julilili42/papers huggingface dataset:
Wind erosion on the north‐eastern Tibetan Plateau: constraints from OSL and U‐Th dating of playa salt crust in the Qaidam Basin
2013-10-08

ABSTRACT The arid Qaidam Basin is the largest (~3.88 × 10 4 km 2 ) basin on the north‐eastern Tibetan Plateau. Wind erosion in the area has been regarded as an important trigger for intra‐basin tectonic balance upheaval, geomorphologic development and as a major supplier of dust to the Chinese Loess Plateau downwind. An initial estimate of the rate of wind erosion (Kapp et al ., 2011) based on geological cross‐sections has suggested up to 3.2 × 10 4 km 3 of sediments has been deflated over the past 2.8 Ma, lowering the landscape by an average of 0.29 mm/yr. In this paper we re‐evaluate this estimate by dating surface crusts present on three playas within the basin. Understanding the development of these playas is crucial to assessing the overall role of the wind in shaping the regional landscape because they are typically capped with a thick salt crust which effectively protects them from wind erosion. Optically stimulated luminescence (OSL) and U‐series dating from a pit section and from the top of a deep drill core, together with results from magnetostratigraphy and a climate proxy record correlated to the marine oxygen isotope record, are used here to determine the age of the playa plains and suggest that the salt crusts have an age of c . 0.1 Ma. This young age and the wide distribution of resistant thick salt crusts of the playa plains indicate a much lower degree of wind erosion than previously suggested. The crusts protect the surface from significant surface erosion (including sediment exhumation and unloading) and whilst some wind erosion does occur, it is unlikely to be sufficient to trigger tectonic uplift of the basin or to be a major dust source for the Loess Plateau as previously suggested. Copyright © 2013 John Wiley &amp; Sons, Ltd.
Plasmodium falciparum Polymorphisms Associated with Ex Vivo Drug Susceptibility and Clinical Effectiveness of Artemisinin-Based Combination Therapies in Benin
2013-10-08

ABSTRACT Artemisinin-based combination therapies (ACTs) are the main option to treat malaria, and their efficacy and susceptibility must be closely monitored to avoid resistance. We assessed the association of Plasmodium falciparum polymorphisms and ex vivo drug susceptibility with clinical effectiveness. Patients enrolled in an effectiveness trial comparing artemether-lumefantrine ( n = 96), fixed-dose artesunate-amodiaquine ( n = 96), and sulfadoxine-pyrimethamine ( n = 48) for the treatment of uncomplicated malaria 2007 in Benin were assessed. pfcrt , pfmdr1 , pfmrp1 , pfdhfr , and pfdhps polymorphisms were analyzed pretreatment and in recurrent infections. Drug susceptibility was determined in fresh baseline isolates by Plasmodium lactate dehydrogenase enzyme-linked immunosorbent assay (ELISA). A majority had 50% inhibitory concentration (IC 50 ) estimates (the concentration required for 50% growth inhibition) lower than those of the 3D7 reference clone for desethylamodiaquine, lumefantrine, mefloquine, and quinine and was considered to be susceptible, while dihydroartemisinin and pyrimethamine IC 50 s were higher. No association was found between susceptibility to the ACT compounds and treatment outcome. Selection was observed for the pfmdr1 N86 allele in artemether-lumefantrine recrudescences (recurring infections) (4/7 [57.1%] versus 36/195 [18.5%]), and of the opposite allele, 86Y, in artesunate-amodiaquine reinfections (new infections) (20/22 [90.9%] versus 137/195 [70.3%]) compared to baseline infections. The importance of pfmdr1 N86 in lumefantrine tolerance was emphasized by its association with elevated lumefantrine IC 50 s. Genetic linkage between N86 and Y184 was observed, which together with the low frequency of 1246Y may explain regional differences in selection of pfmdr1 loci. Selection of opposite alleles in artemether-lumefantrine and artesunate-amodiaquine recurrent infections supports the strategy of multiple first-line treatment. Surveillance based on clinical, ex vivo , molecular, and pharmacological data is warranted.
The presence and prognostic impact of apoptotic and nonapoptotic disseminated tumor cells in the bone marrow of primary breast cancer patients after neoadjuvant chemotherapy
2013-10-08

Abstract Introduction Neoadjuvant systemic therapy of primary breast cancer (PBC) patients offers the possibility to monitor treatment response. However, patients might have metastatic relapse despite achieving a pathologic complete response (pCR). This indicates that local response to therapy must not be representative for systemic treatment efficacy. Therefore, the aim of this study was to compare local response with systemic tumor cell dissemination by determining the presence of disseminated tumor cells (DTCs), including apoptotic tumor cells, in the bone marrow (BM) of PBC patients after neoadjuvant chemotherapy (NACT). Methods DTCs were detected by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology (DTC status). The presence of apoptotic tumor cells was determined by using the M30 antibody (M30 status). This antibody detects a neo-epitope that is expressed only during early apoptosis. Results BM aspirates from 400 PBC patients that had completed NACT were eligible for this study. Of these, 167 (42%) patients were DTC positive (DTC status). The M30 status was investigated in 308 patients. Apoptotic (M30-positive) tumor cells were detected in 89 (29%) of these. Whereas the DTC status was not correlated ( P = 0.557) to local treatment response (that is, pCR or a clinical complete/partial response), the presence of M30-positive tumor cells was significantly higher in patients that responded to therapy ( P = 0.026). Additionally, DTC-positive patients were at an increased risk for disease relapse (hazard ratio, 1.87; 95% CI, 1.11 to 3.15; P = 0.019). Conclusion The presence of DTC is independent of therapy response of the primary tumor. As patients that are DTC positive after NACT have an unfavorable outcome, they might benefit from additional systemic treatment.
Expression of platelet-bound stromal-cell derived factor-1 (SDF-1) and number of CD34+progenitor cells in patients with congestive heart failure
2013-10-08

Platelet-bound stromal cell-derived factor-1 (SDF-1) plays a crucial role in attachment of circulating CD34(+) progenitor cells to the vascular wall, facilitating tissue healing after injury. However there is no evidence about expression of platelet-bound SDF-1 in patients with congestive heart failure (CHF). The aim of our study was to evaluate expression of platelet-bound SDF-1 and number of CD34(+) progenitor cells in patients with CHF. Forty-eight patients with idiopathic dilated cardiomyopathy (DCM) and 61 patients with ischaemic cardiomyopathy (ICM) were consecutively enrolled into the study. Blood taken from 109 consecutive patients was studied for surface expression of platelet-bound SDF-1 and number of CD34(+) progenitor cells by flow cytometry. The highest expression of platelet-bound SDF-1 was observed in patients with severe impairment of left ventricular systolic function compared with patients with mild or moderate impairment of left ventricular systolic function (mild vs. moderate vs. severe impairment of left ventricular systolic function: MFI ± SD: 35.6 ± 34 vs. 101.45 ± 73 vs. 124.86 ± 86.7, Kruskal-Wallis p < 0.001). Similar to platelet-bound SDF-1 number of CD34(+) progenitor cells was the highest in severe impairment of left ventricular systolic function (mild vs. moderate vs. severe impairment of left ventricular systolic function: mean ± SD: 260.4 ± 177.5 vs. 580.7 ± 340.5 vs. 640.82 ± 370.6, Kruskal-Wallis p < 0.001). Platelet-bound SDF-1 expression was associated with number of circulating CD34(+) progenitor cells (r = 0.454, p < 0.001) in patients with CHF. Expression of platelet-bound SDF-1 and number of CD34(+) cells were higher in patients with DCM compared with patients with ICM (p < 0.001 for both) and inversely correlated with age and aspirin therapy. Platelet-bound SDF-1 and CD34(+) progenitor cells are especially increased in patients with severe impairment of left ventricular systolic function in CHF.
Combination of high on-treatment platelet aggregation and low deaggregation better predicts long-term cardiovascular events in PCI patients under dual antiplatelet therapy
2013-10-08

High on-treatment platelet reactivity is associated with short-term major cardiovascular (CV) events in patients undergoing percutaneous coronary intervention (PCI). Maximum and final aggregation assessed by light transmission aggregometry (LTA) have both been used to predict short-term outcome after PCI, however their long-term prognostic impact remains controversial. There is currently no information regarding the prognostic role of deaggregation and its added value in combination with established aggregation parameters. About 1279 patients with symptomatic coronary artery disease (CAD) undergoing PCI were enrolled in this monocentric study. On-treatment platelet aggregation under clopidogrel maintenance therapy, as well as deaggregation was determined by maximum and final aggregation (5 min after adding of the agonist). Deaggregation was defined as slope of the tangent between Aggmax +0.5 min. Primary endpoints were the composite of myocardial infarction, stroke, and CV death or stent thrombosis according to the ARC criteria. Low deaggregation, defined as values in the lowest tertile (<1.5), was more frequent in patients with acute coronary syndromes (ACS) compared to patients with stable angina pectoris (SAP), ACS: 29.6% vs. SAP: 22.0%, p = 0.001. The combination of high on-treatment platelet reactivity, defined by the upper tertile of Aggmax and low deaggregation, was associated with significantly increased risk for combined long-term CV events. The combination of low deaggregation and high on-treatment platelet reactivity is associated with higher risk for recurrent events in patients with CAD undergoing PCI. Thus, deaggregation might be a more sensitive parameter providing added value in terms of risk prediction for long-term recurrent CV events in relation with established aggregation parameters.
Risk and the Role of Collateral in Debt Renegotiation
2013-10-08

Abstract In his basic model of debt renegotiation, Bester ( ) argues that collateral is more effective if high‐risk projects are financed. This result, however, depends crucially on the definition of risk. Using the second‐order stochastic dominance criterion, introduced by Rothschild and Stiglitz ( ), we show that a project's high risk, induced by a high probability of default, does not improve the effectiveness of collateral. Instead it turns out that, given the expected return, the probability of default has no impact on the collateral's effectiveness. Moreover, a higher risk of the project caused by a higher loss given default makes the use of collateral even less effective.
Sorption and transformation of the reactive tracers resazurin and resorufin in natural river sediments
2013-10-08

Abstract. Resazurin (Raz) and its reaction product resorufin (Rru) have increasingly been used as reactive tracers to quantify metabolic activity and hyporheic exchange in streams. Previous works have indicated that these compounds undergo sorption in stream sediments. We present a series of laboratory column and batch experiments on Raz and Rru transport, sorption, and transformation within sediments with different physicochemical properties under neutral and alkaline conditions. The data of the column experiments were fitted by a model accounting for physical transport, equilibrium and kinetic sorption, and three first-order reactions. The most likely parameters and their uncertainty were determined by a Markov-Chain Monte Carlo approach. Linear and non-linear sorption isotherms of both compounds were obtained by batch experiments. We found that kinetic sorption dominates sorption of both Raz and Rru, with characteristic timescales of sorption in the order of &gt; 80 min. The linear sorption models for both Raz and Rru appeared adequate for concentrations that are typically applied in field-tracer tests. The supposed two-site sorption model helps interpreting transient tracer tests using the Raz–Rru system.
On the Dissociation between Microsaccade Rate and Direction after Peripheral Cues: Microsaccadic Inhibition Revisited
2013-10-09

Microsaccades during fixation exhibit distinct time courses of frequency and direction modulations after stimulus onsets, but the mechanisms for these modulations are unresolved. On the one hand, microsaccade rate drops within &lt;100 ms after stimulus onset, a phenomenon described as microsaccadic inhibition. On the other, the directions of the rare microsaccades that do occur during inhibition are, surprisingly, the most highly correlated with stimulus location. Here we show, using a combined computational and experimental approach, that these apparently dichotomous observations can simply result from a single mechanism: the phase resetting by stimulus onsets of ongoing microsaccadic oscillatory rhythms during fixation. Using experiments on monkeys and model simulations, we show that stimulus onsets act as countermanding stimuli, such as those in large saccadic countermanding tasks: they cancel an upcoming movement program and start a competing one, thus implementing phase resetting. We also show that the rare microsaccades occurring during microsaccadic inhibition are simply noncanceled movements in the countermanding framework and that they reflect the instantaneous state of visual representations expected in spatial maps representing stimuli. Remarkably, a dynamic interaction between the efficacy of the countermanding process and the metrics of the microsaccade being countermanded not only explains microsaccade rate changes, but it also predicts the time course patterns of microsaccade directions and amplitudes. Our parsimonious framework for understanding microsaccadic modulations around stimulus onsets allows analyzing microsaccades (and larger saccades) using the extensive toolkit of oscillatory dynamical systems often used for modeling spiking neurons, and it constrains neural models of microsaccade triggering.
Imbricaric Acid and Perlatolic Acid: Multi-Targeting Anti-Inflammatory Depsides from Cetrelia monachorum
2013-10-09

In vitro screening of 17 Alpine lichen species for their inhibitory activity against 5-lipoxygenase, microsomal prostaglandin E2 synthase-1 and nuclear factor kappa B revealed Cetrelia monachorum (Zahlbr.) W.L. Culb. & C.F. Culb. As conceivable source for novel anti-inflammatory compounds. Phytochemical investigation of the ethanolic crude extract resulted in the isolation and identification of 11 constituents, belonging to depsides and derivatives of orsellinic acid, olivetolic acid and olivetol. The two depsides imbricaric acid (4) and perlatolic acid (5) approved dual inhibitory activities on microsomal prostaglandin E2 synthase-1 (IC50 = 1.9 and 0.4 μM, resp.) and on 5-lipoxygenase tested in a cell-based assay (IC50 = 5.3 and 1.8 μM, resp.) and on purified enzyme (IC50 = 3.5 and 0.4 μM, resp.). Additionally, these two main constituents quantified in the extract with 15.22% (4) and 9.10% (5) showed significant inhibition of tumor necrosis factor alpha-induced nuclear factor kappa B activation in luciferase reporter cells with IC50 values of 2.0 and 7.0 μM, respectively. In a murine in vivo model of inflammation, 5 impaired the inflammatory, thioglycollate-induced recruitment of leukocytes to the peritoneum. The potent inhibitory effects on the three identified targets attest 4 and 5 a pronounced multi-target anti-inflammatory profile which warrants further investigation on their pharmacokinetics and in vivo efficacy.
Flame spray pyrolysis for sensing at the nanoscale
2013-10-10

Progress in developing novel gas sensors based on semiconducting metal oxides (SMOX) has been hindered by the cumbersome fabrication technologies currently employed. They involve time intensive synthesis procedures for gaining sensitive materials and preparation of the inks employed for realizing sensing layers. In this paper we review the opportunities offered by the relatively young method of flame spray pyrolysis, with which it is possible not only to synthesize a broad selection of SMOX in pure or doped form, but also to simultaneously deposit thick and highly porous gas sensitive films on a variety of substrates. In less than ten years the properties of nine base materials have been evaluated for all most relevant target gases and the obtained results are promising for future development.
A Structure-Guided Mutation in the Major Capsid Protein Retargets BK Polyomavirus
2013-10-10

Viruses within a family often vary in their cellular tropism and pathogenicity. In many cases, these variations are due to viruses switching their specificity from one cell surface receptor to another. The structural requirements that underlie such receptor switching are not well understood especially for carbohydrate-binding viruses, as methods capable of structure-specificity studies are only relatively recently being developed for carbohydrates. We have characterized the receptor specificity, structure and infectivity of the human polyomavirus BKPyV, the causative agent of polyomavirus-associated nephropathy, and uncover a molecular switch for binding different carbohydrate receptors. We show that the b-series gangliosides GD3, GD2, GD1b and GT1b all can serve as receptors for BKPyV. The crystal structure of the BKPyV capsid protein VP1 in complex with GD3 reveals contacts with two sialic acid moieties in the receptor, providing a basis for the observed specificity. Comparison with the structure of simian virus 40 (SV40) VP1 bound to ganglioside GM1 identifies the amino acid at position 68 as a determinant of specificity. Mutation of this residue from lysine in BKPyV to serine in SV40 switches the receptor specificity of BKPyV from GD3 to GM1 both in vitro and in cell culture. Our findings highlight the plasticity of viral receptor binding sites and form a template to retarget viruses to different receptors and cell types.
Positron Emission Tomography/Computed Tomographic and Magnetic Resonance Imaging in a Murine Model of Progressive Atherosclerosis Using 64 Cu-Labeled Glycoprotein VI-Fc
2013-10-10

Background— Plaque erosion leads to exposure of subendothelial collagen, which may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion using 64 Cu-labeled GPVI-Fc (fragment crystallized). Methods and Results— Four-week-old male apolipoprotein E–deficient (ApoE −/− ) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wild-type (WT) mice served as controls (n=6). Another group of WT mice received a ligation injury of the left carotid artery (n=6) or sham procedure (n=4). All mice received a total activity of ≈12 MBq 64 Cu-GPVI-Fc by tail vein injection followed by delayed (24 hours) positron emission tomography using a NanoPET/computed tomographic scanner (Mediso, Hungary; Bioscan, USA) with an acquisition time of 1800 seconds. Seventy-two hours after positron emission tomography/computed tomography, all mice were scanned 2 hours after intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-specific MR contrast agent. MRI was performed on a 3-T clinical scanner (Philips Healthcare, Best, The Netherlands). In ApoE −/− mice, the 64 Cu-GPVI-Fc uptake in the aortic arch was significantly higher compared with WT mice (ApoE −/− : 13.2±1.5 Bq/cm 3 versus WT mice: 5.1±0.5 Bq/cm 3 ; P =0.028). 64 Cu-GPVI-Fc uptake was also higher in the injured left carotid artery wall compared with the intact right carotid artery of WT mice and as a trend compared with sham procedure (injured: 20.7±1.3 Bq/cm 3 versus intact: 2.3±0.5 Bq/cm 3 ; P =0.028 versus sham: 12.7±1.7 Bq/cm 3 ; P =0.068). Results were confirmed by ex vivo histology and in vivo MRI with elastin-specific MR contrast agent that measures plaque burden and vessel wall remodeling. Higher R1 relaxation rates were found in the injured carotid wall with a T1 mapping sequence (injured: 1.44±0.08 s −1 versus intact: 0.91±0.02 s −1 ; P =0.028 versus sham: 0.97±0.05 s −1 ; P =0.068) and in the aortic arch of ApoE −/− mice compared with WT mice (ApoE −/− : 1.49±0.05 s −1 versus WT: 0.92±0.04 s −1 ; P =0.028). Conclusions— 64 Cu-GPVI-Fc positron emission tomographic imaging allows identification of exposed subendothelial collagen in injured WT and high-fat diet–fed ApoE −/− mice.
Differential cystine and dibasic amino acid handling after loss of function of the amino acid transporter b0,+AT (Slc7a9) in mice
2013-10-10

Cystinuria is an autosomal recessive disease caused by mutations in SLC3A1 ( rBAT) and SLC7A9 ( b 0,+ AT). Gene targeting of the catalytic subunit ( Slc7a9) in mice leads to excessive excretion of cystine, lysine, arginine, and ornithine. Here, we studied this non-type I cystinuria mouse model using gene expression analysis, Western blotting, clearance, and brush-border membrane vesicle (BBMV) uptake experiments to further characterize the renal and intestinal consequences of losing Slc7a9 function. The electrogenic and BBMV flux studies in the intestine suggested that arginine and ornithine are transported via other routes apart from system b 0,+ . No remarkable gene expression changes were observed in other amino acid transporters and the peptide transporters in the intestine and kidney. Furthermore, the glomerular filtration rate (GFR) was reduced by 30% in knockout animals compared with wild-type animals. The fractional excretion of arginine was increased as expected (∼100%), but fractional excretions of lysine (∼35%), ornithine (∼16%), and cystine (∼11%) were less affected. Loss of function of b 0,+ AT reduced transport of cystine and arginine in renal BBMVs and completely abolished the exchanger activity of dibasic amino acids with neutral amino acids. In conclusion, loss of Slc7a9 function decreases the GFR and increases the excretion of several amino acids to a lesser extent than expected with no clear regulation at the mRNA and protein level of alternative transporters and no increased renal epithelial uptake. These observations indicate that transporters located in distal segments of the kidney and/or metabolic pathways may partially compensate for Slc7a9 loss of function.
Modulation of intracellular calcium homeostasis blocks autophagosome formation
2013-10-11

Cellular stress responses often involve elevation of cytosolic calcium levels, and this has been suggested to stimulate autophagy. Here, however, we demonstrated that agents that alter intracellular calcium ion homeostasis and induce ER stress-the calcium ionophore A23187 and the sarco/endoplasmic reticulum Ca (2+)-ATPase inhibitor thapsigargin (TG)-potently inhibit autophagy. This anti-autophagic effect occurred under both nutrient-rich and amino acid starvation conditions, and was reflected by a strong reduction in autophagic degradation of long-lived proteins. Furthermore, we found that the calcium-modulating agents inhibited autophagosome biogenesis at a step after the acquisition of WIPI1, but prior to the closure of the autophagosome. The latter was evident from the virtually complete inability of A23187- or TG-treated cells to sequester cytosolic lactate dehydrogenase. Moreover, we observed a decrease in both the number and size of starvation-induced EGFP-LC3 puncta as well as reduced numbers of mRFP-LC3 puncta in a tandem fluorescent mRFP-EGFP-LC3 cell line. The anti-autophagic effect of A23187 and TG was independent of ER stress, as chemical or siRNA-mediated inhibition of the unfolded protein response did not alter the ability of the calcium modulators to block autophagy. Finally, and remarkably, we found that the anti-autophagic activity of the calcium modulators did not require sustained or bulk changes in cytosolic calcium levels. In conclusion, we propose that local perturbations in intracellular calcium levels can exert inhibitory effects on autophagy at the stage of autophagosome expansion and closure.