julilili42/papers huggingface dataset:
Triggering of Suicidal Erythrocyte Death by Bexarotene
2016-01-01

Background/Aims: The retinoid X receptor agonist bexarotene is utilized for the treatment of cutaneous T-cell lymphoma and is effective in several further malignancies. The substance counteracts tumor growth in part by triggering suicidal death or apoptosis of tumor cells. Side effects of bexarotene treatment include anemia. Theoretically, bexarotene induced anemia could be secondary to stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling potentially stimulating eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), induction of oxidative stress, increase of ceramide abundance, as well as activation of staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, D4476 sensitive casein kinase 1, and zVAD sensitive caspases. The present study explored, whether bexarotene induces eryptosis and, if so, whether its effect involves Ca2+ entry, oxidative stress, ceramide, kinases and/or caspases. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) abundance from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was estimated from hemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to bexarotene (≥ 0.4 μg/ml) significantly increased the percentage of annexin-V-binding cells without significantly modifying forward scatter. Bexarotene significantly increased Fluo3-fluorescence and DCFDA fluorescence. Bexarotene tended to increase ceramide abundance, an effect, however, not reaching statistical significance. The effect of bexarotene on annexin-V-binding was significantly blunted by removal of extracellular Ca2+ and by addition of D4476 (10 μM), but not by addition of staurosporine (1 μM), SB203580 (2 μM), or zVAD (10 μM). Conclusions: Bexarotene triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to Ca2+ entry, oxidative stress, and activation of D4476 sensitive casein kinase.
3D Gaze Estimation using Eye Vergence
2016-01-01

We propose a fast and robust method to estimate the 3D gaze position based on the eye vergence information extracted from eye-tracking data. This method is specially designed for Point-of-Regard (PoR) estimation in non-virtual environments with the aim to make it applicable to the study of human visual attention deployment in natural scenarios. Our approach starts with a calibration step at different depth distances in order to achieve the best depth approximation. In addition, we investigate the distance range, for which state-of-the-art eyetracking technology allows 3D gaze estimation based on eye vergence. Our method provides a mean accuracy of 1.2◦ at a working distance between 200 mm and 400 mm from the user without requiring calibrated lights or cameras.
Combined Administration of the GPVI-Fc Fusion Protein Revacept with Low-Dose Thrombolysis in the Treatment of Stroke
2016-01-01

In contrast to using the equally effective full dose of rtPA, intracranial bleeding was not increased by low-dose rtPA combined with Revacept. Therefore, addition of Revacept to low-dose rtPA does not incur safety risks, but improves efficacy of treatment.
Chorein Sensitive Orai1 Expression and Store Operated Ca2+ Entry in Rhabdomyosarcoma Cells
2016-01-01

Background: Chorein, a protein encoded by VPS13A (vacuolar protein sorting-associated protein 13A), is defective in chorea acanthocytosis, a rare disease characterized by acanthocytosis of red blood cells and neuronal cell death with progressive hyperkinetic movement disorder, cognitive dysfunction, behavioral abnormalities and chronic hyperkalemia. Chorein is highly expressed in ZF rhabdomyosarcoma cells and counteracts apoptosis of those cells. Chorein is effective in part by interacting with and fostering stimulation of phosphoinositide-3-kinase (PI3K)-p85-subunit. PI3K dependent signaling includes the serum and glucocorticoid inducible kinase SGK1. The kinase activates NFκB with subsequent up-regulation of the Ca2+ channel subunit Orai1, which accomplishes store operated Ca2+ entry (SOCE). Orai1 and SOCE have been shown to confer survival of tumor cells. The present study thus explored whether chorein impacts on Orai1 expression and SOCE. Methods: In rhabdomyosarcoma cells chorein, Orai1, NFκB and SGK1 transcript levels were quantified by RT-PCR, Orai1 protein abundance by Western blotting, FACS analysis and confocal laser microscopy, [Ca2+]i utilizing Fura-2 fluorescence, and SOCE from the increase of [Ca2+]i following store depletion with extracellular Ca2+ removal and inhibition of the sarcoendoplasmatic reticular Ca2+ ATPase with thapsigargin. Results: The mRNA coding for chorein was most abundant in drug resistant, poorly differentiated human ZF rhabdomyosarcoma cells. Chorein silencing significantly decreased Orai1 transcript levels and Orai1 protein expression, as well as SGK1 and NFκB transcript levels. SOCE in ZF rhabdomyosarcoma cells was significantly blunted by chorein silencing, Orai1 inhibitor 2-APB (50 μM), SGK1 inhibitor EMD638683 (50 μM, 10 h) and NFκB inhibitor wogonin (50 μM, 24 h). Conclusion: Chorein is a stimulator of Orai1 expression and thus of store operated Ca2+ entry. The effect may involve SGK1 and NFκB.
Stimulating Effect of Elvitegravir on Suicidal Erythrocyte Death
2016-01-01

Background/Aims: The antiviral drug Elvitegravir is used for the treatment of Human Immunodeficiency Virus (HIV) infections. The present study explored whether the drug is able to trigger eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, activated p38 kinase and activated caspases. The present study explored, whether Elvitegravir induces eryptosis and, if so, to shed light on the mechanisms involved. Methods: Phosphatidylserine abundance at the erythrocyte surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, abundance of reactive oxygen species (ROS) from DCFDA dependent fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to Elvitegravir (≥ 1.5 μg/ml) significantly increased the percentage of annexin-V-binding cells, and significantly decreased forward scatter. Elvitegravir (2.5 μg/ml) significantly increased Fluo3-fluorescence, but did not significantly modify DCFDA fluorescence or ceramide abundance. The effect of Elvitegravir on annexin-V-binding was significantly blunted by removal of extracellular Ca2+, but not in the presence of p38 kinase inhibitor SB203580 (2 μM) or in the presence of pancaspase inhibitor zVAD (10 μM). Conclusions: Elvitegravir triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to entry of extracellular Ca2+.
Stimulation of Eryptosis by Combretastatin A4 Phosphate Disodium (CA4P)
2016-01-01

Background/Aims: Combretastatin A4 phosphate disodium (CA4P) is utilized for the treatment of malignancy. The substance has previously been shown to trigger suicidal cell death or apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), ceramide, oxidative stress and ATP depletion. The present study explored, whether CA4P induces eryptosis and, if so, to gain insight into mechanisms involved. Methods: Flow cytometry has been employed to estimate phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) abundance from DCF fluorescence, glutathione (GSH) abundance from CMF fluorescence and ceramide abundance from fluorescent antibodies. In addition cytosolic ATP levels were quantified utilizing a luciferin-luciferase-based assay and hemolysis was estimated from hemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to CA4P (≥ 50 μM) significantly increased the percentage of annexin-V-binding cells and significantly decreased forward scatter. CA4P did not appreciably increase hemolysis. Hundred μM CA4P significantly increased Fluo3-fluorescence. The effect of CA4P (100 μM) on annexin-V-binding was significantly blunted, but not abolished, by removal of extracellular Ca2+. CA4P (≥ 50 μM) significantly decreased GSH abundance and ATP levels but did not significantly increase ROS or ceramide. Conclusions: CA4P triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to entry of extracellular Ca2+ and energy depletion.
Stimulation of Erythrocyte Cell Membrane Scrambling by Quinine
2016-01-01

Background/Aims: The analkaloid drug quinine is utilized mainly for the chemoprophylaxis of malaria. The multiple side effects of quinine include hemolytic anemia and hemolytic uremic syndrome, disorders involving suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling contributing to stimulation of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide and D4476 sensitive casein kinase. The present study explored the putative effect of quinine on eryptosis and elucidated cellular mechanisms involved. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ROS formation from DCF dependent fluorescence, and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to quinine (≥ 50 μM) significantly increased the percentage of annexin-V-binding cells without significantly affecting forward scatter. Quinine significantly increased Fluo3-fluorescence, DCF fluorescence and ceramide abundance. The effect of quinine on annexin-V-binding was significantly blunted by removal of extracellular Ca2+ and by addition of D4476 (10 μM). Conclusions: Quinine triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to Ca2+ entry, oxidative stress, ceramide and D4476 sensitive casein kinase.
A New Tool for Transbronchial Cryobiopsies in the Lung: An Experimental Feasibility ex vivo Study
2016-01-01

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Transbronchial cryobiopsy (TBCB) is a minimally invasive procedure to establish a diagnosis of interstitial lung disease though with the disadvantage that samples have to be extracted together with the bronchoscope. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; The aim of the present study was to evaluate the feasibility of a new cryoprobe with which biopsy samples can be obtained through the working channel of the flexible bronchoscope. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; The feasibility of obtaining transbronchial specimens with TBCB was tested and the technique was compared to transbronchial forceps biopsy (TBFB) in a prospectively randomized ex vivo animal study using a standard flexible bronchoscopy technique. The rate of successful biopsies and the duration of the sampling procedure were recorded for both methods. Size and quality of the biopsies were histologically evaluated and measured. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Biopsy samples could be obtained in 93.3% of TBCB and in 79.0% of TBFB procedures (p = 0.182). Sampling procedure time did not differ in any clinically relevant manner between the two methods. The mean specimen area of TBCB samples was significantly higher compared to that of TBFB samples (8.08 ± 5.80 vs. 2.61 ± 2.14 mm&lt;sup&gt;2&lt;/sup&gt;; p &lt; 0.0001). TBCB specimens showed less artifacts and a significantly higher percentage of alveolar tissue (53.57 vs. 25.42%; p = 0.0285) than TBFB specimens. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; It is feasible to retrieve TBCB samples of good quality and size with the new mini cryoprobe through the working channel of the bronchoscope, while the bronchoscope remains within the central airways throughout the whole procedure. Further studies are necessary to evaluate the safety and efficacy in an in vivo setting.
Linguistically Aware Information Retrieval: Providing Input Enrichment for Second Language Learners
2016-01-01

How can second language teachers retrieve texts that are rich in terms of the grammatical constructions to be taught, but also address the content of interest to the learners?We developed an Information Retrieval system that identifies the 87 grammatical constructions spelled out in the official English language curriculum of schools in Baden-Württemberg (Germany) and reranks the search results based on the selected (de)prioritization of grammatical forms.In combination with a visualization of the characteristics of the search results, the approach effectively supports teachers in prioritizing those texts that provide the targeted forms.The approach facilitates systematic input enrichment for language learners as a complement to the established notion of input enhancement: while input enrichment aims at richly representing the selected forms and categories in a text, input enhancement targets their presentation to make them more salient and support noticing.
A systematic review on diagnostic procedures for specific language impairment: The sensitivity and specificity issues
2016-01-01

Background: Identification of children with specific language impairment (SLI) has been viewed as both necessity and challenge. Investigators and clinicians use different tests and measures for this purpose. Some of these tests/measures have good psychometric properties, but it is not sufficient for diagnostic purposes. A diagnostic procedure can be used for identification a specific population with confidence only when its sensitivity and specificity are acceptable. In this study, we searched for tests/measures with predefined sensitivity and specificity for identification of preschool children with SLI from their typically developing peers. Materials and Methods: A computerized search in bibliographic databases from 2000 to August 2015 was performed with the following keywords: “specific language impairment” or SLI” and “primary language impairment” or ‘PLI’ with at least one of the followings: “diagnosis,” “identification,” “accuracy,” “sensitivity,” and “specificity.” In addition, the related citations and reference lists of the selected articles were considered. Results: The results of reviewing 23 included studies show that the index measures used in studies vary in accuracy with the sensitivity ranging from 16% to 100% and the specificity ranging from 14% to 100%. Conclusion: These varieties in sensitivity and specificity of different tests/measures confirm the necessity of attention to the diagnostic power of tests/measures before their use as diagnostic tool. Further, the results indicate there are some promising tests/measures that the available evidence supports their performances in the diagnosis of SLI in preschool-aged children, yet the place of a reference standard for the diagnosis of SLI is vacant among investigations.
Systemic Therapy of Cholangiocarcinoma
2016-01-01

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Cholangiocarcinoma (CC) is the second most common primary malignant liver disease. During the last decades, various novel therapies have been introduced in the field of oncology; nevertheless, the number of treatment options for CC is still limited. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In this article, current palliative chemotherapy concepts as well as new drug therapies are outlined. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Gemcitabine and cisplatin are the standard treatment of care for patients with inoperable CC. Second-line chemotherapy is not standardized yet and is dependent on the first-line compounds. Antibodies against VEGFR and EGFR showed mixed or negative results. New molecular systemic treatments are not established yet. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Many clinical trials are still ongoing and new therapeutic strategies, including immunotherapies, are under active investigation.
CXCR1 Regulates Pulmonary Anti-<b><i>Pseudomonas</i></b> Host Defense
2016-01-01

&lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt; is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-&lt;i&gt;P. aeruginosa&lt;/i&gt; immunity remain incompletely understood. Here we demonstrate, by studying an airway &lt;i&gt;P. aeruginosa&lt;/i&gt; infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against &lt;i&gt;P. aeruginosa&lt;/i&gt;. Mechanistically, CXCR1 regulates anti-&lt;i&gt;Pseudomonas&lt;/i&gt; neutrophil responses through modulation of reactive oxygen species and interference with Toll-like receptor 5 expression. These studies define CXCR1 as a novel, noncanonical chemokine receptor that regulates pulmonary anti-&lt;i&gt;Pseudomonas&lt;/i&gt; host defense with broad implications for CF, COPD and other infectious lung diseases.
Early complications and performance of 327 heat-pressed lithium disilicate crowns up to five years
2016-01-01

Heat pressed lithium disilicate crowns showed an excellent performance. Besides a careful luting, dentists should be aware of patients' biological prerequisites (grade of caries, oral hygiene) to reach full success with these crowns.
Exploring Olfactory Function and Its Relation with Behavioral and Cognitive Impairment in Amyotrophic Lateral Sclerosis Patients: A Cross-Sectional Study
2016-01-01

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Behavioral and cognitive impairment are common in amyotrophic lateral sclerosis (ALS) and represent a continuum with frontotemporal dementia (FTD). Olfactory dysfunction has been described in a subset of ALS patients and might be associated with frontotemporal and insular cortex dysfunction. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To evaluate olfaction dysfunction in ALS patients and its relationship with either cognition or behavioral impairment. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; 28 consecutive ALS patients underwent an extensive cognitive and behavioral battery and were classified as patients with normal cognition (ALS-N, n = 11) or with part of the ALS-FTD spectrum (n = 17), including either cognitive or behavioral impairment or dementia. Odor verbal and visual identification and discrimination were investigated in patients and age-matched controls using a test adapted from the Sniffin' Sticks. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Olfactory function was significantly different between ALS-FTD spectrum patients and controls (p &lt; 0.001) and inversely correlated with behavioral and cognitive performance. The 10-point cutoff distinguished ALS-N from ALS-FTD spectrum patients with a sensitivity and specificity of 71 and 100%, respectively. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Hyposmia is common in a subset of ALS patients and strongly associated with behavioral and cognitive impairment. Olfactory testing may represent an early screening tool in order to identify ALS subjects with cognitive/behavioral dysfunction. Further studies in larger series are mandatory in order to better investigate clinical and pathological aspects in this group of patients.
Hybrid Metric-Topological 3D Occupancy Grid Maps for Large-scale Mapping
2016-01-01

This paper presents a large-scale 3D environment mapping solution for mobile robots that is based on hybrid metric-topological maps. If a robot performs simultaneous localization and mapping (SLAM) while exploring an unknown environment, sometimes loops are closed and the whole SLAM graph has to be optimized. If a conventional occupancy grid mapping algorithm using a monolithic map is used, the whole occupancy grid map has to be rebuilt after optimization, which for large maps can easily become too time consuming for real-time operation. In the same way, path planning on very large occupancy grid maps can become computationally too expensive. Hybrid metric-topological maps can solve both problems. The global metric map is divided into sub-maps and a global topological graph is formed on the map. This allows recomputing only isolated areas of the map, whereas others can remain unchanged. The topological graph allows efficient path planning on the hybrid map. We show that the hybrid mapping approach presented here is considerably faster than conventional methods. Within the same time, it can generate more detailed maps of large environments. The computation time for maps with identical level of detail can be improved by up to two orders of magnitude.
Enhanced Immobilization of Polycyclic Aromatic Hydrocarbons in Contaminated Soil Using Forest Wood-Derived Biochar and Activated Carbon under Saturated Conditions, and the Importance of Biochar Particle Size
2016-01-01

Leaching behavior of organic contaminants such as polycyclic aromatic hydrocarbons (PAHs) can be altered in the presence of organic amendments through enhanced sorption of PAHs to the amended soil.The aim of the present study was to investigate the influence of biochar in two forms (i.e., crushed and pulverized), and granular activated carbon on immobilization and leaching behavior of selected PAHs from contaminated soil into water using the column leaching test.The influence of biochar particle size on leaching behavior of PAHs in biochar-amended soil was also evaluated for the first time in this study.Results showed relatively high initial concentrations of naphthalene, fluorene, and pyrene for unamended column (B1).Strong sorption of all PAHs to soil was observed in this study.At the end of the experiment less than one percent of the solid phase content of the sum of PAHs was released into water in columns B3 and B4.Change in pH due to the application of organic amendments did not affect PAH leaching results.The addition of pulverized biochar and granular activated carbon to soil remarkably reduced mobilization and leaching of the studied PAHs in most cases; however, higher molecular weight PAHs (i.e., pyrene, benzo(b)fluoranthene, and indeno(1,2,3cd)) were mobilized in the presence of crushed biochar in soil.The controlling role of biochar particle size on mobilization and release of PAHs in soil was observed.The application of pulverized biochar and activated carbon increased colloid content of the column effluents while reducing their dissolved organic carbon (DOC) content, suggesting a more significant role of colloid-facilitated transport than DOC-associated transport of PAHs in their leaching from carbon-amended soils, particularly for higher molecular weight PAHs.Based on the obtained results, pulverized biochar and granular activated carbon demonstrated promising and comparable performance in immobilizing PAHs in soil and reducing their leaching from soil into water through enhanced sorption of PAH compounds, which is markedly favorable in terms of soil remediation.