bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topological analog signal processing
Authors: Zangeneh-Nejad Farzad , Fleury Romain 
Published: May 2019

AbstractAnalog signal processors have attracted a tremendous amount of attention recently, as they potentially offer much faster operation and lower power consumption than their digital versions. Yet, they are not preferable for large scale applications due to the considerable observational errors caused by their excessive sensitivity to environmental and structural variations. Here, we demonstrate both theoretically and experimentally the unique relevance of topological insulators for alleviating the unreliability of analog signal processors. In particular, we achieve an important signal processing task, namely resolution of linear differential equations, in an analog system that is protected by topology against large levels of disorder and geometrical perturbations. We believe that our strategy opens up large perspectives for a new generation of robust all-optical analog signal processors, which can now not only perform ultrafast, high-throughput, and power efficient signal processing tasks, but also compete with their digital counterparts in terms of reliability and flexibility.
Multilevel fine-scale diversity challenges the ‘cryptic species’ concept
Authors: Korshunova Tatiana , Picton Bernard , Furfaro Giulia , Mariottini Paolo , Pontes Miquel , Prkić Jakov , Fletcher Karin , Malmberg Klas , Lundin Kennet , Martynov Alexander 
Published: May 2019

Abstract‘Cryptic’ species are an emerging biological problem that is broadly discussed in the present study. Recently, a cryptic species definition was suggested for those species which manifest low morphological, but considerable genetic, disparity. As a case study we present unique material from a charismatic group of nudibranch molluscs of the genus Trinchesia from European waters to reveal three new species and demonstrate that they show a dual nature: on one hand, they can be considered a ‘cryptic’ species complex due to their overall similarity, but on the other hand, stable morphological differences as well as molecular differences are demonstrated for every species in that complex. Thus, this species complex can equally be named ‘cryptic’, ‘pseudocryptic’ or ‘non-cryptic’. We also present evidence for an extremely rapid speciation rate in this species complex and link the species problem with epigenetics. Available metazoan-wide data, which are broadly discussed in the present study, show the unsuitability of a ‘cryptic’ species concept because the degree of crypticity represents a continuum when a finer multilevel morphological and molecular scale is applied to uncover more narrowly defined species making the ‘cryptic’ addition to ‘species’ redundant. Morphological and molecular methods should be applied in concordance to form a fine-scale multilevel taxonomic framework, and not necessarily implying only an a posteriori transformation of exclusively molecular-based ‘cryptic’ species into morphologically-defined ‘pseudocryptic’ ones. Implications of the present study have importance for many fields, including conservation biology and fine-scale biodiversity assessments.
The Rabl configuration limits topological entanglement of chromosomes in budding yeast
Authors: Pouokam Maxime , Cruz Brian , Burgess Sean , Segal Mark R. , Vazquez Mariel , Arsuaga Javier 
Published: May 2019

AbstractThe three dimensional organization of genomes remains mostly unknown due to their high degree of condensation. Biophysical studies predict that condensation promotes the topological entanglement of chromatin fibers and the inhibition of function. How organisms balance between functionally active genomes and a high degree of condensation remains to be determined. Here we hypothesize that the Rabl configuration, characterized by the attachment of centromeres and telomeres to the nuclear envelope, helps to reduce the topological entanglement of chromosomes. To test this hypothesis we developed a novel method to quantify chromosome entanglement complexity in 3D reconstructions obtained from Chromosome Conformation Capture (CCC) data. Applying this method to published data of the yeast genome, we show that computational models implementing the attachment of telomeres or centromeres alone are not sufficient to obtain the reduced entanglement complexity observed in 3D reconstructions. It is only when the centromeres and telomeres are attached to the nuclear envelope (i.e. the Rabl configuration) that the complexity of entanglement of the genome is comparable to that of the 3D reconstructions. We therefore suggest that the Rabl configuration is an essential player in the simplification of the entanglement of chromatin fibers.
Information diffusion backbones in temporal networks
Authors: Zhan Xiu-Xiu , Hanjalic Alan , Wang Huijuan 
Published: May 2019

AbstractProgress has been made in understanding how temporal network features affect the percentage of nodes reached by an information diffusion process. In this work, we explore further: which node pairs are likely to contribute to the actual diffusion of information, i.e., appear in a diffusion trajectory? How is this likelihood related to the local temporal connection features of the node pair? Such deep understanding of the role of node pairs is crucial to tackle challenging optimization problems such as which kind of node pairs or temporal contacts should be stimulated in order to maximize the prevalence of information spreading. We start by using Susceptible-Infected (SI) model, in which an infected (information possessing) node could spread the information to a susceptible node with a given infection probability β whenever a contact happens between the two nodes, as the information diffusion process. We consider a large number of real-world temporal networks. First, we propose the construction of an information diffusion backbone GB(β) for a SI spreading process with an infection probability β on a temporal network. The backbone is a weighted network where the weight of each node pair indicates how likely the node pair appears in a diffusion trajectory starting from an arbitrary node. Second, we investigate the relation between the backbones with different infection probabilities on a temporal network. We find that the backbone topology obtained for low and high infection probabilities approach the backbone GB(β → 0) and GB(β = 1), respectively. The backbone GB(β → 0) equals the integrated weighted network, where the weight of a node pair counts the total number of contacts in between. Finally, we explore node pairs with what local connection features tend to appear in GB(β = 1), thus actually contribute to the global information diffusion. We discover that a local connection feature among many other features we proposed, could well identify the (high-weight) links in GB(β = 1). This local feature encodes the time that each contact occurs, pointing out the importance of temporal features in determining the role of node pairs in a dynamic process.
Non-invasive, Brain-controlled Functional Electrical Stimulation for Locomotion Rehabilitation in Individuals with Paraplegia
Authors: Selfslagh Aurelie , Shokur Solaiman , Campos Debora S. F. , Donati Ana R. C. , Almeida Sabrina , Yamauti Seidi Y. , Coelho Daniel B. , Bouri Mohamed , Nicolelis Miguel A. L. 
Published: May 2019

AbstractSpinal cord injury (SCI) impairs the flow of sensory and motor signals between the brain and the areas of the body located below the lesion level. Here, we describe a neurorehabilitation setup combining several approaches that were shown to have a positive effect in patients with SCI: gait training by means of non-invasive, surface functional electrical stimulation (sFES) of the lower-limbs, proprioceptive and tactile feedback, balance control through overground walking and cue-based decoding of cortical motor commands using a brain-machine interface (BMI). The central component of this new approach was the development of a novel muscle stimulation paradigm for step generation using 16 sFES channels taking all sub-phases of physiological gait into account. We also developed a new BMI protocol to identify left and right leg motor imagery that was used to trigger an sFES-generated step movement. Our system was tested and validated with two patients with chronic paraplegia. These patients were able to walk safely with 65–70% body weight support, accumulating a total of 4,580 steps with this setup. We observed cardiovascular improvements and less dependency on walking assistance, but also partial neurological recovery in both patients, with substantial rates of motor improvement for one of them.
Shear force modulates the activity of acid-sensing ion channels at low pH or in the presence of non-proton ligands
Authors: Barth Daniel , Fronius Martin 
Published: May 2019

AbstractAcid-sensing ion channels (ASICs) belong to the degenerin/epithelial sodium channel protein family that form mechanosensitive ion channels. Evidence as to whether or not ASICs activity is directly modulated by mechanical force is lacking. Human ASICs (hASIC1V3, hASIC2a and hASIC3a) were heterologously expressed as homomeric channels in Xenopus oocytes and two-electrode voltage-clamp recordings were performed. hASIC3a was expressed in HEK-293 cells and currents measured by whole-cell patch-clamp recordings. ASIC currents in response to shear force (SF) were measured at pH 7.4, acidic pH, or in the presence of non-proton ligands at pH 7.4. SF was applied via a fluid stream generated through a pressurized perfusion system. No effect was observed at pH 7.4. Increased transient currents for each homomeric channel were observed when elevated SF was applied in conjunction with acidic pH (6.0–4.0). The sustained current was not (hASIC2a) or only slightly increased (hASIC1V3 and hASIC3a). SF-induced effects were not seen in water injected oocytes and were blocked by amiloride. Non-proton ligands activated a persistent current in hASIC1V3 and cASIC1 (MitTx) and hASIC3a (GMQ) at pH 7.4. Here SF caused a further current increase. Results suggest that ASICs do have an intrinsic ability to respond to mechanical force, supporting their role as mechanosensors in certain local environments.
Improved contrast of affibody-mediated imaging of HER3 expression in mouse xenograft model through co-injection of a trivalent affibody for in vivo blocking of hepatic uptake
Authors: Rosestedt Maria , Andersson Ken G. , Rinne Sara S. , Leitao Charles Dahlsson , Mitran Bogdan , Vorobyeva Anzhelika , Ståhl Stefan , Löfblom John , Tolmachev Vladimir , Orlova Anna 
Published: May 2019

AbstractHuman epidermal growth factor receptor type 3 (HER3) plays a crucial role in the progression of many cancer types. In vivo radionuclide imaging could be a reliable method for repetitive detection of HER3-expression in tumors. The main challenge of HER3-imaging is the low expression in tumors together with endogenous receptor expression in normal tissues, particularly the liver. A HER3-targeting affibody molecule labeled with radiocobalt via a NOTA chelator [57Co]Co-NOTA-Z08699 has demonstrated the most favorable biodistribution profile with the lowest unspecific hepatic uptake and high activity uptake in tumors. We hypothesized that specific uptake of labeled affibody monomer might be selectively blocked in the liver but not in tumors by a co-injection of non-labeled corresponding trivalent affibody (Z08699)3. Biodistribution of [57Co]Co-NOTA-Z08699 and [111In]In-DOTA-(Z08699)3 was studied in BxPC-3 xenografted mice. [57Co]Co-NOTA-Z08699 was co-injected with unlabeled trivalent affibody DOTA-(Z08699)3 at different monomer:trimer molar ratios. HER3-expression in xenografts was imaged using [57Co]Co-NOTA-Z08699 and [57Co]Co-NOTA-Z08699: DOTA-(Z08699)3. Hepatic activity uptake of [57Co]Co-NOTA-Z08699: DOTA-(Z08699)3 decreased with increasing monomer:trimer molar ratio. The tumor activity uptake and tumor-to-liver ratios were the highest for the 1:3 ratio. SPECT/CT images confirmed the biodistribution data. Imaging of HER3 expression can be improved by co-injection of a radiolabeled monomeric affibody-based imaging probe together with a trivalent affibody.
A novel data fusion method for the effective analysis of multiple panels of flow cytometry data
Authors: Tinnevelt Gerjen H. , van Staveren Selma , Wouters Kristiaan , Wijnands Erwin , Verboven Kenneth , Folcarelli Rita , Koenderman Leo , Buydens Lutgarde M. C. , Jansen Jeroen J. 
Published: May 2019

AbstractMulticolour flow cytometry (MFC) is used to measure multiple cellular markers at the single-cell level. Cellular markers may be coloured with different panels of fluorescently-labelled antibodies to enable cell identification or the detection of activated cells in pre-defined, ‘gated’ specific cell subsets. The number of markers that can be used per measurement is technologically limited however, requiring every panel to be analysed in a separate aliquot measurement. The combined analyses of these dedicated panels may enhance the predictive ability of these measurements and could enrich the interpretation of the immunological information. Here we introduce a fusion method for MFC data, based on DAMACY (Discriminant Analysis of Multi-Aspect Cytometry data), which can combine information from complementary panels. This approach leads to both enhanced predictions and clearer interpretations in comparison with the analysis of separate measurements. We illustrate this method using two datasets: the response of neutrophils evoked by a systemic endotoxin challenge and the activated immune status of the innate cells, T cells and B cells in obese versus lean individuals. The data fusion approach was able to detect cells that do not individually show a difference between clinical phenotypes but do play a role in combination with other cells.
PiPred – a deep-learning method for prediction of π-helices in protein sequences
Authors: Ludwiczak Jan , Winski Aleksander , da Silva Neto Antonio Marinho , Szczepaniak Krzysztof , Alva Vikram , Dunin-Horkawicz Stanislaw 
Published: May 2019

AbstractCanonical π-helices are short, relatively unstable secondary structure elements found in proteins. They comprise seven or more residues and are present in 15% of all known protein structures, often in functionally important regions such as ligand- and ion-binding sites. Given their similarity to α-helices, the prediction of π-helices is a challenging task and none of the currently available secondary structure prediction methods tackle it. Here, we present PiPred, a neural network-based tool for predicting π-helices in protein sequences. By performing a rigorous benchmark we show that PiPred can detect π-helices with a per-residue precision of 48% and sensitivity of 46%. Interestingly, some of the α-helices mispredicted by PiPred as π-helices exhibit a geometry characteristic of π-helices. Also, despite being trained only with canonical π-helices, PiPred can identify 6-residue-long α/π-bulges. These observations suggest an even higher effective precision of the method and demonstrate that π-helices, α/π-bulges, and other helical deformations may impose similar constraints on sequences. PiPred is freely accessible at: https://toolkit.tuebingen.mpg.de/#/tools/quick2d. A standalone version is available for download at: https://github.com/labstructbioinf/PiPred, where we also provide the CB6133, CB513, CASP10, and CASP11 datasets, commonly used for training and validation of secondary structure prediction methods, with correctly annotated π-helices.
Systemic inflammation is associated with malaria and preterm birth in women living with HIV on antiretrovirals and co-trimoxazole
Authors: McDonald Chloe R. , Weckman Andrea M. , Conroy Andrea L. , Olwoch Peter , Natureeba Paul , Kamya Moses R. , Havlir Diane V. , Dorsey Grant , Kain Kevin C. 
Published: May 2019

AbstractWomen living with HIV (WLHIV) have an increased risk of malaria in pregnancy (MiP). It is unclear if MiP in WLHIV causes a systemic inflammatory response and increases the risk of adverse birth outcomes, especially for women receiving antiretroviral therapy (ART) and daily trimethoprim-sulfamethoxazole (TMP/SXT). We analyzed repeated plasma samples in a cohort of malaria-exposed Ugandan WLHIV receiving ART and daily TMP/SXT to examine changes in inflammatory markers across pregnancy and their association with birth outcomes. Concentrations of CHI3L1, CRP, IL-18BP, IL-6, sICAM-1, and sTNFR2 were quantified by ELISA in 1115 plasma samples collected over pregnancy from 326 women. MiP was associated with increased sTNFR2, sICAM-1 and IL-18BP concentrations across pregnancy. Women who delivered preterm had elevated concentrations of sTNFR2 and altered levels of IL-6 during pregnancy. Women with sTNFR2 concentrations in the highest quartile within 6 weeks of delivery had an increased relative risk of preterm birth. Our results indicate that despite daily TMP/SXT, MiP in WLHIV induced a systemic inflammatory response that was associated with an increased risk of preterm birth. These findings highlight the need for additional strategies to protect WLHIV from malaria infection in pregnancy to promote healthy outcomes for mother and child.
Synthesis and in vivo characterization of 18F-labeled difluoroboron-curcumin derivative for β-amyloid plaque imaging
Authors: Kim Hyunjung , Im Young Hoon , Ahn Jinhee , Yang Jehoon , Choi Joon Young , Lee Kyung-Han , Kim Byung-Tae , Choe Yearn Seong 
Published: May 2019

AbstractPositron emission tomography imaging of β-amyloid (Aβ) plaques has proven useful in the diagnosis of Alzheimer’s disease. A previous study from our group showed that 4′-O-[18F]fluoropropylcurcumin has poor brain permeability, which is thought to be due to its rapid metabolism. In this study, we synthesized difluoroboron complexes of fluorine-substituted curcumin derivatives (1–4) and selected one of them based on the in vitro binding assays. The selected ligand 2 was found to distinctively stain Aβ plaques in APP/PS1 transgenic mouse brain sections. Radioligand [18F]2 was synthesized via a two-step reaction consisting of [18F]fluorination and subsequent aldol condensation. Biodistribution and metabolism studies indicated that radioligand [18F]2 was converted to polar radioactive products and trapped in the normal mouse brain. In contrast, optical images of mice acquired after injection of 2 showed moderate fluorescence signal intensity in the mouse brain at 2 min with a decrease in the signal within 30 min. In the ex vivo optical images, the fluorescence signals in major tissues disappeared within 30 min. Taken together, these results suggest that [18F]2 may be converted to polar 18F-labeled blue-shifted fluorescent products. Further structural modifications are thus needed to render the radioligand metabolically stable.
Precision oncology of lung cancer: genetic and genomic differences in Chinese population
Authors: Shen Hongbing , Zhu Meng , Wang Cheng 
Published: May 2019

AbstractKnowledge of the lung cancer genome has experienced rapid growth over the past decade. Genome-wide association studies and sequencing studies have identified dozens of genetic variants and somatic mutations implicated in the development of lung cancer in both Chinese and Caucasian populations. With the accumulating evidence, heterogeneities in lung cancer susceptibility were observed in different ethnicities. In this review, the progress on germline-based genetic variants and somatic-based genomic mutations associated with lung cancer and the differences between Chinese and Caucasian populations were systematically summarized. In the analysis of the genetic predisposition to lung cancer, 6 susceptibility loci were shared by Chinese and Caucasian populations (3q28, 5p15, 6p21, 9p21.3, 12q13.13 and 15q25), 14 loci were specific to the Chinese population (1p36.32, 5q31.1, 5q32, 6p21.1, 6q22.2, 6p21.32, 7p15.3, 10p14, 10q25.2, 12q23.1, 13q22, 17q24.3, 20q13.2, and 22q12), and 12 loci were specific to the Caucasian population (1p31.1, 2q32.1, 6q27, 8p21.1, 8p12, 10q24.3, 11q23.3, 12p13.33, 13q13.1, 15q21.1, 20q13.33 and 22q12.1). In the analysis of genomic and somatic alterations, different mutation rates were observed for EGFR (Chinese: 39–59% vs. TCGA: 14%), KRAS (Chinese: 7–11% vs. TCGA: 31%), TP53 (Chinese: 44% vs. TCGA: 53%), CDKN2A (Chinese: 22% vs. TCGA: 15%), NFE2L2 (Chinese: 28% vs. TCGA: 17%), STK11 (Chinese: 4–7% vs. TCGA: 16%), KEAP1 (Chinese: 3–5% vs. TCGA: 18%), and NF1 (Chinese: <2% vs. TCGA: 12%). In addition, frequently amplified regions encompassing genes involved in cytoskeletal organization or focal adhesion were identified only in Chinese patients. These results provide a comprehensive description of the genetic and genomic differences in lung cancer susceptibility between Chinese and Caucasian populations and may contribute to the development of precision medicine for lung cancer treatment and prevention.
Detecting false-positive disease references in veterinary clinical notes without manual annotations
Authors: Kennedy Noel , Brodbelt Dave C. , Church David B. , O’Neill Dan G. 
Published: May 2019

AbstractClinicians often include references to diseases in clinical notes, which have not been diagnosed in their patients. For some diseases terms, the majority of disease references written in the patient notes may not refer to true disease diagnosis. These references occur because clinicians often use their clinical notes to speculate about disease existence (differential diagnosis) or to state that the disease has been ruled out. To train classifiers for disambiguating disease references, previous researchers built training sets by manually annotating sentences. We show how to create very large training sets without the need for manual annotation. We obtain state-of- the-art classification performance with a bidirectional long short-term memory model trained to distinguish disease references between patients with or without the disease diagnosis in veterinary clinical notes.
Structural and biochemical analyses of the nuclear pore complex component ELYS identify residues responsible for nucleosome binding
Authors: Kobayashi Wataru , Takizawa Yoshimasa , Aihara Maya , Negishi Lumi , Ishii Hajime , Kurumizaka Hitoshi 
Published: May 2019

AbstractThe nuclear pore complex embedded within the nuclear envelope is the essential architecture for trafficking macromolecules, such as proteins and RNAs, between the cytoplasm and nucleus. The nuclear pore complex assembly occurs on chromatin in the post-mitotic phase of the cell cycle. ELYS (MEL-28/AHCTF1) binds to the nucleosome, which is the basic chromatin unit, and promotes assembly of the complex around the chromosomes in cells. Here we show that the Arg-Arg-Lys (RRK) stretch of the C-terminal ELYS region plays an essential role in the nucleosome binding. The cryo-EM structure and the crosslinking mass spectrometry reveal that the ELYS C-terminal region directly binds to the acidic patch of the nucleosome. These results provide mechanistic insight into the ELYS-nucleosome interaction, which promotes the post-mitotic nuclear pore complex formation around chromosomes in cells.