julilili42/papers huggingface dataset:
Development of a novel triple-target imaging strategy for the characterization of plaque inflammation in ApoE-/- mice
2013-08-02

Introduction: Myocardial infarction and stroke due to the rupture or erosion of atherosclerotic plaques are one of the leading causes of mortality and morbidity. Thus, the distinction between rupture-prone and inactive atherosclerotic lesions for early or preventive treatment is a major clinical goal. Multiple molecules have been found to be involved in the progression and rupture of atherosclerotic lesions. Here, we present a novel triple-target imaging strategy for the diagnosis and characterization of inflamed plaques using antibodies against vascular cell adhesion molecule 1 (VCAM-1), lectin-like ox-LDL receptor (LOX-1) and glycoprotein VI (GPVI). Methods and results: To proof efficient binding of the monoclonal antibodies against human VCAM-1, LOX-1 and GPVI, we incubated cultures of human umbilical vein endothelial cells (HUVECs) with TNF-α or angiotensin II to increase the expression of VCAM-1 and LOX-1, respectively. After labeling with fluorescent dyes and visualization by fluorescence microscopy, all three antibodies demonstrated specific binding to HUVEC when compared to non-specific control antibodies. Thereafter, antibodies were conjugated to the fluorescent dyes DyLight 680, DyLight 755 (both Thermo Scientific) and Qdot 800 (Invitrogen) for simultaneous imaging with the IVIS spectrum from Caliper Life Sciences. A total of nine ApoE-/- mice were euthanized after 3 and 6 month of western type diet, their aortic arches removed and imaged after incubation with the three specific and the control antibodies using filter configurations for the selective imaging of each fluorescent dye. The VCAM-1, LOX-1 and GPVI antibody constructs showed specific binding to atherosclerotic plaques (p<0.05 for all three) at both time points in comparison with their controls. Conclusions: In this proof-of-concept study, we were able to develop a triple-target strategy for imaging atherosclerotic plaques in ApoE-/- mice. The strategy of targeting different inflammatory markers by molecular imaging offers an opportunity to characterize plaque inflammation and potentially discriminate between rupture-prone and inactive plaques.
Enhanced migration of bone marrow-derived cells mediated by VCAM-1/VLA-4 interaction improves cardiac function in virus-induced dilated cardiomyopathy
2013-08-02

Aims: Endogenous circulation of bone marrow-derived cells (BMCs) was observed in patients with dilated cardiomyopathy (DCM) who showed cardiac upregulation of Vascular Cell Adhesion Protein-1 (VCAM-1). However, the underlying pathophysiology is currently unknown. Thus, we aimed to analyze circulation, homing and G-CSF based mobilization of BMCs in a murine model of virus-induced DCM.
Increased soluble ST2 predicts long-term mortality in patients with stable coronary artery disease
2013-08-02

Background: Soluble ST2 (sST2) has emerged as a strong prognostic biomarker in patients with heart failure and myocardial infarction. There is no published data on sST2 in patients with stable coronary artery disease (CAD). Therefore, the aim of this study was to evaluate the long-term prognostic value of sST2 in patients with stable CAD.
Speckle-tracking echocardiography and cardiac MRI for assessment of left ventricular reverse remodeling after percutaneous mitral valve repair
2013-08-02

Background: Severe mitral regurgitation (MR) causes remodeling of the left ventricle (LV). After surgical mitral valve repair (MVR) reverse remodeling of the LV has been observed. Aim of this study was to assess if percutaneous MVR with the MitraClip system can also induce a reverse LV remodeling. Patients and methods: We prospectively included 33 consecutive patients with symptomatic moderate-to-severe MR and high perioperative risk undergoing percutaneous MVR. Patients underwent transthoracic echocardiography (LV volumes, LV stroke volume, ejection fraction, diameter of mitral annulus) and strain analysis (global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS)) by speckle-tracking echocardiography and by MRI prior to the procedure and three months after the procedure. Results: Three months after MitraClip procedure reverse LV remodeling was documented by a significant reduction of LV endsystolic (116.2±71.0 mL to 102.9±58.3 mL, p<0.001) and enddiastolic (181.3±75.2 mL to 174.3±66.8 mL, p=0.030) volumes and an improvement of LV stroke volume (65.1±23.1 mL to 71.4±21.6 mL, p=0.011) and LV ejection fraction (38.4±12.9% to 40.3±12.0%; p=0.026). Diameter of mitral annulus was significantly reduced (44.5±6.0 mm to 42.2±5.4 mm, p=0.001). Of note, a significant improvement of GLS was found in both echocardiography (p=0.002) and MRI (p=0.001). No significant changes were seen with regard to GRS and GCS. Reverse LV remodeling was associated with significant improvement in NYHA classification (p=0.005) and 6 minute walk test (254±138 m vs. 306±105 m; p<0.017). Conclusions: Successful percutaneous MRV not only leads to an improvement of MR, but additionally allows a reverse LV remodeling within 3 months, which might contribute to the symptomatic and prognostic success in these patients.
Severe cardiac autonomic failure as risk predictor in patients undergoing aortic valve replacement or transcatheter aortic valve implantation
2013-08-02

Background: A substantial number of patients with aortic valve stenosis (AS) suffer from severe cardiac autonomic failure (SAF) defined as combination of abnormal heart rate turbulence and deceleration capacity. Here we hypothesized that presence of SAF is a strong and independent predictor of adverse outcome in patients with severe AS undergoing aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI). Methods: We included 161 consecutive patients with severe AS in sinus rhythm who underwent AVR (n=53) or TAVI (n=108) at our institution. Twenty-four hour Holter recordings were performed prior to operation. SAF was assessed according previously published technologies. SAF was considered present if Turbulence Onset ≥0%, Turbulence Slope ≤2.5ms/RRI and deceleration capacity ≤4.5ms. Multivariable analyses included SAF, age ≥80 years, increased levels of brain natriuretic peptides and the logistic Euro Score. Primary endpoint was two-year all-cause mortality. Results: During a median follow of 312 days, 11 patients died. Twenty-three of 161 patients (14.3%) were SAF-positive prior to operation. SAF-positive patients had a cumulative mortality rate of 32.6% compared to 4.2% in SAF-negative patients (p<0.0001; Figure 1). Multivariably, SAF was the only independent predictor of mortality (hazard ratio 6.1; 95% CI 1.7-21.5; p=0.006). Figure 1 Discussion: Presence of SAF is a strong and independent predictor of mortality in patients who undergo AVR or TAVI.
Refining long-term prediction of cardiovascular risk in diabetes
2013-08-02

Aim: Cardiovascular risk assessment in patients with diabetes relies on traditional cardiovascular risk factors. However, numerous novel biomarkers have been found to be predictors of cardiovascular disease, which might significantly improve risk prediction in diabetic patients. The purpose of this study was to improve prediction of cardiovascular risk in diabetic patients by investigating 135 evolving biomarkers encompassing various pathophysiologic pathways. Based on selected biomarkers a clinically applicable prediction algorithm for long-term cardiovascular mortality in this growing patient population was designed. Methods: We prospectively enrolled 864 diabetic patients of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study with a median follow-up of 9.6 years. Independent risk factors were selected using bootstrapping based on a Cox regression analysis. Results: The following seven variables were selected for the final multivariate model: NT-proBNP, age, male sex, renin, diabetes duration, Lp-PLA2 and 25-OH vitamin D3. The risk score based on the aforementioned variables demonstrated an excellent discriminatory power for 10-year survival free from cardiovascular death with a C-statistic of 0.76 (P<0.001), which was significantly better than the established U.K. Prospective Diabetes Study (UKPDS) risk engine (C-statistic=0.64,P<0.001). Net reclassification confirmed a significant improvement of individual risk prediction by 22% (95% CI:14-30%) compared to the UKPDS risk engine (P<0.001). Conclusion: Our score based on traditional risk factors and reinforced with novel biomarkers outperforms previous risk algorithms. The score allows more accurate classification of cardiovascular risk in diabetic patients and an individualized treatment potentially improving survival.
Impaired platelet Ca2+ signaling and thrombus formation due to excessive 1,25 (OH)2 vitamin D concentrations in klotho-deficient mice
2013-08-02

Background: Platelets are activated by increase of cytosolic Ca2+ concentration ([Ca2+]i) following stimulation of store operated Ca2+ entry (SOCE), which is accomplished by the pore forming unit Orai1 and its regulator STIM1. In other cell types Ca2+ transport across the cell membrane is regulated by 1,25(OH)2 vitamin D. Formation of 1,25(OH)2 vitamin D is inhibited by anti-aging protein klotho. Thus, 1,25(OH)2 vitamin D plasma levels are excessive in klotho-deficient mice (kl/kl), which suffer from severe vascular calcification, early appearance of age related disorders and a life span shortened to some 12 weeks. The present study explored whether klotho deficiency impacts on [Ca2+]i regulation and function of platelets. Methods and results: As a result, SOCE and agonist-induced [Ca2+]i increase were significantly blunted in platelets from kl/kl mice. Similarly, degranulation, integrin αIIbβ3 activation as well as aggregation and in vitro thrombus formation were significantly impaired in platelets from kl/kl mice. Low vitamin D diet (LVD) normalized plasma 1,25(OH)2 vitamin D concentrations in klotho-deficient mice and abrogated impaired Ca2+ signaling as well as Ca2+-dependent activation of platelets from kl/kl mice. Platelet and megakaryocyte mRNA levels and protein expression of platelet SOCE-mediating molecules STIM1 and Orai1 were significantly reduced in kl/kl mice, an effect reversed after treatment with LVD. The effect of excessive Treatment with 1,25(OH)2 vitamin D mimicked the phenotype of megakaryocytes from klotho-deficient mice since 1,25(OH)2 vitamin D-treated megakaryocytic MEG-01 cells displayed significantly decreased mRNA levels and protein abundance of STIM1 and Orai1. Nuclear abundance of NF-κB subunits p50 and p65 were significantly lower in megakaryocytes derived from kl/kl mice than in megakaryocytes from klotho wildtype mice, an effect again found reversed in megakaryocytes from kl/kl mice treated with LVD. Transfection of MEG-01 cells with p50/p65 significantly increased STIM1 and Orai1 expression on mRNA as well as on protein level. Conclusions: In conclusion, klotho deficiency leads to blunted SOCE in platelets resulting in impaired thrombus formation at least in part due to impairment of NF-κB-dependent STIM1 and Orai1 expression in megakaryocytes by excessive 1,25(OH)2 vitamin D levels.
Towards a unified paradigm for sequence‐based identification of fungi
2013-08-03

Abstract The nuclear ribosomal internal transcribed spacer ( ITS ) region is the formal fungal barcode and in most cases the marker of choice for the exploration of fungal diversity in environmental samples. Two problems are particularly acute in the pursuit of satisfactory taxonomic assignment of newly generated ITS sequences: (i) the lack of an inclusive, reliable public reference data set and (ii) the lack of means to refer to fungal species, for which no Latin name is available in a standardized stable way. Here, we report on progress in these regards through further development of the UNITE database ( http://unite.ut.ee ) for molecular identification of fungi. All fungal species represented by at least two ITS sequences in the international nucleotide sequence databases are now given a unique, stable name of the accession number type (e.g. H ymenoscyphus pseudoalbidus | GU 586904| SH 133781.05 FU ), and their taxonomic and ecological annotations were corrected as far as possible through a distributed, third‐party annotation effort. We introduce the term ‘species hypothesis’ ( SH ) for the taxa discovered in clustering on different similarity thresholds (97–99%). An automatically or manually designated sequence is chosen to represent each such SH. These reference sequences are released ( http://unite.ut.ee/repository.php ) for use by the scientific community in, for example, local sequence similarity searches and in the QIIME pipeline. The system and the data will be updated automatically as the number of public fungal ITS sequences grows. We invite everybody in the position to improve the annotation or metadata associated with their particular fungal lineages of expertise to do so through the new Web‐based sequence management system in UNITE .
Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2
2013-08-05

Mechanotransduction in the mammalian auditory system depends on mechanosensitive channels in the hair bundles that project from the apical surface of the sensory hair cells. Individual stereocilia within each bundle contain a core of tightly packed actin filaments, whose length is dynamically regulated during development and in the adult. We show that the actin-binding protein epidermal growth factor receptor pathway substrate 8 (Eps8)L2, a member of the Eps8-like protein family, is a newly identified hair bundle protein that is localized at the tips of stereocilia of both cochlear and vestibular hair cells. It has a spatiotemporal expression pattern that complements that of Eps8. In the cochlea, whereas Eps8 is essential for the initial elongation of stereocilia, Eps8L2 is required for their maintenance in adult hair cells. In the absence of both proteins, the ordered staircase structure of the hair bundle in the cochlea decays. In contrast to the early profound hearing loss associated with an absence of Eps8, Eps8L2 null-mutant mice exhibit a late-onset, progressive hearing loss that is directly linked to a gradual deterioration in hair bundle morphology. We conclude that Eps8L2 is required for the long-term maintenance of the staircase structure and mechanosensory function of auditory hair bundles. It complements the developmental role of Eps8 and is a candidate gene for progressive age-related hearing loss.
Analysis of Genome-Wide Association Studies of Alzheimer Disease and of Parkinson Disease to Determine If These 2 Diseases Share a Common Genetic Risk
2013-08-05

Our findings therefore imply that loci that increase the risk of both PD and AD are not widespread and that the pathological overlap could instead be “downstream” of the primary susceptibility genes that increase the risk of each disease.
Development, validation, and initial results of the Angioedema Activity Score
2013-08-06

Abstract Background Recurrent angioedema ( R ec A ) is a frequent clinical problem characterized by suddenly occurring cutaneous and/or mucosal swellings. Depending on their location, R ec A may be painful, hindering, disfiguring, or even life‐threatening. The assessment of disease activity in affected patients is important to guide treatment decisions. Currently, however, there is no standardized and validated outcome measure available to do so. Objective To develop and validate the first specific patient‐reported outcome instrument to assess disease activity in R ec A patients, the A ngioedema A ctivity S core ( AAS ). Methods After a set of potential AAS items was developed, item evaluation and reduction were performed by means of impact analysis, factor analysis, regression analysis, and by checking for face validity. In addition, the items of the final AAS questionnaire were tested for their validity and reliability during a 12‐week validation study. Results In total, data from 110 and 80 R ec A patients were used during the AAS item evaluation and validation phase, respectively. The resulting AAS consisted of five items and was found to have a one‐dimensional structure and excellent internal consistency. It correlated well with other measures of disease activity and quality‐of‐life impairment, thus demonstrating its convergent validity. In addition, the known‐groups validity and test–retest reliability of the AAS were found to be good. Conclusions The AAS is the first validated and reliable tool to determine disease activity in R ec A patients, and it may serve as a valuable instrument in future clinical studies and routine patient care.
The Single-Stranded DNA-Binding Protein WHIRLY1 Represses WRKY53 Expression and Delays Leaf Senescence in a Developmental Stage-Dependent Manner in Arabidopsis
2013-08-06

Leaf senescence in plants involves both positive and negative transcriptional regulation. In this work, we show evidence for the single-stranded DNA-binding protein WHIRLY1 (WHY1) that functions as an upstream suppressor of WRKY53 in a developmental stage-dependent manner during leaf senescence in Arabidopsis (Arabidopsis thaliana). The why1 mutant displayed an early-senescence phenotype. In this background, the expression levels of both WRKY53 and the senescence-associated protease gene SAG12 increased. WHY1 bound to the sequence region that contains an elicitor response element motif-like sequence, GNNNAAATT, plus an AT-rich telomeric repeat-like sequence in the WRKY53 promoter in in vivo and in vitro mutagenesis assays as well as in a chromatin immunoprecipitation assay. This binding to the promoter of WRKY53 was regulated in a developmental stage-dependent manner, as verified by chromatin immunoprecipitation-polymerase chain reaction assay. This direct interaction was further determined by a transient expression assay in which WHY1 repressed β-GLUCURONIDASE gene expression driven by the WRKY53 promoter. Genetic analysis of double mutant transgenic plants revealed that WHY1 overexpression in the wrky53 mutant (oeWHY1wrky53) had no effect on the stay-green phenotype of the wrky53 mutant, while a WHY1 knockout mutant in the wrky53 mutant background (why1wrky53) generated subtle change in the leaf yellow/green phenotype. These results suggest that WHY1 was an upstream regulator of WRKY53 during leaf senescence.
Constructive semantics, admissibility of rules and the validity of Peirce's law
2013-08-06

Journal Article Constructive semantics, admissibility of rules and the validity of Peirce's law Get access Wagner De Campos Sanz, Wagner De Campos Sanz * Universidade Federal de Goiás, Faculdade de Filosofia, Campus II, Goiânia, GO 74001-970, Brasil *E-mail: wsanz@uol.com.br Search for other works by this author on: Oxford Academic Google Scholar Thomas Piecha, Thomas Piecha Universität Tübingen, Wilhelm-Schickard-Institut für Informatik, Sand 13, 72076 Tübingen, Germany Search for other works by this author on: Oxford Academic Google Scholar Peter Schroeder-Heister Peter Schroeder-Heister Universität Tübingen, Wilhelm-Schickard-Institut für Informatik, Sand 13, 72076 Tübingen, Germany Search for other works by this author on: Oxford Academic Google Scholar Logic Journal of the IGPL, Volume 22, Issue 2, April 2014, Pages 297–308, https://doi.org/10.1093/jigpal/jzt029 Published: 06 August 2013 Article history Received: 21 December 2012 Published: 06 August 2013
In-Flight Calibration of the Energetic Gamma-Ray Experiment Telescope (Egret) on the Compton Gamma-Ray Observatory
2013-08-06

The Energetic Gamma-Ray Experiment Telescope (EGRET) on the Compton Gamma-Ray Observatory has been operating for over seven years since its launch in 1991 April. This span of time far exceeds the design lifetime of two years. As the instrument has aged, several changes have occurred due to spark chamber gas exchanges as well as some hardware degradation and failures, all of which have an influence on the instrument sensitivity. This paper describes post-launch measurements and analysis that are done to calibrate the instrument response functions. The updated instrument characteristics are incorporated into the analysis software.
Highly parallelized inference of large genome‐based phylogenies
2013-08-07

SUMMARY Genome Blast Distance Phylogeny ( GBDP ) infers distances and phylogenetic relationships between organisms from completely or partially sequenced genomes. It is well suited for parallelization as pairwise distances are calculated independently. As exemplar data for a high‐performance cluster implementation that executes many pairwise genome comparisons in parallel, we here used sequences from the Genomic Encyclopedia of Bacteria and Archaea project. Phylogenies were inferred from genome‐scale nucleotide and amino acid data with all variants of GBDP , including novel adaptations to amino acid sequences and approaches yielding trees with branch support. The dependency of phylogenetic accuracy, average branch support as well as performance indicators such as running time and disk space consumption on details of genome comparison, distance calculation, and phylogenetic inference was examined in detail. If combined with conservative measures for branch support, GBDP appears to infer reasonable phylogenetic relationships of microorganisms with a comparatively low computational cost. Due to the linear speed‐up of the cluster, benchmarks reveal an overall computation time of less than 24 h required for the 7750 pairwise genome/proteome comparisons of the Genomic Encyclopedia of Bacteria and Archaea data set that is opposed to an estimated running time of about 30 days for the non‐parallelized version. Copyright © 2013 John Wiley &amp; Sons, Ltd.
Cherry Picking: A Characterization of the Temporal Hybridization Number for a Set of Phylogenies
2013-08-07

Recently, we have shown that calculating the minimum-temporal-hybridization number for a set [Formula: see text] of rooted binary phylogenetic trees is NP-hard and have characterized this minimum number when [Formula: see text] consists of exactly two trees. In this paper, we give the first characterization of the problem for [Formula: see text] being arbitrarily large. The characterization is in terms of cherries and the existence of a particular type of sequence. Furthermore, in an online appendix to the paper, we show that this new characterization can be used to show that computing the minimum-temporal hybridization number for two trees is fixed-parameter tractable.