julilili42/papers huggingface dataset:
Oxidative stress in cystic fibrosis lung disease: an early event, but worth targeting?
2014-06-30

A recent study showed that oxidative stress occurs early in CF lung disease and represents a potential drug target http://ow.ly/vdH2POxidative stress is a universal biological response, which plays a major role in a variety of inflammatory disease conditions, such as cardiovascular diseases or sepsis.In the lung, harmful oxidative stress mainly occurs in nonresolving pathologies, such as cystic fibrosis (CF) lung disease [1,2] or, to a lesser extent, chronic obstructive pulmonary disease [3,4].In CF, neutrophils are continuously recruited to the airways and liberate their toxic ingredients, particularly proteases and oxidants, in an uncontrolled fashion [5].Anti-proteases and anti-oxidants shield the lung from free proteolytic and oxidative damage [6].However, in CF the amount and duration of neutrophilic inflammation overwhelms these defence systems [2,7].The released proteases and reactive oxygen species, physiologically the neutrophil's major armamentarium to kill intracellular pathogens, as evidenced in patients with chronic granulomatous disease [8], degrade extracellular matrix components and immune receptors and oxidise proteins in the CF airway microenvironment in an uncontrolled manner.Glutathione is the major antioxidant shield in the epithelial lining fluid of the human lung and protects this vulnerable area from oxidative stress.Previous reports supported the concept that the cystic fibrosis transmembrane conductance regulator (CFTR) itself transports glutathione, providing a potential explanation for the low glutathione levels in CF airways [9][10][11].Alternatively to this CFTR-linked mechanism, activated neutrophils are also capable of oxidising and thereby disabling glutathione [12].To date, the relative contribution of these two mechanisms and the time-point when glutathione loss occurs in CF lung disease in vivo remains poorly understood.In this issue of the European Respiratory Journal, KETTLE et al.[13] take a closer look at the relationship between glutathione and neutrophilic inflammation by studying bronchoalveolar lavage fluid from 167 infants with CF with a mean age of 3 years.KETTLE et al. [13] studied a whole panel of glutathione oxidation products and neutrophil-derived enzymes that can oxidise glutathione.This study provides evidence that: 1) loss of glutathione occurs early in CF lung disease; 2) oxidised glutathione closely correlates with neutrophil-derived products, mainly hypochlorous acid; and 3) pulmonary infection enhances oxidative stress and oxidative loss of glutathione.The question arises of how specific are these findings for CF and what are the therapeutic consequences?We know that glutathione levels in airway lining fluids are low in a number of inflammatory conditions beyond CF, including severe asthma [14].In previous studies, glutathione levels were found to be decreased in
Characterization of rapid neutrophil extracellular trap formation and its cooperation with phagocytosis in human neutrophils
2014-06-30

Neutrophils, as the first cellular line of innate host defense, employ phagocytosis and formation of neutrophil extracellular traps (NETs) to combat infections. Classical NET formation induced by phorbol myristate acetate requires several hours to complete. However, recent studies demonstrated rapid NET formation in neutrophils upon stimulation by platelets, Staphylococcus aureus or fungal products. Here we describe that antibody- or complement-induced phagocytosis triggers rapid NET formation. In contrast to classical NETosis, chemical inhibition of NADPH oxidase as well as using NADPH oxidase-deficient patient neutrophils did not affect rapid NET formation. Although phagocytosis and rapid NET formation may not be the prerequisite of each other, cooperation of phagocytosis and rapid NET formation may be essential to improve the efficiency of defense mechanisms in combating disseminating bacteria. Dissecting the differential mechanisms of NET formation is crucial to develop novel therapeutic strategies for infectious and auto-immune diseases where NETs play an essential role.
Soft X-ray characterisation of the long-term properties of supergiant fast X-ray transients
2014-06-30

We perform the first high-sensitivity soft X-ray long-term monitoring with Swift/XRT of three relatively unexplored Supergiant Fast X-ray Transients (SFXTs), IGR J08408-4503, IGR J16328-4726, and IGR J16465-4507, whose hard X-ray duty cycles are the lowest measured among the SFXT sample, and compare their properties with those of the prototypical SFXTs. The behaviour of J08408 and J16328 resembles that of other SFXTs, and it is characterized by a relatively high inactivity duty cycle (IDC) and pronounced dynamic range (DR) in the X-ray luminosity. Like the SFXT prototypes, J08408 shows two distinct populations of flares, the first one associated with the brightest outbursts ( erg s ), the second one comprising less bright events with 10 erg s . This double-peaked distribution seems to be a ubiquitous feature of the extreme SFXTs. The lower DR of J16328 suggests it is an intermediate SFXT. We find J16465 is characterized by IDC 5% and DR 40, reminiscent of classical supergiant HMXBs. The duty cycles measured with XRT are found to be comparable with those reported previously by BAT and INTEGRAL, when the higher limiting sensitivities of these instruments are taken into account and sufficiently long observational campaigns are available. We prove that no clear correlation exists between the duty cycles of the SFXTs and their orbital periods, which makes it difficult to interpret the SFXT peculiar variability by only using arguments related to the properties of supergiant star winds. Our findings favour the idea that a correct interpretation of the SFXT phenomenology requires a mechanism to strongly reduce the mass accretion rate onto the compact object during most of its orbit around the companion, as proposed in a number of theoretical works. [Abridged]
Photosynthesis in a different light: spectro-microscopy for in vivo characterization of chloroplasts
2014-06-30

During photosynthesis, energy conversion at the two photosystems is controlled by highly complex and dynamic adaptation processes triggered by external factors such as light quality, intensity, and duration, or internal cues such as carbon availability. These dynamics have remained largely concealed so far, because current analytical techniques are based on the investigation of isolated chloroplasts lacking full adaptation ability and are performed at non-physiologically low temperatures. Here, we use non-invasive in planta spectro-microscopic approaches to investigate living chloroplasts in their native environment at ambient temperatures. This is a valuable approach to study the complex function of these systems, because an intrinsic property-the fluorescence emission-is exploited and no additional external perturbations are introduced. Our analysis demonstrates a dynamic adjustment of not only the photosystemI/photosystemII (PSI/PSII) intensity ratio in the chloroplasts but also of the capacity of the LHCs for energy transfer in response to environmental and internal cues.
Pensar a Dios: imagen y relación con dios en la poesía de Nicanor Parra y Gabriela Mistral.
2014-06-30

This paper deals with a comparative analysis between Nicanor Parra ́s and Gabriela Mistral ́s poetry, focusing on the diverse experiences, images, and attitudes toward God that these poetic speakers assume. Starting from a selection of their poems, an answer will be intended to respond the question about their conception of the divine that we understand as characteristic of the new questioning spaces emerging during the 20th century.
Deficient approaches to human neuroimaging
2014-07-01

Functional magnetic resonance imaging (fMRI) is the workhorse of imaging-based human cognitive neuroscience. The use of fMRI is ever-increasing; within the last 4 years more fMRI studies have been published than in the previous 17 years. This large body of research has mainly focused on the functional localization of condition- or stimulus-dependent changes in the blood-oxygenation-level dependent signal. In recent years, however, many aspects of the commonly practiced analysis frameworks and methodologies have been critically reassessed. Here we summarize these critiques, providing an overview of the major conceptual and practical deficiencies in widely used brain-mapping approaches, and exemplify some of these issues by the use of imaging data and simulations. In particular, we discuss the inherent pitfalls and shortcomings of methodologies for statistical parametric mapping. Our critique emphasizes recent reports of excessively high numbers of both false positive and false negative findings in fMRI brain mapping. We outline our view regarding the broader scientific implications of these methodological considerations and briefly discuss possible solutions.
Arabidopsis SNAREs SYP61 and SYP121 Coordinate the Trafficking of Plasma Membrane Aquaporin PIP2;7 to Modulate the Cell Membrane Water Permeability
2014-07-01

Abstract Plant plasma membrane intrinsic proteins (PIPs) are aquaporins that facilitate the passive movement of water and small neutral solutes through biological membranes. Here, we report that post-Golgi trafficking of PIP2;7 in Arabidopsis thaliana involves specific interactions with two syntaxin proteins, namely, the Qc-SNARE SYP61 and the Qa-SNARE SYP121, that the proper delivery of PIP2;7 to the plasma membrane depends on the activity of the two SNAREs, and that the SNAREs colocalize and physically interact. These findings are indicative of an important role for SYP61 and SYP121, possibly forming a SNARE complex. Our data support a model in which direct interactions between specific SNARE proteins and PIP aquaporins modulate their post-Golgi trafficking and thus contribute to the fine-tuning of the water permeability of the plasma membrane.
High-speed force mapping on living cells with a small cantilever atomic force microscope
2014-07-01

The imaging speed of the wide-spread force mapping mode for quantitative mechanical measurements on soft samples in liquid with the atomic force microscope (AFM) is limited by the bandwidth of the z-scanner and viscous drag forces on the cantilever. Here, we applied high-speed, large scan-range atomic force microscopy and small cantilevers to increase the speed of force mapping by ≈10−100 times. This allowed resolving dynamic processes on living mouse embryonic fibroblasts. Cytoskeleton reorganization during cell locomotion, growth of individual cytoskeleton fibers, cell blebbing, and the formation of endocytic pits in the cell membrane were observed. Increasing the force curve rate from 2 to 300 Hz increased the measured apparent Young's modulus of the cells by about 10 times, which facilitated force mapping measurements at high speed.
Triple‐echo steady‐state T2 relaxometry of the human brain at high to ultra‐high fields
2014-07-01

Quantitative MRI techniques, such as T 2 relaxometry, have demonstrated the potential to detect changes in the tissue microstructure of the human brain with higher specificity to the underlying pathology than in conventional morphological imaging. At high to ultra‐high field strengths, quantitative MR‐based tissue characterization benefits from the higher signal‐to‐noise ratio traded for either improved resolution or reduced scan time, but is impaired by severe static ( B 0 ) and transmit ( B 1 ) field heterogeneities. The objective of this study was to derive a robust relaxometry technique for fast T 2 mapping of the human brain at high to ultra‐high fields, which is highly insensitive to B 0 and B 1 field variations. The proposed method relies on a recently presented three‐dimensional (3D) triple‐echo steady‐state (TESS) imaging approach that has proven to be suitable for fast intrinsically B 1 ‐insensitive T 2 relaxometry of rigid targets. In this work, 3D TESS imaging is adapted for rapid high‐ to ultra‐high‐field two‐dimensional (2D) acquisitions. The achieved short scan times of 2D TESS measurements reduce motion sensitivity and make TESS‐based T 2 quantification feasible in the brain. After validation in vitro and in vivo at 3 T, T 2 maps of the human brain were obtained at 7 and 9.4 T. Excellent agreement between TESS‐based T 2 measurements and reference single‐echo spin‐echo data was found in vitro and in vivo at 3 T, and T 2 relaxometry based on TESS imaging was proven to be feasible and reliable in the human brain at 7 and 9.4 T. Although prominent B 0 and B 1 field variations occur at ultra‐high fields, the T 2 maps obtained show no B 0 ‐ or B 1 ‐related degradations. In conclusion, as a result of the observed robustness, TESS T 2 may emerge as a valuable measure for the early diagnosis and progression monitoring of brain diseases in high‐resolution 2D acquisitions at high to ultra‐high fields. Copyright © 2014 John Wiley &amp; Sons, Ltd.
Increase of fast nutrient cycling in grassland microcosms through insect herbivory depends on plant functional composition and species diversity
2014-07-01

Nutrient cycling in terrestrial ecosystems is affected by various factors such as plant diversity and insect herbivory. While several studies suggest insect herbivory to depend on plant diversity, their interacting effect on nutrient cycling is unclear. In a greenhouse experiment with grassland microcosms of one to six plant species of two functional groups (grasses and legumes), we tested the influence of plant species richness (diversity) and functional composition on plant community biomass production, insect foliar herbivory, soil microbial biomass, and nutrient concentrations in throughfall. To manipulate herbivory, zero, three or six generalist grasshoppers ( Chorthippus parallelus ) were added to the plant communities. Increasing plant species richness increased shoot biomass and grasshopper performance, without significantly affecting root biomass or insect herbivory. Plant functional composition affected all of these parameters, e.g. legume communities showed the highest shoot biomass, the lowest grasshopper performance and suffered the least herbivory. Nutrient concentrations (dissolved mineral N, PO 4 ‐P, SO 4 ‐S) and pH in throughfall increased with herbivory. PO 4 ‐P and pH increases were positively affected by plant diversity, especially under high herbivore pressure. Plant functional composition affected several throughfall variables, sometimes fully explaining diversity effects. Increasing plant diversity tended to increase soil microbial biomass, but only under high herbivore pressure. Faeces quantities strongly correlated with changes in pH and PO 4 ‐P; frass may therefore be an important driver of throughfall pH and a main source of PO 4 ‐P released from living plants. Our results indicate that insect herbivory may significantly influence fast nutrient cycling processes in natural communities, particularly so in managed grasslands.
An ESL timing &amp; power estimation and simulation framework for heterogeneous socs
2014-07-01

Consideration of an embedded system's timing behaviour and power consumption at system-level is an ambitious task. Sophisticated tools and techniques exist for power and timing estimations of individual components such as custom hard- and software as well as IP components. But prediction of the composed system behaviour can hardly be made without considering all system components. In this paper we present an ESL framework for timing and power aware rapid virtual system prototyping of heterogeneous SoCs consisting of software, custom hardware and 3 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">rd</sup> party IP components. Our proposed flow combines system-level timing and power estimation techniques with platform-based rapid prototyping. Virtual executable proto-types are generated from a functional C/C++ description, which then allows to study different platforms, mapping alternatives, and power management strategies. We propose an efficient code annotation technique for timing and power, that enables fast host execution and collection of power traces, based on domain-specific workload scenarios.
Cryptic species revealed by molecular phylogenetic analysis of sequences obtained from basidiomata of Tulasnella
2014-07-01

Delimitation of species and the search for a proper threshold for defining phylogenetic species in fungi are under discussion. In this study, morphological and molecular data are correlated to delimit species of Tulasnella, the most important mycobionts of Orchidaceae, which suffer from poor taxonomy. Resupinate basidiomata of Tulasnella species were collected in Ecuador and Germany, and 11 specimens (seven from Ecuador, four from Germany) were assigned to traditional species concepts by use of morphological keys. The specimens were compared by micro-anatomical examination with 75 specimens of Tulasnella borrowed from fungaria to obtain better insights on variation of characters. Sequences of the ITS region (127) were obtained after cloning from the fresh basidiomata and from pure cultures. Proportional variability of ITS sequences was analyzed within and among the cultures and the specimens designated to different morphospecies. Results suggested an intragenomic variation of less than 2%, an intraspecific variation of up to 4% and an interspecific divergence of more than 9% in Tulasnella. Cryptic species in Tulasnella, mostly from Ecuador, were revealed by phylogenetic analyses with 4% intraspecific divergence as a minimum threshold for delimiting species. Conventional diagnostic morphological characters appeared insufficient for species characterization. Arguments are presented for molecular delimitation of the established species Tulasnella albida, T. asymmetrica, T. eichleriana, T. cf. pinicola, T. tomaculum and T. violea.
Independent Freshman Admission and Educational Inequality in the Access to Elite Higher Education
2014-07-01

Over the past decade, China has undertaken a significant institutional reform of its admission system in elite higher education (namely, Independent Freshman Admission, IFA), adopting a multistage selection strategy characterized by recommendation and interviews as an alternative channel of admission to the national college entrance examination (gaokao). Using IFA administrative data from Peking University, we reveal the mechanism of educational inequality through criterion transformations from standard test scores to comprehensive evaluations on competence. Significant associations were found between students' socioeconomic status origins, prior academic credentials, and whether they passed the selection process. This study contributes a unique and representative case of Chinese elite universities explaining why privileged groups maintained their advantages in this reform as well as in a rapidly expanded system of higher education. It also provides a better understanding of social stratification and elite reproduction in contemporary China.
Paleoclimatic significance of rare earth element record of the calcareous lacustrine sediments from a long core (SG-1) in the western Qaidam Basin, NE Tibetan Plateau
2014-07-01

Rare earth elements (REEs) have been widely applied as provenance tracer, but few studies focus on the potential paleoclimatic implications in long-term sedimentary sequences. This study analyzed REEs in the calcareous lacustrine sediments from a 938.5 m long core (SG-1) in the western Qaidam Basin in order to evaluate the usefulness of their abundance and fractionation in understanding the paleoclimatic evolution in the drainage area. We used acetic acid (HOAc) to leach the labile fraction of REEs, and citrate–bicarbonate–dithionite (CBD) to extract REEs associated with Fe–Mn oxides/oxyhydroxides. Four REE phases in the core sediments were identified, including HOAc leachate, HOAc residue, CBD extraction, and the bulk phase. On average, portion of REEs in HOAc residue constitutes about 80% of the bulk phase, while those portions from HOAc leachate and CBD extraction make up 18% and 3%, respectively. The REE's characteristics in the HOAc residue phase, and to a lesser extent in the bulk phase, remain stable along the core, while those in HOAc leachate and CBD extraction vary dramatically. REE abundance and fractionation in HOAc leachate and the CBD extraction phases with other well studied climatic proxies in the core are compared. The REE abundance and the degree of fractionation of HOAc leachate and CBD extraction phases provide sensitive proxies for the intensity of chemical weathering in the source area, which relate to climate change in the drainage area. The REE records in the core SG-1 reveal a long-term weakening of chemical weathering since 2.77 Ma in the western Qaidam Basin.
On a possible explanation of the DLS puzzle
2014-07-01

\\n The enhancement in the dilepton spectrum observed in heavy-ion collisions for invariant electron-positron masses in the range has recently been traced back to a corresponding enhancement in np collisions relative to pp collisions. Whereas the dilepton spectra in the latter are understood quantitatively, theoretical descriptions fail to describe the much higher dilepton rate in np collisions at beam energies below 2GeV, in particular regarding the region . We show that the missing strength can be attributed to ρ\\n0-channel π\\n+\\nπ\\n− production, which is dominated by the t-channel ΔΔ excitation and the recently found isoscalar dibaryonic resonance structure at 2.37 GeV. These processes do not contribute in pp collisions, but only in np collisions.\\n
Clinical Translation in the Virtual Liver Network
2014-07-01

The liver is the central detoxifying organ, continuously removing xenobiotics from the vascular system. Given its role in drug metabolism, a functional understanding of liver physiology is crucial to optimizing drug efficacy and patient safety. The Virtual Liver Network (VLN), a German national flagship research program, focuses on producing validated computer models of human liver physiology. These models are used to analyze patient‐derived data and thereby gain mechanistic insights in the processes underlying drug pharmacokinetics (PK). CPT Pharmacometrics Syst. Pharmacol . (2014) 3, e127; doi: 10.1038/psp.2014.25 ; published online 30 July 2014
Fragmentation of colliding planetesimals with water content
2014-07-01

Abstract We investigate the outcome of collisions of Ceres-sized planetesimals composed of a rocky core and a shell of water ice. These collisions are not only relevant for explaining the formation of planetary embryos in early planetary systems, but also provide insight into the formation of asteroid families and possible water transport via colliding small bodies. Earlier studies show characteristic collision velocities exceeding the bodies' mutual escape velocity which—along with the distribution of the impact angles—cover the collision outcome regimes ‘partial accretion’, ‘erosion’, and ‘hit-and-run’ leading to different expected fragmentation scenarios. Existing collision simulations use bodies composed of strengthless material; we study the distribution of fragments and their water contents considering the full elasto-plastic continuum mechanics equations also including brittle failure and fragmentation.
Development of First Lead Structures for Phosphoinositide 3-Kinase-C2γ Inhibitors
2014-07-01

The importance of complete elucidation of the biological functions of phosphoinositide 3-kinases (PI3K) was realized years ago. They generate 3-phosphoinositides, which are known to function as important second messengers in many inter- and intracellular signaling pathways. However, the functional role of class II PI3Ks is still unclear. Herein, we describe the synthesis of a panel of compounds that were tested against all eight mammalian PI3K-isoforms. We found inhibitors with some selectivity for class II PI3K-C2γ and also compounds with preferred inhibition of class II PI3K-C2β, providing structural leads to develop selective tool compounds.