bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease
Authors: Whitesell Jennifer D. , Buckley Alex R. , Knox Joseph E. , Kuan Leonard , Graddis Nile , Pelos Andrew , Mukora Alice , Wakeman Wayne , Bohn Phillip , Ho Anh , Hirokawa Karla E. , Harris Julie A. 
Published: October 2018

AbstractA variety of Alzheimer's disease (AD) mouse models overexpress mutant forms of human amyloid precursor protein (APP), producing high levels of amyloid β (Aβ) and forming plaques. However, the degree to which these models mimic spatiotemporal patterns of Aβ deposition in brains of AD patients is unknown. Here, we mapped the spatial distribution of Aβ plaques across age in three APP‐overexpression mouse lines (APP/PS1, Tg2576, and hAPP‐J20) using in vivo labeling with methoxy‐X04, high throughput whole brain imaging, and an automated informatics pipeline. Images were acquired with high resolution serial two‐photon tomography and labeled plaques were detected using custom‐built segmentation algorithms. Image series were registered to the Allen Mouse Brain Common Coordinate Framework, a 3D reference atlas, enabling automated brain‐wide quantification of plaque density, number, and location. In both APP/PS1 and Tg2576 mice, plaques were identified first in isocortex, followed by olfactory, hippocampal, and cortical subplate areas. In hAPP‐J20 mice, plaque density was highest in hippocampal areas, followed by isocortex, with little to no involvement of olfactory or cortical subplate areas. Within the major brain divisions, distinct regions were identified with high (or low) plaque accumulation; for example, the lateral visual area within the isocortex of APP/PS1 mice had relatively higher plaque density compared with other cortical areas, while in hAPP‐J20 mice, plaques were densest in the ventral retrosplenial cortex. In summary, we show how whole brain imaging of amyloid pathology in mice reveals the extent to which a given model recapitulates the regional Aβ deposition patterns described in AD.
“Through‐Space” Relativistic Effects on NMR Chemical Shifts of Pyridinium Halide Ionic Liquids
Authors: Ariai Jama , Saielli Giacomo 
Published: October 2018

AbstractWe have investigated, using two‐component relativistic density functional theory (DFT) at ZORA‐SO‐BP86 and ZORA‐SO‐PBE0 level, the occurrence of relativistic effects on the 1H, 13C, and 15N NMR chemical shifts of 1‐methylpyridinium halides [MP][X] and 1‐butyl‐3‐methylpyridinium trihalides [BMP][X3] ionic liquids (ILs) (X=Cl, Br, I) as a result of a non‐covalent interaction with the heavy anions. Our results indicate a sizeable deshielding effect in ion pairs when the anion is I− and I3−. A smaller, though nonzero, effect is observed also with bromine while chlorine based anions do not produce an appreciable relativistic shift. The chemical shift of the carbon atoms of the aromatic ring shows an inverse halogen dependence that has been rationalized based on the little C‐2s orbital contribution to the σ‐type interaction between the cation and anion. This is the first detailed account and systematic theoretical investigation of a relativistic heavy atom effect on the NMR chemical shifts of light atoms in the absence of covalent bonds. Our work paves the way and suggests the direction for an experimental investigation of such elusive signatures of ion pairing in ILs.
Efficient CRISPR/Cas9‐Mediated Mutagenesis in Primary Murine T Lymphocytes
Authors: Huang Bonnie , Johansen Kristoffer Haurum , Schwartzberg Pamela L. 
Published: October 2018

AbstractThe ability to alter gene expression directly in T lymphocytes has provided a powerful tool for understanding T cell biology, signaling, and function. Manipulation of T cell clones and primary T cells has been accomplished primarily through overexpression or gene‐silencing studies using cDNAs or shRNAs, respectively, which are often delivered by retroviral or lentiviral transduction or direct transfection methods. The recent development of CRISPR/Cas9‐based mutagenesis has revolutionized genomic editing, allowing unprecedented genetic manipulation of many cell types with greater precision and ease. This article outlines a protocol for CRISPR/Cas9‐mediated mutagenesis in primary T lymphocytes from Cas9 transgenic mice using retroviral delivery of guide RNAs. © 2018 by John Wiley & Sons, Inc.
Production of 5‐Hydroxymethylfurfural from D‐Fructose in Low‐Transition‐Temperature Mixtures Enhanced by Chloride Anions and Low Amounts of Organic Acids
Authors: Istasse Thibaut , Bockstal Lauris , Richel Aurore 
Published: October 2018

AbstractThe use of safe and sustainable solvents able to solvate reagents and to catalyze their reactions at temperatures below 100 °C is an innovative strategy to develop future lignocellulosic biorefineries. Many low‐transition‐temperature mixtures (LTTMs) have been investigated for this purpose. Among them, natural deep eutectic solvents (NADESs) have been proposed as cheap and renewable alternatives to ionic liquids for the synthesis of bio‐based chemical building blocks. We compare herein the ability of several organic acids/choline chloride/water LTTMs to perform D‐fructose dehydration to 5‐hydroxymethylfurfural (5‐HMF). The addition of chloride salts as well as an increased proportion of choline chloride promotes 5‐HMF formation, which seems to indicate a beneficial effect of chloride anions on D‐fructose dehydration. Besides improving selectivity by at least 10 %, increasing the choline chloride/acid ratio could enhance the biodegradability of the LTTMs. Unlike other acidic components, maleic and citric acids are especially selective at early D‐fructose conversion. Maleic acid was the most selective acidic component among the tested chemicals, achieving an 80 % 5‐HMF molar yield in 1 h at 90 °C.
Surface Nonpolarization of g‐C3N4 by Decoration with Sensitized Quantum Dots for Improved CO2 Photoreduction
Authors: Feng Huajun , Guo Qiaoqi , Xu Yingfeng , Chen Ting , Zhou Yuyang , Wang Yigang , Wang Meizhen , Shen Dongsheng 
Published: October 2018

AbstractPhotocatalytic conversion of CO2 can provide a solution for simultaneously addressing global warming and solar fuel generation. However, its applicability is presently limited by the unsatisfactory photoconversion efficiency of the state‐of‐art photocatalysts. In this regard, enhancing CO2 adsorption through surface modification could be an efficient way to improve the photoconversion efficiency. Herein, doping of nonpolar carbon quantum dots (CQDs) onto g‐C3N4 is reported for the construction of a metal‐free heterojunction photocatalyst (CQDs/g‐C3N4). CQDs offer several advantages such as band‐gap reduction and electron‐withdrawing effect to improve light absorption and photocarrier separation efficiency. However, this study reveals that nonpolar CQDs could also improve CO2 adsorption, photoinduced H2 production, reaction kinetics, and alter CO2 photoreduction pathways to generate CH4. Consequently, the CQDs/g‐C3N4 could generate six times more CO and CH4 without detectable H2 compared to pristine g‐C3N4, under similar conditions. Therefore, this study demonstrates a promising strategy for efficient adsorption, activation, and subsequent photoreduction of CO2 by nonpolar surface modification of g‐C3N4.
Fast and lightweight detection and filtering method for low‐rate TCP targeted distributed denial of service (LDDoS) attacks
Authors: Şimşek Mehmet , Şentürk Arafat 
Published: October 2018

SummaryDetection and filtering of low‐rate distributed denial of service (LDDoS) attacks is hard since their behavior is similar to legitimate users' behavior. In the literature, there are many filtering approaches and metrics for LDDoS attacks. However, most of the LDDoS detection methods in the literature only monitor congestion state. Actually, precongestion period that the attack has already started has valuable information about the attack. In this study, we proposed a method that uses precongestion period for metric calculation. Also, most of LDDoS filtering approaches have high false‐positive and false‐negative rates and also require long period of time for detection. Additionally, we developed an efficient method for detection and filtering of LDDoS attacks. According to the experimental results, the proposed LDDoS detection method has zero false‐positive and false‐negative rates under the scenarios; attack detection time is significantly reduced with using the proposed metric calculation approach. Also, the proposed method has a simple logic, and it requires simple calculations. This increases the applicability of the developed method.
Drug resistance in Mycobacterium tuberculosis and targeting the l,d‐transpeptidase enzyme
Authors: Gokulan Kuppan , Varughese Kottayil I. 
Published: October 2018

AbstractTuberculosis (TB) is a disease that has afflicted mankind for thousands of years, but in the last seven decades, much progress has been made in anti‐TB therapy. Early drugs, such as para‐aminosalicylic acid, streptomycin, isoniazid, and rifamycins were very effective in combatting the disease, giving rise to the hope that TB would be eradicated from the face of the earth by 2010. Despite that optimism, TB continues to kill more than a million people annually worldwide. A major reason for our inability to contain TB is the emergence drug resistance in Mycobacterium tuberculosis. This commentary is based on our recent publication on the structure of l,d‐transpeptidase enzyme, relevant to drug resistance. As a background, we briefly outline the history and development of anti‐TB therapy. Based on the crystal structure, we suggest a potential direction for designing more potent drugs against TB.
Pelagic food webs of humic lakes show low short‐term response to forest harvesting
Authors: Deininger A. , Jonsson A. , Karlsson J. , Bergström A.‐K. 
Published: October 2018

AbstractForest harvest in the boreal zone can increase the input of terrestrial materials such as dissolved organic carbon (DOC) and nitrate (NO3−) into nearby aquatic ecosystems, with potential effects on phytoplankton growth through enhanced nutrient (i.e., positive) or reduced light availability (i.e., negative), which may affect ecosystem productivity and consumer resource use. Here, we conducted forest clear‐cutting experiments in the catchments of four small, humic, and nitrogen‐limited unproductive boreal lakes (two controls and two clear‐cut, 18% and 44% of area cut) with one reference and two impact years. Our aim was to assess the effects of forest clear‐cutting on pelagic biomass production and consumer resource use. We found that pelagic biomass production did not change after two years of forest clear‐cutting: Pelagic primary and bacterial production (PP, BP), PP:BP ratio, chl a, and seston carbon (seston C) were unaffected by clear‐cutting; neither did tree harvest affect seston stoichiometry (i.e., N:phosphorus [P], C:P) nor induce changes in zooplankton resource use, biomass, or community composition. In conclusion, our findings suggest that pelagic food webs of humic lakes (DOC > 15 mg/L) might be resilient to a moderate form of forest clear‐cutting, at least two years after tree removal, before mechanical site preparation (e.g., mounding, plowing) and when leaving buffer strips along lakes and incoming streams. Thus, pelagic food web responses to forest clear‐cutting might not be universal, but could depend on factors such as the time scale, share of catchment logged, and the forest practices involved, including the application of buffer strips and site preparation.
Impact of an interatrial shunt device on survival and heart failure hospitalization in patients with preserved ejection fraction
Authors: Kaye David M. , Petrie Mark C. , McKenzie Scott , Hasenfuβ Gerd , Malek Filip , Post Martijn , Doughty Robert N. , Trochu Jean‐Noël , Gustafsson Finn , Lang Irene , Kolodziej Adam , Westenfeld Ralf , Penicka Martin , Rosenberg Mark , Hausleiter Jörg , Raake Philip , Jondeau Guillaume , Bergmann Martin W. , Spelman Tim , Aytug Huseyin , Ponikowski Piotr , Hayward Chris ,   on behalf of the REDUCE LAP‐HF study investigators
Published: October 2018

AbstractAimsImpaired left ventricular diastolic function leading to elevated left atrial pressures, particularly during exertion, is a key driver of symptoms and outcomes in heart failure with preserved ejection fraction (HFpEF). Insertion of an interatrial shunt device (IASD) to reduce left atrial pressure in HFpEF has been shown to be associated with short‐term haemodynamic and symptomatic benefit. We aimed to investigate the potential effects of IASD placement on HFpEF survival and heart failure hospitalization (HFH).Methods and resultsHeart failure with preserved ejection fraction patients participating in the Reduce Elevated Left Atrial Pressure in Patients with Heart Failure study (Corvia Medical) of an IASD were followed for a median duration of 739 days. The theoretical impact of IASD implantation on HFpEF mortality was investigated by comparing the observed survival of the study cohort with the survival predicted from baseline data using the Meta‐analysis Global Group in Chronic Heart Failure heart failure risk survival score. Baseline and post‐IASD implant parameters associated with HFH were also investigated. Based upon the individual baseline demographic and cardiovascular profile of the study cohort, the Meta‐analysis Global Group in Chronic Heart Failure score‐predicted mortality was 10.2/100 pt years. The observed mortality rate of the IASD‐treated cohort was 3.4/100 pt years, representing a 33% lower rate (P = 0.02). By Kaplan–Meier analysis, the observed survival in IASD patients was greater than predicted (P = 0.014). Baseline parameters were not predictive of future HFH events; however, poorer exercise tolerance and a higher workload‐corrected exercise pulmonary capillary wedge pressure at the 6 months post‐IASD study were associated with HFH.ConclusionsThe current study suggests IASD implantation may be associated with a reduction in mortality in HFpEF. Large‐scale ongoing randomized studies are required to confirm the potential benefit of this therapy.
Impedance Detection of 3‐Phenoxybenzoic Acid Comparing Wholes Antibodies and Antibody Fragments for Biomolecular Recognition
Authors: Pali Madhavi , Suni Ian I. 
Published: October 2018

AbstractAntibody fragments for detection of 3‐phenoxybenzoic acid (3‐PBA) are created by disulfide bond cleavage with tris(2‐carboxyethyl)phosphine (TCEP). These antibody fragments are employed to improve the sensitivity for 3‐PBA detection by electrochemical impedance spectroscopy (EIS). The sensitivity and detection limit are compared for biomolecular recognition by both polyclonal antibodies and antibody fragments immobilized through amide bond formation atop a self‐assembled monolayer (SAM) on an Au electrode, as well as antibody fragments directly attached to Au through Au−S covalent bond formation. The detection limit for 3‐PBA is dramatically improved (1.1×10−8 M) for direct immobilization of antibody fragments through Au−S covalent bond formation relative to immobilization of either polyclonal antibodies (2.1×10−5 M) or antibody fragments (1.7×10−5 M) through amide bond formation. This can be attributed primarily to the much lower charge transfer resistance (Rct) and higher ionic permeability obtained at biosensor interfaces that do not include an Au‐thiol SAM, allowing easier detection of further changes in Rct. In addition, the exponential dependence of the electron tunnelling rate on biomolecular film thickness increases the sensitivity of the antibody fragments modestly relative to polyclonal antibodies. This is the first quantitative comparison of the use of antibodies and antibody fragments for biomolecular recognition within impedance biosensors.
Early Paleogene strike‐slip transition of the Tan–Lu Fault Zone across the southeast Bohai Bay Basin: Constraints from fault characteristics in its adjacent basins
Authors: Wang Guangzeng , Li Sanzhong , Wu Zhiping , Suo Yanhui , Guo Lingli , Wang Pengcheng 
Published: October 2018

The Tan–Lu Fault Zone (TLFZ) is the largest continental‐scale strike‐slip fault zone in East China. It experienced a complex Meso‐Cenozoic deformation and controlled the development and evolution of the Bohai Bay Basin (BBB). Though its Mesozoic sinistral and Cenozoic dextral motions have been well documented, its strike‐slip transition history and mechanism from sinistral to dextral motions in the Early Paleogene remain poorly understood. To investigate these issues, we made a thorough analysis on the fault geometry and kinematics as well as the response of depocentre in the Early Paleogene of the sags adjacent to the TLFZ across the southeast BBB. The results show that the WNW‐/NW‐, E‐W‐, and ENE‐/NE‐trending extensional faults developed in the Early Paleogene of those sags share almost the same geometrical and kinematic features. Such features indicate that the TLFZ is sinistral in Ek3‐Ek2 depositional stage, extension dominated in Ek1 depositional stage, and dextral in Es4L depositional stage. Such strike‐slip transition of the TLFZ is a comprehensive effect of the plate events around the Eurasian Plate. The NNW‐directed subduction of the Pacific to the Eurasian plates triggers the sinistral motion of the TLFZ during 65–55 Ma, but this sinistral motion is terminated by the far‐field effect of the NNE‐directed India–Eurasia collision initiating at 55 Ma. Then, the kinematic adjustment of the Pacific Plate from NNW to WNW breaks the stress balance exerted on the TLFZ by the subduction of the Pacific to Eurasian plates and the India–Eurasia collision and makes it turn into dextral motion gradually during 48–42 Ma.
Cluster failure revisited: Impact of first level design and physiological noise on cluster false positive rates
Authors: Eklund Anders , Knutsson Hans , Nichols Thomas E. 
Published: October 2018

AbstractMethodological research rarely generates a broad interest, yet our work on the validity of cluster inference methods for functional magnetic resonance imaging (fMRI) created intense discussion on both the minutia of our approach and its implications for the discipline. In the present work, we take on various critiques of our work and further explore the limitations of our original work. We address issues about the particular event‐related designs we used, considering multiple event types and randomization of events between subjects. We consider the lack of validity found with one‐sample permutation (sign flipping) tests, investigating a number of approaches to improve the false positive control of this widely used procedure. We found that the combination of a two‐sided test and cleaning the data using ICA FIX resulted in nominal false positive rates for all data sets, meaning that data cleaning is not only important for resting state fMRI, but also for task fMRI. Finally, we discuss the implications of our work on the fMRI literature as a whole, estimating that at least 10% of the fMRI studies have used the most problematic cluster inference method (p = .01 cluster defining threshold), and how individual studies can be interpreted in light of our findings. These additional results underscore our original conclusions, on the importance of data sharing and thorough evaluation of statistical methods on realistic null data.
Differential responsivity of neurons in perirhinal cortex, lateral entorhinal cortex, and dentate gyrus during time‐bridging learning
Authors: Suter Eugénie E. , Weiss Craig , Disterhoft John F. 
Published: October 2018

AbstractMany studies have focused on the function of hippocampal region CA1 as a critical site for associative memory, but much less is known about changes in the afferents to CA1. Here we report the activity of multiple single neurons from perirhinal and entorhinal cortex and from dentate gyrus during trace eyeblink conditioning as well as consolidated recall, and in pseudo‐conditioned control rabbits. We also report an analysis of theta activity filtered from the local field potential (LFP). Our results show early associative changes in single‐neuron firing rate as well as theta oscillations in lateral entorhinal cortex (EC) and dentate gyrus (DG), and increases in the number of responsive neurons in perirhinal cortex. In both EC and DG, a subset of neurons from conditioned animals exhibited an elevated baseline firing rate and large responses to the conditioned stimulus and trace period. A similar population of cells has been seen in DG and in medial, but not lateral, EC during spatial tasks, suggesting that lateral EC contains cells responsive to a temporal associative task. In contrast to recent studies in our laboratory that found significant CA1 contributions to long‐term memory, the activity profiles of neurons within EC and DG were similar for conditioned and pseudoconditioned rabbits during post‐consolidation sessions. Collectively these results demonstrate that individual subregions of medial temporal lobe differentially support new and remotely acquired memories. Neuron firing profiles were similar on training trials when conditioned responses were and were not exhibited, demonstrating that these temporal lobe regions represent the CS–US association and do not control the behavioral response. The analysis of theta activity revealed that theta power was modulated by the conditioning stimuli in both the conditioned and pseudoconditioned groups and that although both groups exhibited a resetting of phase to the corneal airpuff, only the conditioned group exhibited a resetting of phase to the whisker conditioned stimulus.
MicroRNA and Human Bone Health
Authors: Cheng Vincent Ka‐Fai , Au Philip Chun‐Ming , Tan Kathryn CB , Cheung Ching‐Lung 
Published: October 2018

ABSTRACTThe small non‐coding microRNAs (miRNAs) are post‐transcription regulators that modulate diverse cellular process in bone cells. Because optimal miRNA targeting is essential for their function, single‐nucleotide polymorphisms (SNPs) within or proximal to the loci of miRNA (miR‐SNPs) or mRNA (PolymiRTS) could potentially disrupt the miRNA‐mRNA interaction, leading to changes in bone metabolism and osteoporosis. Recent human studies of skeletal traits using miRNA profiling, genomewide association studies, and functional studies started to decipher the complex miRNA regulatory network. These studies have indicated that miRNAs may be a promising bone marker. This review focuses on human miRNA studies on bone traits and discusses how genetic variants affect bone metabolic pathways. Major ex vivo investigations using human samples supported with animal and in vitro models have shed light on the mechanistic role of miRNAs. Furthermore, studying the miRNAs’ signatures in secondary osteoporosis and osteoporotic medications such as teriparatide (TPTD) and denosumab (DMab) have provided valuable insight into clinical management of the disease. © 2018 The Authors.JBMR PlusPublished by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research