julilili42/papers huggingface dataset:
Experimental Evidence of Helical Flow in Porous Media
2015-11-04

Helical flow leads to deformation of solute plumes and enhances transverse mixing in porous media. We present experiments in which macroscopic helical flow is created by arranging different materials to obtain an anisotropic macroscopic permeability tensor with spatially variable orientation. The resulting helical flow entails twisting streamlines which cause a significant increase in lateral mass exchange and thus a large enhancement of plume dilution (up to 235%) compared to transport in homogenous media. The setup may be used to effectively mix solutes in parallel streams similarly to static mixers, but in porous media.
Peroxisome proliferator-activated receptor alpha, PPARα, directly regulates transcription of cytochrome P450 CYP2C8
2015-11-04

The cytochrome P450, CYP2C8, metabolizes more than 60 clinically used drugs as well as endogenous substances including retinoic acid and arachidonic acid. However, predictive factors for interindividual variability in the efficacy and toxicity of CYP2C8 drug substrates are essentially lacking. Recently we demonstrated that peroxisome proliferator-activated receptor alpha (PPARα), a nuclear receptor primarily involved in control of lipid and energy homeostasis directly regulates the transcription of CYP3A4. Here we investigated the potential regulation of CYP2C8 by PPARα. Two linked intronic SNPs in PPARα (rs4253728, rs4823613) previously associated with hepatic CYP3A4 status showed significant association with CYP2C8 protein level in human liver samples (N = 150). Furthermore, siRNA-mediated knock-down of PPARα in HepaRG human hepatocyte cells resulted in up to ∼60 and ∼50% downregulation of CYP2C8 mRNA and activity, while treatment with the PPARα agonist WY14,643 lead to an induction by >150 and >100%, respectively. Using chromatin immunoprecipitation scanning assay we identified a specific upstream gene region that is occupied in vivo by PPARα. Electromobility shift assay demonstrated direct binding of PPARα to a DR-1 motif located at positions -2762/-2775 bp upstream of the CYP2C8 transcription start site. We further validated the functional activity of this element using luciferase reporter gene assays in HuH7 cells. Moreover, based on our previous studies we demonstrated that WNT/β-catenin acts as a functional inhibitor of PPARα-mediated inducibility of CYP2C8 expression. In conclusion, our data suggest direct involvement of PPARα in both constitutive and inducible regulation of CYP2C8 expression in human liver, which is further modulated by WNT/β-catenin pathway. PPARA gene polymorphism could have a modest influence on CYP2C8 phenotype.
Ketoacidosis in a non-diabetic woman who was fasting during lactation
2015-11-04

Ketoacidosis is a potential complication of type 1 diabetes. Severe ketoacidosis with a blood pH below 7.0 is only rarely seen in other diseases.Three weeks after delivery, a young woman was admitted because of tachypnoe and tachycardia. Blood gas analysis showed a severe metabolic acidosis with a high anion gap. Further workup revealed the presence of ketone bodies in the urine with normal blood glucose and no history of diabetes. The patient reported that she had not eaten for days because of abdominal pain. After initial treatment in the ICU and immediate re-feeding, the patient's condition rapidly improved.While under normal circumstances fasting causes at most only mild acidosis, it can be dangerous during lactation. Prolonged fasting in combination with different forms of stress puts breast feeding women at risk for starvation ketoacidosis and should therefore be avoided.
A role of goals for social inhibition of return?
2015-11-04

The social inhibition of return (sIOR) effect refers to the finding that response initiation times are longer if a movement is executed to a location where another person has responded to just before. Previous studies have examined the influence of the goal of the action on sIOR. In these studies, however, the movement endpoint and to-be-attained goal (e.g., touching/pressing a response key) were at the same spatial location. In the present two experiments, we disentangled movement endpoint and goal's identity and locations by means of introducing action effects that followed directly from a movement. Similar methods were previously shown powerful enough to clearly show the importance of action goals for other phenomena—a finding consistent with effect-based theories of action control, such as the ideomotor theory. The results of the present study revealed that sIOR was shaped by the movement endpoint location, not the goal's identity or location. That is, in both experiments, an sIOR effect was observed, but the magnitude of the sIOR effect was not modulated by repetitions/switches of goals or their locations. Thus, results indicate that goals play a negligible role in the emergence of the sIOR and, consequently, highlight the importance of action observation for the emergence of the sIOR effect.
Timing matters! The neural signature of intuitive judgments differs according to the way information is presented
2015-11-04

One can conceive of intuition as the preliminary perception of coherence. Since this requires holistic perception, it is hypothesized that underlying processing strategies are dependent on the possibility to obtain all relevant information at once. The present study used magnetoencephalography (MEG) to investigate neural mechanisms underlying intuitive coherence perception when semantic concepts are presented all together (simultaneously) or one after the other (sequentially). With simultaneous presentation, absolute activation increases in the left OFC when participants recognize coherence. With sequential presentation activation increases in the right OFC when participants conclude that there is no common associate between the words presented. Behavioral performance was similar in the two experiments. These results demonstrate that the way information is revealed over time changes the processing of intuitive coherence perception. We propose that such changes must be taken into account to disentangle the neural and behavioral mechanisms underlying different accounts of intuition and related phenomena.
High-level Proofs about Low-level Programs
2015-11-04

Functional verification of low-level code requires abstractions over the memory model to be effective, since the number of side-conditions induced by byte- addressed memory is prohibitive even with modern automated reasoners. We pro- pose a flexible solution to this challenge: assertions contain explicit memory layouts which carry the necessary side-conditions as invariants. The memory-related proof obligations arising during verification can then be solved using specialized auto- matic proof procedures. The remaining verification conditions about the content of data structures directly reflect a developer's understanding. The development is formalized in Isabelle/HOL.
Semi-automatic Proofs about Object Graphs in Separation Logic
2015-11-04

Published correctness proofs of garbage collectors in separation logic to date depend on extensive manual, interactive formula manipulations. This paper shows that the approach of symbolic execution in separation logic, as first developed by Smallfoot, also encompasses reasoning about object graphs given by the reachability of objects. This approach yields semi-automatic proofs of two central garbage collection algorithms: Schorr-Waite graph marking and Cheney's collector. Our framework is developed as a conservative extension of Isabelle/HOL. Our verification environment re-uses the Simpl framework for classical Hoare logic.
MicroRNA-15b/16 Enhances the Induction of Regulatory T Cells by Regulating the Expression of Rictor and mTOR
2015-11-05

Abstract CD4+ regulatory T cells (Tregs) are essential for controlling immune responses and preventing autoimmunity. Their development requires regulation of gene expression by microRNAs (miRNAs). To understand miRNA function in Treg development, we searched for important miRNAs and their relevant target genes. Of the more abundantly expressed miRNAs in Tregs, only miR-15b/16, miR-24, and miR-29a impacted the production of in vitro–induced Tregs (iTregs) in overexpression and blocking experiments. miRNA mimics for these significantly enhanced the induction of iTregs in Dicer−/− CD4+ T cells. Furthermore, the overexpression of miR-15b/16 in conventional CD4+ T cells adoptively transferred into Rag2−/− mice increased the in vivo development of peripheral Tregs and diminished the severity of autoimmune colitis. In searching for targets of miR-15b/16, we observed that the mammalian target of rapamycin (mTOR) signaling pathway was enhanced in Dicer−/− CD4+ T cells, and its pharmacological inhibition restored induction of iTregs. Suppression of mTOR signaling is essential for induction of iTregs from naive CD4+ T cells, and the mTORC2 component, Rictor, contained a functional target site for miR-15b/16. Rictor was more abundantly expressed in Dicer−/− T cells as was mTOR, and their expression was downregulated by the overexpression of miR-15b/16. This led to a reduction in mTOR signaling, as measured by phosphorylation of the downstream target, ribosomal protein S6. Finally, knockdown of Rictor by small interfering RNAs enhanced Treg induction in Dicer−/− CD4+ T cells. Therefore, an important mechanism of miRNA regulation of Treg development is through regulation of the mTOR signaling pathway.
Decoupling of a giant planet from its disk in an inclined binary system
2015-11-05

\\n Context. We explore the dynamical evolution of a planet that is embedded in a circumstellar disk, as part of a binary system where the orbital plane of the companion star is significantly tilted with respect to the initial disk plane. \\n Aims. Our aim is to test whether the planet remains within the disk and continues to migrate towards the star in a Type I/II mode, in spite of the secular perturbations of the companion star. Our findings, could explain why observed exoplanets have significant inclination in relation to the equatorial plane of their host star. \\n Methods. We used two different smoothed particle hydrodynamic codes, VINE and PHANTOM, to model the evolution of a star+disk+planet system with a companion star over time. \\n Results. After an initial coupled evolution, the inclinations of the disk and the planet begin to differ significantly. The period of oscillation of the disk inclination, in relation to the initial plane, becomes shorter for the planet, which evolves independently after about 104 yr, following a perturbed N-body behaviour. However, the planet continues to migrate towards the star because, during its orbital motion, it crosses the disk plane, and friction with the gas causes angular momentum loss. \\n Conclusions. In a significantly inclined binary system, disks and planets are not dynamically coupled for small binary separations but evolve almost independently. The planet abandons the disk, and because of the onset of a significant mutual inclination, it interacts with the gas only when its orbit intersects the disk plane. The drift of the planet towards the star is not due to Type I/II, where the planet is embedded in the disk, but to the friction with the gas while crossing the disk.\\n
Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice
2015-11-05

Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] formation and regulator of mineral metabolism. In klotho hypomorphic ( kl/kl) mice, excessive 1,25(OH) 2 D 3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO 3 affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO 3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO 3 did not significantly affect plasma concentrations of 1,25(OH) 2 D 3 and Ca 2+ but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice.
Multivariate assessment of event-related potentials with the t-CWT method
2015-11-05

Hopefully, the publication of both the t-CWT source code and its underlying mathematical algorithm along with a didactic geometric introduction to some basic concepts of multivariate statistics would make t-CWT more accessible to both users and developers in the field of neuroscience research.
Cytokinin response factors regulate PIN-FORMED auxin transporters
2015-11-06

Auxin and cytokinin are key endogenous regulators of plant development. Although cytokinin-mediated modulation of auxin distribution is a developmentally crucial hormonal interaction, its molecular basis is largely unknown. Here we show a direct regulatory link between cytokinin signalling and the auxin transport machinery uncovering a mechanistic framework for cytokinin-auxin cross-talk. We show that the CYTOKININ RESPONSE FACTORS (CRFs), transcription factors downstream of cytokinin perception, transcriptionally control genes encoding PIN-FORMED (PIN) auxin transporters at a specific PIN CYTOKININ RESPONSE ELEMENT (PCRE) domain. Removal of this cis-regulatory element effectively uncouples PIN transcription from the CRF-mediated cytokinin regulation and attenuates plant cytokinin sensitivity. We propose that CRFs represent a missing cross-talk component that fine-tunes auxin transport capacity downstream of cytokinin signalling to control plant development.
The effect of normal and insulating layers on 0-πtransitions in Josephson junctions with a ferromagnetic barrier
2015-11-06

Using the Usadel approach, we provide a formalism that allows us to calculate the critical current density of 21 different types of Josephson junctions (JJs) with a ferromagnetic (F) barrier and additional insulating (I) or/and normal (N) layers inserted between the F layer and superconducting (S) electrodes. In particular, we obtain that in SFS JJs, even a thin additional N layer between the S layer and F layer may noticeably change the thickness dF of the F layer at which the 0-π transitions occur. For certain values of dF, a 0-π transition can even be achieved by changing only the N layer thickness. We use our model to fit experimental data of SIFS and SINFS tunnel junctions.
Optimization of a large‐volume injection method for compound‐specific isotope analysis of polycyclic aromatic compounds at trace concentrations
2015-11-06

Rationale Compound‐specific isotope analysis (CSIA) of persistent organic contaminants can be used for source apportioning in the environment if appropriate sensitivity can be achieved. This paper describes the optimization and validation of a sensitive analytical approach for the determination of the carbon isotope composition of semi‐volatile organic compounds, such as polycyclic aromatic hydrocarbons (PAHs). Methods Analyses are based on the introduction of up to 150 μL of organic extracts by means of programmed temperature vaporization–large‐volume injection combined with gas chromatography coupled to isotope ratio mass spectrometry (PTV‐LVI‐GC/IRMS). To allow for the analysis of more volatile, low‐molecular‐weight PAHs, the PTV injector was equipped with a sub‐ambient/cryogenic cooling. Accuracy, precision, linearity and determination limits for application in isotope analysis were evaluated for a set of individual PAHs ranging from two‐ to five‐ring molecular structures. The method was exemplified by determining the δ 13 C values of individual PAHs in soil samples in a source apportionment study at a contaminated site. Results The choice of PTV injection parameters is crucial to prevent isotope fractionation during injection and largely depends on the analytes to be determined. The observed isotope fractionation effect on semi‐volatiles depends on the applied solvent and injection temperature and demonstrates the importance of performing appropriate tests with given PTV parameters for each of the compounds of interest. The proposed PTV‐LVI‐GC/IRMS method allows the carbon isotope ratio (δ 13 C value) of individual PAHs to be determined accurately and precisely at concentrations of 0.04–0.1 ng μL −1 even for volatile PAHs such as naphthalene or acenaphthene. Conclusions LVI with PTV injector cooling allows for the isotopic analysis of volatile and semi‐volatile PAHs at trace concentrations, thus considerably expanding the applicability of CSIA in environmental studies. Copyright © 2015 John Wiley &amp; Sons, Ltd.
Cultural Studies
2015-11-06

Abstract For more than five decades, cultural studies has developed theoretical, conceptual, and methodological approaches in order to engage with the political relevance of culture, namely with questions of power, of subordination and resistance, hegemony, and subalternity. Focusing on aspects connected to “the politics of culture or the culture of politics” (Stuart Hall), cultural studies' key contribution to the research area of political communication is its interest in a rearticulation both of “the political” as well as of “communication,” which has produced a markedly different and expanded model of political communication. Within the ongoing debate among cultural studies scholars, repoliticization is a keyword. It is, for example, part of the debate on the institutionalization of cultural studies and its political relevance, the debate on cultural studies bridging theoretical knowledge production and political/pedagogic practices, and the debate about the political relevance of cultural studies' research agendas. Consequently, cultural studies offers a wide variety of theoretical and practical approaches that are worth taking into account when researching “the political” in political communication. As such, cultural studies has become a vital and vitalizing paradigm for rethinking “the political.”
Platelet-derived HMGB1 is a critical mediator of thrombosis
2015-11-08

Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation and acute ischemic events. The damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets in multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 in thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation of HMGB1 and determined that platelet-derived HMGB1 is a critical mediator of thrombosis. Mice lacking HMGB1 in platelets exhibited increased bleeding times as well as reduced thrombus formation, platelet aggregation, inflammation, and organ damage during experimental trauma/hemorrhagic shock. Platelets were the major source of HMGB1 within thrombi. In trauma patients, HMGB1 expression on the surface of circulating platelets was markedly upregulated. Moreover, evaluation of isolated platelets revealed that HMGB1 is critical for regulating platelet activation, granule secretion, adhesion, and spreading. These effects were mediated via TLR4- and MyD88-dependent recruitment of platelet guanylyl cyclase (GC) toward the plasma membrane, followed by MyD88/GC complex formation and activation of the cGMP-dependent protein kinase I (cGKI). Thus, we establish platelet-derived HMGB1 as an important mediator of thrombosis and identify a HMGB1-driven link between MyD88 and GC/cGKI in platelets. Additionally, these findings suggest a potential therapeutic target for patients sustaining trauma and other inflammatory disorders associated with abnormal coagulation.
Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells
2015-11-08

The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs) and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix‐ (collagen−/laminin+ binding‐) selected fraction of enriched spermatogonia. Single‐cell transcriptional profiling by Fluidigm BioMark system of a long‐term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs) and human fibroblasts (hFibs) revealed that haGSCs showed a characteristic germ‐ and pluripotency‐associated gene expression profile with some similarities to hESCs and with a significant distinction from somatic hFibs. Genome‐wide comparisons with microarray analysis confirmed that different haGSC colonies exhibited gene expression heterogeneity with more or less pluripotency. The results of this study confirm that haGSCs are adult stem cells with a specific molecular gene expression profile in vitro , related but not identical to true pluripotent stem cells. Under ES‐cell conditions haGSC colonies could be selected and maintained in a partial pluripotent state at the molecular level, which may be related to their cell plasticity and potential to differentiate into cells of all germ layers.
α2A‐Adrenergic receptor polymorphisms and mRNA expression levels are associated with delay discounting in cocaine users
2015-11-08

Abstract Cocaine users characteristically display preferences for smaller immediate rewards over larger delayed rewards, and this delay discounting (DD) has been proposed as an endophenotype of cocaine addiction. Recent evidence suggests that the norepinephrine system and more specifically the α 2A ‐adrenergic receptor ( ADRA2A ) are impacted by chronic cocaine use while also being potentially involved in the neural mechanisms underlying DD. Hence, we investigated the effects of ADRA2A polymorphisms and ADRA2A mRNA expression levels on DD of cocaine users and stimulant‐naïve controls. Two hundred and twenty‐three participants (129 cocaine users and 94 stimulant‐naïve healthy controls) completed a computerized DD paradigm and were genotyped for three single nucleotide polymorphisms (SNPs; rs1800544, rs521674 and rs602618) in the ADRA2A gene, while their peripheral ADRA2A mRNA expression was quantified in whole blood samples. The three SNPs were in near‐perfect linkage disequilibrium. Accordingly, significant group*genotype interactions were found for all three ADRA2A variants revealing steeper DD in cocaine users (but not in controls) carrying the G‐allele of SNP rs1800544, the T‐allele of rs521674 and the C‐allele of rs602618. Similarly, high ADRA2A mRNA expression levels were significantly associated with a reduced tendency to choose smaller more immediate rewards (over larger delayed rewards) in cocaine users but not in controls. As the relationship between DD and cocaine use was moderated by ADRA2A SNPs and by peripheral ADRA2A gene expression, we propose that the norepinephrine system is involved in DD deficits observed in cocaine using individuals. Consequently, pharmacological compounds targeting ADRA2A s might be considered for the symptom‐specific treatment of delay aversion in stimulant addiction.