Miracle-dz/UniFAR-FTUs huggingface dataset:
The TALE homeodomain transcription factor MEIS1 activates the pro‐metastatic melanoma cell adhesion molecule Mcam to promote migration of pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly types of cancer, and the majority of pancreatic cancer deaths is caused by metastasis. Therapeutic options for systemic disease are limited, in particular due to the heterogeneous events leading to tumor dissemination. Previous studies highlighted an association of the homeodomain transcription factor MEIS1 with a ductal phenotype in pancreatic tissue architecture. Using immunohistochemistry, we demonstrate that MEIS1 is expressed in aberrant duct structures of Ela‐TGFα transgenic mice as well as in pancreatic intraepithelial neoplasia (PanINs), primary PDAC, and metastatic disease in Ptf1aCre/+;LSL‐KrasG12D/+ mice. To assess a putative role of MEIS1 in the progression of PDAC, MEIS1 overexpressing pancreatic cancer cell lines were generated by retroviral gene delivery and assessed for proliferation and migration. MEIS1 did not affect proliferation but increased migration in a subset of cell lines tested. Subsequent genome wide expression analysis identified upregulation of the pro‐metastatic gene melanoma cell adhesion molecule (Mcam) in migrating cells. Employing DNA‐pulldown and chromatin immunoprecipitation (ChIP) assays we reveal interaction of MEIS1 with the enhancer‐DNA of Mcam and its transcriptional activation to facilitate migration of pancreatic cancer cells in vitro. Activation of Mcam through MEIS1 occurs in a cell type dependent fashion, reflecting the different routes that lead to metastasis in vivo. To our knowledge, these results show for the first time a pro‐metastatic function of Mcam in pancreatic cancer. © 2016 Wiley Periodicals, Inc.
Activation of the Cpx Envelope Stress Response Down-Regulates Expression of Several Locus of Enterocyte Effacement-Encoded Genes in Enteropathogenic Escherichia coli

ABSTRACT The Cpx two-component system regulates an extracytoplasmic stress response that functions to rid the envelope of misfolded and mislocalized proteins that may interfere with normal cellular processes. The Cpx pathway is also involved in pathogenesis. This study investigated the role of the Cpx response in enteropathogenic Escherichia coli (EPEC) type III secretion (T3S). It was determined that a functional Cpx pathway is not required for T3S but that pathway activation inhibits secretion by reducing the cellular pools of T3S substrates. The EPEC T3S system structural components, as well as a number of its substrates, are encoded on the locus of enterocyte effacement (LEE) pathogenicity island. Transcriptional fusions to the five major operons of the LEE were constructed and examined under Cpx pathway-activating conditions. Induction of the Cpx response caused a decrease in the transcription of several LEE operons, with the most pronounced effect on LEE4 and LEE5. Collectively, these two operons encode components of the T3S translocation apparatus, the bacterial adhesin intimin, and the translocated bacterial receptor Tir. These data show for the first time that activation of the Cpx envelope stress response in EPEC inhibits T3S of both translocators and effectors, likely through down regulation of LEE transcription. Coupled with recent findings, our results suggest that Cpx-mediated down regulation of virulence is a conserved theme in a number of bacterial pathogens.
Tubuloglomerular feedback in ACE-deficient mice.

In these experiments, we used a strain of angiotensin converting enzyme (ACE) germline null mutant mice, generated by J. H. Krege and co-workers (J. H. Krege, S. W. M. John, L. L. Langenbach, J. B. Hodgin, J. R. Hagaman, E. S. Bachman, J. C. Jennette, D. A. O'Brien, and O. Smithies. Nature 375: 146-148, 1995), to examine the effect of chronic ACE deficiency on the magnitude of tubuloglomerular feedback (TGF) responses. The genotype was determined by PCR on DNA extracted from the tail and was verified after each experiment by assessment of the blood pressure response to an injection of ANG I. To assess TGF responsiveness, we determined the change in stop-flow pressure (PSF) caused by increasing NaCl concentration at the macula densa by using micropuncture techniques. When loop of Henle flow rate was increased from 0 to 40 nl/min, PSF fell from a mean of 42.3 ± 1.95 to 33.6 ± 2.09 mmHg ( n = 6, P = 0.005) in wild-type mice (+/+), fell from 40.6 ± 2.35 to 38.6 ± 1.93 mmHg in heterozygous (+/-) mice ( n = 7, P = 0.014), and did not change in homozygous ACE (-/-) mice [36.7 ± 2.02 mmHg vs. 36.4 ± 2.01 mmHg; n = 4, P = not significant (NS)]. During an infusion of ANG II at a dose that did not significantly elevate blood pressure (70 ng ⋅ kg-1 ⋅ min-1), TGF response magnitude (PSF 0 - PSF 40) increased from 6.5 ± 1.4 to 9.8 ± 1.19 mmHg in +/+ ( P = 0.006), from 1.14 ± 0.42 to 4.6 ± 1.3 mmHg in +/- ( P = 0.016), and from 0.42 ± 0.25 to 4.02 ± 1.06 in -/- mice ( P = 0.05). Absence of TGF responses in ACE null mutant mice and restoration of near-normal responses during an acute infusion of ANG II supports previous conclusions that ANG II is an essential component in the signal transmission pathway that links the macula densa with the glomerular vascular pole.
Hybrid ablation for persistent atrial fibrillation: how to merge the best from both worlds.

A close collaboration between the cardiac surgeon and the electrophysiologist in a hybrid fashion has represented a novel and intriguing opportunity in order to address the most common supra-ventricular tachyarrhythmia (i.e., atrial fibrillation) and to overcome the drawbacks and suboptimal results of both catheter ablation and minimally invasive surgical procedures, especially in the most complex and chronic scenarios.
PERINATAL BRAIN IRON DEFICIENCY INCREASES THE VULNERABILITY OF RAT HIPPOCAMPUS TO HYPOXIC ISCHEMIC INSULT. † 1419

Fetal brain iron deficiency occurs in human pregnancies complicated by diabetes mellitus or intrauterine growth retardation. Because neurocognitive deficits are more common in the offspring of these pregnancies, we tested the hypothesis that perinatal brain iron deficiency predisposes the neonatal hippocampus, a structure important for memory processing, to injury. Brain iron concentration was reduced by 45% in 45 neonatal rats by maternal dietary iron restriction during gestation. Right-sided neuronal injury in four hippocampal subareas was induced by hypoxic-ischemic insult (ipsilateral carotid artery ligation and subsequent hypoxia on postnatal d 7) and was quantified histochemically on d 8 by cytochrome c oxidase activity (n = 30), and on d 14 by Nissl staining (n = 15). Acute right-sided cytochrome c oxidase activity loss occurred in CA1 (P = 0.02), CA3c (P < 0.001) and dentate gyrus (P < 0.001) in the iron-deficient group, whereas only CA1 (P = 0. 003) was affected in the iron-sufficient group. Long-term right-sided Nissl substance loss occurred in CA1 (P = 0.001), CA3a,b (P < 0.001) and dentate gyrus (P = 0.008) in the iron-deficient group, but only in CA1 (P = 0.004) in the iron-sufficient group. No increase in right-sided free-iron staining was present in either group. Perinatal iron deficiency predisposes the neonatal hippocampus to a greater acute loss of neuronal metabolic activity after an hypoxic-ischemic event, suggesting compromised cellular energetics. The subsequently greater loss of hippocampal neuronal integrity suggests poorer recoverability after injury in the perinatal iron-deficient brain.
Using the Technology Acceptance Model to Predict Website Usage : Extensions and Empirical Test

Many organisations today are trying to increase the number of visits to their website, as well as the frequency and duration of their visits once they get there. In this paper, we empirically investigate an extension of the Technology Acceptance Model (TAM, originally developed by Davis, 1989) to explain the individual acceptance and usage of a website. The project extends TAM with two “website” constructs: “perceived entertainment value” and “perceived presentation attractiveness”. To validate our model, we partnered with a Dutch portal site, that had over 300 000 subscribers at the time the research was conducted. Our measurement instrument was programmed into an online survey which was offered to every 20th subscriber that entered the portal. The survey was online for three subsequent days in Spring 2000, and resulted in a sample size of 887 respondents. The empirical test delivered the following results. In the first place, Entertainment Value is an equal partner to Usefulness, enjoying equally high or higher correlations with Website Usage. Second, Ease-ofUse does not seem to influence Website Usage directly, but indirectly through Usefulness. Likewise, Attractiveness does not appear to influence Website Usage directly, but indirectly through Entertainment value. The paper discusses these findings and considers the contributions and limitations of the extended TAM model for IS researchers.
General Growth Mixture Analysis of Adolescents' Developmental Trajectories of Anxiety: The Impact of Untested Invariance Assumptions on Substantive Interpretations

Substantively, this study investigates potential heterogeneity in the developmental trajectories of anxiety in adolescence. Methodologically, this study demonstrates the usefulness of general growth mixture analysis (GGMA) in addressing these issues and illustrates the impact of untested invariance assumptions on substantive interpretations. This study relied on data from the Montreal Adolescent Depression Development Project (MADDP), a 4-year follow-up of more than 1,000 adolescents who completed the Beck Anxiety Inventory each year. GGMA models relying on different invariance assumptions were empirically compared. Each of these models converged on a 5-class solution, but yielded different substantive results. The model with class-varying variance–covariance matrices was retained as providing a better fit to the data. These results showed that although elevated levels of anxiety might fluctuate over time, they clearly do not represent a transient phenomenon. This model was then validated in relation to multiple predictors (mostly related to school violence) and outcomes (grade-point average, school dropout, depression, loneliness, and drug-related problems).
A single daily dose of soybean phytosterols in ground beef decreases serum total cholesterol and LDL cholesterol in young, mildly hypercholesterolemic men.

BACKGROUND Consumption of phytosterol-supplemented margarine lowers total plasma cholesterol (TC) and LDL-cholesterol concentrations in older middle-aged hypercholesterolemic individuals. The effects of incorporating phytosterols into lower-fat foods on the plasma lipids of young men at increased risk of developing cardiovascular disease have not been studied. OBJECTIVE We tested the hypothesis that a single daily dose of soybean phytosterols added to ground beef will lower plasma TC and LDL-cholesterol concentrations in mildly hypercholesterolemic young men. DESIGN In a triple-blind, 4-wk study, 34 male college students with elevated plasma TC (5.85 +/- 0.70 mmol/L), LDL cholesterol (4.02 +/- 0.60 mmol/L), and TC:HDL cholesterol (5.5 +/- 1.2) were randomly assigned to the control (ground beef alone) or treatment (ground beef with 2.7 g of phytosterols) group. The phytosterol mixture was two-thirds esterified and one-third nonesterified and consisted of beta-sitosterol (48%), campesterol (27%), and stigmasterol (21%). RESULTS Consumption of phytosterol-supplemented ground beef lowered plasma TC and LDL-cholesterol concentrations and TC:HDL cholesterol from baseline by 9.3%, 14.6%, and 9.1%, respectively (P < 0.001). The LDL particle size did not change, suggesting that the decrease was primarily of particle number. The decreases were similar in subjects with (n = 8) and without (n = 9) a family history of premature cardiovascular disease. No significant changes were found in the control group. CONCLUSION Phytosterol-supplemented ground beef effectively lowers plasma TC and LDL cholesterol and has the potential to become a functional food to help reduce the risk of cardiovascular disease.
Joint Eurographics -ieee Tcvg Symposium on Visualization (2003) Visual Hierarchical Dimension Reduction for Exploration of High Dimensional Datasets

Traditional visualization techniques for multidimensional data sets, such as parallel coordinates, glyphs, and scatterplot matrices, do not scale well to high numbers of dimensions. A common approach to solving this problem is dimensionality reduction. Existing dimensionality reduction techniques usually generate lower dimensional spaces that have little intuitive meaning to users and allow little user interaction. In this paper we propose a new approach to handling high dimensional data, named Visual Hierarchical Dimension Reduction (VHDR), that addresses these drawbacks. VHDR not only generates lower dimensional spaces that are meaningful to users, but also allows user interactions in most steps of the process. In VHDR, dimensions are grouped into a hierarchy, and lower dimensional spaces are constructed using clusters of the hierarchy. We have implemented the VHDR approach into XmdvTool, and extended several traditional multidimensional visualization methods to convey dimension cluster characteristics when visualizing the data set in lower dimensional spaces. Our case study of applying VHDR to a real data set supports our belief that this approach is effective in supporting the exploration of high dimensional data sets.
Line-scan focal modulation microscopy.

We report the development of a line-scan focal modulation microscope (LSFMM) that is capable of high-speed image acquisition ( > 40 ? fps ) with uncompromised optical sectioning capability. The improved background rejection and axial resolution of this imaging modality, enabled by focal modulation, are quantified with three-dimensional imaging data obtained from fluorescent beads. The signal-to-background ratio for the LSFMM system is one- to two-orders of magnitude higher than that for line-scanning confocal systems when imaging deep (up to 100 ? m) into a turbid medium of optical properties similar to biological tissues. The imaging performance of LSFMM, in terms of both spatial and temporal resolutions, is further demonstrated with in vivo imaging experiments with live zebrafish larvae.
Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men.

BACKGROUND Short-term high copper intake does not appear to affect indexes of copper status or functions related to copper status, but the effects of long-term high copper intake are unknown. OBJECTIVE A study was conducted in men to determine the effect of long-term high copper intake on indexes of copper status, oxidant damage, and immune function. DESIGN Nine men were confined to a metabolic research unit (MRU) for 18 d and were fed a 3-d rotating menu providing an average of 1.6 mg Cu/d. The men continued the study under free-living conditions for 129 d and supplemented their usual diets with 7 mg Cu/d. The men then returned to the MRU for 18 d of the same diet as during the first period, except that copper intake was 7.8 mg/d. Plasma copper, ceruloplasmin activity, ceruloplasmin protein, plasma malondialdehyde, benzylamine oxidase activity, erythrocyte superoxide dismutase, hair copper, urinary copper, and urinary thiobarbituric acid-reactive substances were measured during each MRU period. RESULTS Ceruloplasmin activity, benzylamine oxidase, and superoxide dismutase were significantly higher at the end of the second MRU period than at the end of the first. Urinary copper excretion, hair copper concentrations, and urinary thiobarbituric acid-reactive substances were significantly higher during the second MRU period than during the first. Polymorphonuclear cell count, the percentage of white blood cells, lymphocyte count, and interleukin 2R were affected by copper supplementation. Antibody titer for the Beijing strain of influenza virus was significantly lower in supplemented subjects after immunization than in unsupplemented control subjects. CONCLUSIONS Under highly controlled conditions, long-term high copper intake results in increases in some indexes of copper status, alters an index of oxidant stress, and affects several indexes of immune function. The physiologic implications of these changes are unknown.
Left atrial appendage occlusion versus standard medical care in patients with atrial fibrillation and intracerebral haemorrhage: a propensity score-matched follow-up study.

AIMS The aim of this study was to investigate the prognosis in patients with atrial fibrillation (AF) and intracerebral haemorrhage (ICH) having a left atrial appendage occlusion (LAAO) versus patients receiving standard medical therapy. METHODS AND RESULTS A total of 151 patients from the Nordic countries with AF and previous ICH who underwent LAAO using the AMPLATZER Cardiac Plug or the AMPLATZER AMULET were compared to a propensity score-matched group of 151 patients receiving standard medical therapy. The two groups were matched so that their risks for stroke and bleeding were similar (CHA2DS2-VASc and HAS-BLED scores). The standard care patients were identified from the Danish Stroke Registry among 787 patients with AF and ICH. The primary endpoint was a composite of all-cause mortality, ischaemic stroke and major bleeding. Patients with AF and a prior ICH treated with LAAO had a lower risk of the composite outcome as compared to patients treated with standard medical care (events/1,000 years [95% confidence interval]: 53.3 [44.3-64.1] vs. 366.7 [298.2-450.9]; hazard ratio 0.16 [0.07-0.37]). CONCLUSIONS LAAO is suggested to be of major clinical benefit in AF patients having sustained an ICH. These results have to be confirmed in a randomised clinical trial.
Primary visual cortex reflects behavioral performance in the attentional blink

When two masked targets are presented in a rapid sequence, attentional limitations are reflected in reduced identification accuracy for the second target (T2). We used functional magnetic resonance imaging to disentangle the distinct neural substrates of T2 processing during this attentional blink phenomenon. Spatially separating the two targets allows the retinotopic localization of the different stimuli's encoding sites in primary visual cortex (V1) and thus enables activation elicited by each target to be differentially measured in V1. The encoding location of the second target mirrored T2 identification accuracy in a retinotopically specific manner. These results are the first evidence for effects of behavioral performance on hemodynamic responses in V1 under conditions of the attentional blink.
Habitual physical activity in children: the role of genes and the environment.

BACKGROUND Understanding the factors that contribute to physical inactivity in children is important because sedentary behavior strongly relates to metabolic disorders such as obesity and diabetes. OBJECTIVE We aimed to quantify the genetic and environmental influences on physical activity energy expenditure (PAEE) in 100 sex-concordant dizygotic (n = 38) and monozygotic (n = 62) twin pairs aged 4-10 y. DESIGN Resting metabolic rate (RMR) was assessed by using respiratory gas exchange, total energy expenditure (TEE) by using doubly labeled water, and body composition by using dual-energy X-ray absorptiometry. Structural equation modeling was used to partition the phenotypic variance into additive genetic (a2) and common (c2) and unshared (e2) environmental components. RESULTS Because PAEE [TEE - (RMR + 0.1 x TEE)] depends on body weight, which is highly heritable, we tested several models: 1) after adjustment for age, sex, ethnicity, study date, season, and weight, a2 explained none of the phenotypic variance in PAEE (95% CI: 0%, 38%), whereas c2 and e2 accounted for 69% (33%, 77%; P = 0.001) and 31% (23%, 39%; P < 0.001) of the variance, respectively; 2) after adjustment for the cofactors in model 1, a2 explained 19% of the phenotypic variance in TEE (0%, 60%; P = 0.13), whereas c2 and e2 accounted for 59% (16%, 79%; P = 0.007) and 23% (17%, 31%; P < 0.0001) of the variance, respectively; 3) in models adjusted as above (excluding weight), a2 explained no variance in physical activity level (TEE/RMR) (0%, 32%; P = 0.50), whereas c2 and e2 explained 65% (34%, 60%; P = 0.001) and 35% (28%, 45%; P < 0.0001) of the variance, respectively. CONCLUSIONS Our data suggest that the familial resemblance in physical activity in these children is explained predominantly by shared environmental factors and not by genetic variability.
Model completeness results for expansions of the ordered field of real numbers by restricted Pfaffian functions and the exponential function

Recall that a subset of R is called semi-algebraic if it can be represented as a (finite) boolean combination of sets of the form {~ α ∈ R : p(~ α) = 0}, {~ α ∈ R : q(~ α) > 0} where p(~x), q(~x) are n-variable polynomials with real coefficients. A map from R to R is called semi-algebraic if its graph, considered as a subset of R, is so. The geometry of such sets and maps (“semi-algebraic geometry”) is now a widely studied and flourishing subject that owes much to the foundational work in the 1930s of the logician Alfred Tarski. He proved ([11]) that the image of a semi-algebraic set under a semi-algebraic map is semi-algebraic. (A familiar simple instance: the image of {〈a, b, c, x〉 ∈ R : a 6= 0 and ax +bx+c = 0} under the projection map R×R→ R is {〈a, b, c〉 ∈ R : a 6= 0 and b−4ac ≥ 0}.) Tarski’s result implies that the class of semi-algebraic sets is closed under firstorder logical definability (where, as well as boolean operations, the quantifiers “∃x ∈ R . . . ” and “∀x ∈ R . . . ” are allowed) and for this reason it is known to logicians as “quantifier elimination for the ordered ring structure on R”. Immediate consequences are the facts that the closure, interior and boundary of a semialgebraic set are semi-algebraic. It is also the basis for many inductive arguments in semi-algebraic geometry where a desired property of a given semi-algebraic set is inferred from the same property of projections of the set into lower dimensions. For example, the fact (due to Hironaka) that any bounded semi-algebraic set can be triangulated is proved this way. In the 1960s the analytic geometer Lojasiewicz extended the above theory to the analytic context ([8]). The definition of a semi-analytic subset of R is the same as above except that for the basic sets the p(~x)’s and q(~x)’s are allowed to be analytic functions and we only insist that the boolean representations work locally around each point of R (allowing different representations around different points). It is also necessary to restrict the maps to be proper (with semi-analytic graph). With this restriction it is true that the image of a semi-analytic set, known as a sub-analytic set, is semi-analytic provided that the target space is either R or R. Counterexamples have been known since the beginning of this century for maps to R for m ≥ 3. (They are due to Osgood, see [8].) However, the situation was clarified in 1968 by Gabrielov ([5]) who showed that the class of sub-analytic sets