDH derived from double heterozygous mouse crosses. H6PDH knock out (KO) adrenals were 69% larger than WT while 11β-HSD1 KO and double KO (DKO) adrenals were ∼30% larger than WT – indicative of increased HPA axis drive in KO animals. ACTH-stimulated circulating corticosterone concentrations were 2·2-fold higher in H6PDH KO animals and ∼1·5-fold higher in 11β-HSD1 KO and DKO animals compared with WT, proportional to the observed adrenal hypertrophy. KO of H6PDH resulted in a substantial increase in urinary DHC metabolites in males (65%) and females (61%). KO of 11β-HSD1 alone or in combination with H6PDH led to significant increases (36 and 42% respectively) in urinary DHC metabolites in females only. Intermediate 11β-HSD1/H6PDH heterozygotes maintained a normal HPA axis. Urinary steroid metabolite profile by gas chromatography/mass spectrometry as a biomarker assay may be beneficial in assaying HPA axis status clinically in cases of congenital and acquired 11β-HSD1/H6PDH deficiency.
Sorafenib Sensitizes (−)-Gossypol-Induced Growth Suppression in Androgen-Independent Prostate Cancer Cells via Mcl-1 Inhibition and Bak Activation

The natural BH3-mimetic (−)-gossypol shows promising efficacy in ongoing phase II/III clinical trials for human prostate cancer. Here, we show for the first time, that treatment with (−)-gossypol and multikinase inhibitor sorafenib synergistically suppresses the growth of androgen-independent prostate cancer cells (AI-PC) in vitro and in vivo. Our data suggest that sorafenib attenuates (−)-gossypol-induced Mcl-1 upregulation in AI-PCs. In this way, it serves as a potent chemosensitizer to affect cell death. Interestingly, (−)-gossypol and sorafenib induce cell death via two distinct pathways among different AI-PCs; DU145 cells via apoptosis and PC-3 via autophagy. The appointed death pathway may depend on the level of proapoptotic protein Bak, although the level of antiapoptotic protein Bcl-2 plays some role in it. DU145 cells with high Bak level prefer apoptosis induction, whereas PC-3 cells with low Bak prefer the induction of autophagy. Furthermore, inhibiting nondominant death pathways, that is, autophagy in DU145 and apoptosis in PC-3, enhances cell killing by (−)-gossypol/sorafenib combination therapy. Ultimately, our data expose a new action for sorafenib as an enhancer of (−)-gossypol-induced cell growth suppression and reveal a novel cell death mode by Bak activation manners in AI-PCs. These new insights may facilitate the rational design of clinical trials by selecting patients most likely to benefit from the Bcl-2–targeted molecular therapy. Mol Cancer Ther; 11(2); 416–26. ©2011 AACR.
What makes a motivating teacher? Teachers’ motivation and beliefs as predictors of their autonomy-supportive style

Findings from several studies suggest that teachers who embrace an autonomy-supportive style vis-à-vis their students promote student motivation. However, the question of what makes teachers adopt this supportive style remains unanswered. Using Self-Determination Theory as a framework, we suggest that teachers’ own motivation and their beliefs about student motivation are predictors of their tendency to opt for an autonomy-supportive rather than a controlling style. One hundred and fifty-four teachers completed a questionnaire designed to assess their type of motivation to teach, what they believe is desirable student motivation, and the level to which they opt for behaviors that support student autonomy. Our findings suggest: Firstly, that teachers who teach out of interest and enjoyment, and value their work (autonomous motivation), tend to believe that the learning of students who are autonomously motivated benefits more; secondly, that teachers who believe that autonomous motivation is desirable for their students’ learning also tend to opt for an autonomy-supportive rather than a controlling style; thirdly, that teachers who are autonomously motivated themselves are more likely to adopt an autonomy-supportive style, especially when they also believe that autonomous motivation is desirable for their students’ learning. The study’s findings highlight the importance of a teacher’s own motivation and beliefs as factors that promote autonomy-supportive behavior in the classroom.
Prognostic role of human papillomavirus in esophageal cancer : a meta-analysis

Objective: Previous studies have assessed the relationship between human papillomavirus (HPV) infection and the prognosis of esophageal cancer, but the conclusion remains controversial. The objective of this meta-analysis was to systemically review the literature and to comprehensively evaluate the relationship between HPV and esophageal cancer. Materials and Methods: Literature searches were performed in Embase, Medline and PubMed databases to identify studies focusing on the relationship between HPV infection and overall survival (OS) of esophageal cancer before September 30, 2015. Overall hazard ratio (HR) with 95% confidence interval (95% CI) was pooled to evaluate this relationship. Subgroup analyses were performed by study region, HPV type, and therapy strategy. Results: Eight studies involving 1034 patients with esophageal cancer were included for meta-analysis. The pooled analysis showed that HPV infection caused a significantly worse OS in esophageal cancer patients (HR, 1.32; 95% CI, 1.06-1.65). Subgroup analyses showed a significant correlation between HPV infection and OS in multiple types of HPV infection subgroup (HR, 1.32; 95% CI, 1.00-1.73) and in multiple therapies subgroup (HR, 1.33; 95% CI, 1.03-1.73). Conclusion: HPV infection predicted a significantly worse prognosis in patients with esophageal cancer, and HPV might act as a promising prognostic factor for esophageal cancer.
Morphological Study of Eggs from Five Mexican Species and Two Morphotypes in the Genus Triatoma (Laporte, 1832)

ABSTRACT: We describe and compare the morphology and morphometry of the egg exochorion for five species and two morphotypes of Mexican triatomines with scanning electron microscopy. The results show differences in egg ornamentation for each species, including between morphotypes. Polygonal ornamentation was observed in each species, including pentagons, octagons and, in certain cases, a majority of hexagons. We observed small perforations in T. protracta protracta, small spheres on the T. lecticularia polygons, a crown with festoons in T. barberi, and less complex ornamentation in T. mexicana. Through morphometric analysis, significant differences in egg dimensions were determined for the studied species.
Reality-based generation of virtual environments for digital earth

Abstract Digital Earth essentially consists of 3D and moreD models and attached semantic information (attributes). Techniques for generating such models efficiently are required very urgently. Reality-based 3D modelling using images as prime data source plays an important role in this context. Images contain a wealth of information that can be advantageously used for model generation. Images are increasingly available from satellite, aerial and terrestrial platforms. This contribution briefly describes some of the problems which we encounter if the process of model generation is to be automatised. With the help of some examples from Digital Terrain Model generation, Cultural Heritage and 3D city modelling we show briefly what can be achieved. Special attention is directed towards the use of model helicopters for image data acquisition. Some problems with interactive visualisation are discussed. Also, issues surrounding R&D, professional practice and education are also addressed.
Cost Effective Storage using Extent Based Dynamic Tiering

Multi-tier systems that combine SSDs with SAS/FC and/or SATA disks mitigate the capital cost burden of SSDs, while benefiting from their superior I/O performance per unit cost and low power. Though commercial SSD-based multi-tier solutions are available, configuring such a system with the optimal number of devices per tier to achieve performance goals at minimum cost remains a challenge. Furthermore, these solutions do not leverage the opportunity to dynamically consolidate load and reduce power/operating cost. Our extent-based dynamic tiering solution, EDT, addresses these limitations via two key components of its design. A Configuration Adviser EDT-CA determines the adequate mix of storage devices to buy and install to satisfy a given workload at minimum cost, and a Dynamic Tier Manager EDT-DTM performs dynamic extent placement once the system is running to satisfy performance requirements while minimizing dynamic power consumption. Key to the cost minimization of EDT-CA is its ability to simulate the dynamic extent placement afforded by EDT-DTM. Key to the overall effectiveness of EDT-DTM is its ability to consolidate load within tiers when feasible, rapidly respond to unexpected changes in the workload, and carefully control the overhead due to extent migration. Our results using production workloads show that EDT incurs lower capital and operating cost, consumes less power, and delivers similar or better performance relative to SAS-only storage systems as well as other simpler approaches to extent-based tiering.
Simulation of Electronic DNA Sequencing Based on Intrinsic Molecular Charges

We model and simulate the use of ion sensitive field-effect transistor for electronic deoxyribonucleic acid (DNA) sequencing using its intrinsic molecular charge on the backbone. In this model, biological layer is treated as an ion-permeable charged membrane in solving Poisson equation. Sensor I–V characteristics are simulated, showing that the shifts of device threshold voltage respond to the DNA base-extension reaction. The simulation reveals the effects of DNA surface density, the length of a single-stranded DNA, and salt concentration on sensor performance. The simulation results demonstrate good agreement with the published experimental data, therefore, could be a good guide to actual biosensor design and fabrication.
Tabletop File System Access: Associative and Hierarchical Approaches

This paper presents the design of two tabletop file system interfaces: OriTop, a novel associative access approach to file system interaction, where users navigate multiple file systems by selecting focus files; and the Browser, a hierarchical interface that is based upon the same mental model as conventional desktop file system access. We report a qualitative study with ten users to explore both approaches. OnTop was found to better facilitate collaboration on file access and use, while the more familiar hierarchical model of the Browser was found to be more natural on very early use and has a clear role-particularly in cases where the associative approach fails.
Robustness of an effective diffusivity diagnostic in oceanic flows

The robustness of Nakamura’s effective diffusivity diagnostic for quantifying eddy diffusivities of tracers within a streamwise-average framework is carefully examined in an oceanographic context, and the limits of its applicability are detailed. The near-surface Southern Ocean geostrophic flow, obtained from altimetric observations, is chosen for particular examination since it exhibits strong eddy activity. Careful analysis indicates that the effective diffusivity calculation is not strongly sensitive to the resolution of the velocity field or to the tracer initial conditions (after a spinup time of 3 months), and that a numerical diffusivity of 50 m 2 s 21 is appropriate to resolve the Batchelor scale at a computational resolution of 1/208. The spatial variability of the effective diffusivity is examined and shown to be related to the eddy kinetic energy (EKE), mean zonal current (u), and phase speed of the eddies (c), following the streamwise averge of EKE/(u 2 c) 2 , in agreement with linear baroclinic instability theory. The temporal variability of the effective diffusivity over the period 1996‐2001 indicates significant variability on seasonal time scales with a magnitude of 610%215%. Interannual variations are investigated and discussed in the context of changes in the wind stress associated with the southern annular mode.
Expression of simian CETP in normolipidemic Fisher rats has a profound effect on large sized apoE-containing HDL Published, JLR Papers in Press, September 1, 2002. DOI 10.1194/jlr.M200253-JLR200

In order to investigate the direct effect of cholesteryl ester transfer protein (CETP) on the structure and composition of HDL in vivo, simian CETP was expressed in Fisher rat that spontaneously displays high plasma levels of HDL1. In the new CETPTg rat line, the production of active CETP by the liver induced a significant 48% decrease in plasma HDL cholesterol, resulting in a 34% decrease in total cholesterol level (P < 0.01 in both cases). Among the various plasma HDL subpopulations, the largest HDL were those mostly affected by CETP, with a 74% decrease in HDL1 versus a significantly weaker 38% decrease in smaller HDL2 (P < 0.0001). Apolipoprotein E (apoE)-containing HDL1 were selectively affected by CETP expression, whereas apoA content of HDL remained unmodified. The reduction in the apoE content of serum HDL observed in CETPTg rats compared to controls (53%, P < 0.02) suggests that apoE in HDL may constitute in vivo a major determinant of their ability to interact with CETP. These results bring new insight into the lack of HDL1 in plasma from CETP-deficient heterozygotes despite their substantial 50% decrease in CETP activity. In addition, they indicate that HDL1 constitute reliable and practicable sensors of very low plasma CETP activity in vivo.
SYNTACTIC PERFORMANCE IN ONLINEWRITTEN DISCOURSE BY AN ENGLISH/SWEDISH BILINGUAL WITH ASPERGER'S SYNDROME: A CASE STUDY

The present article described syntactic performance by an English/Swedish bilingual participant with Asperger syndrome. The participant's syntactic performance was investigated by means of observing the participant's status updates onFacebook, a social networking platform. Two observation sessions involved one week each, with the interval of six months between the sessions.It was theorised that the bilingual participant's syntactic performance would be exacerbated by code- switching. The participant's data were tagged in computer software CLAN. Results of the data analysis indicated that the hypothesis was not supported: the participant's syntactic performance exhibited no
Superoxide-mediated amplification of the oxygen-induced switch from [4Fe-4S] to [2Fe-2S] clusters in the transcriptional regulator FNR

In Escherichia coli, the switch between aerobic and anaerobic metabolism is controlled primarily by FNR (regulator of fumarate and nitrate reduction), the protein that regulates the transcription of >100 genes in response to oxygen. Under oxygen-limiting conditions, FNR binds a [4Fe-4S]2+ cluster, generating a transcriptionally active dimeric form. Upon exposure to oxygen the cluster converts to a [2Fe-2S]2+ form, leading to dissociation of the protein into monomers, which are incapable of binding DNA with high affinity. The mechanism of cluster conversion together with the nature of the products of conversion is of considerable current interest. Here, we demonstrate that [4Fe-4S]2+ to [2Fe-2S]2+ cluster conversion, in both native and reconstituted [4Fe-4S] FNR, proceeds via a one electron oxidation of the cluster, to give a [3Fe-4S]1+ cluster intermediate, with the release of one Fe2+ ion and a superoxide ion. The cluster intermediate subsequently rearranges spontaneously to form the [2Fe-2S]2+ cluster, with the release of a Fe3+ ion and, as previously shown, two sulfide ions. Superoxide ion undergoes dismutation to hydrogen peroxide and oxygen. This mechanism, a one electron activation of the cluster, coupled to catalytic recycling of the resulting superoxide ion back to oxygen, provides a means of amplifying the sensitivity of [4Fe-4S] FNR to its signal molecule.
On the Motor Theory of Speech Perception

3:'ine. W U. (t96cl. Worcl and Oú7crr. Canrbriclge. Ma*.: MIT pre,s. rcneler, l(. t(., Korvr:maki. J. and Rosenúal, R. (1972). Minimal Cues in ¡he Vocal C. oÌ'un jcârion of Afect: J udging ! morio", ft "; ó;,;_M;:;. ìioär,. ¡r_, oJ lsycholinguisti Rci? arch. t: 26965. Smiú, B. C. (2oo6a). Whar I l{norv When I Know a Language,, in E. Lepore and :l c Sûnrl (eds.), Trre oxford Handbook of phírosophy i nü*in'. 'i*Íi,¿, o"¡*a Univeniry press.
Improving the Scalability of Semi-Markov Conditional Random Fields for Named Entity Recognition

This paper presents techniques to apply semi-CRFs to Named Entity Recognition tasks with a tractable computational cost. Our framework can handle an NER task that has long named entities and many labels which increase the computational cost. To reduce the computational cost, we propose two techniques: the first is the use of feature forests, which enables us to pack feature-equivalent states, and the second is the introduction of a filtering process which significantly reduces the number of candidate states. This framework allows us to use a rich set of features extracted from the chunk-based representation that can capture informative characteristics of entities. We also introduce a simple trick to transfer information about distant entities by embedding label information into non-entity labels. Experimental results show that our model achieves an F-score of 71.48% on the JNLPBA 2004 shared task without using any external resources or post-processing techniques.
AIB1 Is a Conduit for Kinase-Mediated Growth Factor Signaling to the Estrogen Receptor

ABSTRACT Growth factor modulation of estrogen receptor (ER) activity plays an important role in both normal estrogen physiology and the pathogenesis of breast cancer. Growth factors are known to stimulate the ligand-independent activity of ER through the activation of mitogen-activated protein kinase (MAPK) and the direct phosphorylation of ER. We found that the transcriptional activity of AIB1, a ligand-dependent ER coactivator and a gene amplified preferentially in ER-positive breast cancers, is enhanced by MAPK phosphorylation. We demonstrate that AIB1 is a phosphoprotein in vivo and can be phosphorylated in vitro by MAPK. Finally, we observed that MAPK activation of AIB1 stimulates the recruitment of p300 and associated histone acetyltransferase activity. These results suggest that the ability of growth factors to modulate estrogen action may be mediated through MAPK activation of the nuclear receptor coactivator AIB1.
A Universal Primal-Dual Convex Optimization Framework

We propose a new primal-dual algorithmic framework for a prototypical constrained convex optimization template. The algorithmic instances of our framework are universal since they can automatically adapt to the unknown Holder continuity degree and constant within the dual formulation. They are also guaranteed to have optimal convergence rates in the objective residual and the feasibility gap for each Holder smoothness degree. In contrast to existing primal-dual algorithms, our framework avoids the proximity operator of the objective function. We instead leverage computationally cheaper, Fenchel-type operators, which are the main workhorses of the generalized conditional gradient (GCG)-type methods. In contrast to the GCG-type methods, our framework does not require the objective function to be differentiable, and can also process additional general linear inclusion constraints, while guarantees the convergence rate on the primal problem.
Zn2+ -induced cell death is mediated by the induction of intracellular ROS in ARPE-19 cells

Purpose. Recent studies have shown that Zn 2+ induced cell death in retinal pigment epithelial cells. Here we sought to investigate the mode of Zn 2+ -induced cell death and the role of reactive oxygen species (ROS) in human retinal pigment epithelial cell line, ARPE-19 cells. Methods. Cell viability was measured by MTT assay. Cell death of ARPE-19 cells was measured by annexin V-fluorescein isothiocyanate (FITC) binding assay, TUNEL assay. The formation of intracellular ROS was measured using 2',7'-dichlorofluorescein diacetate (DCFH-DA). The activation of mitogen-activated protein kinase (MAPK) was examined by Western blot analysis. Results. This study demonstrated that Zn 2+ treatment induced both necrosis and apoptosis in ARPE-19 cells. Exposure of ARPE-19 cells to Zn 2+ led to the activation of ERK1/2, JNK1/2/3, and p38 MAPKs. The activation of these MAPKs was blocked by treatment with the antioxidant, N-acetylcystein (NAC). More importantly, inhibition of ROS production by NAC completely prevented Zn 2+ -induced cell death in RPE cells. Conclusions. This study suggests that Zn 2+ induces both apoptosis and necrosis in ARPE-19 cells and that its cytotoxicity may depend on the induction of intracellular ROS.
Assessing Optical Properties and Refractive Index of Combustion Aerosol Particles Through Combined Experimental and Modeling Studies

The variability of optical properties of combustion particles generated from a propane diffusion flame under varying fuel-to-air (C/O) ratios was studied with a three-wavelength nephelometer, a particle soot absorption photometer, and an integrating sphere photometer. Information on particle size distribution, morphology, and elemental carbon to total carbon (EC/TC) ratios were obtained from scanning mobility particle sizer measurements, transmission electron microscopy analyses, and thermal-optical analyses. Particles generated under a low C/O ratio (0.22) showed high elemental carbon fraction (EC/TC = 0.77) and low brown carbon to equivalent black carbon (BrC/EBC) ratio (0.01), and were aggregates composed of small primary particles. Rayleigh–Debye–Gans theory reproduced experimental single-scattering albedo, ω, absorption, and scattering Ångström exponents within 56, 3, and 18%, respectively. In contrast, particles produced under a high C/O ratio (0.60) showed low elemental carbon fraction (EC/TC = 0.09) and high BrC/EBC ratio >100, and were smaller and spherical in shape. Their optical properties were better modeled with Mie theory. By minimizing the difference between calculated and measured ω and Ångström exponents, refractive indices of OC at three visible wavelengths were deduced. Contrary to the widely accepted assumption that refractive index of BC is wavelength independent, BC-rich particles exhibited absorption Ångström exponent >1.0 which implies some degree of wavelength dependence. Copyright 2015 American Association for Aerosol Research