bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Plasmodium knowlesi Merozoite Surface Protein‐119 (PkMSP‐119) novel binding peptides from a phage display library
Authors: Goh Xiang Ting , Chua Kek Heng , Kee Boon Pin , Lim Yvonne A. L.
Published: November 2019

Objective

Plasmodium knowlesi, the fifth human malaria parasite, has caused mortality in humans. We aimed to identify P. knowlesi novel binding peptides through a random linear dodecapeptide phage display targeting the 19‐kDa fragment of Merozoite Surface Protein‐1 protein.

Methods

rPkMSP‐119 protein was heterologously expressed using Expresso® Solubility and Expression Screening System and competent E. cloni® 10G cells according to protocol. Three rounds of biopanning were performed on purified rPkMSP‐119 to identify binding peptides towards rPkMSP‐119 using Ph.D.™‐12 random phage display library. Binding sites of the identified peptides to PkMSP‐119 were in silico predicted using the CABS‐dock web server.

Results

Four phage peptide variants that bound to PkMSP‐119 were identified after three rounds of biopanning, namely Pkd1, Pkd2, Pkd3 and Pkd4. The sequences of both Pkd1 and Pkd2 consist of a large number of histidine residues. Pkd1 showed positive binding signal with 6.1× vs. BSA control. Docking results showed that Pkd1 and Pkd2 were ideal binding peptides for PkMSP‐119.

Conclusion

We identified two novel binding peptides of PkMSP‐119, Pkd1 (HFPFHHHKLRAH) and Pkd2 (HPMHMLHKRQHG), through phage display. They provide a valuable starting point for the development of novel therapeutics.
Multilocus data of a manakin species reveal cryptic diversification moulded by vicariance
Authors: Reis Camila Alves , Dias Cleyssian , Araripe Juliana , Aleixo Alexandre , Anciães Marina , Sampaio Iracilda , Schneider Horacio , do Rêgo Péricles Sena
Published: November 2019

We used molecular tools and a multilocus approach to investigate the phylogeography of Lepidothrix coronata across most of its ample range. We sequenced six DNA fragments to produce phylogenies, molecular dating estimates, analyses of the dynamics of the demographic history of the species and a biogeographic analysis to estimate the events and changes in the ancestral distribution of the species. The results indicated the presence of four well‐established lineages, with high levels of divergence. These lineages are delineated by well‐defined geographic barriers, with one lineage, restricted to the west of the Andes, being the first to diverge from the complex. The other three lineages are exclusive to the Amazonian distribution of the species, with two being found north of the Amazon River, and the third, south of the Amazon. Some of the relationships found between these lineages were distinct from those described in previous studies. Important disagreements were found between the mtDNA phylogeny and that of the multilocus analysis, in relation to the lineages located to the west of the Andes. We propose that past introgression events may have influenced shifts in the relationships between lineages, despite the fact that the groups were well defined in both the phylogenies. The biogeographic analysis indicates that the lineages arose through successive vicariance events, which had a primary role in the diversification of the group. Two or three genetically structured subclades were also found within each Amazonian lineage, although these subclades are not isolated by an obvious geographic barrier.
New morphological data for Leonseius regularis (De Leon) (Acari: Phytoseiidae) and a description of a new species of the genus from Brazil

Authors: Carvalho Adeilma N. De , Argolo Poliane S. , Ferragut Francisco , Moraes Gilberto J. De , Beaulieu Frédéric , Navia Denise , Oliveira Aníbal R.
Published: November 2019

The genus Leonseius Chant & McMurtry (Phytoseiidae: Typhlodrominae) was proposed to accommodate Typhloseiopsis regularis De Leon, 1965, a species with a troubled taxonomic history that was previously classified in the genera Typhlodromus Scheuten, Diadromus Athias-Henriot  and Chanteius Wainstein. Due to its Amblyseius-like appearance (long s4, Z4 and Z5, most other setae minute; atypical for a typhlodromine), the poor descriptions of reproductive structures (spermatheca, spermatodactyl), and probably also because at the time it was a monotypic genus, researchers over the years have based the species-level identification of Leonseius regularis mainly on dorsal and ventral idiosomal chaetotaxy and setal length. In a survey of phytoseiid mites conducted in cacao plantations (Theobroma cacao L.: Malvaceae) of the municipality of Ilhéus, Bahia, northeastern Brazil, we identified two distinct morphotypes among specimens initially identified as L. regularis. Herein we provide new morphological data for L. regularis to complement the original description and previous redescriptions, and then describe Leonseius elbanhawyi Carvalho, Ferragut & Oliveira sp. nov., from cacao, distinguishing it from L. regularis by its spermatheca and spermatodactyl. Also, the diagnosis of Leonseius is amended.
Assessing stability of metal tellurides as alternative photomask materials for extreme ultraviolet lithography
Authors: Luong Vu , Philipsen Vicky , Opsomer Karl , Rip Jens , Hendrickx Eric , Heyns Marc , Detavernier Christophe , Laubis Christian , Scholze Frank
Published: November 2019

Tellurium (Te) is one of the elements with highest extinction coefficient κ at the 13.5 nm extreme-ultraviolet (EUV) wavelength. It is being considered as an alternative absorber material for binary photomasks in EUV lithography. The absorber material is required to remain chemically stable during EUV exposure, at elevated temperatures up to 150 °C, during mask cleaning, and in the low hydrogen pressure environment that is present in the EUV scanner. However, Te is known to react with oxygen and hydrogen, forming less EUV absorbing TeO2 and more volatile H2Te, respectively. Since the melting temperature of Te is only 449.5 °C at normal pressure, alloying Te with a more stable metal might result in a high κ material that will remain thermally and chemically stable over a wider range of operating conditions. In this paper, the authors report on the stability assessment of metal telluride (M-Te) alloys for the EUV absorber material. They combined Te with high κ metals, noble metals, and etchable metals. High κ and noble M-Te materials are both thermally more stable than etchable M-Te, but they cannot be patterned easily for use in an EUV photomask. High κ M-Te exhibits polycrystal morphology at room temperature compared to quasiamorphous noble M-Te though both can crystallize at a higher temperature. Hydrogen stability and cleaning solution stability of M-Te materials are improved considerably compared to Te, but their higher surface reactivity cannot be completely mitigated without the addition of an inert capping layer. Furthermore, etchable M-Te alloys are easily oxidized during deposition, resulting in lower electron density and hence lower κ. Nevertheless, M-Te alloys may be a way to stabilize Te for usage as the EUV absorber material.
Acoustic and linguistic factors affecting perceptual dissimilarity judgments of voices
Authors: Perrachione Tyler K. , Furbeck Kristina T. , Thurston Emily J.
Published: November 2019

The human voice is a complex acoustic signal that conveys talker identity via individual differences in numerous features, including vocal source acoustics, vocal tract resonances, and dynamic articulations during speech. It remains poorly understood how differences in these features contribute to perceptual dissimilarity of voices and, moreover, whether linguistic differences between listeners and talkers interact during perceptual judgments of voices. Here, native English- and Mandarin-speaking listeners rated the perceptual dissimilarity of voices speaking English or Mandarin from either forward or time-reversed speech. The language spoken by talkers, but not listeners, principally influenced perceptual judgments of voices. Perceptual dissimilarity judgments of voices were always highly correlated between listener groups and forward/time-reversed speech. Representational similarity analyses that explored how acoustic features (fundamental frequency mean and variation, jitter, harmonics-to-noise ratio, speech rate, and formant dispersion) contributed to listeners' perceptual dissimilarity judgments, including how talker- and listener-language affected these relationships, found the largest effects relating to voice pitch. Overall, these data suggest that, while linguistic factors may influence perceptual judgments of voices, the magnitude of such effects tends to be very small. Perceptual judgments of voices by listeners of different native language backgrounds tend to be more alike than different.
Lexical bias in word recognition by cochlear implant listeners
Authors: Gianakas Steven P. , Winn Matthew B.
Published: November 2019

When hearing an ambiguous speech sound, listeners show a tendency to perceive it as a phoneme that would complete a real word, rather than completing a nonsense/fake word. For example, a sound that could be heard as either /b/ or /ɡ/ is perceived as /b/ when followed by _ack but perceived as /ɡ/ when followed by “_ap.” Because the target sound is acoustically identical across both environments, this effect demonstrates the influence of top-down lexical processing in speech perception. Degradations in the auditory signal were hypothesized to render speech stimuli more ambiguous, and therefore promote increased lexical bias. Stimuli included three speech continua that varied by spectral cues of varying speeds, including stop formant transitions (fast), fricative spectra (medium), and vowel formants (slow). Stimuli were presented to listeners with cochlear implants (CIs), and also to listeners with normal hearing with clear spectral quality, or with varying amounts of spectral degradation using a noise vocoder. Results indicated an increased lexical bias effect with degraded speech and for CI listeners, for whom the effect size was related to segment duration. This method can probe an individual's reliance on top-down processing even at the level of simple lexical/phonetic perception.
Why Do Older Adults Play Golf? An Evaluation of Factors Related to Golf Participation by Older Adults
Authors: Stenner Brad J. , Mosewich Amber D. , Buckley Jonathan D.
Published: November 2019

Golf is a popular sport for older adults, and is therefore an important source of physical activity. This study investigated the reasons for golf participation in an older population using the Golf Participation Questionnaire for Older Adults. The participants (N = 3,262, 82.5% male) completed the questionnaire online. The most important reasons for participation were fun, a pleasant playing environment, and competition, with reasons related to health being relatively less important. The female participants rated fun, a pleasant playing environment, and a feeling that participation made them part of a community as more important reasons for participating than males. Although health-related factors were identified as important reasons for golf participation in older adults, non-health-related factors were also more important. Strategies to promote golf participation by older adults, as a means of increasing physical activity, should emphasize aspects related to fun, a pleasant playing environment, and engagement in competition.
Minimized lithium trapping by isovalent isomorphism for high initial Coulombic efficiency of silicon anodes
Authors: Zhu Bin , Liu Guoliang , Lv Guangxin , Mu Yu , Zhao Yunlei , Wang Yuxi , Li Xiuqiang , Yao Pengcheng , Deng Yu , Cui Yi , Zhu Jia
Published: November 2019

The effect of isovalent isomorphism to minimize lithium trapping enables a high initial Coulombic efficiency of Si anode.
Conserved Patterns of Symmetric Inversion in the Genome Evolution of
Bordetella
Respiratory Pathogens
Authors: Weigand Michael R. , Peng Yanhui , Batra Dhwani , Burroughs Mark , Davis Jamie K. , Knipe Kristen , Loparev Vladimir N. , Johnson Taccara , Juieng Phalasy , Rowe Lori A. , Sheth Mili , Tang Kevin , Unoarumhi Yvette , Williams Margaret M. , Tondella M. Lucia
Published: November 2019

Bordetella pertussis
is the primary agent of whooping cough (pertussis). The
Bordetella
genus includes additional pathogens of animals and humans, including some that cause pertussis-like respiratory illness. The chromosome of
B. pertussis
has previously been shown to exhibit considerable structural rearrangement, but insufficient data have prevented comparable investigation in related species. In this study, we analyze chromosome structure variation in several
Bordetella
species to gain a generalized understanding of rearrangement patterns in this genus. Just as in
B. pertussis
, we observed inversions in other species that likely result from common mutational processes. We used these data to further predict additional, unobserved inversions, suggesting that specific genome structures may be preferred in each species.
Latitudinal variation in snowshoe hare (Lepus americanus) body mass: a test of Bergmann’s rule
Authors: Gigliotti Laura C. , Berg Nathan D. , Boonstra Rudy , Cleveland Shawn M. , Diefenbach Duane R. , Gese Eric M. , Ivan Jacob S. , Kielland Knut , Krebs Charles J. , Kumar Alexander V. , Mills L. Scott , Pauli Jonathan N. , Underwood H. Brian , Wilson Evan C. , Sheriff Michael J.
Published: November 2019

The relationship between body size and latitude has been the focus of dozens of studies across many species. However, results of testing Bergmann’s rule — that organisms in colder climates or at higher latitudes possess larger body sizes — have been inconsistent across studies. We investigated whether snowshoe hares (Lepus americanus Erxleben, 1777) follow Bergmann’s rule by investigating differences in body mass using data from six published studies and from data of 755 individual hares captured from 10 populations across North America covering 26° of north latitude. We also explored alternative hypotheses related to variation in hare body mass, including winter severity, length of growing season, elevation, and snow depth. We found body mass of hares varied throughout their range, but the drivers of body mass differed based on geographic location. In northern populations, females followed Bergmann’s rule, whereas males did not. In northern populations, male mass was related to mean snow depth. In contrast, in southern populations, body mass of both sexes was related to length of the growing season. These differences likely represent variation in the drivers of selection. Specifically, in the north, a large body size is beneficial to conserve heat because of low winter temperatures, whereas in the south, it is likely due to increased food supply associated with longer growing seasons.
A turtle population study in an isolated urban wetland complex in Ontario reveals a few surprises
Authors: Dupuis-Désormeaux Marc , D’Elia Vince , Burns Ryan , White Brittany , MacDonald Suzanne E.
Published: November 2019

We report on the results of the first mark–recapture survey of freshwater turtles in an isolated urban wetland complex in one of Canada’s fastest growing municipalities. Although we found turtles in every surveyed wetland, the density and assemblage of turtles in smaller wetlands were significantly different than in larger wetland bodies. We also documented two species of turtles that were thought to be absent from this wetland complex, the Northern Map turtle and Eastern Musk turtle. We noted that a wetland that was bisected by a high-traffic road showed a male-skewed sex ratio in the population of Midland Painted turtles but not in the population of Eastern Snapping turtles. As a whole, the sex ratios inside the wetland complex were not skewed. These results reinforce the conclusions of a previous study of a single wetland within this same complex that had found a correlation between road mortality and a male-skewed sex ratio in Midland painted turtles. We discuss population sources and sinks within the complex and the importance of protecting the overland corridors that support the safe turtle movements within this provincially significant wetland complex.
Sampling the $$\mu \nu $$SSM for displaced decays of the tau left sneutrino LSP at the LHC
Authors: Kpatcha Essodjolo , Lara Iñaki , López-Fogliani Daniel E. , Muñoz Carlos , Nagata Natsumi , Otono Hidetoshi , de Austri Roberto Ruiz
Published: November 2019

Within the framework of the $$\mu \nu \mathrm{SSM}$$μνSSM, a displaced dilepton signal is expected at the LHC from the decay of a tau left sneutrino as the lightest supersymmetric particle (LSP) with a mass in the range 45–100 GeV. We compare the predictions of this scenario with the ATLAS search for long-lived particles using displaced lepton pairs in pp collisions, considering an optimization of the trigger requirements by means of a high level trigger that exploits tracker information. The analysis is carried out in the general case of three families of right-handed neutrino superfields, where all the neutrinos get contributions to their masses at tree level. To analyze the parameter space, we sample the $$\mu \nu $$μνSSM for a tau left sneutrino LSP with proper decay length $$c\tau > 0.1 \, \hbox {mm}$$cτ>0.1mm using a likelihood data-driven method, and paying special attention to reproduce the current experimental data on neutrino and Higgs physics, as well as flavor observables. The sneutrino is special in the $$\mu \nu \mathrm{SSM}$$μνSSM since its couplings have to be chosen so that the neutrino oscillation data are reproduced. We find that important regions of the parameter space can be probed at the LHC run 3.
Thermodynamics of the Schwarzschild and Reissner–Nordström black holes under the Snyder–de Sitter model
Authors: Hassanabadi H. , Maghsoodi E. , Chung Won Sang , de Montigny M.
Published: November 2019

This paper examines the effects of a new form of the extended generalized uncertainty principle in the Snyder–de Sitter model on the thermodynamics of the Schwarzschild and Reissner–Nordström black holes. Firstly, we present a generalization of the minimal length uncertainty relation with two deformation parameters. Then we obtain the corrected mass–temperature relation, entropy and heat capacity for Schwarzschild black hole. Also we investigate the effect of the corrected uncertainty principle on the thermodynamics of the charged black holes. Our discussion of the corrected entropy involves a heuristic analysis of a particle which is absorbed by the black hole. Finally, we compare the thermodynamics of a charged black hole with the thermodynamics of a Schwarzschild black hole and with the usual forms, that is, without corrections to the uncertainty principle.
Error Estimation of Polynomial Chaos Approximations in Transient Structural Dynamics
Authors: Dao T. D. , Serra Q. , Berger S. , Florentin E.
Published: November 2019

Usually, within stochastic framework, a testing dataset is used to evaluate the approximation error between a surrogate model (e.g., a polynomial chaos expansion) and the exact model. We propose here another method to estimate the quality of an approximated solution of a stochastic process, within the context of structural dynamics. We demonstrate that the approximation error is governed by an equation based on the residue of the approximate solution. This problem can be solved numerically using an approximated solution, here a coarse Monte Carlo simulation. The developed estimate is compared to a reference solution on a simple case. The study of this comparison makes it possible to validate the efficiency of the proposed method. This validation has been observed using different sets of simulations. To illustrate the applicability of the proposed approach to a more challenging problem, we also present a problem with a large number of random parameters. This illustration shows the interest of the method compared to classical estimates.
An Efficient Implementation of the CRT Algorithm Based on an Interval-Index Characteristic and Minimum-Redundancy Residue Code
Authors: Selianinau Mikhail
Published: November 2019

The Chinese remainder theorem (CRT), which appeared in ancient China, is widely used in many modern computer applications. This paper presents the CRT implementation by using the interval-index characteristic and minimum redundancy residue code. The proposed algorithm does not use large modulo addition operations and provides low computational complexity compared to conventional non-redundant RNS. The efficiency factors of using the minimally redundant RNS increase with the number [Formula: see text] of non-redundant moduli, asymptotically approaching the threshold [Formula: see text]. The new approach presented here will have a significant impact on many non-modular operations in RNS arithmetic, which currently use the CRT.
A PROPOSAL FOR MULTI-ASSET GENERALIZED VARIANCE SWAPS
Authors: BISWAS SUBHOJIT , MUKHERJEE DIGANTA
Published: November 2019

This paper proposes swaps on two important new measures of generalized variance, namely the maximum eigenvalue and trace of the covariance matrix of the assets involved. We price these generalized variance swaps for financial markets with Markov-modulated volatilities. We consider multiple assets in the portfolio for theoretical purpose and demonstrate our approach with numerical examples taking three stocks in the portfolio. The results obtained in this paper have important implications for the commodity sector where such swaps would be useful for hedging risk.
Reliable Communication and Latency Bound Generation in Wireless Cyber-Physical Systems
Authors: Munir Sirajum , Yang Hao-Tsung , Lin Shan , Nirjon S. M. Shahriar , Lin Chen , Hoque Enamul , Stankovic John A. , Whitehouse Kamin
Published: November 2019

Low-power wireless communication has been widely used in cyber-physical systems that require time-critical data delivery. Achieving this goal is challenging because of link burstiness and interference. Based on significant empirical evidence of 21 days and over 3.6 M packet transmissions per link, we propose both routing and scheduling algorithms that produce latency bounds of the real-time periodic streams and accounts for both link bursts and interference. The solution is achieved through the definition of a new metric
B
max
that characterizes links by their maximum burst length, and by choosing a novel least-burst-route that minimizes the sum of worst-case burst lengths over all links in the route. With extensive data-driven analysis, we show that our algorithms outperform existing solutions by achieving accurate latency bound with much less energy consumption. In addition, a testbed evaluation consisting of 48 nodes spread across a floor of a building shows that we obtain 100% reliable packet delivery within derived latency bounds. We also demonstrate how performance deteriorates and discuss its implications for wireless networks with insufficient high-quality links.
Dry Aligning Dilute Active Matter
Authors: Chaté Hugues
Published: November 2019

Active matter physics is about systems in which energy is dissipated at some local level to produce work. This is a generic situation, particularly in the living world but not only. What is at stake is the understanding of the fascinating, sometimes counterintuitive, emerging phenomena observed, from collective motion in animal groups to in vitro dynamical self-organization of motor proteins and biofilaments.

Dry aligning dilute active matter (DADAM) is a corner of the multidimensional, fast-growing domain of active matter that has both historical and theoretical importance for the entire field. This restrictive setting only involves self-propulsion/activity, alignment, and noise, yet unexpected collective properties can emerge from it.

This review provides a personal but synthetic and coherent overview of DADAM, focusing on the collective-level phenomenology of simple active particle models representing basic classes of systems and on the solutions of the continuous hydrodynamic theories that can be derived from them. The obvious fact that orientational order is advected by the aligning active particles at play is shown to be at the root of the most striking properties of DADAM systems: ( a) direct transitions to orientational order are not observed; ( b) instead generic phase separation occurs with a coexistence phase involving inhomogeneous nonlinear structures; ( c) orientational order, which can be long range even in two dimensions, is accompanied by long-range correlations and anomalous fluctuations; ( d) defects are not point-like, topologically bound objects.
Gestational Exposure to Common Endocrine Disrupting Chemicals and Their Impact on Neurodevelopment and Behavior
Authors: Nesan Dinushan , Kurrasch Deborah M.
Published: November 2019

Endocrine disrupting chemicals are common in our environment and act on hormone systems and signaling pathways to alter physiological homeostasis. Gestational exposure can disrupt developmental programs, permanently altering tissues with impacts lasting into adulthood. The brain is a critical target for developmental endocrine disruption, resulting in altered neuroendocrine control of hormonal signaling, altered neurotransmitter control of nervous system function, and fundamental changes in behaviors such as learning, memory, and social interactions. Human cohort studies reveal correlations between maternal/fetal exposure to endocrine disruptors and incidence of neurodevelopmental disorders. Here, we summarize the major literature findings of endocrine disruption of neurodevelopment and concomitant changes in behavior by four major endocrine disruptor classes:bisphenol A, polychlorinated biphenyls, organophosphates, and polybrominated diphenyl ethers. We specifically review studies of gestational and/or lactational exposure to understand the effects of early life exposure to these compounds and summarize animal studies that help explain human correlative data.
Antitumor activity and combined inhibitory effect of ceritinib with gemcitabine in pancreatic cancer
Authors: Jamshed Muhammad Babar , Munir Fahad , Shahid Numan , Sadiq Ussama , Muhammad Syed Aun , Ghanem Noor Bader , Zhong Hong , Li Xiaokun , Zhang Qiyu
Published: November 2019

Pancreatic cancer (PC) is predominantly incurable and is primarily treated with gemcitabine, but drug resistance commonly develops. Thus, new medicines are needed. Ceritinib (LDK378) is a second-generation tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) with antitumor activity in various cancers. However, studies involving ceritinib for the treatment of PC are inadequate. We analyzed the combined effects of ceritinib and gemcitabine on PC and their mechanism of action. Three PC cell lines were used to evaluate the antitumor effects of ceritinib combined with gemcitabine. We analyzed cell viability using CCK-8 assays, determined apoptosis levels through flow cytometry, and analyzed autophagy and cell signaling pathways by Western blotting and tissue array analysis with samples from xenograft models. Ceritinib strongly inhibited the proliferation of PC cells in a dose-dependent manner, induced apoptosis, and inhibited autophagy and cell migration by regulating relevant factors. Ceritinib in combination with gemcitabine exhibited significant growth inhibition and additive antitumor effects in vitro. In vivo, gemcitabine and ceritinib reduced tumor size by up to 30%. In our study, ALK was shown to be highly expressed in various PC cells and tissues. Ceritinib strongly inhibited the levels of activated ALK in PC cells with subsequent effects on the downstream mediators STAT3, AKT, and ERK. In addition, ceritinib inhibited tumor progression in xenograft models. Overall, our research shows that ceritinib inhibits the ALK signaling pathway, leading to cell growth/angiogenesis inhibition in PC and the induction of apoptosis. We recommend using ceritinib as a new treatment for PC.

NEW & NOTEWORTHY These data proved that ceritinib inhibits the anaplastic lymphoma kinase signaling pathway, leading to cell growth/angiogenesis inhibition and the induction of apoptosis by inhibiting STAT3, AKT, and ERK pathway in pancreatic cancer (PC). We recommend using ceritinib as a new treatment for PC.
Inhibition of tyrosine kinase receptor signaling attenuates fibrogenesis in an ex vivo model of human renal fibrosis
Authors: Bigaeva Emilia , Stribos Elisabeth G. D. , Mutsaers Henricus A. M. , Piersma Bram , Leliveld Anna M. , de Jong Igle J. , Bank Ruud A. , Seelen Marc A. , van Goor Harry , Wollin Lutz , Olinga Peter , Boersema Miriam
Published: November 2019

Poor translation from animal studies to human clinical trials is one of the main hurdles in the development of new drugs. Here, we used precision-cut kidney slices (PCKS) as a translational model to study renal fibrosis and to investigate whether inhibition of tyrosine kinase receptors, with the selective inhibitor nintedanib, can halt fibrosis in murine and human PCKS. We used renal tissue of murine and human origins to obtain PCKS. Control slices and slices treated with nintedanib were studied to assess viability, activation of tyrosine kinase receptors, cell proliferation, collagen type I accumulation, and gene and protein regulation. During culture, PCKS spontaneously develop a fibrotic response that resembles in vivo fibrogenesis. Nintedanib blocked culture-induced phosphorylation of platelet-derived growth factor receptor and vascular endothelial growth factor receptor. Furthermore, nintedanib inhibited cell proliferation and reduced collagen type I accumulation and expression of fibrosis-related genes in healthy murine and human PCKS. Modulation of extracellular matrix homeostasis was achieved already at 0.1 μM, whereas high concentrations (1 and 5 μM) elicited possible nonselective effects. In PCKS from human diseased renal tissue, nintedanib showed limited capacity to reverse established fibrosis. In conclusion, nintedanib attenuated the onset of fibrosis in both murine and human PCKS by inhibiting the phosphorylation of tyrosine kinase receptors; however, the reversal of established fibrosis was not achieved.
Toll-like receptor 4-mediated respiratory syncytial virus disease and lung transcriptomics in differentially susceptible inbred mouse strains
Authors: Marzec Jacqui , Cho Hye-Youn , High Monica , McCaw Zachary R. , Polack Fernando , Kleeberger Steven R.
Published: November 2019

Respiratory syncytial virus (RSV) causes severe lower respiratory tract disease in infants, young children, and susceptible adults. The pathogenesis of RSV disease is not fully understood, although toll-like receptor 4 (TLR4)-related innate immune response is known to play a role. The present study was designed to determine TLR4-mediated disease phenotypes and lung transcriptomics and to elucidate transcriptional mechanisms underlying differential RSV susceptibility in inbred strains of mice. Dominant negative Tlr4 mutant (C3H/HeJ, HeJ, Tlr4Lps-d) and its wild-type (C3H/HeOuJ, OuJ, Tlr4Lps-n) mice and five genetically diverse, differentially responsive strains bearing the wild-type Tlr4Lps-n allele were infected with RSV. Bronchoalveolar lavage, histopathology, and genome-wide transcriptomics were used to characterize the pulmonary response to RSV. RSV-induced lung neutrophilia [1 day postinfection (pi)], epithelial proliferation (1 day pi), and lymphocytic infiltration (5 days pi) were significantly lower in HeJ compared with OuJ mice. Pulmonary RSV expression was also significantly suppressed in HeJ than in OuJ. Upregulation of immune/inflammatory ( Cxcl3, Saa1) and heat shock protein ( Hspa1a, Hsph1) genes was characteristic of OuJ mice, while cell cycle and cell death/survival genes were modulated in HeJ mice following RSV infection. Strain-specific transcriptomics suggested virus-responsive ( Oasl1, Irg1, Mx1) and epidermal differentiation complex ( Krt4, Lce3a) genes may contribute to TLR4-independent defense against RSV in resistant strains including C57BL/6J. The data indicate that TLR4 contributes to pulmonary RSV pathogenesis and activation of cellular immunity, the inflammasome complex, and vascular damage underlies it. Distinct transcriptomics in differentially responsive Tlr4-wild-type strains provide new insights into the mechanism of RSV disease and potential therapeutic targets.
Association between Sarcopenia and Renal Function in Patients with Diabetes: A Systematic Review and Meta-Analysis
Authors: Ida Satoshi , Kaneko Ryutaro , Imataka Kanako , Murata Kazuya
Published: November 2019

Previous studies involving patients with diabetes have indicated that sarcopenia is related to renal function. The objective of the present study was to investigate the association between sarcopenia and urinary albumin level, urinary protein level, and estimated glomerular filtration rate (eGFR) in patients with diabetes. A meta-analysis of observational studies was conducted. A literature search was performed using MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov. Data were extracted from studies investigating the association between sarcopenia and urinary albumin level, urinary protein level, and eGFR and by calculating odds ratio (OR) and 95% confidence intervals (CIs). Statistical analysis was performed using a random-effects model to calculate pooled OR and 95% CI. Six studies (2662 patients) that met the criteria were included in the meta-analysis. Sarcopenia was significantly associated with urinary albumin level with a pooled OR of 2.11 (95% CI, 1.55–2.88;P<0.001). The pooled ORs of the associations between sarcopenia and urinary protein level and decreased eGFR were 1.82 (95% CI, 1.13–2.92;P=0.01) and 3.75 (95% CI, 1.24–11.41), respectively. Sarcopenia was significantly associated with urinary albumin level, urinary protein level, and decreased eGFR. However, further investigations are needed, including meta-analyses with a larger number of studies.
Benign Subcutaneous Nodules and Hypereosinophilic Syndrome: A Rare Presentation of an Uncommon Entity
Authors: Pal Rimesh , Yanamandra Uday , Kumar Prasanna , Banerjee Nirmalya
Published: November 2019

A 40-year-old gentleman presented with a history of multiple swellings involving his face, scalp, left axilla, back, and right thigh for the past 8 years. For the last 6 months, he developed intermittent low-grade fever, anorexia, weight loss, and gradually worsening breathlessness. On evaluation, the patient was found to have abnormally elevated absolute eosinophil count. Workup for the etiology of eosinophilia was unrewarding. All investigations related to an underlying myeloproliferative disorder were negative. Hence, a clinical possibility of angiolymphoid hyperplasia with eosinophilia (ALHE) was kept which was confirmed on histopathology. In the absence of other causes of hypereosinophilia, a clinical diagnosis of “associated hypereosinophilic syndrome” secondary to ALHE was made. He was managed with oral corticosteroids. The absolute eosinophil count reduced markedly, while the swellings showed a more gradual response, shrinking in size by about 50% following two months of therapy. The index case thus highlights a rather unusual presentation of ALHE.
Polynomial‐Based Google Map Graphical Password System against Shoulder‐Surfing Attacks in Cloud Environment
Authors: Zhou Zhili , Yang Ching-Nung , Yang Yimin , Sun Xingming
Published: November 2019

Text password systems are commonly used for identity authentication to access different kinds of data resources or services in cloud environment. However, in the text password systems, the main issue is that it is very hard for users to remember long random alphanumeric strings due to the long‐term memory limitation of the human brain. To address this issue, graphical passwords are accordingly proposed based on the fact that humans have better memory for images than alphanumeric strings. Recently, a Google map graphical password (GMGP) system is proposed, in which a specific location of Google Map is preset as a password for authentication. Unfortunately, the use of graphical passwords increases the risk of exposing passwords under shoulder‐surfing attacks. A snooper can easily look over someone’s shoulder to get the information of a location on map than a text password from a distance, and thus the shoulder‐surfing attacks are more serious for graphical passwords than for text passwords. To overcome this issue, we design a polynomial‐based Google map graphical password (P‐GMGP) system. The proposed P‐GMGP system can not only resist the shoulder‐surfing attacks effectively, but also need much fewer challenge‐response rounds than the GMGP system for authentication. Moreover, the P‐GMGP system is extended to allow a user to be authenticated in cloud environment effectively and efficiently.
Salivary Metabolomics Fingerprint of Chronic Apical Abscess with Sinus Tract: A Pilot Study
Authors: Montis Noemi , Cotti Elisabetta , Noto Antonio , Fattuoni Claudia , Barberini Luigi
Published: November 2019

Chronic apical abscess (CAA) is a lesion of apical periodontitis mostly characterized by areas of liquefactive necrosis with disintegrating polymorphonuclear neutrophils surrounded by macrophages. Its presence leads to local bacterial infection, systemic inflammatory response, pain, and swelling. The use of a novel approach for the study of CAA, such as metabolomics, seems to be important since it has proved to be a powerful tool for biomarkers discovery which could give novel molecular insight on CAA. So, the aim of this study was to verify the possibility to identify the metabolic fingerprint of CAA through the analysis of saliva samples. Nineteen patients were selected for this study: eleven patients affected by CAA with a sinus tract constituted the study group whereas eight patients without clinical and radiographic signs of CAA formed the healthy control group. Saliva samples were collected from each subject and immediately frozen at −80°C. Metabolomic profiles were obtained using a gas chromatography/mass spectrometry instrument. Subsequently, in order to compare the two groups, a multivariate statistical model was built that resulted to be statistically significant. The class of metabolites characterizing the CAA patients was closely related to the bacterial catabolism, tissue necrosis, and presence of a sinus tract. These preliminary results, for the first time, indicate that saliva samples analyzed by means of GC/MS metabolomics may be useful for identifying the presence of CAA, leading to new insights into this disease.
Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2
Authors: Wang Rong , Luo Yongzheng , Lu Yadong , Wang Daojuan , Wang Tingyu , Pu Wenyuan , Wang Yong
Published: November 2019

Ulcerative colitis (UC) is a common chronic remitting disease driven through altered immune responses with production of inflammatory cytokines. Oxidant/antioxidant balance is also suggested to be an important factor for the recurrence and progression of UC. Maggots are known as a traditional Chinese medicine also known as “wu gu chong.” NF-E2-related factor-2 (Nrf2) transcription factor regulates the oxidative stress response and also represses inflammation. The aim of this study was to investigate the effects of maggot extracts on the amelioration of inflammation and oxidative stress in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and evaluate if the maggot extracts could repress inflammation and oxidative stress using RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In the present study, we found that the maggot extracts significantly prevented the loss of body weight and shortening of colon length in UC induced by DSS. Furthermore, DSS-induced expression of proinflammatory cytokines at both mRNA and protein levels in the colon was also attenuated by the maggot extracts. In addition, the maggot extracts could significantly suppress the expression of interleukin- (IL-) 1β, IL-6, TNF-α, NFκB p65, p-IκB, p22-phox, and gp91-phox in LPS-stimulated RAW 264.7 cells and colonic tissues. The maggot extracts increased the level of Nrf2 and prevented the degradation of Nrf2 through downregulating the expression of Keap1, which resulted in augmented levels of HO-1, SOD, and GSH-Px and reduced levels of MPO and MDA. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of the maggot extracts in mice with colitis and RAW 264.7 cells. Taken together, our data for the first time confirmed that the maggot extracts ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf2/HO-1 pathway. This study sheds light on the possible development of an effective therapeutic strategy for inflammatory bowel diseases.
Flecainide-Associated Cardiogenic Shock in a Patient with Atrial Fibrillation
Authors: Gjermeni Erind , Bollmann Andreas , Hindricks Gerhard , Müssigbrodt Andreas
Published: November 2019

Flecainide is a frequently used antiarrhythmic drug, recommended by current guidelines as a first-line treatment option for restoring and maintaining sinus rhythm in patients with atrial fibrillation and no significant structural heart disease. In overdose, it can induce severe cardiogenic shock. Cardiogenic shock after a therapeutic dose of flecainide in patients without contraindication has not yet been reported in literature. Case Summary. We report a case of flecainide-associated cardiogenic shock in a 52-year-old woman with paroxysmal atrial fibrillation after a therapeutic dose of flecainide. Pharmacological cardioversion of symptomatic tachyarrhythmic atrial fibrillation with flecainide was unsuccessful and shortly after, she developed cardiogenic shock with severely reduced LVEF. Electrical cardioversion was also unsuccessful. Coronarography was unremarkable, and the cardiac MRI showed no signs of inflammation or fibrosis. After amiodarone loading, she converted to SR. This rare but severe complication despite adequate treatment could be explained by increased susceptibility to negative inotropic effect of flecainide as a consequence of marked tachycardia. Therefore, cautious monitoring after new administration of flecainide or the administration of a higher dose is advisable.
Plasma Fibrin Clot Properties Are Unfavorably Altered in Women following Venous Thromboembolism Associated with Combined Hormonal Contraception
Authors: Piróg Magdalena , Piwowarczyk Sławomir , Undas Anetta
Published: November 2019

The use of hormonal contraception is associated with an increased risk of venous thromboembolism (VTE). Unfavorably altered fibrin clot phenotype has been reported in patients following unprovoked VTE who are at risk of recurrences. It remains unknown whether fibrin clot characteristics in women with contraception-related VTE differ from those in unprovoked VTE. We studied three age-matched groups of women: (1) after contraception-related VTE, (n=48) (2) after unprovoked VTE (n=48), and (3) controls (n=48). Plasma fibrin clot permeability (Ks), turbidity of clot formation, efficiency of fibrinolysis using clot lysis time (CLT), and rate of increase in D-dimer during lytic clot degradation (D-Drate), along with thrombin generation and fibrinolysis proteins were determined. Compared with the controls, patients following contraception-related and unprovoked VTE formed faster (lag phase, -8.8% and -20.4%, respectively) fibrin clots of increased density (Ks, -8.6% and -13.4%, respectively) displaying impaired fibrinolysis as evidenced by prolonged CLT (+11.5% and +14.5%, respectively) and lower D-Drate (-7.1% and -5.6%, respectively), accompanied with higher plasminogen activator inhibitor-1 (PAI-1, +14.9% and +17.8%, respectively) and elevated peak thrombin generation (+63.8% and +36.7%, respectively). The only differences between women with unprovoked and contraception-related VTE were lower fibrin mass in plasma clots (D-Dmax, -8.6%), along with higher peak thrombin generation (+19.8%) and shorter lag phase (-6.8%) in the latter group. This study suggests that women after contraception-related VTE, similar to those following unprovoked VTE, have denser fibrin clot formation and impaired clot lysis. These findings might imply higher risk of VTE recurrence in women with the prothrombotic clot phenotype.
Particulate Scale Multiparticle Finite Element Method Modeling on the 2D Compaction and Release of Copper Powder
Authors: Zhou Liwen , Han Peng , Liu Kun , Feng Lianghua , Liu Guangqiang
Published: November 2019

Herein, two‐dimensional (2D) single‐action die compaction process of copper (Cu) powder was simulated by the multiparticle finite element method (MPFEM) at particulate scale. The initial packing structure, generated by the discrete element method (DEM), was used as an input for the FEM model, where the mesh division of each particle was discretized. The evolution of macro‐ and microscopic properties, such as relative density, stress distribution, particle deformation, void filling behavior, and force transmission, during compaction and pressure release processes have been systematically studied. The results revealed that the force is mainly concentrated on largely deformed regions of the particles during compaction and formed a contact force network, which hindered the densification process. In the compact, the shorter side of the large void edges rendered higher stress than the longer side. On the other hand, the stress distribution of small void edges remained uniform. After pressure release, large residual stress was observed at the contact area of the adjacent particles and the maximum stress was observed at the particles’ edges. Moreover, the residual stress did not proceed to the interior of the particles. Meanwhile, the stress of large void edges has been completely released but exhibited a nonuniform distribution. The smaller fraction of void filling resulted in a larger reduction of the released stress after pressure removal. Also, the particles closer to the upper die exhibited higher average equivalent von Mises stress inside the particles during compaction and pressure release processes.
Familial Exudative Vitreoretinopathy-Related Disease-Causing Genes and Norrin/β-Catenin Signal Pathway: Structure, Function, and Mutation Spectrums
Authors: Xiao Hongtao , Tong Yuna , Zhu Yuxuan , Peng Min
Published: November 2019

Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by incomplete vascularization/abnormality of peripheral retina. Four of the identified disease-causing genes of FEVR were NDP, FZD4, LRP5, and TSPAN12, the protein coded by which were the components of the Norrin/β-catenin signal pathway. In this review, we summarized and discussed the spectrum of mutations involving these four genes. By the end of 2017, the number of FEVR causing mutations reported for NDP, FZD4, LRP5, and TSPAN12 was, respectively, 26, 121, 58, and 40. Three most frequently reported mutations were c. 362G > A (p.R121Q) of NDP, c. 313A > G (p.M105V), and c.1282_1285delGACA (p.D428SfsX2) of FZD4. Mutations have a tendency to cluster in some “hotspots” domains which may be responsible for protein interactions.
Evolutionary Game Analysis of Chinese Food Quality considering Effort Levels
Authors: Yang Song , Zhuang Jincai , Wang Aifeng , Zhang Yancai
Published: November 2019

Food safety accidents occur frequently, which has caused great harm to people’s health. With the consideration that food quality requires the joint efforts of all members of the food supply chain and that quality‐improving efforts for food have a positive external effect, we focus on the quality‐improving effort level, which is very important for food quality and safety. This paper builds an evolutionary game model and employs the replicated dynamic equation to study evolutionarily stable strategies of suppliers and producers. Furthermore, simulation experiments are conducted to verify the modeling analyses and demonstrate the influences of game parameters. The research results show that the behavioral strategies are closely related to the factors such as the ratios of the input to the output, the cost of quality‐improving efforts, the hitchhiking benefits, and the initial strategy. Only when the punishing dynamics of the government exceeds a certain value, both participants can choose the quality‐improving effort strategy. Based on the results, this paper has provided some inspiration for policy‐making of government institutions.