bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms with human tongue squamous cell carcinoma
Authors: Lai Heqing , Xu Guochao , Meng Haifeng , Zhu Haiying
Published: July 2019

Objective: To study the association between SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms and risk of human tongue squamous cell carcinoma (TSCC).

Methods: Sanger sequencing was used to determine the genotypes of SP1 rs1353058818 and STAT3 rs1053004 loci in 240 TSCC patients and 240 controls. Levels of hsa-miR-149-5p and hsa-miR-21-5p and expression levels of SP1 and STAT3 proteins in tumor tissues and adjacent normal tissues of TSCC patients were ascertained.

Results: Carrying the SP1 rs1353058818 locus deletion allele was a high risk factor for TSCC (OR = 2.997, 95% CI: 1.389–6.466, P = 0.003). The STAT3 rs1053004 locus A allele was a protective factor for TSCC (OR = 0.604, 95% CI: 0.460-0.793, P < 0.001). There was a negative correlation between SP1 mRNA and hsa-miR-149-5p in tumor and adjacent normal tissues (r = −0.81, −0.77). The expression of SP1 protein in tumor tissues of the SP1 rs1353058818 locus DD genotype was significantly higher than in tissues of the ID type, and in tissues of type II it was the lowest. STAT3 mRNA was positively correlated with hsa-miR-21-5p in tumor and adjacent normal tissues (r = 0.75, 0.78). The expression level of STAT3 protein in tumor tissues of patients with STAT3 rs1053004 locus GG genotype was significantly higher than in patients with type GA, and it was the lowest in patients with type AA.

Conclusion: Polymorphisms in the SP1 rs1353058818 and STAT3 rs1053004 loci are associated with the risk of human TSCC.
Layer‐dependent resistance variability assessment on 2048 8‐layer 3D vertical RRAMs
Authors: Gao Rui , Lei Dengyun , He Zhiyuan , En Yunfei , Huang Yun
Published: June 2019

Non‐filament 3D vertical RRAM (VRRAM) is a promising technology for emerging high‐density memory applications. In this Letter, the layer‐dependent resistance variability at both low resistance state (LRS) and high resistance state (HRS) is assessed on state‐of‐the‐art 8‐layer 3D VRRAMs. 2048 devices are measured with the aid of an FPGA‐controlled relay matrix which enables automated switching of devices without changing the cabling. The results show LRS exhibits little layer dependence while both the average and the standard variation of HRS decrease from the top layer to the bottom layer. A qualitative speculation is proposed to explain the observation based on the high‐resolution transmission electronic microscope image. This work is beneficial for future 3D VRRAM circuit design and performance improvement.
Performance and optimisation of agent compression and forwarding system for correlated sources
Authors: Xu Dazhuan , Chen Dan , Zhang Ruidan
Published: June 2019

A system for the correlated Gaussian sources to perform compression forwarding via the multi‐relay network in the additive white Gaussian noise channel is proposed in this study. The characteristic of the newly proposed system is that it is composed of two parts: an analogue sensor network from the sources to multiple relay nodes and a digital communication network from multiple relay nodes to the destination node. The sensors can only perform simple analogue signal transmission, but the encoder set up at each relay can carry out complex distributed source coding DSC and then send the coded digital signals to the destination node. In this study, the authors establish the rate–distortion function of DSC based on the Chief Executive Officer problem. Combined with the channel capacity theorem, an optimal power allocation scheme is first proposed. The quantisation signal‐to‐noise ratio (SNR) at the destination node is used to evaluate the performance of the system under different correlations between sources. For the case of independent sources, a closed‐form expression for the quantisation SNR is derived and they compare the optimised agent compress‐and‐forward system with the traditional amplify‐and‐forward system to verify that the proposed system can achieve better SNR performance.
Analytical model for optimal data transmission policy in two‐way relay network coding under phase type arrivals
Authors: Gunasekara Charith
Published: June 2019

The authors consider a scenario in which two wireless nodes communicate via a single access‐point with two buffers using network coding. The access point first pairs each data packet being sent from each node and then performs the network coding operation. Packets arriving at the access point that are unable to be paired are instead loaded into one of the two buffers at the access point. When one of the buffers is empty and the other is not, network coding is not possible. When this happens, the access point must either wait for a network coding opportunity, or transmit the unpaired packet without coding. The authors analyse the trade‐off that arises between decreasing packet delay time, and increasing efficiency of the wireless spectrum usage as double‐ended push‐out queueing theory problem under phase type data arrivals. They use this model to resolve the optimal threshold policy and analyse the performance of the system.
Energy and spectral efficient SMC‐MAC protocol in distributed cognitive radio networks
Authors: Thakur Prabhat , Singh Ghanshyam
Published: June 2019

Communication industry demands the frameworks, which allow significant improvement in energy efficiency with spectral efficiency, however, these two do not always coincide and may even conflict sometimes in cognitive radio networks. In addition to this, the distributed network structures are preferred over centralised structures due to ease of deployment as well as less information exchange between the cognitive users which reduce the network‐overhead. Therefore, in this study, the authors have proposed a framework to enhance the spectral as well as energy efficiency by exploiting the novel frame structure in the distributed cognitive radio networks. A self‐scheduled multichannel‐medium access control (SMC‐MAC) protocol has been proposed in which the contention and sharing intervals are exploited for the efficient spectrum and energy utilisation. Moreover, the closed‐form expressions of the spectral efficiency, power consumption and energy efficiency for the proposed SMC‐MAC protocols are derived. Furthermore, the relation between energy and spectral efficiency for the proposed framework is also derived. The numerically simulated results are presented to validate the proposed work and Monte‐Carlo simulations are performed for the random events in order to support the numerically simulated results.
Hybrid PS–GW optimised PTS scheme for PAPR reduction in OFDM system
Authors: Ravi Kumar P. , Naganjaneyulu P.V. , Satya Prasad K.
Published: June 2019

The most famous and attractive strategy used in wireless communication for huge transmission of data with higher rate was orthogonal frequency division multiplexing (OFDM) approach. Efficient methods are important for PAPR reduction in high‐speed wireless communication systems. The reduction of PAPR in OFDM system has been carried out with one of the most familiar approach called Partial transmit sequences (PTS). Various techniques are already presented for reducing the PAPR, some of them are, clipping, SLM, and PTS. From that PTS is considered as an efficient method because the PAPR was reduced by PTS without causing any signal distortion. In this work, PTS along with hybridization optimization algorithm named as PS–GW will be implemented to get the minimum performance on PAPR and computational complexity. The PS–GW is a combination of both the Particle Swarm Optimization (PSO) and Grey Wolf Optimizer (GWO) which search the optimal combination of phase rotational factors efficiently. A fundamental thought in this method was that the capacity of exploitation in PSO was enhanced with the capacity of investigation in GWO to create a two variations in quality. The results produced by this proposed method shows that the reduction was effectively determined in both PAPR and computational complexity.
Game theoretic handover optimisation for dense small cells heterogeneous networks
Authors: Alhabo Mohanad , Zhang Li , Nawaz Naveed , Al‐Kashoash Hayder
Published: June 2019

In this study, the authors formulate a non‐cooperative game approach in which all base stations compete in a selfish manner to transmit at higher power. Each base station in the network is considered as a player in the game. The solution of the game is obtained by finding the optimal point, namely the Nash equilibrium. The proposed method, named efficient handover game theoretic, targets to manage the handover in dense small cell heterogeneous networks. Each player in the game optimises its payoff by adjusting the transmission power so as to enhance the overall performance in terms of throughput, handover, energy consumption, and load balancing. In order to choose the preferred transmission power for each player, the payoff function takes into account the gain of increasing the transmission power, energy consumption, base station load, and unnecessary handover. The cell selection is performed using the technique for order preference by similarity to an ideal solution (TOPSIS). A game theoretical approach is implemented and evaluated for dense small cell heterogeneous networks to validate the enhancement achieved in the proposed method. Results show that the proposed game theoretical approach provides a throughput enhancement while reducing the power consumption in addition to minimise the unnecessary handover and balance the load between base stations.
Powertrain EV synchronous reluctance motor design with redundant topology with novel control
Authors: Herrera Danilo , Villegas Javier , Galván Eduardo , Carrasco Juan Manuel
Published: June 2019

A doubly three‐phase fed synchronous reluctance machine (SynRM) is designed for electrical vehicle powertrain application. SynRM aims to deliver instant power and high power density, high torque at low speeds and high power at high speeds, wide speed range, high efficiency throughout its range of operation, ruggedness, high safety at a reasonable cost. Under these requirements, a 60 kW, 9000 rpm and 400 Nm SynRM has been designed. The main objective is to demonstrate the SynRM powertrain operation behaviour and determinate the operation points electrically and thermally. To reach the proposed SynRM goal, a new direct torque control algorithm based on output regulation subspace theory control is presented. The winding motor topology is galvanic isolated, so it is possible to operate with the six phases directly to the load and because of that, the combination with a back‐to‐back (B2B) converter becomes so profitable. To validate the system, two B2B full‐converters and two motors (SynRM and induction machine) were used in a real test bench. Finally, a simulated and real efficiency map is obtained covering different drive cycles range. Some remarks about normal and failure mode of operation are presented.
Voltage‐dependent load model‐based short‐term distribution network planning considering carbon tax surplus
Authors: Melgar‐Dominguez Ozy Daniel , Pourakbari‐Kasmaei Mahdi , Lehtonen Matti , Mantovani José Roberto Sanches
Published: June 2019

Nowadays, strategies to cope with environmental issues play a crucial role in the development of planning methodologies for electric distribution networks (EDNs). The primary goal of these methodologies is to find the equilibrium point, for which the EDN provides a high‐quality service with the most environmentally‐committed operation. Based on this fact, an alternative strategic approach for short‐term EDN planning is presented. This decision‐making scheme is based on classical investment actions to enhance the EDN performance in which the investment and operating costs, as well as the carbon tax surpluses, are minimised simultaneously. Unlike the traditional short‐term planning methods and to explore a more accurate approach, the electricity demand is represented by the voltage‐dependent exponential load model. By using this representation, substantial benefits related to energy saving can be achieved. To validate the proposed planning scheme, several test cases considering constant power demand and voltage‐dependent representation are widely studied on a 135‐node distribution network. Additionally, the scalability of the proposed planning scheme is studied by using two medium distribution networks of 42‐ and 417‐node. Numerical results confirm the robustness and applicability of the presented approach as an appropriate way of promoting to an efficient and low carbon tax surplus network.
Cooperative perception in autonomous ground vehicles using a mobile‐robot testbed
Authors: Sridhar Srivatsan , Eskandarian Azim
Published: June 2019

Autonomous vehicles are limited in their perception capabilities to the field of view of their onboard sensors. Additionally, the environment may not be completely perceivable due to the presence of occlusions and blind spots. To overcome this challenge, wireless vehicle‐to‐vehicle communication could be employed to send and receive sensory information about the surroundings among vehicles within the vicinity. This form of cooperative perception (CP) turns every vehicle into a moving sensor platform, extending each vehicle's field of view and line of sight. This study proposes one such technique for CP over a short range. The system uses visual and inertial sensors, augmented by a positioning system, to perform cooperative relative localisation between two vehicles that share a common field of view. This allows one vehicle to locate the other vehicle in its frame of reference. Subsequently, information about objects in the field of view of one vehicle, localised using a monocular camera is relayed to the other vehicle through communication. A mobile multi‐robot testbed was developed to emulate autonomous vehicles and to experimentally evaluate the proposed method through a series of driving scenario test cases, in which CP could be effective and crucial to the safety and comfort of driving.
Design of triple‐band and triplex slot antenna using triple‐mode cavity resonator
Authors: Wu Yu‐Ming , Wong Sai‐Wai , Lin Jing‐Yu , Yang Yang , Zhang Long , Choi Wai‐Wa , Zhu Lei , He Yejun
Published: June 2019

A class of triple‐band and triplex cavity‐backed slot antenna is proposed by using three fundamental modes in a single metal cavity: TE011, TE101, and TM110 modes, simultaneously. These three resonant modes can be excited by changing the position of the feeding slot without any extra components configured inside the cavity. By opening a single radiation slot, a single band triple‐mode cavity‐backed slot antenna is achieved. By opening three slots at three side walls of the cavity, a triple‐band cavity‐backed slot antenna is realised with three different radiation directions at three different operation frequencies. Moreover, a triplex triple‐band antenna can be formed by combining a single slot antenna and three input ports in the proposed rectangular cavity. Finally, a triple‐band multi‐directional cavity‐backed slot antenna prototype and a triplex triple‐band cavity‐backed single slot antenna prototype are fabricated and tested. The tested results are in good agreement with the simulated results, which indicates the feasibility of the proposed design methodology.
Design and packaging of a compact circularly polarised planar antenna for 2.45‐GHz RFID mobile readers
Authors: Gautam Anil Kumar , Farhan Mohd. , Agrawal Niraj , Rambabu Karumudi
Published: June 2019

In this study, a novel design and packaging of miniaturised planar microstrip antenna with circular polarisation (CP) that is suitable for 2.45‐GHz radio‐frequency identification (RFID) applications is proposed. The circular polarisation is realised by truncating the corners of the left to right diagonal and 76% of miniaturisation is achieved by incorporating two slots in each of the four directions and one at the centre of the square‐shaped radiator. This type of miniaturisation method is known in the literature but combining with CP radiation is a novel approach. The radiator of the designed antenna has a compact size of 19.6 × 19.6 mm2 with an overall size of the antenna 30 × 30 × 1.6 mm3, and this technique offers 76% miniaturisation in antenna size. Finally, a prototype antenna is fabricated and experimentally characterised to verify the design concept as well as to validate the simulation results. The designed antenna achieves measured return loss bandwidth of around 80 MHz (2.42– 2.5 GHz) and axial ratio bandwidth of 21 MHz (2.447–2.468 GHz). The proposed antenna is a good candidate for RFID mobile reader applications as it shows a good radiation performance, when it is installed in various types of housing.
Flexoelectricity in ferroelectric materials
Authors: Zhou Wanfeng , Chen Pan , Chu Baojin
Published: June 2019

Flexoelectricity is a gradient electromechanical effect that exists in all solid dielectrics. The effect was first predicted in the late 1950s, but received little interest because it was expected to be small. The experimentally measured large flexoelectric response in ferroelectric ceramics led to the revival of the field in the early 2000s. In this study, the progress made in the flexoelectric field is reviewed. The authors’ focus will be primarily on the experimental studies related to the flexoelectric effect. The techniques employed to measure the flexoelectric coefficients are first summarised. A compilation of the flexoelectric coefficients of different ferroelectrics reported in the literature will be presented. An unresolved issue in this field is that the measured flexoelectric coefficients in ferroelectric materials are normally much greater than the theoretically predicted values, and the mechanisms proposed to explain this issue are discussed. Finally, the efforts toward the applications of the flexoelectric effect are reviewed.
The runaway greenhouse radius inflation effect
Authors: Turbet Martin , Ehrenreich David , Lovis Christophe , Bolmont Emeline , Fauchez Thomas
Published: June 2019

Planets similar to Earth but slightly more irradiated are expected to enter into a runaway greenhouse state, where all surface water rapidly evaporates, forming an optically thick H2O-dominated atmosphere. For Earth, this extreme climate transition is thought to occur for an increase of only ~6% in solar luminosity, though the exact limit at which the transition would occur is still a highly debated topic. In general, the runaway greenhouse is believed to be a fundamental process in the evolution of Earth-sized, temperate planets. Using 1D radiative-convective climate calculations accounting for thick, hot water vapor-dominated atmospheres, we evaluate the transit atmospheric thickness of a post-runaway greenhouse atmosphere, and find that it could possibly reach over a thousand kilometers (i.e., a few tens of percent of the Earth’s radius). This abrupt radius inflation resulting from the runaway-greenhouse-induced transition could be detected statistically by ongoing and upcoming space missions. These include satellites such as TESS, CHEOPS, and PLATO combined with precise radial velocity mass measurements using ground-based spectrographs such as ESPRESSO, CARMENES, or SPIRou. This radius inflation could also be detected in multiplanetary systems such as TRAPPIST-1 once masses and radii are known with good enough precision. This result provides the community with an observational test of two points. The first point is the concept of runaway greenhouse, which defines the inner edge of the traditional habitable zone, and the exact limit of the runaway greenhouse transition. In particular, this could provide an empirical measurement of the irradiation at which Earth analogs transition from a temperate to a runaway greenhouse climate state. This astronomical measurement would make it possible to statistically estimate how close Earth is from the runaway greenhouse. Second, it could be used as a test for the presence (and statistical abundance) of water in temperate, Earth-sized exoplanets.
Elevated Complement C3 and C4 Levels are Associated with Postnatal Pregnancy-Related Venous Thrombosis
Authors: Dahm Anders E. A. , Jacobsen Eva Marie , Wik Hilde Skuterud , Jacobsen Anne Flem , Mollnes Tom Eirik , Kanse Sandip M. , Sandset Per Morten
Published: June 2019

High levels of complement C3 are associated with venous thrombosis (VT) in the general population. We investigated if high C3 and C4 levels were associated with pregnancy-related VT. We undertook the Norwegian VIP study, a case–control study of VT in pregnancy or within 3 months postpartum (cases, n = 313) and women without pregnancy-related VT (controls, n = 353). Determinants of C3 and C4 in the control women were investigated with linear regression and the odds ratio (OR) for pregnancy-related VT was calculated with logistic regression. We found that levels of C3 and C4 were associated with body mass index (BMI), C-reactive protein (CRP); with the coagulation factors (F) fibrinogen, FVIII, and FIX; and with the coagulation inhibitors antithrombin, protein C, protein S, and tissue factor pathway inhibitor. These associations were influenced by CRP levels. The crude OR for pregnancy-related VT was 1.8 (95% confidence interval [CI], 1.1–3.0) for C3 above the 90th percentile and 2.0 (95% CI, 1.2–3.2) for C4 above the 90th percentile. Stratification in antenatal and postnatal VT showed that C3 and C4 were only associated with postnatal VT with an OR for high C3 of 3.0 (95% CI, 1.8–5.0), and for high C4 of 2.6 (95% CI, 1.5–4.6). Adjustment for high FIX and BMI reduced the ORs. We conclude that the association between postnatal VT and C3 and C4 suggests that there is clinically relevant crosstalk between the complement and the coagulation system.
Identification of 58 Mutations (26 Novel) in 94 of 109 Symptomatic Spanish Probands with Protein C Deficiency
Authors: Martos Laura , Fernández-Pardo Álvaro , López-Fernández María F. , Ibáñez Francisco , Herrero Sonia , Tàssies Dolors , González-Porras José R. , Solmoirago María J. , Costa María J. , Reverter Juan C. , Marco Pascual , Roldán Vanessa , Lecumberri Ramón , Velasco Francisco , Oto Julia , Iruin Gemma , Alonso María N. , Vayá Amparo , Bonanad Santiago , Ferrando Fernando , Martí Edelmira , Cid Ana R. , Plana Emma , Oña Francisca , Cuesta Isabel , González-López Tomás J. , España Francisco , Medina Pilar , Navarro Silvia ,   on behalf of the Working Group of the Spanish Society of Thrombosis Haemostasis (SETH)
Published: June 2019

Presently, no data on the molecular basis of hereditary protein C (PC) deficiency in Spain is available. We analyzed the PC gene (PROC) in 109 patients with symptomatic PC deficiency and in 342 relatives by sequencing the 9 PROC exons and their flanking intron regions. In 93 probands, we found 58 different mutations (26 novel). Thirty-seven consisted of a nucleotide change, mainly missense mutations, 1 was a 6-nucleotide insertion causing the duplication of 2 amino acids, and 4 were deletions of 1, 3, 4, and 16 nucleotides. Nine mutations caused type II deficiencies, with the presence of normal antigen levels but reduced anticoagulant activity. Using a PC level of 70% as lowest normal limit, we found no mutations in 16 probands and 25 relatives with PC levels ≤ 70%. On the contrary, 4 probands and 12 relatives with PC levels > 70% carried the mutation identified in the proband. The spectrum of recurrent mutations in Spain is different from that found in the Netherlands, where the most frequent mutations were p.Gln174* and p.Arg272Cys, and is more similar to that found in France, where the most frequent were p.Arg220Gln and p.Pro210Leu. In our study, p.Val339Met (9 families), p.Tyr166Cys (7), p.Arg220Gln (6), and p.Glu58Lys (5) were the most prevalent. This study confirms the considerable heterogeneity of the genetic abnormality in PC deficiencies, and allowed genetic counseling to those individuals whose PC levels were close to the lower limit of the normal reference range.
Platelet–Neutrophil Crosstalk in Atherothrombosis
Authors: Pircher Joachim , Engelmann Bernd , Massberg Steffen , Schulz Christian
Published: June 2019

Atherothrombosis is a frequent cause of cardiovascular mortality. It is mostly triggered by plaque rupture and exposure of the thrombogenic subendothelial matrix, which initiates platelet aggregation and clot formation. Current antithrombotic strategies, however, target both thrombosis and physiological hemostasis and thereby increase bleeding risk. Thus, there is an unmet clinical need for optimized therapies. Neutrophil activation and consecutive interactions of neutrophils and platelets contribute mechanistically to thromboinflammation and arterial thrombosis, and thus present a potential therapeutic target. Platelet–neutrophil interactions are mediated through adhesion molecules such as P-selectin and P-selectin glycoprotein ligand 1 as well as glycoprotein Ib and macrophage-1 antigen, which mediate physical cell interactions and intracellular signaling. Release of soluble mediators as well as direct signaling between platelets and neutrophils lead to their reciprocal activation and neutrophil release of extracellular traps, scaffolds of condensed chromatin that play a prothrombotic role in atherothrombosis. In this article, we review the role of neutrophils and neutrophil-derived prothrombotic molecules in platelet activation and atherothrombosis, and highlight potential therapeutic targets.
Long-term expansion and differentiation of adult murine epidermal stem cells in 3D organoid cultures
Authors: Boonekamp Kim E. , Kretzschmar Kai , Wiener Dominique J. , Asra Priyanca , Derakhshan Sepideh , Puschhof Jens , López-Iglesias Carmen , Peters Peter J. , Basak Onur , Clevers Hans
Published: June 2019

Mammalian epidermal stem cells maintain homeostasis of the skin epidermis and contribute to its regeneration throughout adult life. While 2D mouse epidermal stem cell cultures have been established decades ago, a long-term, feeder cell- and serum-free culture system recapitulating murine epidermal architecture has not been available. Here we describe an epidermal organoid culture system that allows long-term, genetically stable expansion of adult epidermal stem cells. Our epidermal expansion media combines atypically high calcium concentrations, activation of cAMP, FGF, and R-spondin signaling with inhibition of bone morphogenetic protein (BMP) signaling. Organoids are established robustly from adult mouse skin and expand over at least 6 mo, while maintaining the basal-apical organization of the mouse interfollicular epidermis. The system represents a powerful tool to study epidermal homeostasis and disease in vitro.
Nonparametric inference of interaction laws in systems of agents from trajectory data
Authors: Lu Fei , Zhong Ming , Tang Sui , Maggioni Mauro
Published: June 2019

Inferring the laws of interaction in agent-based systems from observational data is a fundamental challenge in a wide variety of disciplines. We propose a nonparametric statistical learning approach for distance-based interactions, with no reference or assumption on their analytical form, given data consisting of sampled trajectories of interacting agents. We demonstrate the effectiveness of our estimators both by providing theoretical guarantees that avoid the curse of dimensionality and by testing them on a variety of prototypical systems used in various disciplines. These systems include homogeneous and heterogeneous agent systems, ranging from particle systems in fundamental physics to agent-based systems that model opinion dynamics under the social influence, prey–predator dynamics, flocking and swarming, and phototaxis in cell dynamics.
Predicting microbial growth in a mixed culture from growth curve data
Authors: Ram Yoav , Dellus-Gur Eynat , Bibi Maayan , Karkare Kedar , Obolski Uri , Feldman Marcus W. , Cooper Tim F. , Berman Judith , Hadany Lilach
Published: June 2019

Determining the fitness of specific microbial genotypes has extensive application in microbial genetics, evolution, and biotechnology. While estimates from growth curves are simple and allow high throughput, they are inaccurate and do not account for interactions between costs and benefits accruing over different parts of a growth cycle. For this reason, pairwise competition experiments are the current “gold standard” for accurate estimation of fitness. However, competition experiments require distinct markers, making them difficult to perform between isolates derived from a common ancestor or between isolates of nonmodel organisms. In addition, competition experiments require that competing strains be grown in the same environment, so they cannot be used to infer the fitness consequence of different environmental perturbations on the same genotype. Finally, competition experiments typically consider only the end-points of a period of competition so that they do not readily provide information on the growth differences that underlie competitive ability. Here, we describe a computational approach for predicting density-dependent microbial growth in a mixed culture utilizing data from monoculture and mixed-culture growth curves. We validate this approach using 2 different experiments with
Escherichia coli
and demonstrate its application for estimating relative fitness. Our approach provides an effective way to predict growth and infer relative fitness in mixed cultures.
Unexpected host dependency of Antarctic Nanohaloarchaeota
Authors: Hamm Joshua N. , Erdmann Susanne , Eloe-Fadrosh Emiley A. , Angeloni Allegra , Zhong Ling , Brownlee Christopher , Williams Timothy J. , Barton Kirston , Carswell Shaun , Smith Martin A. , Brazendale Sarah , Hancock Alyce M. , Allen Michelle A. , Raftery Mark J. , Cavicchioli Ricardo
Published: June 2019

In hypersaline environments, Nanohaloarchaeota (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, Nanohaloarchaeota [DPANN] superphylum) are thought to be free-living microorganisms. We report cultivation of 2 strains of Antarctic Nanohaloarchaeota and show that they require the haloarchaeon
Halorubrum lacusprofundi
for growth. By performing growth using enrichments and fluorescence-activated cell sorting, we demonstrated successful cultivation of
Candidatus
Nanohaloarchaeum antarcticus, purification of
Ca.
Nha. antarcticus away from other species, and growth and verification of
Ca.
Nha. antarcticus with
Hrr. lacusprofundi
; these findings are analogous to those required for fulfilling Koch’s postulates. We use fluorescent in situ hybridization and transmission electron microscopy to assess cell structures and interactions; metagenomics to characterize enrichment taxa, generate metagenome assembled genomes, and interrogate Antarctic communities; and proteomics to assess metabolic pathways and speculate about the roles of certain proteins. Metagenome analysis indicates the presence of a single species, which is endemic to Antarctic hypersaline systems that support the growth of haloarchaea. The presence of unusually large proteins predicted to function in attachment and invasion of hosts plus the absence of key biosynthetic pathways (e.g., lipids) in metagenome assembled genomes of globally distributed Nanohaloarchaeota indicate that all members of the lineage have evolved as symbionts. Our work expands the range of archaeal symbiotic lifestyles and provides a genetically tractable model system for advancing understanding of the factors controlling microbial symbiotic relationships.
Regulation of nuclear epigenome by mitochondrial DNA heteroplasmy
Authors: Kopinski Piotr K. , Janssen Kevin A. , Schaefer Patrick M. , Trefely Sophie , Perry Caroline E. , Potluri Prasanth , Tintos-Hernandez Jesus A. , Singh Larry N. , Karch Kelly R. , Campbell Sydney L. , Doan Mary T. , Jiang Helen , Nissim Itzhak , Nakamaru-Ogiso Eiko , Wellen Kathryn E. , Snyder Nathaniel W. , Garcia Benjamin A. , Wallace Douglas C.
Published: June 2019

Diseases associated with mitochondrial DNA (mtDNA) mutations are highly variable in phenotype, in large part because of differences in the percentage of normal and mutant mtDNAs (heteroplasmy) present within the cell. For example, increasing heteroplasmy levels of the mtDNA tRNA
Leu(UUR)
nucleotide (nt) 3243A > G mutation result successively in diabetes, neuromuscular degenerative disease, and perinatal lethality. These phenotypes are associated with differences in mitochondrial function and nuclear DNA (nDNA) gene expression, which are recapitulated in cybrid cell lines with different percentages of m.3243G mutant mtDNAs. Using metabolic tracing, histone mass spectrometry, and NADH fluorescence lifetime imaging microscopy in these cells, we now show that increasing levels of this single mtDNA mutation cause profound changes in the nuclear epigenome. At high heteroplasmy, mitochondrially derived acetyl-CoA levels decrease causing decreased histone H4 acetylation, with glutamine-derived acetyl-CoA compensating when glucose-derived acetyl-CoA is limiting. In contrast, α-ketoglutarate levels increase at midlevel heteroplasmy and are inversely correlated with histone H3 methylation. Inhibition of mitochondrial protein synthesis induces acetylation and methylation changes, and restoration of mitochondrial function reverses these effects. mtDNA heteroplasmy also affects mitochondrial NAD
+
/NADH ratio, which correlates with nuclear histone acetylation, whereas nuclear NAD
+
/NADH ratio correlates with changes in nDNA and mtDNA transcription. Thus, mutations in the mtDNA cause distinct metabolic and epigenomic changes at different heteroplasmy levels, potentially explaining transcriptional and phenotypic variability of mitochondrial disease.
The Planets in Aztec Culture
Authors: Milbrath Susan
Published: July 2019

The Spanish chronicles do not mention planets other than Venus, although they compare certain Aztec gods with classical gods such as Jupiter and Mars. Creation myths recorded by the Spanish chroniclers frequently name Venus gods, most notably Ehecatl-Quetzalcoatl and Tlahuizcalpantecuhtli. The focus on Venus seen in these texts is also mirrored in colonial period Aztec codices, which feature several Venus gods as rulers of calendar periods associated with the 260-day calendar. The famous Aztec Calendar Stone represents Venus symbols prominently in an image showing the predicted demise of the Sun in an eternal solar eclipse, to be accompanied by earthquakes. Venus is apparently seen as the cause of a total solar eclipse in the Codex Borgia, a pre-conquest codex from Tlaxcala, a community neighboring the Aztecs in central Mexico. Although no pre-conquest Aztec codices survive, the painted screenfold books attributed to neighboring communities in central Mexico provide evidence of the kinds of almanacs that were probably also found in Preconquest Aztec screenfold books. The Codex Borgia has two Venus almanacs associated with heliacal rise events and another focusing on dates that coordinate with events involving Venus and possibly other planets. A unique narrative in the Codex Borgia traces Venus over the course of a year, representing different aspects of the synodical cycle. The transformation of Venus in the narrative is evidenced by subtle changes in the Venus god, Quetzalcoatl, who represents the planet Venus throughout the synodical cycle. Another god, Tlahuizcalpantecuhtli (“lord of dawn”), appears in the narrative associated with Venus as the morning star and also is represented in a death aspect during superior conjunction. This is in keeping with Aztec legends that tell how the Sun killed Tlahuizcalpantecuhtli with his solar rays. The Borgia narrative also helps identify Xolotl as the planet Mercury and provides hints about other planets that may be linked with different aspects of Tezcatlipoca, an Aztec god who ruled the night sky.
ValTrendsDB: bringing Protein Data Bank validation information closer to the user
Authors: Horský Vladimír , Bendová Veronika , Toušek Dominik , Koča Jaroslav , Svobodová Radka
Published: June 2019

Structures in PDB tend to contain errors. This is a very serious issue for authors that rely on such potentially problematic data. The community of structural biologists develops validation methods as countermeasures, which are also included in the PDB deposition system. But how are these validation efforts influencing the structure quality of subsequently published data? Which quality aspects are improving, and which remain problematic? We developed ValTrendsDB, a database that provides the results of an extensive exploratory analysis of relationships between quality criteria, size and metadata of biomacromolecules. Key input data are sourced from PDB. The discovered trends are presented via precomputed information-rich plots. ValTrendsDB also supports the visualization of a set of user-defined structures on top of general quality trends. Therefore, ValTrendsDB enables users to see the quality of structures published by selected author, laboratory or journal, discover quality outliers, etc. ValTrendsDB is updated weekly.

Availability and implementation

Freely accessible at http://ncbr.muni.cz/ValTrendsDB. The web interface was implemented in JavaScript. The database was implemented in C++.

Supplementary information

Supplementary data are available at Bioinformatics online.
A river runs through it: tree frog genomics supports the Dead Sea Rift as a rare phylogeographical break
Authors: Dufresnes Christophe , Mazepa Glib , Jablonski Daniel , Sadek Riyad A , Litvinchuk Spartak N
Published: June 2019

Phylogeographical breaks can be viewed as regional hotspots of diversity where the genetic integrity of incipient species is put to the test. We focus on an understudied species transition from the Middle East, namely the Dead Sea Rift in the Levant region, which presumably divided the tree frogs Hyla savignyi and H. felixarabica. Combining multilocus genetic analyses (mitochondrial DNA and RAD-sequencing) with ecological niche modelling, we test whether the rift effectively acts as a biogeographical barrier preventing this pair from admixing and merging. The answer is yes: despite weak signs of introgression, all parapatric populations were assigned to either species without cyto-nuclear discordance. Yet, the projected distributions under present and glacial conditions largely overlapped in the area, meaning their current parapatric ranges do not represent an ecological transition. Instead, we hypothesize that H. savignyi and H. felixarabica are maintained apart by limited opportunities for dispersal across the barren Jordan Valley, combined with advanced reproductive isolation. Therefore, the Dead Sea Rift may represent a rare phylogeographical break, and we encourage international efforts to assess its contribution to the rich biodiversity of the Middle East.
How the Cluster-randomized Trial “Works”
Authors: Hurley James C
Published: June 2019

Cluster-randomized trials (CRTs) are able to address research questions that randomized controlled trials (RCTs) of individual patients cannot answer. Of great interest for infectious disease physicians and infection control practitioners are research questions relating to the impact of interventions on infectious disease dynamics at the whole-of-population level. However, there are important conceptual differences between CRTs and RCTs relating to design, analysis, and inference. These differences can be illustrated by the adage “peas in a pod.” Does the question of interest relate to the “peas” (the individual patients) or the “pods” (the clusters)? Several examples of recent CRTs of community and intensive care unit infection prevention interventions are used to illustrate these key concepts. Examples of differences between the results of RCTs and CRTs on the same topic are given.
Altered Intestinal Permeability and Fungal Translocation in Ugandan Children With Human Immunodeficiency Virus
Authors: Dirajlal-Fargo Sahera , El-Kamari Vanessa , Weiner Lukasz , Shan Lingpeng , Sattar Abdus , Kulkarni Manjusha , Funderburg Nicholas , Nazzinda Rashidah , Karungi Christine , Kityo Cissy , Musiime Victor , McComsey Grace A
Published: June 2019

Background

Children with perinatally acquired human immunodeficiency virus (HIV; PHIVs) face a lifelong cumulative exposure to HIV and antiretroviral therapy (ART). The relationship between gut integrity, microbial translocation, and inflammation in PHIV is poorly understood.

Methods

This is a cross-sectional study in 57 PHIVs, 59 HIV-exposed but uninfected children, and 56 HIV-unexposed and -uninfected children aged 2–10 years old in Uganda. PHIVs were on stable ART with HIV-1 RNA <400 copies/mL. We measured markers of systemic inflammation, monocyte activation, and gut integrity. Kruskal-Wallis tests were used to compare markers by group and the Spearman correlation was used to assess correlations between biomarkers.

Results

The mean age of all participants was 7 years and 55% were girls. Among PHIVs, the mean CD4 % was 34%, 93% had a viral load ≤20 copies/mL, and 79% were on a nonnucleoside reverse transcriptase inhibitor regimen. Soluble cluster of differentiation 14 (sCD14), beta-D-glucan (BDG), and zonulin were higher in the PHIV group (P ≤ .01). Intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide binding protein (LBP) did not differ between groups (P > .05). Among PHIVs who were breastfed, levels of sCD163 and interleukin 6 (IL6) were higher than levels in PHIV who were not breastfed (P < .05). Additionally, in PHIVs with a history of breastfeeding, sCD14, BDG, LBP, zonulin, and I-FABP correlated with several markers of systemic inflammation, including high-sensitivity C-reactive protein, IL6, d-dimer, and systemic tumor necrosis factor receptors I and II (P ≤ .05).

Conclusions

Despite viral suppression, PHIVs have evidence of altered gut permeability and fungal translocation. Intestinal damage and the resultant bacterial and fungal translocations in PHIVs may play a role in the persistent inflammation that leads to many end-organ diseases in adults.

Despite viral suppression, children with perinatally acquired human immunodeficiency virus (HIV) in Uganda have evidence of alterations in intestinal permeability and fungal translocation, compared to HIV-exposed but uninfected and HIV-unexposed children, which may play a role in HIV-associated chronic inflammation.
Emergence and Transmission of Drug-/Multidrug-resistant Mycobacterium leprae in a Former Leprosy Colony in the Brazilian Amazon
Authors: Rosa Patrícia S , D’Espindula Helena R S , Melo Ana C L , Fontes Amanda N B , Finardi Amanda J , Belone Andréa F F , Sartori Beatriz G C , Pires Carla A A , Soares Cleverson T , Marques Flávio B , Branco Francisco J D , Baptista Ida M F D , Trino Lázara M , Fachin Luciana R V , Xavier Marília B , Floriano Marcos C , Ura Somei , Diório Suzana M , Delanina Wladimir F B , Moraes Milton O , Virmond Marcos C L , Suffys Philip N , Mira Marcelo T
Published: June 2019

Background

Leprosy has been treated with multidrug therapy, which has been distributed for free across the globe and regarded as highly efficient. However, the impossibility of growing Mycobacterium leprae in axenic media has historically impaired assessments of M. leprae resistance, a parameter only recently detectable through molecular methods.

Methods

A systematic, population-based search for M. leprae resistance in suspected leprosy relapse cases and contacts was performed in Prata Village, an isolated, hyperendemic, former leprosy colony located in the Brazilian Amazon. Results led to an extended active search involving the entire Prata population. Confirmed leprosy cases were investigated for bacterial resistance using a combination of in vivo testing and direct sequencing of resistance genes folP1, rpoB, and gyrA. A molecular epidemiology analysis was performed using data from 17 variable number tandem repeats (VNTR).

Results

Mycobacterium leprae was obtained from biopsies of 37 leprosy cases (18 relapses and 19 new cases): 16 (43.24%) displayed drug-resistance variants. Multidrug resistance to rifampicin and dapsone was observed in 8 relapses and 4 new cases. Single resistance to rifampicin was detected in 1 new case. Resistance to dapsone was present in 2 relapses and 1 new case. Combined molecular resistance and VNTR data revealed evidence of intra-familial primary transmission of resistant M. leprae.

Conclusions

A comprehensive, population-based systematic approach to investigate M. leprae resistance in a unique population revealed an alarming scenario of the emergence and transmission of resistant strains. These findings may be used for the development of new strategies for surveillance of drug resistance in other populations.
A Tentative Tamdy Orthonairovirus Related to Febrile Illness in Northwestern China
Authors: Liu Xiafei , Zhang Xu , Wang Zedong , Dong Zhihui , Xie Songsong , Jiang Mengmeng , Song Ruixia , Ma Jun , Chen Shouyi , Chen Kuncai , Zhang Haoji , Si Xingkui , Li Chang , Jin Ningyi , Wang Yuanzhi , Liu Quan
Published: June 2019

Background

Many novel tick-borne viruses have been discovered by deep-sequencing technology in recent years; however, their medical significance is unknown.

Methods

We obtained clinical data of a patient from Xinjiang, China. Possible pathogens were detected by metagenomic analysis; the causative pathogen Tacheng tick virus 1 (TcTV-1) was found and further confirmed by reverse transcriptase–polymerase chain reaction, viral culture, and sequence analyses. Epidemiological investigation was conducted in the local human population, domestic animals, and ticks by serological/molecular methods.

Results

A 62-year-old woman with a history of tick bite in Qinghe, Xinjiang, presented with fever and rashes. These symptoms were relieved after clinical treatment. TcTV-1 (strain QH1) was isolated from the patient’s cerebrospinal fluid, throat swabs, and urine on day 47 after illness onset. Although the blood and urine showed viral RNA positive on day 73 after illness onset, the virus was only isolated from urine. Serological detection revealed a virus neutralizing antibody titer of 1:40 and 1:80 on day 47 and 73 after illness onset, respectively. No coinfection with other pathogens was detected, suggesting TcTV-1 may be the potential causative pathogen. We detected anti–TcTV-1 antibodies (immunoglobulin G: 10.1%; immunoglobulin M: 4.8%) in the local human population. The viral RNA was also found in cattle (4.9%), sheep (9.2%), and ticks, including Dermacentor marginatus (14.3%), Dermacentor silvarum (11.8%), Dermacentor nuttalli (6.7%), and Hyalomma asiaticum (4.8%).

Conclusions

TcTV-1 may be associated with a febrile illness syndrome, and epidemiological data of the virus in humans and animals necessitate disease surveillance of TcTV-1 infection in China.