julilili42/papers huggingface dataset:
A Whole-Genome Microarray Study ofArabidopsis thalianaSemisolid Callus Cultures Exposed to Microgravity and Nonmicrogravity Related Spaceflight Conditions for 5 Days on Board of Shenzhou 8
2015-01-01

The Simbox mission was the first joint space project between Germany and China in November 2011. Eleven-day-old Arabidopsis thaliana wild type semisolid callus cultures were integrated into fully automated plant cultivation containers and exposed to spaceflight conditions within the Simbox hardware on board of the spacecraft Shenzhou 8. The related ground experiment was conducted under similar conditions. The use of an in-flight centrifuge provided a 1 g gravitational field in space. The cells were metabolically quenched after 5 days via RNA later injection. The impact on the Arabidopsis transcriptome was investigated by means of whole-genome gene expression analysis. The results show a major impact of nonmicrogravity related spaceflight conditions. Genes that were significantly altered in transcript abundance are mainly involved in protein phosphorylation and MAPK cascade-related signaling processes, as well as in the cellular defense and stress responses. In contrast to short-term effects of microgravity (seconds, minutes), this mission identified only minor changes after 5 days of microgravity. These concerned genes coding for proteins involved in the plastid-associated translation machinery, mitochondrial electron transport, and energy production.
Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a HumanIn VitroLiver Model: An Approach to Study DILI
2015-01-01

Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune‐mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2 ± 0.9 × 10 6 cells/g liver tissue with a purity of &gt;80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor‐dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound‐ and donor‐dependent increase in proinflammatory cytokines or in anti‐inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor‐ and compound‐dependent immune response via cytokine production.
Accurate Linear-Time Chinese Word Segmentation via Embedding Matching
2015-01-01

Jianqiang Ma, Erhard Hinrichs. Proceedings of the 53rd Annual Meeting of the Association for Computational Linguistics and the 7th International Joint Conference on Natural Language Processing (Volume 1: Long Papers). 2015.
Resilience at the Transition to Agriculture: The Long-Term Landscape and Resource Development at the Aceramic Neolithic Tell Site of Chogha Golan (Iran)
2015-01-01

The evidence for the slow development from gathering and cultivation of wild species to the use of domesticates in the Near East, deriving from a number of Epipalaeolithic and aceramic Neolithic sites with short occupational stratigraphies, cannot explain the reasons for the protracted development of agriculture in the Fertile Crescent. The botanical and faunal remains from the long stratigraphic sequence of Chogha Golan, indicate local changes in environmental conditions and subsistence practices that characterize a site-specific pathway into emerging agriculture. Our multidisciplinary approach demonstrates a long-term subsistence strategy of several hundred years on wild cereals and pulses as well as on hunting a variety of faunal species that were based on relatively favorable and stable environmental conditions. Fluctuations in the availability of resources after around 10.200 cal BP may have been caused by small-scale climatic fluctuations. The temporary depletion of resources was managed through a shift to other species which required minor technological changes to make these resources accessible and by intensification of barley cultivation which approached its domestication. After roughly 200 years, emmer domestication is apparent, accompanied by higher contribution of cattle in the diet, suggesting long-term intensification of resource management.
Achromatopsia: On the Doorstep of a Possible Therapy
2015-01-01

Achromatopsia (ACHM) is a rare autosomal recessive inherited retinal disorder with an incidence of approximately 1 in 30,000. It presents at birth or early infancy and is typically characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. The symptoms arise from isolated cone dysfunction, which can be caused by mutations in the crucial components of the cone phototransduction cascade. Although ACHM is considered a functionally nonprogressive disease affecting only the cone system, recent studies have described progressive age-dependent changes in retinal architecture. Currently, no specific therapy is available for ACHM; however, gene replacement therapy performed on animal models for three ACHM genes has shown promising results. Accurate genetic and clinical diagnosis of patients may therefore enhance and enable therapeutic intervention in the near future. This short review summarizes the genetic background, pathophysiology, clinical findings, diagnostics, and therapeutic perspectives in ACHM.
The impact of isolated lesions on white-matter fiber tracts in multiple sclerosis patients
2015-01-01

Infratentorial lesions have been assigned an equivalent weighting to supratentorial plaques in the new McDonald criteria for diagnosing multiple sclerosis. Moreover, their presence has been shown to have prognostic value for disability. However, their spatial distribution and impact on network damage is not well understood. As a preliminary step in this study, we mapped the overall infratentorial lesion pattern in relapsing-remitting multiple sclerosis patients (N = 317) using MRI, finding the pons (lesion density, 14.25/cm(3)) and peduncles (13.38/cm(3)) to be predilection sites for infratentorial lesions. Based on these results, 118 fiber bundles from 15 healthy controls and a subgroup of 23 patients showing lesions unilaterally at the predilection sites were compared using diffusion tensor imaging to analyze the impact of an isolated infratentorial lesion on the affected fiber tracts. Fractional anisotropy, mean diffusion as well as axial and radial diffusivity were investigated at the lesion site and along the entire fiber tract. Infratentorial lesions were found to have an impact on the fractional anisotropy and radial diffusivity not only at the lesion site itself but also along the entire affected fiber tract. As previously found in animal experiments, inflammatory attack in the posterior fossa in multiple sclerosis impacts the whole affected fiber tract. Here, this damaging effect, reflected by changes in diffusivity measures, was detected in vivo in multiple sclerosis patients in early stages of the disease, thus demonstrating the influence of a focal immune attack on more distant networks, and emphasizing the pathophysiological role of Wallerian degeneration in multiple sclerosis.
Inhibition of Phosphate-Induced Vascular Smooth Muscle Cell Osteo-/Chondrogenic Signaling and Calcification by Bafilomycin A1 and Methylamine
2015-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;Excessive phosphate concentrations trigger vascular calcification, an active process promoted by osteoinduction of vascular smooth muscle cells (VSMCs) with increased expression and activity of transcription factor RUNX2 (Core-binding factor α1, CBFA1), alkaline phosphatase (ALPL), TGFß1, transcription factor NFAT5, and NFAT5-sensitive transcription factor SOX9. The osteoinductive signaling and vascular calcification of hyperphosphatemic klotho-hypomorphic mice could be reversed by treatment with NH&lt;sub&gt;4&lt;/sub&gt;Cl, effects involving decrease of TGFß1 and inhibition of NFAT5-dependent osteoinductive signaling. Known effects of NH&lt;sub&gt;4&lt;/sub&gt;Cl include alkalinization of acidic cellular compartments. The present study explored whether osteo-/chondrogenic signaling could be influenced by alkalinization of acidic cellular compartments following inhibition of the vacuolar H&lt;sup&gt;+&lt;/sup&gt; ATPase with bafilomycin A1 or following dissipation of the pH gradient across the membranes of acidic cellular compartments with methylamine. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;Primary human aortic smooth muscle cells (HAoSMCs) were treated with high phosphate to trigger osteo-/chondrogenic signaling and calcification in the absence or presence of bafilomycin A1 or methylamine. Calcium content was determined using a QuantiChrom Calcium assay, ALP activity by a colorimetric assay and transcript levels by quantitative RT-PCR. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;High phosphate increased significantly the calcium deposition, &lt;i&gt;CBFA1&lt;/i&gt; and &lt;i&gt;ALPL&lt;/i&gt; mRNA expression as well as alkaline phosphatase activity in HAoSMCs, all effects ameliorated by both, bafilomycin A1 and methylamine. High phosphate further significantly up-regulated the mRNA levels of &lt;i&gt;TGFB1, NFAT5&lt;/i&gt; and &lt;i&gt;SOX9,&lt;/i&gt; effects significantly blunted by additional treatment with bafilomycin A1 or methylamine. Treatment of HAoSMCs with human TGFß1 protein or high phosphate up-regulated &lt;i&gt;NFAT5, SOX9, CBFA1&lt;/i&gt; and &lt;i&gt;ALPL&lt;/i&gt; mRNA expression to similarly high levels which could not be further increased by combined treatment with high phosphate and TGFß1. Bafilomycin A1 failed to reverse the osteo-/chondrogenic signaling triggered by high phosphate together with TGFß1. &lt;b&gt;&lt;i&gt;Conclusions: &lt;/i&gt;&lt;/b&gt;Inhibition of the vacuolar H&lt;sup&gt;+&lt;/sup&gt; ATPase or dissipation of the pH gradient across the membranes of acidic cellular compartments both disrupt osteo-/chondrogenic signaling and calcium deposition in VSMCs, observations supporting the hypothesis that vascular calcification requires acidic cellular compartments.
Bushman Rock Shelter (Limpopo, South Africa): a perspective from the edge of the highveld
2015-01-01

In this paper, we introduce a recently initiated research project conducted at Bushman Rock Shelter, on the northeastern edge of the Highveld plateau in Limpopo Province, South Africa. Previous excavations carried out at the site during the 1960s and 1970s exposed a deep and well-stratified sequence of c. 7 metres of archaeological deposits associated with Later and Middle Stone Age occupations (LSA and MSA). Owing to the lack of contextual information, Bushman Rock Shelter remains poorly studied despite recording cultural and palaeoenvironmental data that are key for the understanding of the South African Stone Age. Here, we propose a synthesis of the 1967–1976 excavations led by Hannes Eloff and provide general background information that will serve as a reference for future research. Our synthesis is based on previous publications by Ina Plug, as well as on Eloff 's field diaries, which were thought to be lost. We complement these observations with data from our own 2014 field season, and pay tribute to the work previously done at the site. Finally, we discuss some aspects of the LSA/MSA contact at the site and comment on the presence of a bifacial lithic component in the upper MSA layers, which is reminiscent of the later Pietersburg.
The Next Generation of Virtual Prototyping: Ultra-Fast Yet Accurate Simulation of HW/SW Systems
2015-01-01

Virtual Prototypes (VPs) have been now widely adopted by industry as platforms for early SW development, HW/SW co-verification, performance analysis and architecture exploration. Yet, rising design complexity, the need to test an increasing amount of software functionality as well as the verification of timing properties pose a growing challenge in the application of VPs. New approaches overcome the accuracy-speed bottleneck of today's virtual prototyping methods. These next-generation VPs are centered around ultra-fast host-compiled software models. Accuracy is obtained by advanced methods, which reconstruct the execution times of the software and model the timing behavior of the operating system, target processor and memory system. It is shown that simulation speed can further be increased by abstract TLM-based communication models and efficient hardware peripheral models. Additionally, an industrial flow for efficient model development is outlined. This support of ultra-fast and accurate HW/SW co-simulation will be a key enabler for successfully developing tomorrow's multiprocessor system-on-chip (MPSoC) platforms.
Activation of Extracellular Signal-Regulated Protein Kinases 1 and 2 (ERK1/2) by Free Fatty Acid Receptor 1 (FFAR1/GPR40) Protects from Palmitate-Induced Beta Cell Death, but Plays no Role in Insulin Secretion
2015-01-01

Aims: GPR40/FFAR1 mediates palmitate-induced stimulation of insulin secretion but its involvement in lipotoxicity is controversial. Our previous observations suggest that FFAR1/GPR40 agonists protect against lipotoxicity although the underlying mechanism remains elusive. The present study examines the role of ERK1/2 and GPR40/FFAR1 in palmitate-induced stimulation of insulin secretion and beta cell death. Methods: Insulin secretion of INS-1E cells was measured by radioimmunoassay. Protein phosphorylation was examined on Western blots. Apoptosis was assessed by TUNEL staining. Results: Palmitate and the GPR40/FFAR1 agonist TUG-469 increased phosphorylation of ERK1/2 at low (2.8 mmol/L) and high (12 mmol/L) glucose but stimulated insulin secretion only at high glucose. The MEK1 inhibitor PD98059 significantly reduced phosphorylation of ERK1/2 but did not reverse the stimulation of secretion induced by glucose, palmitate or TUG-469. PD98059 rather augmented glucose-induced secretion. Prolonged exposure to palmitate stimulated apoptosis, an effect counteracted by TUG-469. PD98059 accentuated palmitate-induced apoptosis and reversed TUG-469-mediated inhibition of cell death. Conclusions: Activation of ERK1/2 by palmitate and GPR40/FFAR1 agonist correlates neither with stimulation of insulin secretion nor with induction of apoptosis. The results suggest a significant anti-apoptotic role of ERK1/2 under conditions of lipotoxicity.
Chorein Sensitive Arrangement of Cytoskeletal Architecture
2015-01-01

Background/Aims: Chorein is a protein expressed in various cell types. Loss of function mutations of the chorein encoding gene VPS13A lead to chorea-acanthocytosis, an autosomal recessive genetic disease characterized by movement disorder and behavioral abnormalities. Recent observations revealed that chorein is a powerful regulator of actin cytoskeleton in erythrocytes, platelets, K562 and endothelial HUVEC cells. Methods: In the present study we have used Western blotting to study actin polymerization dynamics, laser scanning microscopy to evaluate in detail the role of chorein in microfilaments, microtubules and intermediate filaments cytoskeleton architecture and RT-PCR to assess gene transcription of the cytoskeletal proteins. Results: We report here powerful depolymerization of actin microfilaments both, in erythrocytes and fibroblasts isolated from chorea-acanthocytosis patients. Along those lines, morphological analysis of fibroblasts from chorea-acanthocytosis patients showed disarranged microtubular network, when compared to fibroblasts from healthy donors. Similarly, the intermediate filament networks of desmin and cytokeratins showed significantly disordered organization with clearly diminished staining in patient's fibroblasts. In line with this, RT-PCR analysis revealed significant downregulation of desmin and cytokeratin gene transcripts. Conclusion: Our results provide for the first time evidence that defective chorein is accompanied by significant structural disorganization of all cytoskeletal structures in human fibroblasts from chorea-acanthocytosis patients.
Coupling single quantum dots to plasmonic nanocones: optical properties
2015-01-01

Coupling a single quantum emitter, such as a fluorescent molecule or a quantum dot (QD), to a plasmonic nanostructure is an important issue in nano-optics and nano-spectroscopy, relevant for a wide range of applications, including tip-enhanced near-field optical microscopy, plasmon enhanced molecular sensing and spectroscopy, and nanophotonic amplifiers or nanolasers, to mention only a few. While the field enhancement of a sharp nanoantenna increasing the excitation rate of a very closely positioned single molecule or QD has been well investigated, the detailed physical mechanisms involved in the emission of a photon from such a system are, by far, less investigated. In one of our ongoing research projects, we try to address these issues by constructing and spectroscopically analysing geometrically simple hybrid heterostructures consisting of sharp gold cones with single quantum dots attached to the very tip apex. An important goal of this work is to tune the longitudinal plasmon resonance by adjusting the cones' geometry to the emission maximum of the core–shell CdSe/ZnS QDs at nominally 650 nm. Luminescence spectra of the bare cones, pure QDs and hybrid systems were distinguished successfully. In the next steps we will further investigate, experimentally and theoretically, the optical properties of the coupled systems in more detail, such as the fluorescence spectra, blinking statistics, and the current results on the fluorescence lifetimes, and compare them with uncoupled QDs to obtain a clearer picture of the radiative and non-radiative processes.
The Role of Janus Kinase 3 in the Regulation of Na+/K+ ATPase under Energy Depletion
2015-01-01

Background/Aims: Janus kinase-3 (JAK3) is activated during energy depletion. Energy-consuming pumps include the Na+/K+-ATPase. The present study explored whether JAK3 regulates Na+/K+-ATPase in dendritic cells (DCs). Methods: Ouabain (100 μM)-sensitive (Iouabain) and K+-induced (Ipump) outward currents were determined by utilizing whole cell patch-clamp, Na+/K+-ATPase α1-subunit mRNA levels by RT-PCR, Na+/K+-ATPase protein abundance by flow cytometry or immunofluorescence, and cellular ATP by luciferase-assay in DCs from bone marrow of JAK3-knockout (jak3-/-) or wild-type mice (jak3+/+). Ipump was further determined by voltage clamp in Xenopus oocytes expressing JAK3, active A568VJAK3 or inactive K851AJAK3. Results: Na+/K+-ATPase α1-subunit mRNA and protein levels, as well as Ipump and Iouabain were significantly higher in jak3-/-DCs than in jak3+/+DCs. Energy depletion by 4h pre-treatment with 2,4-dinitro-phenol significantly decreased Ipump in jak3+/+ DCs but not in jak3-/-DCs. Cellular ATP was significantly lower in jak3-/-DCs than in jak3+/+DCs and decreased in both genotypes by 2,4-dinitro-phenol, an effect significantly more pronounced in jak3-/-DCs than in jak3+/+DCs and strongly blunted by ouabain in both jak3+/+ and jak3-/-DCs. Ipump and Iouabain in oocytes were decreased by expression of JAK3 and of A568VJAK3 but not of K851AJAK3. JAK3 inhibitor WHI-P154 (4-[(3'-bromo-4'-hydroxyphenyl)amino]-6,7-dimethoxyquinazoline, 22 μM) enhanced Ipump and Iouabain in JAK3 expressing oocytes. The difference between A568VJAK3 and K851AJAK3 expressing oocytes was virtually abrogated by actinomycin D (50 nM). Conclusions: JAK3 down-regulates Na+/K+-ATPase activity, an effect involving gene expression and profoundly curtailing ATP consumption.
Involvement of Ca2+ Activated Cl- Channel Ano6 in Platelet Activation and Apoptosis
2015-01-01

Background/Aims: The ubiquitously expressed Ca2+ Activated Cl- Channel Ano6 participates in the stimulation of cell membrane scrambling. Defective Ano6 underlies the Scott syndrome, an inherited bleeding disorder with impaired scrambling of plasma membrane phospholipids. At least in theory, the bleeding disorder of Scott syndrome may result from impaired platelet function. Activators of platelets include thrombin and collagen related peptide (CRP), which trigger increase of cytosolic Ca2+-activity ([Ca2+]i), production of reactive oxygen species (ROS), degranulation, integrin activation, as well as cell shrinkage and phospholipid scrambling of the cell membrane. The present study thus explored whether Ano6 modifies activation-induced alterations of cytosolic Ca2+-activity ([Ca2+]i), degranulation (P-selectin exposure), integrin activation, phosphatidylserine exposure on the platelet surface and platelet volume. Methods: Platelets from mice lacking Ano6 (ano6-/-) were compared to platelets from corresponding wild-type mice (ano6+/+). [Ca2+]i was estimated from Fluo-3 fluorescence, ROS from DCFDA fluorescence, degranulation from P-selectin abundance, integrin activation from αIIbβ3-integrin abundance, phosphatidylserine abundance from annexin-V-binding, and cell volume from forward scatter. Results: Platelet number in blood was slightly higher in ano6-/- mice than in ano6+/+ mice. Without activation [Ca2+]i and volume were similar in ano6-/- and ano6+/+ platelets as well as ROS abundance, P-selectin abundance, αIIbβ3 integrin activation, and phosphatidylserine exposure were negligible in both genotypes. Thrombin (0.01 U/ml) and CRP (2 or 5 μg/ml) increased [Ca2+]i, ROS abundance, platelet degranulation, αIIbβ3 integrin activation, and triggered annexin-V-binding as well as cell shrinkage, all effects less pronounced in ano6-/- than in ano6+/+ platelets. Conclusions: Genetic knockout of Ano6 blunts thrombin- and CRP-induced activation and apoptosis of blood platelets.
Lactotransferrin Gene Polymorphism Associated with Caries Experience
2015-01-01

Dental caries is a common multifactorial disease, resulting from the interaction of biofilm, cariogenic diet and host response over time. Lactotransferrin (LTF) is a main salivary glycoprotein, which modulates the host immune-inflammatory and antibacterial response. Although a genetic component for caries outcome has been identified, little is known over the genetic aspects underlying its susceptibility. Thus, the aim of this study was to investigate the association between &lt;i&gt;LTF&lt;/i&gt; polymorphisms and caries susceptibility. Six hundred seventy seven 12-year-old students were selected: 346 with (DMFT ≥ 1) and 331 without caries experience (DMFT = 0). Also, individuals concentrating higher levels of disease (polarization group, DMFT ≥ 2, n = 253) were tested against those with DMFT ≤ 1 (n = 424). Along with clinical parameters, three representative &lt;i&gt;LTF&lt;/i&gt; tag SNPs (rs6441989, rs2073495, rs11716497) were genotyped and the results were evaluated using univariate and multivariate analyses. Allele A for tag SNP rs6441989 was found to be significantly less frequent in the polarization group, conferring a protective effect against caries experience [AA + AG × GG (OR: 0.710, 95% CI: 0.514-0.980, p = 0.045)], and remained significantly associated with caries protection in the presence of gingivitis (p = 0.020) and plaque (p = 0.035). These results might contribute to the understanding of the genetic control of caries susceptibility in humans.