julilili42/papers huggingface dataset:
Spin physics and TMD studies at A Fixed-Target ExpeRiment at the LHC (AFTER@LHC)
2015-01-01

We report on the opportunities for spin physics and Transverse-Momentum\\nDependent distribution (TMD) studies at a future multi-purpose fixed-target\\nexperiment using the proton or lead ion LHC beams extracted by a bent crystal.\\nThe LHC multi-TeV beams allow for the most energetic fixed-target experiments\\never performed, opening new domains of particle and nuclear physics and\\ncomplementing that of collider physics, in particular that of RHIC and the EIC\\nprojects. The luminosity achievable with AFTER@LHC using typical targets would\\nsurpass that of RHIC by more that 3 orders of magnitude in a similar energy\\nregion. In unpolarised proton-proton collisions, AFTER@LHC allows for\\nmeasurements of TMDs such as the Boer-Mulders quark distributions, the\\ndistribution of unpolarised and linearly polarised gluons in unpolarised\\nprotons. Using the polarisation of hydrogen and nuclear targets, one can\\nmeasure transverse single-spin asymmetries of quark and gluon sensitive probes,\\nsuch as, respectively, Drell-Yan pair and quarkonium production. The\\nfixed-target mode has the advantage to allow for measurements in the\\ntarget-rapidity region, namely at large x^uparrow in the polarised nucleon.\\nOverall, this allows for an ambitious spin program which we outline here.\\n
Peer Disagreement: A Call for the Revision of Prior Probabilities
2015-01-01

The current debate about peer disagreement has so far mainly focused on the question of whether peer disagreements provide genuine counterevidence to which we should respond by revising our credences. By contrast, comparatively little attention has been devoted to the question by which process, if any, such revision should be brought about. The standard assumption is that we update our credences by conditionalizing on the evidence that peer disagreements provide. In this paper, we argue that non-dogmatist views have good reasons to reject conditionalization. Instead, peer disagreements should be understood to call for a revision of our prior conditional probabilities: rather than merely adding to our original evidence, they pose a challenge to the thought that we have properly assessed the probative force of our original evidence.
Effects of Three Kinds of Curcuminoids on Anti-Oxidative System and Membrane Deformation of Human Peripheral Blood Erythrocytes in High Glucose Levels
2015-01-01

Background/Aims: Curcuminoids are the main bioactive constituents of the rhizome of turmeric. Erythrocytes lesions in diabetes are probably related to hyperglycemia and protein glycation. It has been reported that curcumin prevent lipid peroxidation. However, reports on the effects of demethoxycurcumin and bis-demethoxycurcumin on human erythrocytes at high glucose levels are scarce. Our aim is to investigate the effect of curcuminoids on oxidative stress and membrane of erythrocytes exposed to hyperglycemic condition. Methods: In this study, the different blood samples were treated with two doses of glucose (10 or 30 mM) to mimic hyperglycemia in the presence or absence of three kinds of curcuminoids (5 or 10 μM) in a medium at 37 °C for 24 h (Each experiment consists of 20 blood samples from 10 male and 10 female volunteers). The malondialdehyde was checked by HPLC, antioxidase (GSH and GSSG) were measured by LC/MS, SOD was checked by WST-1 kit, morphology and phospholipid symmetry were detected by flow cytometry, confocal scanning microscope and scanning electron microscope. Results: The results illustrated that all three curcuminoids reduce oxidative stress damage on the membrane and maintain a better profile for erythrocytes. Furthermore, three curcuminoids had benefit effects on antioxidase. Conclusion: The three kinds of curcuminoids supplementation may prevent lipid peroxidation at different intensity and membrane dysfunction of human erythrocytes in hyperglycemia.
SPAK Sensitive Regulation of the Epithelial Na<sup>+</sup> Channel ENaC
2015-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK participates in the regulation of NaCl and Na&lt;sup&gt;+&lt;/sup&gt;,K&lt;sup&gt;+&lt;/sup&gt;,2Cl&lt;sup&gt;-&lt;/sup&gt; cotransport and thus renal salt excretion. The present study explored whether SPAK has similarly the potential to regulate the epithelial Na&lt;sup&gt;+&lt;/sup&gt; channel (ENaC). &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;ENaC was expressed in &lt;i&gt;Xenopus&lt;/i&gt; oocytes with or without additional expression of wild type SPAK, constitutively active &lt;sup&gt;T233E&lt;/sup&gt;SPAK, WNK insensitive &lt;sup&gt;T233A&lt;/sup&gt;SPAK or catalytically inactive &lt;sup&gt;D212A&lt;/sup&gt;SPAK, and ENaC activity estimated from amiloride (50 μM) sensitive current (I&lt;sub&gt;amil&lt;/sub&gt;) in dual electrode voltage clamp experiments. Moreover, Ussing chamber was employed to determine I&lt;sub&gt;amil&lt;/sub&gt; in colonic tissue from wild type mice (&lt;i&gt;spak&lt;/i&gt;&lt;sup&gt;&lt;i&gt;wt/wt&lt;/i&gt;&lt;/sup&gt;) and from gene targeted mice carrying WNK insensitive SPAK (&lt;i&gt;spak&lt;/i&gt;&lt;sup&gt;&lt;i&gt;tg/tg&lt;/i&gt;&lt;/sup&gt;). &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;I&lt;sub&gt;amil&lt;/sub&gt; was observed in ENaC-expressing oocytes, but not in water-injected oocytes. In ENaC expressing oocytes I&lt;sub&gt;amil&lt;/sub&gt; was significantly increased following coexpression of wild-type SPAK and &lt;sup&gt;T233E&lt;/sup&gt;SPAK, but not following coexpression of &lt;sup&gt;T233A&lt;/sup&gt;SPAK or &lt;sup&gt;D212A&lt;/sup&gt;SPAK. Colonic I&lt;sub&gt;amil&lt;/sub&gt; was significantly higher in &lt;i&gt;spak&lt;/i&gt;&lt;sup&gt;&lt;i&gt;wt/wt&lt;/i&gt;&lt;/sup&gt; than in &lt;i&gt;spak&lt;/i&gt;&lt;sup&gt;&lt;i&gt;tg/tg&lt;/i&gt;&lt;/sup&gt; mice. &lt;b&gt;&lt;i&gt;Conclusion: &lt;/i&gt;&lt;/b&gt;SPAK has the potential to up-regulate ENaC.
Regulation of Large Conductance Voltage-and Ca2+-Activated K+ Channels by the Janus Kinase JAK3
2015-01-01

Background/Aims: Janus kinase 3 (JAK3), a tyrosine kinase contributing to the regulation of cell proliferation and apoptosis of lymphocytes and tumour cells, has been shown to modify the expression and function of several ion channels and transport proteins. Channels involved in the regulation of cell proliferation include the large conductance voltage- and Ca2+-activated K+ channel BK. The present study explored whether JAK3 modifies BK channel protein abundance and current. Methods: cRNA encoding Ca2+-insensitive BK channel (BKM513I+Δ899-903) was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild-type JAK3, constitutively active A568VJAK3, or inactive K851AJAK3. Voltage gated K+ channel activity was measured utilizing dual electrode voltage clamp. Moreover, BK channel protein abundance was determined utilizing flow cytometry in CD19+ B lymphocyte cell membranes from mice lacking functional JAK3 (jak3-/-) and corresponding wild-type mice (jak3+/+). Results: BK activity in BKM513I+Δ899-903 expressing oocytes was slightly but significantly decreased by coexpression of wild-type JAK3 and of A568VJAK3, but not by coexpression of K851AJAK3. The BK channel protein abundance in the cell membrane was significantly higher in jak3-/- than in jak3+/+ B lymphocytes. The decline of conductance in BK and JAK3 coexpressing oocytes following inhibition of channel protein insertion by brefeldin A (5 μM) was similar in oocytes expressing BK with JAK3 and oocytes expressing BK alone, indicating that JAK3 might slow channel protein insertion into rather than accelerating channel protein retrieval from the cell membrane. Conclusion: JAK3 is a weak negative regulator of membrane BK protein abundance and activity.
Up-Regulation of Intestinal Phosphate Transporter NaPi-IIb (SLC34A2) by the Kinases SPAK and OSR1
2015-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), kinases controlled by WNK (with-no-K[Lys] kinase), are powerful regulators of cellular ion transport and blood pressure. Observations in gene-targeted mice disclosed an impact of SPAK/OSR1 on phosphate metabolism. The present study thus tested whether SPAK and/or OSR1 contributes to the regulation of the intestinal Na&lt;sup&gt;+&lt;/sup&gt;-coupled phosphate co-transporter NaPi-IIb (SLC34A2). &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;cRNA encoding NaPi-IIb was injected into &lt;i&gt;Xenopus laevis&lt;/i&gt; oocytes without or with additional injection of cRNA encoding wild-type SPAK, constitutively active &lt;sup&gt;T233E&lt;/sup&gt;SPAK, WNK insensitive &lt;sup&gt;T233A&lt;/sup&gt;SPAK, catalytically inactive &lt;sup&gt;D212A&lt;/sup&gt;SPAK, wild-type OSR1, constitutively active &lt;sup&gt;T185E&lt;/sup&gt;OSR1, WNK insensitive &lt;sup&gt;T185A&lt;/sup&gt;OSR1 or catalytically inactive &lt;sup&gt;D164A&lt;/sup&gt;OSR1. The phosphate (1 mM)-induced inward current (I&lt;sub&gt;Pi&lt;/sub&gt;) was taken as measure of phosphate transport. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;I&lt;sub&gt;Pi&lt;/sub&gt; was observed in NaPi-IIb expressing oocytes but not in water injected oocytes, and was significantly increased by co-expression of SPAK, &lt;sup&gt;T233E&lt;/sup&gt;SPAK, OSR1, &lt;sup&gt;T185E&lt;/sup&gt;OSR1 or SPAK+OSR1, but not by co-expression of &lt;sup&gt;T233A&lt;/sup&gt;SPAK, &lt;sup&gt;D212A&lt;/sup&gt;SPAK, &lt;sup&gt;T185A&lt;/sup&gt;OSR1, or &lt;sup&gt;D164A&lt;/sup&gt;OSR1. SPAK and OSR1 both increased the maximal transport rate of the carrier. &lt;b&gt;&lt;i&gt;Conclusions: &lt;/i&gt;&lt;/b&gt;SPAK and OSR1 are powerful stimulators of the intestinal Na&lt;sup&gt;+&lt;/sup&gt;-coupled phosphate co-transporter NaPi-IIb.
Impact of Janus Kinase 3 on Cellular Ca2+ Release, Store Operated Ca2+ Entry and Na+/Ca2+ Exchanger Activity in Dendritic Cells
2015-01-01

Background/Aims: Janus kinase 3 (JAK3), a tyrosine kinase mainly expressed in hematopoietic cells, participates in the signaling stimulating cell proliferation. The kinase is expressed in dendritic cells (DCs), antigen presenting cells involved in the initiation and regulation of antigen-specific T-cell responses. Dendritic cell function is regulated by cytosolic Ca2+ activity ([Ca2+]i). Mediators increasing [Ca2+]i in DCs include ATP and the chemokine receptor CXCR4 ligand CXCL12. The present study explored, whether JAK3 participates in the regulation of [Ca2+]i in DCs. Methods: Fura-2 fluorescence was employed to determine [Ca2+]i, and whole cell patch clamp to decipher electrogenic transport in immature DCs isolated from bone marrow of JAK3-knockout (jak3-/-) or wild-type mice (jak3+/+). Results: Without treatment, [Ca2+]i was similar in jak3-/- and jak3+/+ DCs. Addition of ATP (100 μM) was followed by transient increase of [Ca2+]i reflecting Ca2+ release from intracellular stores, an effect significantly less pronounced in jak3-/- DCs than in jak3+/+ DCs. CXCL12 administration was followed by a sustained increase of [Ca2+]i reflecting receptor operated Ca2+ entry, an effect significantly less rapid in jak3-/- DCs than in jak3+/+ DCs. In addition, the Ca2+ release-activated Ca2+ channel (CRAC) current triggered by IP3-induced Ca2+ store depletion and CXCL12 was significantly higher in DCs from jak3+/+ mice than in jak3-/- mice. Inhibition of sarcoendoplasmatic reticulum Ca2+-ATPase (SERCA) by thapsigargin (1 μM) in the absence of extracellular Ca2+ was followed by a transient increase of [Ca2+]i reflecting Ca2+ release from intracellular stores, and subsequent readdition of extracellular Ca2+ in the continued presence of thapsigargin was followed by a sustained increase of [Ca2+]i reflecting store operated Ca2+ entry (SOCE). Both, Ca2+ release from intracellular stores and SOCE were again significantly lower in jak3-/- DCs than in jak3+/+ DCs. Pretreatment of jak3+/+ DCs with JAK inhibitor WHI-P154 (22 μM, 10 minutes or 24 hours) significantly blunted both thapsigargin induced Ca2+ release and subsequent SOCE. Abrupt replacement of Na+ containing (130 mM) and Ca2+ free (0 mM) extracellular bath by Na+ free (0 mM) and Ca2+ containing (2 mM) extracellular bath increased [Ca2+]i reflecting Na+/Ca2+ exchanger activity, an effect again significantly less pronounced in jak3-/- DCs than in jak3+/+ DCs. Conclusions: JAK3 deficiency is followed by down-regulation of cytosolic Ca2+ release, receptor and store operated Ca2+ entry and Na+/Ca2+ exchanger activity in DCs.
SPAK and OSR1 Sensitive Cell Membrane Protein Abundance and Activity of KCNQ1/E1 K+ Channels
2015-01-01

Background/Aims: KCNQ1/E1 channels are expressed in diverse tissues and serve a variety of functions including endolymph secretion in the inner ear, cardiac repolarization, epithelial transport and cell volume regulation. Kinases involved in regulation of epithelial transport and cell volume include SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are under control of WNK (with-no-K[Lys]) kinases. The present study explored whether KCNQ1/E1 channels are regulated by SPAK and/or OSR1. Methods: cRNA encoding KCNQ1/E1 was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild-type SPAK, constitutively active T233ESPAK, WNK insensitive T233ASPAK, catalytically inactive D212ASPAK, wild-type OSR1, constitutively active T185EOSR1, WNK insensitive T185AOSR1 and catalytically inactive D164AOSR1. Voltage gated K+ channel activity was quantified utilizing dual electrode voltage clamp and KCNQ1/E1 channel protein abundance in the cell membrane utilizing chemiluminescence of KCNQ1/E1 containing an extracellular Flag tag epitope (KCNQ1-Flag/E1). Results: KCNQ1/E1 activity and KCNQ1-Flag/E1 protein abundance were significantly enhanced by wild-type SPAK and T233ESPAK, but not by T233ASPAK and D212ASPAK. Similarly, KCNQ1/E1 activity and KCNQ1-Flag/E1 protein abundance were significantly increased by wild-type OSR1 and T185EOSR1, but not by T185AOSR1 and D164AOSR1. Conclusions: SPAK and OSR1 participate in the regulation of KCNQ1/E1 protein abundance and activity.
Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3
2015-01-01

Background/Aims: Janus kinase 3 (JAK3), a kinase mainly expressed in hematopoietic cells, has been shown to down-regulate the Na+/K+ ATPase and participate in the regulation of several ion channels and carriers. Channels expressed in thymus and regulating the abundance of T lymphocytes include the voltage gated K+ channel KCNE1/KCNQ1. The present study explored whether JAK3 contributes to the regulation of KCNE1/KCNQ1. Methods: cRNA encoding KCNE1/KCNQ1 was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild-type JAK3, constitutively active A568VJAK3, or inactive K851AJAK3. Voltage gated K+ channel activity was measured utilizing two electrode voltage clamp. Results: KCNE1/KCNQ1 activity was significantly increased by wild-type JAK3 and A568VJAK3, but not by K851AJAK3. The difference between oocytes expressing KCNE1/KCNQ1 alone and oocytes expressing KCNE1/KCNQ1 with A568VJAK3 was virtually abrogated by JAK3 inhibitor WHI-P154 (22 μM) but not by inhibition of transcription with actinomycin D (50 nM). Inhibition of KCNE1/KCNQ1 protein insertion into the cell membrane by brefeldin A (5 μM) resulted in a decline of the voltage gated current, which was similar in the absence and presence of A568VJAK3, suggesting that A568VJAK3 did not accelerate KCNE1/KCNQ1 protein retrieval from the cell membrane. Conclusion: JAK3 contributes to the regulation of membrane KCNE1/KCNQ1 activity, an effect sensitive to JAK3 inhibitor WHI-P154.
Self-aligned placement and detection of quantum dots on the tips of individual conical plasmonic nanostructures
2015-01-01

Hybrid structures of few or single quantum dots (QDs) coupled to single optical antennas are of prime interest for nano-optical research. The photoluminescence (PL) signal from single nanoemitters, such as QDs, can be enhanced, and their emission characteristics modified, by coupling them to plasmonic nanostructures. Here, a self-aligned technique for placing nanoscale QDs with about 10 nm lateral accuracy and well-defined molecular distances to the tips of individual nanocones is reported. This way the QDs are positioned exactly in the high near-field region that can be created near the cone apex. The cones are excited in the focus of a radially polarized laser beam and the PL signal of few or single QDs on the cone tips is spectrally detected.
Participatory Design in Parkinson's Research with Focus on the Symptomatic Domains to be Measured
2015-01-01

A participatory design strategy allowed the definition of a consensual list of symptomatic domains. Both the strategy and the achieved results may be of relevance for similar interdisciplinary approaches in the field of PD using a participatory design involving patients, clinicians and technologists.
A spatiotemporal observation of EndMT and mesenchymal cell colonization at the onset of human cardiac valve development
2015-01-01

Elucidation of mechanisms in semilunar valve development may enable the development of new therapies. Here, we found differences in proliferation-associated genes and genes repressed by vascular endothelial growth factor between human semilunar valves from first and second trimester valve leaflets. The proliferation of valve interstitial cells and ventricular valve endothelial cells (VECs) and cellular density declined from the first to the second trimester. Cytoplasmic expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc-1) in VECs (4 weeks), and later cells in the leaflet/annulus junction mesenchyme expressing inactive NFATc-1 (5.5-9 weeks) were detected, indicative of EndMT in valvulogenesis. At this leaflet/annulus junction CD44+ cells clustered during elongation (11 weeks), extending toward the tip along the fibrosal layer in second trimester leaflets. Differing patterns of maturation in the fibrosa and ventricularis were detected via increased fibrosal periostin content, which tracked the presence of the CD44+ cells in the second trimester. We revealed that spatiotemporal NFATc-1 expression actively regulates EndMT during human valvulogenesis, as early as 4 weeks. Additionally, CD44+ cells play a role in leaflet maturation toward the trilaminar structure, possibly via migration of VECs undergoing EndMT, which subsequently ascend from the leaflet/annulus junction.
Human Sterol Regulatory Element-Binding Protein 1a Contributes Significantly to Hepatic Lipogenic Gene Expression
2015-01-01

Background/Aims: Sterol regulatory element-binding protein (SREBP) 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression.
SGK1-Sensitive Regulation of Cyclin-Dependent Kinase Inhibitor 1B (p27) in Cardiomyocyte Hypertrophy
2015-01-01

Background/Aims: The serum- and glucocorticoid-inducible kinase SGK1 participates in the orchestration of cardiac hypertrophy and remodeling. Signaling linking SGK1 activity to cardiac remodeling is, however, incompletely understood. SGK1 phosphorylation targets include cyclin-dependent kinase inhibitor 1B (p27), a protein which suppresses cardiac hypertrophy. The present study explored how effects of SGK1 on nuclear p27 localization might modulate the hypertrophic response in cardiomyocytes. Methods: Experiments were performed in HL-1 cardiomyocytes and in SGK1-deficient (sgk1-/-) and corresponding wild-type (sgk1+/+) mice following pressure overload by transverse aortic constriction (TAC). Transcript levels were quantified by RT-PCR, protein abundance by Western blotting and protein localization by confocal microscopy. Results: In HL-1 cardiomyocytes, overexpression of constitutively active SGK1 (SGK1S422D) but not of inactive SGK1 (SGK1K127N) increased significantly the cell size and transcript levels encoding Acta1, a molecular marker of hypertrophy. Those effects were paralleled by almost complete relocation of p27 in the cytoplasm. Treatment of HL-1 cardiomyocytes with isoproterenol was followed by up-regulation of SGK1 expression. Moreover, isoproterenol treatment stimulated the hypertrophic response and was followed by disappearance of p27 from the nuclei, effects prevented by the SGK1 inhibitor EMD638683. The effect of SGK1S422D overexpression on Acta1 mRNA levels was disrupted by overexpression of p27 and of the p27T197A mutant lacking the SGK1 phosphorylation site, but not of the phosphomimetic p27T197D mutant. In sgk1+/+ mice, TAC increased significantly SGK1 and Acta1 mRNA levels and decreased the nuclear to cytoplasmic protein ratio of p27 in cardiac tissue, effects blunted in the sgk1-/- mice. Conclusion: SGK1-induced hypertrophy of cardiomyocytes involves p27 phosphorylation at T197, which fosters cytoplasmic p27 localization.
A comparison of the psychological refractory period and prioritized processing paradigms: Can the response-selection bottleneck model explain them both?
2015-01-01

Four experiments examined whether well-established phenomena from the psychological refractory period (PRP) paradigm are also observed in the prioritized processing paradigm, as would be expected from a common description of the 2 paradigms with the response selection bottleneck (RSB) model. Consistent with a generalization of the RSB model to the prioritized processing paradigm, Experiments 1 and 2 showed that this paradigm yields effects of SOA and stimulus discriminability analogous to those observed in the PRP paradigm. In Experiments 3 and 4, however, overall RTs and effect sizes differed between the PRP and prioritized processing paradigms in ways that are difficult to explain within the RSB model. Understanding the differences between these 2 paradigms offers considerable promise as a way to extend the RSB model beyond the domain of the PRP paradigm and to generalize our understanding of multitasking interference.