julilili42/papers huggingface dataset:
Can an Infection Hypothesis Explain the Beta Amyloid Hypothesis of Alzheimer’s Disease?
2018-07-24

Alzheimer's disease (AD) is the most frequent type of dementia. The pathological hallmarks of the disease are extracellular senile plaques composed of beta-amyloid peptide (Aβ) and intracellular neurofibrillary tangles composed of pTau. These findings led to the "beta-amyloid hypothesis" that proposes that Aβ is the major cause of AD. Clinical trials targeting Aβ in the brain have mostly failed, whether they attempted to decrease Aβ production by BACE inhibitors or by antibodies. These failures suggest a need to find new hypotheses to explain AD pathogenesis and generate new targets for intervention to prevent and treat the disease. Many years ago, the "infection hypothesis" was proposed, but received little attention. However, the recent discovery that Aβ is an antimicrobial peptide (AMP) acting against bacteria, fungi, and viruses gives increased credence to an infection hypothesis in the etiology of AD. We and others have shown that microbial infection increases the synthesis of this AMP. Here, we propose that the production of Aβ as an AMP will be beneficial on first microbial challenge but will become progressively detrimental as the infection becomes chronic and reactivates from time to time. Furthermore, we propose that host measures to remove excess Aβ decrease over time due to microglial senescence and microbial biofilm formation. We propose that this biofilm aggregates with Aβ to form the plaques in the brain of AD patients. In this review, we will develop this connection between Infection - Aβ - AD and discuss future possible treatments based on this paradigm.
Brain-machine interfaces for rehabilitation in stroke: A review
2018-07-24

Despite encouraging results, motor rehabilitation based on BMIs is still in a preliminary stage, and further improvements are required to boost its efficacy. Invasive and hybrid approaches are promising and might set the stage for the next generation of stroke rehabilitation therapies.
First ground-based measurement of sub-20 GeV to 100 GeV γ-Rays from the Vela pulsar with H.E.S.S. II
2018-07-24

Aims. We report on the measurement and investigation of pulsed high-energy γ -ray emission from the Vela pulsar, PSR B0833−45, based on observations with the largest telescope of H.E.S.S., CT5, in monoscopic mode, and on data obtained with the Fermi -LAT. Methods. Data from 40.3 h of observations carried out with the H.E.S.S. II array from 2013 to 2015 have been used. A dedicated very low-threshold event reconstruction and analysis pipeline was developed to achieve the lowest possible energy threshold. Eight years of Fermi -LAT data were analysed and also used as reference to validate the CT5 telescope response model and analysis methods. Results. A pulsed γ -ray signal at a significance level of more than 15 σ is detected from the P2 peak of the Vela pulsar light curve. Of a total of 15 835 events, more than 6000 lie at an energy below 20 GeV, implying a significant overlap between H.E.S.S. II-CT5 and the Fermi -LAT. While the investigation of the pulsar light curve with the LAT confirms characteristics previously known up to 20 GeV in the tens of GeV energy range, CT5 data show a change in the pulse morphology of P2, i.e. an extreme sharpening of its trailing edge, together with the possible onset of a new component at 3.4 σ significance level. Assuming a power-law model for the P2 spectrum, an excellent agreement is found for the photon indices (Γ ≃ 4.1) obtained with the two telescopes above 10 GeV and an upper bound of 8% is derived on the relative offset between their energy scales. Using data from both instruments, it is shown however that the spectrum of P2 in the 10–100 GeV has a pronounced curvature; this is a confirmation of the sub-exponential cut-off form found at lower energies with the LAT. This is further supported by weak evidence of an emission above 100 GeV obtained with CT5. In contrast, converging indications are found from both CT5 and LAT data for the emergence of a hard component above 50 GeV in the leading wing (LW2) of P2, which possibly extends beyond 100 GeV. Conclusions. The detection demonstrates the performance and understanding of CT5 from 100 GeV down to the sub-20 GeV domain, i.e. unprecedented low energy for ground-based γ -ray astronomy. The extreme sharpening of the trailing edge of the P2 peak found in the H.E.S.S. II light curve of the Vela pulsar and the possible extension beyond 100 GeV of at least one of its features, LW2, provide further constraints to models of γ -Ray emission from pulsars.
Big Banks and Macroeconomic Outcomes: Theory and Cross‐Country Evidence of Granularity
2018-07-24

Abstract Does the mere presence of big banks affect macroeconomic outcomes? We develop a theory of granularity for the banking sector by modeling heterogeneous banks charging variable markups. Using data for a large set of countries, we show that the banking sector is indeed “granular,” as the right tail of the bank size distribution follows a power law. We demonstrate empirically that the presence of big banks, measured by a high degree of market concentration, is associated with a positive and significant relationship between bank‐level credit growth and aggregate growth of credit or GDP.
Synthesis and Pd-catalyzed coupling of1-C-stannylated glycals
2018-07-24

1-Tributylstannyl glycals were applied as versatile tools in the Pd(0)-mediated synthesis of glycal phthalonitrile conjugates. Likewise, selective homo-coupling of 1-tributylstannyl glycals furnishing C1-C1' linked glycal dimers was investigated by using Pd(II)-species. For both Stille type couplings the rate-accelerating effect of copper(I) thiophene-2-carboxylate (CuTC) was exploited. The synthesis of stannylated glycal precursors was significantly improved by establishing a one-pot two-step procedure via glycosyl sulfoxides.
Reliability and Accuracy of Peri-Interventional Stenosis Grading in Peripheral Artery Disease Using Color-Coded Quantitative Fluoroscopy: A Phantom Study Comparing a Clinical and Scientific Postprocessing Software
2018-07-24

Purpose . To assess quantitative stenosis grading by color-coded fluoroscopy using an in vitro pulsatile flow phantom. Methods . Three different stenotic tubes (80%, 60%, and 40% diameter restriction) and a nonstenotic reference tube were compared regarding their different flow behavior by using contrast-enhanced fluoroscopy with a flat-detector system for visualisation purposes. Time-density curves (TDC), area under the curve (AUC), time-to-peak (TTP), and different ROI sizes were analyzed in three independent measurements using two different postprocessing software solutions. In addition, exemplary TDCs of a patient with a high-grade stenosis before and after stent angioplasty were acquired. Results . Color-coded fluoroscopy enabled depiction of differences in AUC and TDC between high-grade (80%), middle (60%), low-grade (40%), and nonstenotic tubes. The best correlation between high-, middle-, and low-grade stenosis was appreciated in ROIs behind the stenosis. This effect was enhanced by using longer integration times (5s, 7s) and a maximum frame rate of image acquisition for analysis (correlation coefficient rho=0.9284 at 5s). TTP showed no significant differences between high- and low-grade stenosis. Conclusions . Various clinical studies in the literature already demonstrated reproducible and reliable stenosis grading by analyzing TDCs acquired with color-coded fluoroscopy. In contrast to TTP, AUC values derived in ROIs behind the stenosis proved to be reliable parameters for stenosis grading. However, our results also demonstrate that several factors are able to significantly impact the evaluation of AUC values. More precisely, accuracy of acquired AUC values can be improved by choosing longer integration times, a large ROI size adapted to the vessel diameter, and a higher frame rate of image acquisition.
Development and characterization of 6-gap bakelite Multi-gap Resistive Plate Chamber
2018-07-24

The Multi-gap Resistive Plate Chamber (MRPC) is an advanced form of Resistive Plate Chamber (RPC) detector where the gas gap is divided into sub-gaps. MRPCs are known for their good time resolution and detection efficiency for charged particles. They have found suitable applications in several high energy physics experiments like ALICE in LHC, CERN, Geneva, Switzerland, and STAR in RHIC, BNL, USA. As they have very good time resolution and are of low cost, they can be a suitable replacement for very expensive scintillators used in Positron Emission Tomography Imaging. The MRPCs that are being used nowadays are developed with glass electrodes. We have made an attempt to develop a 6-gap MRPC using bakelite electrodes. The outer electrodes are of dimensions 15 cm 15 cm 0.3 cm and the inner electrodes are of dimension 14 cm 14 cm 0.05 cm. The glossy finished electrode surfaces have not been treated with any oil like linseed, silicone for smoothness. The performance of the detector has been studied measuring the efficiency, noise rate and time resolution with cosmic rays. This effort is towards the development of a prototype for Positron Emission Tomography with the Time-Of-Flight technique using MRPCs. Details of the development procedure and performance studies have been presented here.
Label‐free high‐speed wide‐field imaging of single microtubules using interference reflection microscopy
2018-07-25

Summary When studying microtubules in vitro , label free imaging of single microtubules is necessary when the quantity of purified tubulin is too low for efficient fluorescent labelling or there is concern that labelling will disrupt function. Commonly used techniques for observing unlabelled microtubules, such as video enhanced differential interference contrast, dark‐field and more recently laser‐based interferometric scattering microscopy, suffer from a number of drawbacks. The contrast of differential interference contrast images depends on the orientation of the microtubules, dark‐field is highly sensitive to impurities and optical misalignments. In addition, all of these techniques require costly optical components such as Nomarski prisms, dark‐field condensers, lasers and laser scanners. Here we show that single microtubules can be imaged at high speed and with high contrast using interference reflection microscopy without the aforementioned drawbacks. Interference reflection microscopy is simple to implement, requiring only the incorporation of a 50/50 mirror instead of a dichroic in a fluorescence microscope, and with appropriate microscope settings has a similar signal‐to‐noise ratio to differential interference contrast and fluorescence. We demonstrated the utility of interference reflection microscopy by high‐speed imaging and tracking of dynamic microtubules at 100 frames per second. In conclusion, the optical quality of interference reflection microscopy falls within the range of other microscope techniques, being inferior to some and superior to others, depending on the metric used and, with minimal microscope modification, can be used to study the dynamics of unlabelled microtubules. Lay description The cytoskeleton gives a cell its shape and plays a major role in its movement and division. It's also helps organise the content of cells and is the base for intracellular transport. Important components of the cytoskeleton are microtubules, which are hollow cylindrical beams (25 nm in diameter) that assemble from protein building blocks called tubulin. Deficiencies in microtubules are related to many diseases including cancer and Alzheimer. Given their important role, microtubules are heavily investigated in many laboratories. One way to study microtubules is to isolate them from cells and image them using light microscopy. Over the years a number of imaging techniques have been used. These techniques have a number of drawbacks which are addressed by ongoing efforts which this work is a part of. Here, we present a method based on light interference that produce high quality images of microtubules. The technique is cheap and easy to implement making it accessible to a wide base of researchers.
Threatened individuals prefer positive information during Internet search: An experimental laboratory study
2018-07-25

The Internet is the main source for information search and it is increasingly used in the health domain. Such self-relevant Internet searches are most probably accompanied by affective states such as threat (e.g., being afraid of a serious illness). Thus, threat can influence the entire Internet search process. Threat is known to elicit a preference for positive information. This positive bias has recently been shown for separate steps of the Internet search process (i.e., selection of links, scanning of webpages, and recall of information). To extend this research, the present study aimed at investigating the influence of threat across the Internet search process. We expected that threatened individuals similarly prefer positive information during this process. An experimental laboratory study was conducted with undergraduate students (N = 114) enrolled in a broad range of majors. In this study, threat was manipulated and then participants were to complete a preprogrammed, realistic Internet search task which was used to assess selection of links, scanning of webpages, and recall of information. The results supported our hypothesis and revealed that, during the Internet search task, threatened individuals directed more attention to positive information (i.e., selected more positive links and scanned positive webpages longer) and, as a consequence, also recalled more positive information than non-threatened individuals. Thus, our study shows that not only separate steps but also the Internet search process as such is susceptible to being influenced by affective states such as threat.
Testing the Kerr nature of the supermassive black hole in Ark 564
2018-07-26

Einstein's theory of general relativity has been extensively tested in weak gravitational fields, mainly with experiments in the Solar System and observations of radio pulsars, and current data agree well with the theoretical predictions. Nevertheless, there are a number of scenarios beyond Einstein's gravity that have the same predictions for weak fields and present deviations only when gravity becomes strong. Here we try to test general relativity in the strong field regime. We fit the X-ray spectrum of the supermassive black hole in Ark 564 with a disk reflection model beyond Einstein's gravity, and we are able to constrain the black hole spin and the Johannsen deformation parameters and separately. For , we find and with a 99% confidence level. For , we get and with a 99% confidence level. Our measurements are thus consistent with the hypothesis that the supermassive compact object in Ark 564 can be described by the Kerr metric.
Spin ballet for sweet encounters: saturation-transfer difference NMR and X-ray crystallography complement each other in the elucidation of protein–glycan interactions
2018-07-26

Biomolecular NMR spectroscopy has limitations in the determination of protein structures: an inherent size limit and the requirement for expensive and potentially difficult isotope labelling pose considerable hurdles. Therefore, structural analysis of larger proteins is almost exclusively performed by crystallography. However, the diversity of biological NMR applications outperforms that of any other structural biology technique. For the characterization of transient complexes formed by proteins and small ligands, notably oligosaccharides, one NMR technique has recently proven to be particularly powerful: saturation-transfer difference NMR (STD-NMR) spectroscopy. STD-NMR experiments are fast and simple to set up, with no general protein size limit and no requirement for isotope labelling. The method performs best in the moderate-to-low affinity range that is of interest in most of glycobiology. With small amounts of unlabelled protein, STD-NMR experiments can identify hits from mixtures of potential ligands, characterize mutant proteins and pinpoint binding epitopes on the ligand side. STD-NMR can thus be employed to complement and improve protein–ligand complex models obtained by other structural biology techniques or by purely computational means. With a set of protein–glycan interactions from our own work, this review provides an introduction to the technique for structural biologists. It exemplifies how crystallography and STD-NMR can be combined to elucidate protein–glycan (and other protein–ligand) interactions in atomic detail, and how the technique can extend structural biology from simplified systems amenable to crystallization to more complex biological entities such as membranes, live viruses or entire cells.
Tectonic controls of Holocene erosion in a glaciated orogen
2018-07-26

Abstract. Recent work has highlighted a strong, worldwide, alpine glacial impact on orogen erosion rates over the last 2 Ma. While it may be assumed that glaciers increased erosion rates when active, the degree to which past glaciations influence Holocene erosion rates through the adjustment of topography is not known. In this study, we investigate the influence of long-term tectonic and post-glacial topographic controls on erosion in a glaciated orogen: the Olympic Mountains, USA. We present 14 new 10Be and 26Al analyses which constrain Holocene erosion rates across the Olympic Mountains. Basin-averaged erosion rates scale with basin-averaged values of 5 km local relief, channel steepness, and hillslope angle throughout the range, similar to observations from non-glaciated orogens. These erosion rates are not related to mean annual precipitation or the marked change in Pleistocene alpine glacier size across the range, implying that glacier modification of topography and modern precipitation parameters do not exert strong controls on these rates. Rather, we find that despite spatial variations in glacial modification of topography, patterns of recent erosion are similar to those from estimates of long-term tectonic rock uplift. This is consistent with a tectonic model where erosion and rock uplift patterns are controlled by the deformation of the Cascadia subduction zone.
Two-qubit causal structures and the geometry of positive qubit-maps
2018-07-26

We study quantum causal inference in a set-up proposed by Ried et al. [Nat.\\nPhys. 11, 414 (2015)] in which a common-cause scenario can be mixed with a\\ncause-effect scenario, and for which it was found that quantum mechanics can\\nbring an advantage in distinguishing the two scenarios: Whereas in classical\\nstatistics, interventions such as randomized trials are needed, a quantum\\nobservational scheme can be enough to detect the causal structure if the common\\ncause results from a maximally entangled state. We analyze this setup in terms\\nof the geometry of unital positive but not completely positive qubit-maps,\\narising from the mixture of qubit-channels and steering maps. We find the range\\nof mixing parameters that can generate given correlations, and prove a quantum\\nadvantage in a more general setup, allowing arbitrary unital channels and\\ninitial states with fully mixed reduced states. This is achieved by\\nestablishing new bounds on signed singular values of sums of matrices. Based on\\nthe geometry, we quantify and identify the origin of the quantum advantage\\ndepending on the observed correlations, and discuss how additional constraints\\ncan lead to a unique solution of the problem.\\n
Real-Time Imaging Reveals Augmentation of Glutamate-Induced Ca2+ Transients by the NO-cGMP Pathway in Cerebellar Granule Neurons
2018-07-26

Dysfunctions of NO-cGMP signaling have been implicated in various neurological disorders. We have studied the potential crosstalk of cGMP and Ca2+ signaling in cerebellar granule neurons (CGNs) by simultaneous real-time imaging of these second messengers in living cells. The NO donor DEA/NO evoked cGMP signals in the granule cell layer of acute cerebellar slices from transgenic mice expressing a cGMP sensor protein. cGMP and Ca2+ dynamics were visualized in individual CGNs in primary cultures prepared from 7-day-old cGMP sensor mice. DEA/NO increased the intracellular cGMP concentration and augmented glutamate-induced Ca2+ transients. These effects of DEA/NO were absent in CGNs isolated from knockout mice lacking NO-sensitive guanylyl cyclase. Furthermore, application of the cGMP analogues 8-Br-cGMP and 8-pCPT-cGMP, which activate cGMP effector proteins such as cyclic nucleotide-gated cation channels and cGMP-dependent protein kinases (cGKs), also potentiated glutamate-induced Ca2+ transients. Western blot analysis failed to detect cGK type I or II in our primary CGNs. The addition of phosphodiesterase (PDE) inhibitors during cGMP imaging showed that CGNs degrade cGMP mainly via Zaprinast-sensitive PDEs, most likely PDE5 and/or PDE10, but not via PDE1, 2, or 3. In sum, these data delineate a cGK-independent NO-cGMP signaling cascade that increases glutamate-induced Ca2+ signaling in CGNs. This cGMP–Ca2+ crosstalk likely affects neurotransmitter-stimulated functions of CGNs.
Four-Membered Lutetaheterocycles
2018-07-26

The four-membered metallacyclic lutetium complexes TptBu,MeLu[CH2(SiMe2)NR] were synthesized via protonolysis of TptBu,MeLuMe2 (TptBu,Me = hydrotris(3-methyl-5-tert-butylpyrazolyl)borato) with silylamines HN(SiMe3)R (R = SiMe3, C6H3(CF3)2-3,5 (ArCF3)). The sterically less demanding amine HN(SiHMe2)2 led to the isolation of the heteroleptic complex TptBu,MeLuMe[N(SiHMe2)2]. The accessibility of the complex TptBu,MeLu[CH2(SiMe2)NArCF3] to intramolecular ring opening was explored using HOCH2tBu, affording lutetium neopentoxide complexes TptBu,MeLu[N(SiMe3)ArCF3](OCH2tBu) and TptBu,MeLu(OCH2tBu)2. Treatment of TptBu,MeLu[CH2(SiMe2)NArCF3] with H3SiPh resulted in an unusual ring hydrogen/silyl group exchange and formation of TptBu,MeLu[CH(SiH2Ph)(SiMe2)NArCF3], retaining the four-membered lutetaheterocycle. All complexes were fully characterized by NMR/IR spectroscopy, elemental analysis, and X-ray crystallography.
Hopf bifurcation in a model for adult T‐cell leukemia
2018-07-26

This paper is concerned with Hopf bifurcation and its stability for the model related to the disease of human T‐cell lymphotropic virus type I (HTLV‐I). In fact, we are considering Hopf bifurcation of the system because it plays an important role in indicating when the disease can return to a steady state condition. The model consists of CD4 + T‐cell subsets of healthy, latently infected, and actively infected cells, as well as for leukemia cells. Latently infected T‐cells may harbor the virus for several years until they become activated and able to infect susceptible T‐cells. In this model, we apply techniques such as the center manifold and normal‐form theorem to simplify bifurcating and the dimension of the dynamical system. The results are applied to clinical data as an example.