bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing energy release rate and power density by Sr-doping in (Pb,La)(Zr,Sn,Ti)O3 antiferroelectric ceramics
Authors: Xu Ran , Zhu Qingshan , Xu Zhuo , Feng Yujun
Published: September 2021

In practical applications, high power is the ultimate goal of dielectric capacitors, while most research has focused on enhancing energy density. Far less attention is paid to enhancing discharge speed and achieving high power. In the present work, we studied the fast discharge behavior of (Pb0.98−xLa0.02Srx)[(Zr0.50Sn0.50)0.88Ti0.12]0.995O3 antiferroelectric ceramics and investigated the effects of phase transition on energy release rates. By doping Sr content, the antiferroelectricity was enhanced and the sharpness of the hysteresis loop was reduced, suppressing the constant and slow discharge current plateau caused by ferroelectric–antiferroelectric (FE–AFE) switching. As a result, the average power density was enhanced from 0.3 to 4.1 MW/cm3. More importantly, higher power density could be achieved in composition with lower discharge energy density but faster discharge speed. This study proves the significance of discharge speed and provides a new approach to develop dielectric materials for high-power applications.
The life span and dynamics of immiscible viscous fingering in rectilinear displacements
Authors: Kampitsis A. E. , Kostorz W. J. , Muggeridge A. H. , Jackson M. D.
Published: September 2021

We investigate the dynamics, interactions, and decay of immiscible viscous fingers in two and three dimensions over time in a high-aspect ratio (up to 100:1) system. The behavior is related to the viscosity ratio and a macroscopic capillary number. The same four fingering regimes are observed as in miscible displacements (spreading of the interface between wetting and non-wetting fluid but no fingers, the growth of many fingers that can be described by perturbation analysis, non-linear interactions between fingers and decay to a single finger) for low viscosity ratio and high capillary to viscous ratios. At higher viscosity ratios and lower capillary to viscous ratios, periodic tip-splitting and decay results in a fluctuation between one and two fingers at late time. This has not been seen in miscible displacements. We provide a stability plot that can be used to identify when this will occur. Similar behaviors were seen in both two and three dimensions, suggesting that learnings from two-dimensional (2D) linear displacements can be applied to similar three-dimensional (3D) flows. In particular, the square root of the number of fingers seen in the 3D simulations and their decay with time was almost identical to 2D.
Enhanced thermoelectric performance in ductile Ag2S-based materials via doping iodine
Authors: Liu Jin , Xing Tong , Gao Zhiqiang , Liang Jiasheng , Peng Liming , Xiao Jie , Qiu Pengfei , Shi Xun , Chen Lidong
Published: September 2021

Recently, a deformable and ductile inorganic semiconductor Ag2S has attracted intense attention due to its potential application in self-powered wearable and hetero-shaped electronics. However, the thermoelectric figure of merit (zT) of Ag2S is greatly limited by its extremely low carrier concentration. In this study, via doping I into Ag2S-based materials, we tune the carrier concentration into the optimal range as well as suppressing the lattice thermal conductivity. A maximum zT value of 0.26 is achieved for Ag2S0.7Se0.295I0.005 at 300 K, about three times higher than the matrix compound. More importantly, doping I has little effect on the ductility and deformability of Ag2S-based materials. Our study shows that I-doped Ag2S-based materials are good candidates for developing flexible thermoelectric technologies.
Uniquely anisotropic mechanical and thermal responses of hybrid organic–inorganic perovskites under uniaxial strain
Authors: Rahman Muhammad Akif , Giri Ashutosh
Published: September 2021

The complete understanding of the mechanical and thermal responses to strain in hybrid organic–inorganic perovskites holds great potential for their proper functionalities in a range of applications, such as in photovoltaics, thermoelectrics, and flexible electronics. In this work, we conduct systematic atomistic simulations on methyl ammonium lead iodide, which is the prototypical hybrid inorganic–organic perovskite, to investigate the changes in their mechanical and thermal transport responses under uniaxial strain. We find that the mechanical response and the deformation mechanisms are highly dependent on the direction of the applied uniaxial strain with a characteristic ductile- or brittle-like failure accompanying uniaxial tension. Moreover, while most materials shrink in the two lateral directions when stretched, we find that the ductile behavior in hybrid perovskites can lead to a very unique mechanical response where negligible strain occurs along one lateral direction while the length contraction occurs in the other direction due to uniaxial tension. This anisotropy in the mechanical response is also shown to manifest in an anisotropic thermal response of the hybrid perovskite where the anisotropy in thermal conductivity increases by up to 30% compared to the unstrained case before plastic deformation occurs at higher strain levels. Along with the anisotropic responses of these physical properties, we find that uniaxial tension leads to ultralow thermal conductivities that are well below the value predicted with a minimum thermal conductivity model, which highlights the potential of strain engineering to tune the physical properties of hybrid organic–inorganic perovskites.
Scene statistics and noise determine the relative arrangement of receptive field mosaics
Authors: Jun Na Young , Field Greg D. , Pearson John
Published: September 2021

Significance

Across a wide variety of species, cells in the retina specialized for signaling either increases (ON) or decreases (OFF) in light represent one of the most basic building blocks of visual computation. These cells coordinate to form mosaics, with each cell responsible for a small, minimally overlapping portion of visual space, but the ways in which these mosaics could be spatially coordinated with each other are relatively unknown. Here, we show how efficient coding theory, which hypothesizes that the nervous system minimizes the amount of redundant information it encodes, can predict the relative spatial arrangement of ON and OFF mosaics. The most information-efficient arrangements are determined both by levels of noise in the system and the statistics of natural images.
Self-catalytic growth of one-dimensional materials within dislocations in gold
Authors: Portal Lotan , Polishchuk Iryna , Koifman Khristosov Maria , Katsman Alexander , Pokroy Boaz
Published: September 2021

Significance

Dislocation edges on metal surfaces provide loosely bonded atoms, which make the surface more active for chemical corrosion and enhance the chemical reactivity. In this work, we introduce and demonstrate an autocatalytic method in which the dislocation lines in alloys can serve as a template for the growth of a different inorganic material as nanowires. We explain the formation mechanism of an incorporated system of single crystal gold(I)-cyanide nanowires on nanoporous gold during selective dealloying, using the dislocation ends in the prestrained Au-Ag alloy as catalytic centers for crystallization. This method may provide a possible route for controlling the growth direction, shape, and morphology of a crystal according to the original alloy’s slip system.
Can we get human nature right?
Authors: Berent Iris
Published: September 2021

Few questions in science are as controversial as human nature. At stake is whether our basic concepts and emotions are all learned from experience, or whether some are innate. Here, I demonstrate that reasoning about innateness is biased by the basic workings of the human mind. Psychological science suggests that newborns possess core concepts of “object” and “number.” Laypeople, however, believe that newborns are devoid of such notions but that they can recognize emotions. Moreover, people presume that concepts are learned, whereas emotions (along with sensations and actions) are innate. I trace these beliefs to two tacit psychological principles: intuitive dualism and essentialism. Essentialism guides tacit reasoning about biological inheritance and suggests that innate traits reside in the body; per intuitive dualism, however, the mind seems ethereal, distinct from the body. It thus follows that, in our intuitive psychology, concepts (which people falsely consider as disembodied) must be learned, whereas emotions, sensations, and emotions (which are considered embodied) are likely innate; these predictions are in line with the experimental results. These conclusions do not speak to the question of whether concepts and emotions are innate, but they suggest caution in its scientific evaluation.
The conserved fertility factor SPACA4/Bouncer has divergent modes of action in vertebrate fertilization
Authors: Fujihara Yoshitaka , Herberg Sarah , Blaha Andreas , Panser Karin , Kobayashi Kiyonori , Larasati Tamara , Novatchkova Maria , Theussl Hans-Christian , Olszanska Olga , Ikawa Masahito , Pauli Andrea
Published: September 2021

Significance

We show that Bouncer’s homolog in mammals, SPACA4, is required for efficient fertilization in mice. In contrast to fish, in which Bouncer is required for female fertility, SPACA4 is expressed exclusively in the sperm and is required for male fertility. SPACA4 and Bouncer present an intriguing example of homologous proteins that both play key roles in reproduction yet diverged in terms of gene expression pattern and mode of action. Overall, our work identifies SPACA4 as an important sperm protein necessary for zona pellucida penetration during mammalian fertilization. Since human SPACA4 is also expressed exclusively in sperm, we anticipate that our findings in mice will have relevance to human biology.
What we talk about when we talk about colors
Authors: Twomey Colin R. , Roberts Gareth , Brainard David H. , Plotkin Joshua B.
Published: September 2021

Significance

Do we talk about some colors more often than others? And do the colors we communicate about most frequently vary across cultures? A classic finding shows that languages around the world partition colors into words in remarkably similar, although not identical, ways. The biology of human color perception helps explain similar color vocabularies across languages, but less is known about how often speakers need to reference different colors. The inference method we develop reveals extensive variation in communicative needs across colors, and a diversity in needs across 130 languages, which helps explain variation in their color vocabularies. Our results open the door to studying cross-cultural variation in demands on different colors, and factors that drive color demands in linguistic communities.
Iron and chromium co-doped cobalt phosphide porous nanosheets as robust bifunctional electrocatalyst for efficient water splitting
Authors: Sun Shichao , Wang Zhihong , Meng Suci , Yu Rui , Jiang Deli , Chen Min
Published: September 2021

It is still a huge challenge to develop highly efficient and low-cost non-precious metal-based electrocatalysts for overall water splitting in alkaline electrolytes. Herein, Cr and Fe co-doped CoP porous mesh nanosheets (Mesh-CrFe-CoP NSs) were synthesized through hydrolysis reaction, ion exchange etching and subsequent low-temperature phosphating process. The Mesh-CrFe-CoP NSs provides overpotentials at a current density of 10 mA cm−2 under alkaline electrolyte of 103.7 mV and 256.4 mV for HER and OER, respectively. Furthermore, when using Mesh-CrFe-CoP NSs as anode and cathode, the water splitting system could afford a current density of 10 mA cm–2 at 1.55 V, which is better than an electrolytic cell composed of 20% Pt/C and RuO2. The excellent electrocatalytic performance of Mesh-CrFe-CoP NSs is attributed to the co-doping and porous nanostructure. Specifically, the Cr and Fe co-doped porous CoP nanosheets electrocatalyst not only provided abundant exposure active sites, accelerated the entry of liquid and the diffusion of gas, but also regulated the electronic environment of active sites, and thus enhanced the electrochemical performance. This work proposes a strategy for the rational design of highly efficient and stable non-precious metal co-doped phosphide electrocatalysts in the of electrochemical water splitting.
Generation of single attosecond relativistic electron bunch from intense laser interaction with a nanosphere
Authors: Horný Vojtěch , Veisz László
Published: September 2021

Ultrahigh-intensity laser-plasma physics provides unique light and particle beams as well as novel physical phenomena. A recently available regime is based on the interaction between a relativistic intensity few-cycle laser pulse and a sub-wavelength-sized mass-limited plasma target. Here, we investigate the generation of electron bunches under these extreme conditions by means of particle-in-cell simulations. In a first step, up to all electrons are expelled from the nanodroplet and gain relativistic energy from time-dependent local field enhancement at the surface. After this ejection, the electrons are further accelerated as they copropagate with the laser pulse. As a result, a few, or under specific conditions isolated, pC-class relativistic attosecond electron bunches are generated with laser pulse parameters feasible at state-of-the-art laser facilities. This is particularly interesting for some applications, such as generation of attosecond x-ray pulses via Thomson backscattering.
Observational constraint on dark energy from quantum uncertainty *
Authors: Huang Long , Yang Xiaofeng , Liu Xiang
Published: September 2021

We explore the theoretical possibility that dark energy density is derived from massless scalar bosons in vacuum and present a physical model for dark energy. By assuming massless scalar bosons fall into the horizon boundary of the cosmos with the expansion of the universe, we can deduce the uncertainty in the relative position of scalar bosons based on the quantum fluctuation of space-time and the assumption that scalar bosons satisfy P-symmetry under the parity transformation

, which can be used to estimate scalar bosons and dark energy density. Furthermore, we attempt to explain the origin of negative pressure from the increasing entropy density of the Boltzmann system and derive the equation for the state parameter, which is consistent with the specific equations of state for dark energy. Finally, we employ the SNIa Pantheon sample and Planck 2018 CMB angular power spectra to constrain the models and provide statistical results for the cosmology parameters.
Nonlinear dynamics and transport driven by energetic particle instabilities using a gyro-Landau closure model
*
Authors: Spong D.A. , Van Zeeland M.A. , Heidbrink W.W. , Du X. , Varela J. , Garcia L. , Ghai Y.
Published: September 2021

Energetic particle (EP) destabilized Alfvén eigenmode (AE) instabilities are simulated for a DIII-D experimental case with a pulsed neutral beam using a gyro-Landau moments model which introduces EP phase-mixing effects through closure relations. This provides a computationally efficient reduced model which is applied here in the nonlinear regime over timescales that would be difficult to address with more complete models. The long timescale nonlinear evolution and related collective transport losses are examined including the effects of zonal flow/current generation, nonlinear energy cascades, and EP profile flattening. The model predicts frequencies and mode structures that are consistent with experimental observations. These calculations address issues that have not been considered in previous modelling: the EP critical gradient profile evolution in the presence of zonal flows/currents, and the dynamical nature of the saturated state. A strong level of intermittency is present in the predicted instability-driven transport; this is connected to the zonal flow growth and decay cycles and nonlinear energy transfers. Simulation of intermittent AE-enhanced EP transport will be an important issue for the protection of plasma facing components in the next generation of fusion devices.
Numerical evaluation of an Oil free Screw Compressor’s Suction Port design using Ansys CFX and SCORG
Authors: Tankhiwale S , Dagwar A , Rane S , Kovacevic A , Birari A , Abdan S , Asati N
Published: September 2021

Quasi one-dimensional chamber models and experimental methods are commonly adopted by researchers to predict and validate the performance of the oil free screw compressors. However, to understand the scope for improvement in performance as impacted by compressor ports, one needs to know the details of physical processes happening in compression chamber. This can be done by understanding flow field such as internal temperature and pressure with the help of CFD model.

With this CFD setup, comparison of specific power consumption of oil free screw compressor between the axial and radial suction flange is presented in this paper. A hexahedral numerical mesh is used to represent flow field which is generated by SCORGTM. Flow solver ANSYS CFX has been used for study with these single domain deforming rotor grids.

This paper presents the methods used for setting up the CFD model and analysis of specific power consumption for two different suction port geometries, an axial and the radial suction flange. At the design operating condition, although axial suction flange seems to be more favourable in terms of lower suction pressure drops at high operating speed, the radial suction flange when simulated using CFD model predicts almost the similar performance. However, radial suction flange gives an added advantage for ready adaptability with the suction elements like the suction filter. The results of the simulation show that the radial suction flange can be adopted for better compatibility with the oil free package and the CFD model used for the analysis can be used for optimization of the air-end at various operating conditions.
Estimation of radial shaft seal, oil drag and windage loss in twin screw oil injected compressor
Authors: Abdan S , Stosic N , Kovacevic A , Smith I , Asati N
Published: September 2021

The objective of this paper is to study the mechanical power loss arising from radial shaft seal, oil drag, and windage within the twin-screw oil-injected screw compressor. The previous papers in the series presented the evaluation of power loss due to the gears and bearings where it was found that the calculated total power loss was underestimated when compared to the experimental results for different sizes of compressors and different operating conditions. This indicates that few additional contributing elements were missing and needed due consideration to enhance the prediction. Literature review of the basic fluid dynamics and transmission gears confirms that oil drag loss and windage loss can also contribute to the power loss considerably.

This paper presents a review of a few methods for the prediction of the radial shaft seal, oil drag, and windage loss. Predictions with the use of these methods and their comparison with the experimental results are analysed in this paper. Experimental results of three different sizes of the compressors tested in laboratory conditions were taken as reference for the comparison at different operating speeds and pressure ratios. The analysis helps to understand the contribution of each element of the power loss which can help a designer to optimally design a screw compressor.
Experimental Investigation on a Sliding-Vane Expander for Steam Applications
Authors: Costanzo I , Murgia S , Valenti G , Fasani F
Published: September 2021

There are many industrial plants that use steam as an energy vector at different pressure levels, in which pressure reduction is commonly performed by a throttling valve, resulting a totally irreversible process. It is possible to recover this energy through an expander that generates mechanical or electric energy. This work is focused on the analysis of a highly innovative steam expander based on sliding-vane technology. The design principles of the sliding-vane expander and two experimental campaigns are presented. The first experimental campaign allows to assess the reliability of the system with steam as working fluid, the second campaign leads to assess the stability during long-run and the performance of the system. A maximum expander mechanical power of 28 kW is measured. The pressure-Volume diagram of the expansion process is also measured and presented.
Baseline testing of a variable-speed water-cooling Chiller according AHRI standard 550/590
Authors: Hoess A J , Salts N P , Ziviani D , Braun J E , Groll E A
Published: September 2021

A new experimental test facility was designed to test vapor compression chillers of up to 145.9 refrigeration tons (approximately 513 kW). To implement such a large-capacity test facility in a university laboratory research environment, the system design is based on regenerative shell and tube heat exchangers. The capacity load on the chiller can be controlled via a bypass valve that allows a flow change over the internal heat exchangers. In addition to the internal sensors of the chiller, a variety of sensors in the system ensures a detailed recording of data as well as an automation of the test procedure.

The test facility is constructed and commissioned to execute the performance according the AHRI Standard 550/590. The chiller has been tested in full load and part load rating conditions to achieve a characteristic performance line of the machine. Recorded data is averaged and evaluated according to the requirements of the AHRI standard. The results of the baseline testing and the data processing are presented in this paper. A detailed analysis of the outcomes allows a comparison with the manufacturer rated efficiency values.

Finally, the potential instabilities of the test systems that caused problems during the test runs and their reasons are discussed, as well as possibilities to overcome them. The given ability of the test facility for a rapid change between different load conditions allows the arrangement of test cycles to investigate the performance degradation of the twin-screw chiller over time.
Thermodynamic analysis of volume flow rate ratio on the performance of a NH3/CO2 cascade refrigeration system
Authors: Yang Q C , Liu L , Liu G B , Zhao Y Y , Li L S
Published: September 2021

NH3/CO2 cascade refrigeration system is the most potential and promising selection in low temperature applications. To meet the cooling demands of CRS at various working conditions, the capacity regulation of the screw refrigeration compressor is needed. This paper specifically studied the impacts volume flow rate ratio of high temperature cycle (HTC) and low temperature cycle (LTC) on the system performance. The simulation model of CRS including energy and exergy analysis was established. Based on the obtained results with the models, it can be found that there exists an optimum volume flow ratio that makes the maximum COP and exergy efficiency and the optimum volume flow ratio value is different under various working conditions. When the evaporation temperature is -55°C the optimum volume rate ratio is about 2.4 and corresponding maximum COP and exergy efficiency of CRS is 1.031 and 0.346, respectively. The optimum condensing temperature of LTC is -9.75°C. When the volume flow ratio is increasing, which means the motor frequency or rotational speed of HTC compressor increases while the rotational speed of LTC compressor is fixed, the optimum intermediate temperature decreases and the discharge temperature of HTC compressor increases proportionally. The cooling capacity could be enhanced by increasing the volume flow ratio. The obtained results are helpful for the screw refrigeration compressor regulation in CRS under various working conditions and cooling demands.
Conjugate Heat Transfer Simulation and Cooling Optimization of the Flow inside a Screw Compressor
Authors: Willie J F
Published: September 2021

Computational Fluid Dynamics (CFD) as a predictive tool is playing an increasing role in the design and optimization process at Compressors and Vacuum Pumps Systems (CVS) Engineering GmbH. Design optimization using Design of Experiment (DoE) and continuous improvement of our products has led to an increase in the use of CFD and other predictive tools. This paper investigates the use of CFD combined with Conjugate Heat Transfer (CHT) to optimize the flow and the cooling inside a rotary screw compressor.
Preferences of newly qualified healthcare professionals for working with people with dementia: a qualitative study
Authors: Hebditch Molly , Banerjee Sube , Wright Juliet , Daley Stephanie
Published: September 2021

Background

there is little research on preferences in students and newly qualified healthcare professionals for working with people with dementia. Understanding the development of these preferences can help inform strategies to increase workforce capacity in response to current suboptimal dementia care and the increasing numbers of people with dementia.

Objective

to explore the factors that influence career preferences in relation to working with people with dementia. Specifically, to understand how these factors relate to early career doctors’ and nurses’ preferences and how they influence decisions and perspectives on their careers.

Methods

qualitative in-depth interviews were conducted with 27 newly qualified doctors and nurses within 2 years of graduation. This included a subset of participants that had taken part in a dementia educational intervention during their undergraduate training. Transcripts were analysed using grounded theory methods.

Results

the results present six main categories representing complex interlinked factors influencing preferences for working with people with dementia as well as exploring the definition of a career working with people with dementia. The factors include the importance of making a difference; seeing dementia care as a different type of care; its perceived alignment with personal characteristics; perceptions of people with dementia; care environments and career characteristics.

Discussion

this is the first study to explore the factors influencing preferences for working with people with dementia in newly qualified healthcare professionals. It provides useful data to inform workforce planning, and curriculum and practice development to stimulate interest and drive improved quality of care.
Measuring Structural Racism: A Guide for Epidemiologists and Other Health Researchers
Authors: Adkins-Jackson Paris B , Chantarat Tongtan , Bailey Zinzi D , Ponce Ninez A
Published: September 2021

There have been over 100 years of literature discussing the deleterious influence of racism on health. Much of the literature describes racism as a driver of social determinants of health, such as housing, employment, income, and education. More recently, increased attention has been given to measuring the structural nature of a system that advantages one racialized group over others rather than solely relying on individual acknowledgement of racism. Despite these advances, there is still a need for methodological and analytical approaches to complement the aforementioned. This commentary calls on epidemiologists and other health researchers at large to engage the discourse on measuring structural racism. First, we address the conflation between race and racism in epidemiologic research. Next, we offer methodological recommendations (linking of interdisciplinary variables and data sets and leveraging mixed-method and life-course approaches) and analytical recommendations (integration of mixed data, use of multidimensional models) that epidemiologists and other health researchers may consider in health equity research. The goal of this commentary is to inspire the use of up-to-date and theoretically driven approaches to increase discourse among public health researchers on capturing racism as well as to improve evidence of its role as the fundamental cause of racial health inequities.
Regulatory variants at 2q33.1 confer schizophrenia risk by modulating distal gene TYW5 expression
Authors: Li Shiwu , Li Jiao , Liu Jiewei , Wang Junyang , Li Xiaoyan , Huo Yongxia , Li Yifan , Liu Yixing , Li Ming , Xiao Xiao , Luo Xiong-Jian
Published: September 2021

Genome-wide association studies have shown that genetic variants at 2q33.1 are strongly associated with schizophrenia. However, potential causal variants in this locus and their roles in schizophrenia remain unknown. Here, we identified two functional variants (rs796364 and rs281759) that disrupt CTCF, RAD21 and FOXP2 binding at 2q33.1. We systematically investigated the regulatory mechanisms of these two variants with serial experiments, including reporter gene assays and electrophoretic mobility shift assay.

Intriguingly, these two single nucleotide polymorphisms physically interacted with TYW5 and showed the most significant associations with TYW5 expression in human brain. Consistently, CRISPR-Cas9-mediated genome editing confirmed the regulatory effect of the two single nucleotide polymorphisms on TYW5 expression. Additionally, expression analysis indicated that TYW5 was significantly upregulated in brains of schizophrenia cases compared with controls, suggesting that rs796364 and rs281759 might confer schizophrenia risk by modulating TYW5 expression.

We over-expressed TYW5 in mouse neural stem cells and rat primary neurons to mimic its upregulation in schizophrenia and found significant alterations in the proliferation and differentiation of neural stem cells, as well as dendritic spine density following TYW5 overexpression, indicating its important roles in neurodevelopment and spine morphogenesis.

Furthermore, we independently confirmed the association between rs796364 and schizophrenia in a Chinese cohort of 8202 subjects. Finally, transcriptome analysis revealed that TYW5 affected schizophrenia-associated pathways. These lines of evidence consistently revealed that rs796364 and rs281759 might contribute to schizophrenia risk by regulating the expression of TYW5, a gene whose expression dysregulation affects two important schizophrenia pathophysiological processes (i.e. neurodevelopment and dendritic spine formation).
Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer
Authors: Fujisawa Ryosuke , Iwaya Takeshi , Endo Fumitaka , Idogawa Masashi , Sasaki Noriyuki , Hiraki Hayato , Tange Shoichiro , Hirano Tomomi , Koizumi Yuka , Abe Masakazu , Takahashi Tomoko , Yaegashi Mizunori , Akiyama Yuji , Masuda Mari , Sasaki Akira , Takahashi Fumiaki , Sasaki Yasushi , Tokino Takashi , Nishizuka Satoshi S
Published: September 2021

We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses was evaluated by the ratio of the variant allele frequency of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50 or ≤50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy. Mutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1–3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 20 patients with post-/pre-volume ≥50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 versus 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03). Early ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients.
Layer 6A Pyramidal Cell Subtypes Form Synaptic Microcircuits with Distinct Functional and Structural Properties
Authors: Yang Danqing , Qi Guanxiao , Ding Chao , Feldmeyer Dirk
Published: September 2021

Neocortical layer 6 plays a crucial role in sensorimotor co-ordination and integration through functionally segregated circuits linking intracortical and subcortical areas. We performed whole-cell recordings combined with morphological reconstructions to identify morpho-electric types of layer 6A pyramidal cells (PCs) in rat barrel cortex. Cortico-thalamic (CT), cortico-cortical (CC), and cortico-claustral (CCla) PCs were classified based on their distinct morphologies and have been shown to exhibit different electrophysiological properties. We demonstrate that these three types of layer 6A PCs innervate neighboring excitatory neurons with distinct synaptic properties: CT PCs establish weak facilitating synapses onto other L6A PCs; CC PCs form synapses of moderate efficacy, while synapses made by putative CCla PCs display the highest release probability and a marked short-term depression. For excitatory-inhibitory synaptic connections in layer 6, both the presynaptic PC type and the postsynaptic interneuron type govern the dynamic properties of the respective synaptic connections. We have identified a functional division of local layer 6A excitatory microcircuits which may be responsible for the differential temporal engagement of layer 6 feed-forward and feedback networks. Our results provide a basis for further investigations on the long-range CC, CT, and CCla pathways.
Complexity of Genomic Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolates in Colombia Urges the Reinforcement of Whole Genome Sequencing-Based Surveillance Programs
Authors: Saavedra Sandra Yamile , Bernal Johan Fabian , Montilla-Escudero Efraín , Arévalo Stefany Alejandra , Prada Diego Andrés , Valencia María Fernanda , Moreno Jaime , Hidalgo Andrea Melissa , García-Vega Ángela Sofía , Abrudan Monica , Argimón Silvia , Kekre Mihir , Underwood Anthony , Aanensen David M , Duarte Carolina , Donado-Godoy Pilar ,   NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance, Abudahab Khalil , Harste Harry , Muddyman Dawn , Taylor Ben , Wheeler Nicole , David Sophia , Beltran Gabriel , Delgadillo Felipe , Osma Erik C D , Ravikumar K L , Nagaraj Geetha , Shamanna Varun , Govindan Vandana , Prabhu Akshata , Sravani D , Shincy M R , Rose Steffimole , Ravishankar K N , Okeke Iruka N , Oaikhena Anderson O , Afolayan Ayorinde O , Ajiboye Jolaade J , Ewomazino Odih Erkison , Carlos Celia , Lagrada Marietta L , Macaranas Polle Krystle V , Olorosa Agnettah M , Gayeta June M , Herrera Elmer M , Molloy Ali , Stelling John , Vegvari Carolin
Published: September 2021

Background

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging public health problem. This study explores the specifics of CRKP epidemiology in Colombia based on whole genome sequencing (WGS) of the National Reference Laboratory at Instituto Nacional de Salud (INS)’s 2013–2017 sample collection.

Methods

A total of 425 CRKP isolates from 21 departments were analyzed by HiSeq-X10®Illumina high-throughput sequencing. Bioinformatic analysis was performed, primarily using the pipelines developed collaboratively by the National Institute for Health Research Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance (AMR), and AGROSAVIA.

Results

Of the 425 CRKP isolates, 91.5% were carbapenemase-producing strains. The data support a recent expansion and the endemicity of CRKP in Colombia with the circulation of 7 high-risk clones, the most frequent being CG258 (48.39% of isolates). We identified genes encoding carbapenemases blaKPC-3, blaKPC-2, blaNDM-1, blaNDM-9, blaVIM-2, blaVIM-4, and blaVIM-24, and various mobile genetic elements (MGE). The virulence of CRKP isolates was low, but colibactin (clb3) was present in 25.2% of isolates, and a hypervirulent CRKP clone (CG380) was reported for the first time in Colombia. ST258, ST512, and ST4851 were characterized by low levels of diversity in the core genome (ANI > 99.9%).

Conclusions

The study outlines complex CRKP epidemiology in Colombia. CG258 expanded clonally and carries specific carbapenemases in specific MGEs, while the other high-risk clones (CG147, CG307, and CG152) present a more diverse complement of carbapenemases. The specifics of the Colombian situation stress the importance of WGS-based surveillance to monitor evolutionary trends of sequence types (STs), MGE, and resistance and virulence genes.
MMP-2 knockdown blunts age-dependent carotid stiffness by decreasing elastin degradation and augmenting eNOS activation
Authors: Diaz-Canestro Candela , Puspitasari Yustina M , Liberale Luca , Guzik Tomasz J , Flammer Andreas J , Bonetti Nicole R , Wüst Patricia , Costantino Sarah , Paneni Francesco , Akhmedov Alexander , Varga Zsuzsanna , Ministrini Stefano , Beer Jürg H , Ruschitzka Frank , Hermann Matthias , Lüscher Thomas F , Sudano Isabella , Camici Giovanni G
Published: September 2021

Aims

Arterial stiffness is a hallmark of vascular ageing that precedes and strongly predicts the development of cardiovascular diseases. Age-dependent stiffening of large elastic arteries is primarily attributed to increased levels of matrix metalloproteinase-2 (MMP-2). However, the mechanistic link between age-dependent arterial stiffness and MMP-2 remains unclear. Thus, we aimed to investigate the efficacy of MMP-2 knockdown using small-interfering RNA (siRNA) on age-dependent arterial stiffness.

Methods and results

Pulse wave velocity (PWV) was assessed in right carotid artery of wild-type (WT) mice from different age groups. MMP-2 levels in the carotid artery and plasma of young (3 months) and old (20–25 months) WT mice were determined. Carotid PWV as well as vascular and circulating MMP-2 were elevated with increasing age in mice. Old WT mice (18- to 21-month old) were treated for 4 weeks with either MMP-2 or scrambled (Scr) siRNA via tail vein injection. Carotid PWV was assessed at baseline, 2 and 4 weeks after start of the treatment. MMP-2 knockdown reduced vascular MMP-2 levels and attenuated age-dependent carotid stiffness. siMMP-2-treated mice showed increased elastin-to-collagen ratio, lower plasma desmosine (DES), enhanced phosphorylation of endothelial nitric oxide synthase (eNOS), and higher levels of vascular cyclic guanosine monophosphate (cGMP). An age-dependent increase in direct protein–protein interaction between MMP-2 and eNOS was also observed. Lastly, DES, an elastin breakdown product, was measured in a patient cohort (n = 64, 23–86 years old), where carotid-femoral PWV was also assessed; here, plasma levels of DES directly correlated with age and arterial stiffness.

Conclusion

MMP-2 knockdown attenuates age-dependent carotid stiffness by blunting elastin degradation and augmenting eNOS bioavailability. Given the increasing clinical use of siRNA technology, MMP2 knockdown should be investigated further as a possible strategy to mitigate age-dependent arterial stiffness and related CV diseases.
Videoconference microscopy is a reliable alternative to conventional microscopy in the evaluation of Barrett’s esophagus: Zooming into a new era
Authors: Axley Page , Mitchell Rachel , Council Leona , Patel Chirag , Tracht Jessica , Collingwood Robin , Harrison Devin , Redden David , Beasely Mark , Kabir Baig Kondal Kyanam R , Al Diffalha Sameer , Peter Shajan
Published: September 2021

Telepathology, practicing pathology from a distance, allows experts to review cases without the need to transfer glass slides. Due to significant intra- and inter-observer variabilities in the histological evaluation of Barrett’s esophagus (BE), current guidelines recommend expert consultation in cases of dysplasia. We aimed to determine whether telepathology using microscope videoconferencing can be reliably used for evaluation of BE. Biopsies from 62 patients with endoscopic findings of salmon colored mucosa extending ≥1 cm proximal to the gastroesophageal junction were randomly selected to represent benign esophagus, non-dysplastic BE, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma. Three gastrointestinal-trained pathologists reviewed the cases via videoconference microscopy followed by conventional microscopy. Intra-observer and pairwise inter-observer agreements between the conventional microscopy and videoconference methodologies were calculated for each of the three pathologists using Fleiss-Cohen weighted kappa (K) analysis. The intra-observer agreement for each pathologist’s assessment of videoconference microscopy and glass slide readings showed very good reliability (K = 0.94, 95% confidence interval = 0.89–0.99; 0.88, 95% confidence interval = 0.79–0.98; 0.93, 95% confidence interval = 0.90–0.97). Mean pairwise inter-observer agreement was 0.90 for videoconference and 0.91 for conventional microscopy. Diagnosis and grading of BE using videoconference microscopy show similar reliability as conventional microscopy. Based on our findings, we propose that videoconferencing pathology is a valid instrument for evaluating BE.
The extravascular implantable cardioverter-defibrillator: characterization of anatomical parameters impacting substernal implantation and defibrillation efficacy
Authors: Molnár Levente , Crozier Ian , Haqqani Haris , O'Donnell David , Kotschet Emily , Alison Jeffrey , Thompson Amy E , Bhatia Varun A , Papp Roland , Zima Endre , Jermendy Ádám , Apor Astrid , Merkely Béla
Published: September 2021

Aims

The aim of this study is to provide a thorough, quantified assessment of the substernal space as the site of extravascular implantable cardioverter-defibrillator (ICD) lead placement using computed tomography (CT) scans and summarizing adverse events and defibrillation efficacy across anatomical findings. Subcutaneous ICDs are an alternative to transvenous defibrillators but have limitations related to ICD lead distance from the heart. An alternative extravascular system with substernal lead placement has the potential to provide defibrillation at lower energy and pacing therapies from a single device.

Methods and results

A multi-centre, non-randomized, retrospective analysis of 45 patient CT scans quantitatively and qualitatively assessing bony, cardiac, vascular, and other organ structures from two human clinical studies with substernal lead placement. Univariate logistic regression was used to evaluate 15 anatomical parameters for impact on defibrillation outcome and adjusted for multiple comparisons. Adverse events were summarized. Substernal implantation was attempted or completed in 45 patients. Defibrillation testing was successful in 37 of 41 subjects (90%) using ≥10 J safety margin. There were two intra-procedural adverse events in one patient, including reaction to anaesthesia and an episode of transient atrial fibrillation during ventricular fibrillation induction. Anatomical factors associated with defibrillation failure included large rib cage width, myocardium extending very posteriorly, and a low heart position in the chest (P-values <0.05), though not significant adjusting for multiple comparisons.

Conclusion

Retrospective analysis demonstrates the ability to implant within the substernal space with low intra-procedural adverse events and high defibrillation efficacy despite a wide range of anatomical variability.
De Novo Genome Assembly of the Electric Fish Brachyhypopomus occidentalis (Hypopomidae, Gymnotiformes)
Authors: Arias Carlos F , Dikow Rebecca B , McMillan W Owen , De León Luis F
Published: September 2021

The bluntnose knifefish Brachyhypopomus occidentalis is a primary freshwater fish from north-western South America and Lower Central America. Like other Gymnotiformes, it has an electric organ that generates electric discharges used for both communication and electrolocation. We assembled a high-quality reference genome sequence of B. occidentalis by combining Oxford Nanopore and 10X Genomics linked-reads technologies. We also describe its demographic history in the context of the rise of the Isthmus of Panama. The size of the assembled genome is 540.3 Mb with an N50 scaffold length of 5.4 Mb, which includes 93.8% complete, 0.7% fragmented, and 5.5% of missing vertebrate/Actinoterigie Benchmarking Universal Single-Copy Orthologs. Repetitive elements account for 11.04% of the genome, and 34,347 protein-coding genes were predicted, of which 23,935 have been functionally annotated. Demographic analysis suggests a rapid effective population expansion between 3 and 5 Myr, corresponding to the final closure of the Isthmus of Panama (2.8–3.5 Myr). This event was followed by a sudden and constant population decline during the last 1 Myr, likely associated with strong shifts in both precipitation and sea level during the Pleistocene glacial-interglacial cycles. The de novo genome assembly of B. occidentalis will provide novel insights into the molecular basis of both electric signal productions and detection and will be fundamental for understanding the processes that have shaped the diversity of Neotropical freshwater environments.
High-resolution breakpoint junction mapping of proximally extended D4Z4 deletions in FSHD1 reveals evidence for a founder effect
Authors: Lemmers Richard J L F , van der Vliet Patrick J , Granado David San Leon , van der Stoep Nienke , Buermans Henk , van Schendel Robin , Schimmel Joost , de Visser Marianne , van Coster Rudy , Jeanpierre Marc , Laforet Pascal , Upadhyaya Meena , van Engelen Baziel , Sacconi Sabrina , Tawil Rabi , Voermans Nicol C , Rogers Mark , van der Maarel Silvère M
Published: September 2021

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy clinically characterized by weakness in the facial, shoulder girdle and upper a muscles. FSHD is caused by chromatin relaxation of the D4Z4 macrosatellite repeat, mostly by a repeat contraction, facilitating ectopic expression of DUX4 in skeletal muscle. Genetic diagnosis for FSHD is generally based on the sizing and haplotyping of the D4Z4 repeat on chromosome 4 by Southern blotting (SB), molecular combing or single-molecule optical mapping, which is usually straight forward but can be complicated by atypical rearrangements of the D4Z4 repeat. One of these rearrangements is a D4Z4 proximally extended deletion (DPED) allele, where not only the D4Z4 repeat is partially deleted, but also sequences immediately proximal to the repeat are lost, which can impede accurate diagnosis in all genetic methods. Previously, we identified several DPED alleles in FSHD and estimated the size of the proximal deletions by a complex pulsed-field gel electrophoresis and SB strategy. Here, using the next-generation sequencing, we have defined the breakpoint junctions of these DPED alleles at the base pair resolution in 12 FSHD families and 4 control individuals facilitating a PCR-based diagnosis of these DPED alleles. Our resultsshow that half of the DPED alleles are derivates of an ancient founder allele. For some DPED alleles, we found that genetic elements are deleted such as DUX4c, FRG2, DBE-T and myogenic enhancers necessitating re-evaluation of their role in FSHD pathogenesis.