julilili42/papers huggingface dataset:
In Vivo Hypoxia PET Imaging Quantifies the Severity of Arthritic Joint Inflammation in Line with Overexpression of Hypoxia-Inducible Factor and Enhanced Reactive Oxygen Species Generation
2017-02-09

Hypoxia is essential for the development of autoimmune diseases such as rheumatoid arthritis (RA) and is associated with the expression of reactive oxygen species (ROS), because of the enhanced infiltration of immune cells. The aim of this study was to demonstrate the feasibility of measuring hypoxia noninvasively in vivo in arthritic ankles with PET/MRI using the hypoxia tracers <sup>18</sup>F-fluoromisonidazole (<sup>18</sup>F-FMISO) and <sup>18</sup>F-fluoroazomycinarabinoside (<sup>18</sup>F-FAZA). Additionally, we quantified the temporal dynamics of hypoxia and ROS stress using L-012, an ROS-sensitive chemiluminescence optical imaging probe, and analyzed the expression of hypoxia-inducible factors (HIFs). <b>Methods:</b> Mice underwent noninvasive in vivo PET/MRI to measure hypoxia or optical imaging to analyze ROS expression. Additionally, we performed ex vivo pimonidazole-/HIF-1α immunohistochemistry and HIF-1α/2α Western blot/messenger RNA analysis of inflamed and healthy ankles to confirm our in vivo results. <b>Results:</b> Mice diseased from experimental RA exhibited a 3-fold enhancement in hypoxia tracer uptake, even in the early disease stages, and a 45-fold elevation in ROS expression in inflamed ankles compared with the ankles of healthy controls. We further found strong correlations of our noninvasive in vivo hypoxia PET data with pimonidazole and expression of HIF-1α in arthritic ankles. The strongest hypoxia tracer uptake was observed as soon as day 3, whereas the most pronounced ROS stress was evident on day 6 after the onset of experimental RA, indicating that tissue hypoxia can precede ROS stress in RA. <b>Conclusion:</b> Collectively, for the first time to our knowledge, we have demonstrated that the noninvasive measurement of hypoxia in inflammation using <sup>18</sup>F-FAZA and <sup>18</sup>F-FMISO PET imaging represents a promising new tool for uncovering and monitoring rheumatic inflammation in vivo. Further, because hypoxic inflamed tissues are associated with the overexpression of HIFs, specific inhibition of HIFs might represent a new powerful treatment strategy.
An Atelocollagen Coating for Efficient Local Gene Silencing by Using Small Interfering RNA
2017-02-09

In the last decades, many efforts have been made to counteract adverse effects after stenting atherosclerotic coronary arteries. A breakthrough in better vascular wall regeneration was noted in the new era of drug-eluting stents. A novel personalized approach is the development of gene-eluting stents promising an alteration in gene expression involved in regeneration. We investigated a coating system consisting of the polymer atelocollagen (ATCOL) and a specific small interfering RNA (siRNA) for intercellular adhesion molecule-1 (ICAM-1) found on the surface of defective endothelial cells (ECs). We demonstrated very high cell viability, in which EA.hy926 grew on 0.008% or 0.032% ATCOL layers. Additionally, hemocompatibility assays proved the biocompatibility of this coating. The highest transfection efficiency with EA.hy926 was achieved with 5 μg siRNA immobilized in ATCOL after 2 days. The release of fluorescent-labeled siRNA was about 9 days. Long-term knockdown of ICAM-1 was analyzed by flow cytometry, revealing that the coating with 0.008% ATCOL and 5 μg siICAM-1 provoked gene silencing up to 8 days. 5'-RNA ligase-mediated rapid amplification of cDNA ends PCR (RLM-RACE-PCR) demonstrated the specificity of our established ATCOL gene-silencing coating, meaning that our coating is well suited for further investigations in in vivo studies. Herein, we would like to demonstrate that our ATCOL is well-suited for better artery wall regeneration after stent implantation.
Cyclotron resonant scattering feature simulations
2017-02-10

\\n Context. Electron cyclotron resonant scattering features (CRSFs) are observed as absorption-like lines in the spectra of X-ray pulsars. A significant fraction of the computing time for Monte Carlo simulations of these quantum mechanical features is spent on the calculation of the mean free path for each individual photon before scattering, since it involves a complex numerical integration over the scattering cross section and the (thermal) velocity distribution of the scattering electrons. \\n Aims. We aim to numerically calculate interpolation tables which can be used in CRSF simulations to sample the mean free path of the scattering photon and the momentum of the scattering electron. The tables also contain all the information required for sampling the scattering electron’s final spin. \\n Methods. The tables were calculated using an adaptive Simpson integration scheme. The energy and angle grids were refined until a prescribed accuracy is reached. The tables are used by our simulation code to produce artificial CRSF spectra. The electron momenta sampled during these simulations were analyzed and justified using theoretically determined boundaries. \\n Results. We present a complete set of tables suited for mean free path calculations of Monte Carlo simulations of the cyclotron scattering process for conditions expected in typical X-ray pulsar accretion columns (0.01 ≤ B/Bcrit ≤ 0.12, where Bcrit = 4.413 × 1013 G, and 3 keV ≤ kBT ≤ 15 keV). The sampling of the tables is chosen such that the results have an estimated relative error of at most 1/15 for all points in the grid. The tables are available online (see link in footnote, page 1). \\n
Cosmic-muon characterization and annual modulation measurement with Double Chooz detectors
2017-02-10

A study on cosmic muons has been performed for the two identical near and far\\nneutrino detectors of the Double Chooz experiment, placed at 120 and\\n 300 m.w.e. underground respectively, including the corresponding\\nsimulations using the MUSIC simulation package. This characterization has\\nallowed to measure the muon flux reaching both detectors to be (3.64 \\n0.04) 10 cm s for the near detector and (7.00\\n 0.05) 10 cm s for the far one. The seasonal\\nmodulation of the signal has also been studied observing a positive correlation\\nwith the atmospheric temperature, leading to an effective temperature\\ncoefficient of = 0.212 0.024 and 0.355 0.019 for the\\nnear and far detectors respectively. These measurements, in good agreement with\\nexpectations based on theoretical models, represent one of the first\\nmeasurements of this coefficient in shallow depth installations.\\n
Engineering sortase A by screening a second‐generation library using phage display
2017-02-10

Sortase‐mediated ligation is one of the most commonly used chemo‐enzymatic techniques for the site‐specific modification of proteins. We have established a new library of sortase mutants for directed evolution of sortase substrate selectivity. Phage display screens of this second‐generation library yielded sortase mutants that ligate substrate proteins containing an APxTG or FPxTG recognition sequence instead of the canonical LPxTG sorting motif. These findings indicate that the second‐generation sortase library is well suited for sortase engineering in order to increase the versatility of sortase‐mediated ligation. Copyright © 2017 European Peptide Society and John Wiley &amp; Sons, Ltd.
Controlling Near-Infrared Chromophore Electronic Properties through Metal–Ligand Orbital Alignment
2017-02-10

Transition-metal complexes of radical ligands can exhibit low-energy electronic transitions in the near-infrared (NIR) spectral region. NIR band energy and intensity sensitively depend on the degree of electronic coupling of the chromophore. Using the example of open-shell complexes derived from platinum and a 1,4-terphenyldithiophenol, we present a novel approach toward spectroscopically distinct NIR dyes for which the degree of electronic coupling correlates with the relative orientation of radical ligand and metal orbitals. Ligand/metal orbital alignment is modulated by auxiliary phosphine donors and selectively results in electron localized Class II-III or delocalized Class III structures that display distinct NIR transitions at 6500 and 4000 cm<sup>-1</sup>.
Informative Cues Facilitate Saccadic Localization in Blindsight Monkeys
2017-02-10

Patients with damage to the primary visual cortex (V1) demonstrate residual visual performance during laboratory tasks despite denying having a conscious percept. The mechanisms behind such performance, often called blindsight, are not fully understood, but the use of surgically-induced unilateral V1 lesions in macaque monkeys provides a useful animal model for exploring such mechanisms. For example, V1-lesioned monkeys localize stimuli in a forced-choice condition while at the same time failing to report awareness of identical stimuli in a yes-no detection condition, similar to human patients. Moreover, residual cognitive processes, including saliency-guided eye movements, bottom-up attention with peripheral non-informative cues, and spatial short-term memory, have all been demonstrated in these animals. Here we examined whether post-lesion residual visuomotor processing can be modulated by top-down task knowledge. We tested two V1-lesioned monkeys with a visually guided saccade task in which we provided an informative foveal pre-cue about upcoming target location. Our monkeys fixated while we presented a leftward or rightward arrow (serving as a pre-cue) superimposed on the fixation point (FP). After various cue-target onset asynchronies (CTOAs), a saccadic target (of variable contrast across trials) was presented either in the affected (contra-lesional) or seeing (ipsi-lesional) hemifield. Critically, target location was in the same hemifield that the arrow pre-cue pointed towards in 80% of the trials (valid-cue trials), making the cue highly useful for task performance. In both monkeys, correct saccade reaction times were shorter during valid than invalid trials. Moreover, in one monkey, the ratio of correct saccades towards the affected hemifield was higher during valid than invalid trials. We replicated both reaction time and correct ratio effects in the same monkey using a symbolic color cue. These results suggest that V1-lesion monkeys can use informative cues to localize stimuli in the contra-lesional hemifield, consistent with reports of a human blindsight subject being able to direct attention in cueing paradigms. Because the superior colliculus (SC) may contribute to residual visual capabilities after V1 lesions, and because this structure is important for controlling attentional resources, we hypothesize that our results reflect, among others, SC involvement in integrating top-down task knowledge for guiding orienting behavior.
RNA-Eluting Surfaces for the Modulation of Gene Expression as A Novel Stent Concept
2017-02-10

Presently, a new era of drug-eluting stents is continuing to improve late adverse effects such as thrombosis after coronary stent implantation in atherosclerotic vessels. The application of gene expression–modulating stents releasing specific small interfering RNAs (siRNAs) or messenger RNAs (mRNAs) to the vascular wall might have the potential to improve the regeneration of the vessel wall and to inhibit adverse effects as a new promising therapeutic strategy. Different poly (lactic-co-glycolic acid) (PLGA) resomers for their ability as an siRNA delivery carrier against intercellular adhesion molecule (ICAM)-1 with a depot effect were tested. Biodegradability, hemocompatibility, and high cell viability were found in all PLGAs. We generated PLGA coatings with incorporated siRNA that were able to transfect EA.hy926 and human vascular endothelial cells. Transfected EA.hy926 showed significant siICAM-1 knockdown. Furthermore, co-transfection of siRNA and enhanced green fluorescent protein (eGFP) mRNA led to the expression of eGFP as well as to the siRNA transfection. Using our PLGA and siRNA multilayers, we reached high transfection efficiencies in EA.hy926 cells until day six and long-lasting transfection until day 20. Our results indicate that siRNA and mRNA nanoparticles incorporated in PLGA films have the potential for the modulation of gene expression after stent implantation to achieve accelerated regeneration of endothelial cells and to reduce the risk of restenosis.
Drell-Yan lepton angular distributions in perturbative QCD
2017-02-10

We present a comprehensive comparison of the available experimental data for the Drell-Yan lepton angular coefficients and to calculations at leading and next-to-leading order (NLO) of perturbative QCD. To obtain the NLO corrections, we make use of publicly available numerical codes that allow us to compute the Drell-Yan cross section at second order in perturbation theory and from which the contributions we need can be extracted. Our comparisons show that overall perturbative QCD is able to describe the experimental data rather well, even in the fixed-target regime. There appears to be little evidence for effects that go beyond fixed-order collinear factorized perturbation theory, although the presence of such effects is not ruled out. We also address the recent ATLAS data which show tension with NLO theory for the coefficient .
Linguistic Information in Auditory Dynamic Events Contributes to the Detection of Fine, Not Coarse Event Boundaries
2017-02-10

Background. Human observers segment dynamic information into discrete events. That is, although there is continuous sensory information, comprehenders perceive boundaries between two meaningful units of information. In narrative comprehension comprehenders use linguistic, non-linguistic, and physical cues for this event boundary perception. Yet, it is an open question–both from a theoretical and an empirical perspective–how linguistic and non-linguistic cues contribute to this process. The current study explores how linguistic cues contribute to participants’ ability to segment continuous auditory information into discrete, hierarchically structured events. Methods. Native speakers of German and non-native speakers, who neither spoke nor understood German, segmented a German audio drama into coarse and fine events. Whereas native participants could make use of linguistic, non-linguistic, and physical cues for segmentation, non-native participants could only use non-linguistic and physical cues. We analyzed segmentation behavior in terms of the ability to identify coarse and fine event boundaries and the resulting hierarchical structure. Results. Non-native listeners identified essentially the same coarse event boundaries as native listeners but missed some of the fine event boundaries identified by the native listeners. Interestingly, hierarchical event perception (as measured with hierarchical alignment and enclosure) was comparable for native and non-native participants. Discussion. In summary, linguistic cues contributed particularly to the identification of certain fine event boundaries. The results are discussed with regard to the current theories of event cognition.
Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study
2017-02-11

BACKGROUND: Available incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents. METHODS: We established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment. FINDINGS: Between March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0-0) in Sudan to 383 (274-535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178-316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau. INTERPRETATION: Typhoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study. FUNDING: Bill &amp; Melinda Gates Foundation.
Reversal of tumor acidosis by systemic buffering reactivates NK cells to express IFN‐γ and induces NK cell‐dependent lymphoma control without other immunotherapies
2017-02-13

Like other immune cells, natural killer (NK) cells show impaired effector functions in the microenvironment of tumors, but little is known on the underlying mechanisms. Since lactate acidosis, a hallmark of malignant tissue, was shown to contribute to suppression of effective antitumor immune responses, we investigated the impact of tissue pH and lactate concentration on NK‐cell functions in an aggressive model of endogenously arising B‐cell lymphoma. The progressive loss of IFN‐γ production by NK cells observed during development of this disease could be ascribed to decreased pH values and lactate accumulation in the microenvironment of growing tumors. Interestingly, IFN‐γ expression by lymphoma‐derived NK cells could be restored by transfer of these cells into a normal micromilieu. Likewise, systemic alkalization by oral delivery of bicarbonate to lymphoma‐developing mice was capable of enhancing IFN‐γ expression in NK cells and increasing the NK‐cell numbers in the lymphoid organs where tumors were growing. By contrast, NK‐cell cytotoxicity was dampened in vivo by tumor‐dependent mechanisms that seemed to be different from lactate acidosis and could not be restored in a normal milieu. Most importantly, alkalization and the concomitant IFN‐γ upregulation in NK cells were sufficient to significantly delay tumor growth without any other immunotherapy. This effect was strictly dependent on NK cells.
EEG correlates of working memory performance in females
2017-02-13

WM performance is accompanied by changes in EEG in a broad frequency range from theta to higher beta bands. The most pronounced differences in oscillatory activity between individuals with high and low WM performance can be observed in the most challenging WM task.
Applying phasor approach analysis of multiphoton FLIM measurements to probe the metabolic activity of three-dimensional in vitro cell culture models
2017-02-13

Abstract Fluorescence lifetime imaging microscopy (FLIM) can measure and discriminate endogenous fluorophores present in biological samples. This study seeks to identify FLIM as a suitable method to non-invasively detect a shift in cellular metabolic activity towards glycolysis or oxidative phosphorylation in 3D Caco-2 models of colorectal carcinoma. These models were treated with potassium cyanide or hydrogen peroxide as controls, and epidermal growth factor (EGF) as a physiologically-relevant influencer of cell metabolic behaviour. Autofluorescence, attributed to nicotinamide adenine dinucleotide (NADH), was induced by two-photon laser excitation and its lifetime decay was analysed using a standard multi-exponential decay approach and also a novel custom-written code for phasor-based analysis. While both methods enabled detection of a statistically significant shift of metabolic activity towards glycolysis using potassium cyanide, and oxidative phosphorylation using hydrogen peroxide, employing the phasor approach required fewer initial assumptions to quantify the lifetimes of contributing fluorophores. 3D Caco-2 models treated with EGF had increased glucose consumption, production of lactate, and presence of ATP. FLIM analyses of these cultures revealed a significant shift in the contribution of protein-bound NADH towards free NADH, indicating increased glycolysis-mediated metabolic activity. This data demonstrate that FLIM is suitable to interpret metabolic changes in 3D in vitro models.
Strong Isotope Effects on Effective Interactions and Phase Behavior in Protein Solutions in the Presence of Multivalent Ions
2017-02-13

In this article, we have studied the influence of the isotopic composition of the solvent (H<sub>2</sub>O or D<sub>2</sub>O) on the effective interactions and the phase behavior of the globular protein bovine serum albumin in solution with two trivalent salts (LaCl<sub>3</sub> and YCl<sub>3</sub>). Protein solutions with both salts exhibit a reentrant condensation phase behavior. The condensed regime (regime II) in between two salt concentration boundaries (c* < c<sub>s</sub> < c**) is significantly broadened by replacing H<sub>2</sub>O with D<sub>2</sub>O. Within regime II, liquid-liquid phase separation (LLPS) occurs. The samples that undergo LLPS have a lower critical solution temperature (LCST). The value of LCST decreases significantly with increasing solvent fraction of D<sub>2</sub>O. The effective protein-protein interactions characterized by small-angle X-ray scattering demonstrate that although changing the solvent has negligible effects below c*, where the interactions are dominated by electrostatic repulsion, an enhanced effective attraction is observed in D<sub>2</sub>O above c*, consistent with the phase behavior observed. As the LCST-LLPS is an entropy-driven phase transition, the results of this study emphasize the role of entropy in solvent isotope effects.
Limits of size scalability of diffusion and growth: Atoms versus molecules versus colloids
2017-02-13

Understanding fundamental growth processes is key to the control of nonequilibrium structure formation for a wide range of materials on all length scales, from atomic to molecular and even colloidal systems. While atomic systems are relatively well studied, molecular and colloidal growth are currently moving more into the focus. This poses the question to what extent growth laws are size scalable between different material systems. We study this question by analyzing the potential energy landscape and performing kinetic Monte Carlo simulations for three representative systems. While submonolayer (island) growth is found to be essentially scalable, we find marked differences when moving into the third (vertical) dimension.