bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Sprint Duration during Minimal Volume Exercise on Aerobic Capacity and Affect
Authors: Haines Matthew , Broom David , Stephenson John , Gillibrand Warren
Published: October 2020

The aims of this study were to investigate the influence of reduced-exertion, high-intensity interval training (REHIT), comparing a novel shortened-sprint protocol (SSREHIT) against a traditional protocol (TREHIT), on perceptual responses and to determine if changes in peak oxygen uptake (V˙O2peak) are attenuated with shorter sprints. Twenty-four healthy men undertook 15 sessions of SSREHIT or TREHIT. V˙O2peak was determined at baseline and after completion of each exercise condition. Affective (pleasure-displeasure) responses and perceived exertion were assessed during exercise to capture peak responses. Enjoyment was recorded 5-min after cessation of exercise. Compared to baseline, V˙O2peak increased in both groups (6% for SSREHIT [d=− 0.36] and 9% for TREHIT [d=− 0.53], p=0.01). Affective responses were more favourable for SSREHIT (p=0.001, d=1.62), but both protocols avoided large negative peaks of displeasure. Peak ratings of perceived exertion were lower for SSREHIT (p=0.001, d=− 1.71), although there were no differences in enjoyment (d=0.25). The results demonstrate both exercise conditions can increase V˙O2peak without overly compromising perceptual responses. Decreased sprint duration might further circumvent negative perceptual responses but might also attenuate physiological adaptations.
Small Cartilage Defect Management
Authors: Hacken Brittney A. , LaPrade Matthew D. , Stuart Michael J. , Saris Daniel B. F. , Camp Christopher L. , Krych Aaron J.
Published: October 2020

Cartilage defects in the knee are common resulting in significant pain and morbidity over time. These defects can arise in isolation or concurrently with other associated injuries to the knee. The treatment of small (< 2–3 cm2) cartilage deficiencies has changed as our basic science knowledge of tissue healing has improved. Advancements have led to the development of new and more effective treatment modalities. It is important to address any associated knee injuries and limb malalignment. Surgical options are considered when nonoperative treatment fails. The specific procedure depends on individual patient characteristics, lesion size, and location. Debridement/chondroplasty, microfracture, marrow stimulation plus techniques, fixation of unstable osteochondral fragments, osteochondral autograft transfer, and osteochondral allograft transplantation, all have roles in the treatment of small cartilage defects.
Plasma parameters in very high frequency helium and argon plasmas at atmospheric pressure
Authors: Yoshida Kazushi , Nitta Ken , Ohmi Hiromasa , Yasutake Kiyoshi , Kakiuchi Hiroaki
Published: October 2020

A simple procedure has been proposed to estimate atmospheric-pressure (AP) plasma parameters based on the electric field simulation of a very-high-frequency plasma system including the impedance matching unit. The capacitively coupled plasma is generated between metal electrodes with a narrow gap, where the standard Langmuir probe method cannot be applied. The amplitudes of current density (J0) and voltage (V0) between the electrodes are determined by the three-dimensional computer simulation of the system in the impedance matched state using two experimental parameters (i.e., the separations between two parallel-plate capacitors) in the matching unit. Approximate analytical solutions relating the central electron density (n0) and the sheath thickness to J0 and V0 are derived based on a simplified inhomogeneous plasma model with collisional sheaths. The average electron temperature Te is estimated using a power balance relation between the total powers absorbed and lost in the ionizing plasma. The results on power dependences of n0 and Te show reasonable agreement with the predictions by the particle and power balance relations. In the case of AP plasma of Ar or He mixed with impurity or process gas molecules, it is impossible to determine Te. However, n0 can be obtained and the collisional energy loss per electron–ion pair creation (ɛc) can be estimated, which brings certain information on the change of plasma chemistry. Since the proposed procedure is simple and non-intrusive, it might become a useful tool for discussing AP plasma properties in process developments.
Photonic integration of uniform GaAs nanowires in hexagonal and honeycomb lattice for broadband optical absorption
Authors: Behera Saraswati , Fry Paul W. , Francis Henry , Farrer I. , Jin Chaoyuan , Hopkinson Mark
Published: October 2020

We present an experimental approach toward the realization of GaAs nanowires in the form of square, hexagonal, and honeycomb lattices for photonic integration toward enhanced optical properties. We have carried out a design and fabrication process on GaAs wafers using electron beam lithography patterning, reactive ion etching for hard mask removal, and inductively coupled plasma etching of the material. The resulting photonic crystals are analyzed by field emission scanning electron microscopy. Nanowire array designs in a square, hexagonal, and honeycomb lattice with a variable height of nanowires have been studied. Using finite-difference time-domain simulation, we can derive the comparative optical absorption properties of these nanowire arrays. A very high broadband absorbance of >94% over the 400 nm–1000 nm wavelength range is studied for hexagonal and honeycomb arrays, while a square lattice array shows only a maximum of 85% absorption. We report a minimum of 2% reflectance, or 98% optical absorbance, over 450 nm–700 nm and over a wide angle of 45° through hexagonal and honeycomb lattice integration in GaAs. These results will have potential applications toward broadband optical absorption or light trapping in solar energy harvesting.
Efficient anharmonic lattice dynamics calculations of thermal transport in crystalline and disordered solids
Authors: Barbalinardo Giuseppe , Chen Zekun , Lundgren Nicholas W. , Donadio Davide
Published: October 2020

Understanding heat transport in semiconductors and insulators is of fundamental importance because of its technological impact in electronics and renewable energy harvesting and conversion. Anharmonic lattice dynamics provides a powerful framework for the description of heat transport at the nanoscale. One of the advantages of this method is that it naturally includes quantum effects due to atoms vibrations, which are needed to compute the thermal properties of semiconductors widely used in nanotechnology, like silicon and carbon, even at room temperature. While the heat transport picture substantially differs between amorphous and crystalline semiconductors from a microscopic standpoint, a unified approach to simulate both crystals and glasses has been devised. Here, we introduce a unified workflow, which implements both the Boltzmann Transport equation and the quasi-harmonic Green-Kubo methods. We discuss how the theory can be optimized to exploit modern parallel architectures, and how it is implemented in κALDo: a versatile and scalable open-source software to compute phonon transport in solids. This approach is applied to crystalline and partially disordered silicon-based systems, including bulk silicon and clathrates, and on silicon–germanium alloy clathrates with largely reduced thermal conductivity.
Novel flame dynamics in rich mixture of premixed propane–air in a planar microcombustor
Authors: Bhuvan C. H. , Hiranandani Karan , Aravind B. , Nair Vineeth , Kumar Sudarshan
Published: October 2020

This paper reports the first experimental observations of various novel unsteady flame propagation modes in a two-dimensional, high-aspect ratio rectangular quartz channel with a positive wall temperature gradient for rich premixed propane–air mixtures. Various flame propagation modes are observed on progressively increasing the mixture velocity, while keeping the equivalence ratio fixed: FREI (Flame with Repetitive Extinction and Ignition) mode, oscillating FREI mode, oscillating flame mode, and wavy flame mode. The FREI mode resembles the classical FREI flame propagation reported earlier in the literature. In the oscillating FREI mode, the flame front oscillates in the transverse direction between the upper and lower walls of the channel, while propagating upstream as in the classical FREI mode. A sudden peak in flame intensity is observed in this mode before its extinction at an upstream location. In the oscillating flame propagation mode, the flame front anchors itself at an axial location and exhibits periodic oscillations in the transverse direction without extinction. In the wavy flame mode the flame anchoring happens at a location close to the downstream end of the channel. The flame front exhibits visibly irregular fluctuations, while anchored at this axial location. A Fast Fourier transform analysis of the flame intensity data shows that FREI and oscillating FREI modes consist of a single dominant frequency of ∼100 Hz, whereas multiple dominant frequencies are present for oscillating and wavy flame modes. The appearance of these multiple oscillating and propagating flame modes is attributed to flame bifurcation behavior due to thermal-wall coupling in the channel.
Observation of room-temperature long-lived trapped exciton in WS2/RGO heterostructure
Authors: Mondal Anirban , Yadav Rajesh Kumar , Shrivastava Megha , Rout Chandra Sekhar , Karmakar Debjani , Adarsh K. V.
Published: October 2020

In this Letter, we studied the nature of exciton interactions and lifetimes in the WS2/Reduced graphene oxide (WS2/RGO) heterostructure using femtosecond transient absorption spectroscopy. Our studies demonstrate that the key optoelectronic properties of the heterostructure in the strongly coupled regime are substantially different from those of the control WS2 and RGO, promoting the mixing of electronic states at the interfaces leading to the suppression of direct excitons. The combined effect of midgap states and donor levels induced by RGO below the conduction band of WS2 along with the charge transfer to these trap states forms long-lived non-decaying excitons existing more than 1.5 ns, an ultimate time limit in our experiment. These results identify the interfacial trap states as a useful degree of freedom to engineer the lifetime of trapped excitons.
Unexpected bipolar space-charge polarization across transcrystalline interfaces in polypropylene electret films
Authors: Wang J. , Rychkov D. , Nguyen Q. D. , Gerhard R.
Published: October 2020

A double-layer transcrystalline polypropylene (PP) film with a flat central interface layer between its two transcrystalline layers is obtained by recrystallization from the melt between two polytetrafluoroethylene (PTFE) surfaces on both sides of the PP film. Its electret properties are studied and compared with those of a single-layer transcrystalline PP film re-crystallized in contact with only one PTFE surface. Within experimental uncertainty, the two types of transcrystalline films exhibit the same thermal properties and crystallinities. After thermal poling, however, two hetero-charge layers of opposite polarity are found on the internal interfaces of the double-layer transcrystalline films and may together be considered as micrometer-sized dipoles. The unexpected phenomenon does not occur in single-layer transcrystalline samples without a central interface layer, suggesting that the interfaces between the transcrystalline layers and the micrometer-thick central interface layer may be the origin of deeper traps rather than the crystalline structures in the transcrystallites or the spherulites. The origin of the interfacial charges was also studied by means of an injection-blocking charging method, which revealed that intrinsic charge carriers introduced during recrystallization are most likely responsible for the interfacial charges. It is fascinating that a material as familiar as PP can exhibit such intriguing properties with a special bipolar space-charge polarization across the central interface layer after quasi-epitaxial surface moulding into a double-layer transcrystalline form. In addition to applications in electret (micro-)devices for electro-mechanical transduction, the highly ordered structures may also be employed as a new paradigm for studying charge storage and transport in polymer electrets and in dielectrics for DC electrical insulation.
The impact of stretching-enhanced mixing and coalescence on reactivity in mixing-limited reactive flows
Authors: Sen Sabyasachi , Singh Prajwal , Heyman Joris , Le Borgne Tanguy , Bandopadhyay Aditya
Published: October 2020

We analyze the dynamics of solute mixing and reaction in a mixing-limited reactive flow by considering the transport of a tracer in a linear shear flow and in a Rankine vortex. The action of a shear flow, in general, achieves stretching of fluid elements due to the heterogeneous nature of the flow. A vortex flow exhibits not only stretching but also folding of fluid elements in a way that brings adjacent fluid elements closer at every turn. A strong stretching along the tangential direction is accompanied by a concomitant thinning in the radial direction leading to a strong diffusive flux, which may cause the material from neighboring regions of the mixing interface to aggregate. Through a Lagrangian concentration evolution technique, the diffusive strip method, we obtain the concentration field and pinpoint the signature of coalescence of two neighboring concentration regions by analyzing the concentration distribution profiles. The role of substrate deformation on the reaction kinetics of a classical heterogeneous chemical reaction is also studied where we derive analytical expressions for the coupling between the rate of product formation and the Péclet number in different time limits. Finally, the impact of coalescence on reaction rates is studied for a Rankine vortex, a result that holds important implications for simple bimolecular reactions. This analysis is useful to understand scalar dispersion in vortical flow structures and the consequences of stretching-enhanced diffusion in mixing-limited reactive flows.
Infrared spectroscopy and anharmonic theory of H3+Ar2,3 complexes: The role of symmetry in solvation
Authors: McDonald D. C. , Rittgers B. M. , Theis R. A. , Fortenberry R. C. , Marks J. H. , Leicht D. , Duncan M. A.
Published: October 2020

The vibrational spectra of H3+Ar2,3 and D3+Ar2,3 are investigated in the 2000 cm−1 to 4500 cm−1 region through a combination of mass-selected infrared laser photodissociation spectroscopy and computational work including the effects of anharmonicity. In the reduced symmetry of the di-argon complex, vibrational activity is detected in the regions of both the symmetric and antisymmetric hydrogen stretching modes of H3+. The tri-argon complex restores the D3h symmetry of the H3+ ion, with a concomitant reduction in the vibrational activity that is limited to the region of the antisymmetric stretch. Throughout these spectra, additional bands are detected beyond those predicted with harmonic vibrational theory. Anharmonic theory is able to reproduce some of the additional bands, with varying degrees of success.
Recent twists in twisted light: A Perspective on optical vortices from dielectric metasurfaces
Authors: Piccardo Marco , Ambrosio Antonio
Published: October 2020

Optical vortices are the electromagnetic analogue of fluid vortices studied in hydrodynamics. In both cases, the traveling wavefront, either made of light or fluid, is twisted like a corkscrew around its propagation axis—an analogy that also inspired the first proposition of the concept of optical vortices. Even though vortices are one of the most fundamental topological excitations in nature, they are rarely found in their electromagnetic form in natural systems, for the exception of energetic sources in astronomy, such as pulsars, quasars, and black holes. Mostly, optical vortices are artificially created in the laboratory by a rich variety of approaches. Here, we provide our Perspective on a technology that shook up optics in the last decade—metasurfaces, i.e., planar nanostructured metamaterials—with a specific focus on its use for molding and controlling optical vortices.
A numerical study of the aerosol behavior in intra-acinar region of a human lung
Authors: Ciloglu Dogan
Published: October 2020

The determination of the particle dynamics in the human acinar airways having millions of alveoli is critical in preventing potential health problems and delivering therapeutic particles effectively to target locations. Despite its complex geometrical structure and complicate wall movements, the advanced calculation simulations can provide valuable results to accurately predict the aerosol deposition in this region. The objective of this study was to numerically investigate the aerosol particle transport and deposition in the intra-acinar region of a human lung for different breathing scenarios (i.e., light, normal, and heavy activities) during multiple breaths. Idealized intra-acinar models utilized in this study consisted of a respiratory bronchial model, an alveolar duct model, and an alveolar sac model. The particles with 5 μm in diameter released from the inlet of the model were tracked until they deposited or escaped from the computational domain. The results showed that due to the rhythmic alveolar wall movement, the flow field was divided into two regions: one is the low-speed alveolar flow and the other is the channel flow. It was found that the chaotic acinar flow irreversibility played a significant role in the aerosol transport in higher generations. During the succeeding breaths, more particles deposited or escaped to the relating acinar generation and reached the more distal regions of the lung. The number of particles remaining in the suspension at the end of the third cycle ranged from 0.016% to 3%. When the mouth flow rate increased, the number of particles remaining in the suspension reduced, resulting in higher deposition efficiency. The total deposition efficiencies for each flow rate were 24%, 47%, and 77%, respectively. The particle simulation results also showed that more breathing cycle was required for full aerosol particle deposition or escape from the model. In addition to the alveolar wall motion, the type of breathing condition and breathing cycle had a significant effect on the accurate prediction of the aerosol deposition in the intra-acinar region of the human lung.
Dynamic evolution of great ape Y chromosomes
Authors: Cechova Monika , Vegesna Rahulsimham , Tomaszkiewicz Marta , Harris Robert S. , Chen Di , Rangavittal Samarth , Medvedev Paul , Makova Kateryna D.
Published: October 2020

Significance

The male-specific Y chromosome harbors genes important for sperm production. Because Y is repetitive, its DNA sequence was deciphered for only a few species, and its evolution remains elusive. Here we compared the Y chromosomes of great apes (human, chimpanzee, bonobo, gorilla, and orangutan) and found that many of their repetitive sequences and multicopy genes were likely already present in their common ancestor. Y repeats had increased intrachromosomal contacts, which might facilitate preservation of genes and gene regulatory elements. Chimpanzee and bonobo, experiencing high sperm competition, underwent many DNA changes and gene losses on the Y. Our research is significant for understanding the role of the Y chromosome in reproduction of nonhuman great apes, all of which are endangered.
Rational combination therapy for hepatocellular carcinoma with PARP1 and DNA-PK inhibitors
Authors: Wang Chen , Tang Huanyin , Geng Anke , Dai Binghua , Zhang Haiping , Sun Xiaoxiang , Chen Yu , Qiao Zhibing , Zhu Hong , Yang Jiamei , Chen Jiayu , He Qizhi , Qin Nan , Xie Jinru , Tan Rong , Wan Xiaoping , Gao Shaorong , Jiang Ying , Sun Fang-Lin , Mao Zhiyong
Published: October 2020

Significance

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer, and its mortality rate continues to increase. We generated knock-in reporter mouse models for measuring DNA double-strand break (DSB) repair efficiency and demonstrated that both DSB repair pathways are up-regulated in mouse HCCs. We then found that activation of PARP1 and DNA-PKcs is critical to HCC survival both

in vitro and in vivo. Targeting the two proteins to block both DSB repair pathways by combining olaparib and NU7441 synergistically inhibits HCC growth in both orthotopic HCC mouse and human PDX models. Our work not only establishes versatile tools for in vivo analysis of DNA repair, but also implies an effective combination therapy for HCC.
Point process temporal structure characterizes electrodermal activity
Authors: Subramanian Sandya , Barbieri Riccardo , Brown Emery N.
Published: October 2020

Significance

Electrodermal activity (EDA) is a readout of the body’s sympathetic nervous system measured as sweat-induced changes in the electrical conductance properties of the skin. Interest is growing in using EDA to track physiological conditions such as stress levels, sleep quality, and emotional states. The integrate-and-fire physiology underlying EDA production suggests that its interpulse intervals should obey an inverse Gaussian probability model. In an analysis of EDA data recorded in 11 healthy volunteers during quiet wakefulness, we established that the inverse Gaussian model accurately characterized the interpulse intervals. Our findings show a physiologically based statistical model provides a parsimonious and accurate description of EDA.
Crystal structure of tomato spotted wilt virus GNreveals a dimer complex formation and evolutionary link to animal-infecting viruses
Authors: Bahat Yoav , Alter Joel , Dessau Moshe
Published: October 2020

Significance

Tospoviruses are major field crop pathogens that cause significant economic damage, raising global food security concerns. However, their assembly, attachment to their host cells, and genome delivery mechanisms remain unclear. This paper provides detailed structural insights on tospovirus glycoprotein N (GN). The significant knowledge gap regarding the structure and function of envelope glycoproteins from plant viruses in general and tospoviruses in particular impedes our fundamental understanding of these viruses’ host cell recognition and entry mechanisms. Our structural analysis of the tomato spotted wilt virus glycoprotein N (TSWV GN) reveals an evolutionary link between plant- and animal-infecting viruses that extends beyond theBunyaviralesorder, describes a dimerization interface, and provides possible strategies for countermeasures against these important agricultural threats.
Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice
Authors: Bonomo Raiza R. , Cook Tyler M. , Gavini Chaitanya K. , White Chelsea R. , Jones Jacob R. , Bovo Elisa , Zima Aleksey V. , Brown Isabelle A. , Dugas Lara R. , Zakharian Eleonora , Aubert Gregory , Alonzo Francis , Calcutt Nigel A. , Mansuy-Aubert Virginie
Published: October 2020

Significance

The increase in obesity has been accompanied by a rise in the prevalence of peripheral neuropathy. Because there is no disease-modifying therapy, paradigm-shifting research on pain associated with obesity, metabolic syndrome, and type 2 diabetes is urgently needed. Our data suggest that fecal transplantation from lean to obese, insulin-resistant mice decreases obesity-induced hypersensitivity and increases nerve density in the skin. These improvements are accompanied by changes in peripheral nerve system gene expression and inflammatory cells. Finally, our results suggest that circulating butyrate, a metabolite secreted by gut microbiome and absorbed in the blood stream, may be involved by acting directly on peripheral nerve system immune cells and gene expression or pain channels.
Neutral evolution of human enamel–dentine junction morphology
Authors: Monson Tesla A. , Fecker Diego , Scherrer Marc
Published: October 2020

Significance

Of the skeleton, teeth preserve well in the fossil record and have the strongest genetic signature and thus great potential for reconstructing evolutionary processes involved in human origins. The enamel–dentine junction (EDJ) is especially important, because it is more frequently preserved and somewhat decoupled from dietary function. Researchers have used the EDJ to test hypotheses of human evolution, but this trait has not yet been comprehensively studied across human populations. This study is the largest investigation of EDJ morphology to date, spanning 161 archaeological individuals from six continents. These data demonstrate that the EDJ evolves neutrally, and biomedical imaging of EDJ morphology can therefore be used as a noninvasive method to investigate ancient population movement and human genetic structure.
How the T cell signaling network processes information to discriminate between self and agonist ligands
Authors: Ganti Raman S. , Lo Wan-Lin , McAffee Darren B. , Groves Jay T. , Weiss Arthur , Chakraborty Arup K.
Published: October 2020

Significance

Information theory was invented to solve the task of sending reliable communication over an unreliable channel. T cells have extremely reliable signal-processing capacity as they sensitively and specifically respond to a few pathogen-derived peptide ligands displayed in the noisy environment of many self-derived ligands presented on the same antigen-presenting cell. We used information-theoretic concepts to analyze a computational model of the biochemical steps in the T cell signaling network to understand how features of the T cell signaling pathway enable discriminatory ability. Our calculations and experiments suggest that T cells superimpose kinetic proofreading steps that must be spatially localized with the receptor and feedback loops to extract reliable information from a noisy environment.
Convergent evolution of zoonotic
Brucella
species toward the selective use of the pentose phosphate pathway
Authors: Machelart Arnaud , Willemart Kevin , Zúñiga-Ripa Amaia , Godard Thibault , Plovier Hubert , Wittmann Christoph , Moriyón Ignacio , De Bolle Xavier , Van Schaftingen Emile , Letesson Jean-Jacques , Barbier Thibault
Published: October 2020

Significance

Brucella
species are capable of infecting a range of mammals, including humans, with relative host specificity. We hypothesized that metabolism is instrumental in host adaptation and compared the central metabolism of seven species. We demonstrate the existence of two distinct groups, including one overlapping with the classical zoonotic brucellae of domestic livestock that exclusively use the pentose phosphate pathway. Species from the second group rely mostly on the Entner–Doudoroff pathway instead. This metabolic dichotomy arose after the acquisition of two newly identified EDP-inactivating mutations. This selected trait seems to be linked to bacterial pathogenicity in mice. The data fit the hypothesis that
Brucella
has undergone a stepwise metabolic evolution in domestic hosts that might also apply to other pathogens.
The demographic dividend is more than an education dividend
Authors: Kotschy Rainer , Suarez Urtaza Patricio , Sunde Uwe
Published: October 2020

The demographic dividend has long been viewed as an important factor for economic development and provided a rationale for policies aiming at a more balanced age structure through birth control and family planning. Assessing the relative importance of age structure and increases in human capital, recent work has argued that the demographic dividend is related to education and has suggested a dominance of improving education over age structure. Here we reconsider the empirical relevance of shifts in the age distribution for development for a panel of 159 countries over the period 1950 to 2015. Based on a flexible model of age-structured human capital endowments, the results document important interactions between age structure and human capital endowments, suggesting that arguments of clear dominance of education over age structure are unwarranted and lead to potentially misleading policy conclusions. An increase in the working-age population share has a strong and significant positive effect on growth, even conditional on human capital, in line with the conventional notion of a demographic dividend. An increase in human capital only has positive growth effects if combined with a suitable age structure. An increasing share of the most productive age groups has an additional positive effect on economic performance. Finally, the results show considerable heterogeneity in the effect of age structure and human capital for different levels of development. Successful policies for sustainable development should take this heterogeneity into account to avoid detrimental implications of a unidimensional focus on human capital without accounting for demography.
Real-time observation of ligand-induced allosteric transitions in a PDZ domain
Authors: Bozovic Olga , Zanobini Claudio , Gulzar Adnan , Jankovic Brankica , Buhrke David , Post Matthias , Wolf Steffen , Stock Gerhard , Hamm Peter
Published: October 2020

Significance

Allostery is a process in which a signal sensed upon ligand-binding at a distal site is transduced to the effector site, allowing for regulation of the activity of the latter. The propagation of an allosteric signal is a nonequilibrium process, but neither the nature of the signal is known on a molecular level (e.g., whether it is structural or dynamical properties that change) nor its speed. The real-time observation of such a signal requires the design of protein systems, in which one can synchronize ligand (un)binding events. Such a design is presented here, allowing us to investigate its allosteric transition in unprecedented detail.
Segregation of four
Agrobacterium tumefaciens
replicons during polar growth: PopZ and PodJ control segregation of essential replicons
Authors: Robalino-Espinosa J. S. , Zupan J. R. , Chavez-Arroyo A. , Zambryski P.
Published: October 2020

Significance

Bacteria are ubiquitous, essential, and remarkably diverse. Many infectious species do not follow rules established in model bacteria where growth occurs by insertion of new material along the cell length; instead, many pathogens grow from their poles. Pathogenic bacteria also carry multipartite genomes for adaptation to different ecological niches. How multiple chromosomes replicate and segregate in the context of polar growth is largely unknown. Here, four replicons of the plant pathogen
Agrobacterium tumefaciens
exhibit distinct temporal and spatial replication/segregation patterns during the polar growth cycle, and specific proteins, targeted to the nongrowing and new growth poles, regulate replicon transmission. Uncovering the mechanisms underlying polar growth and chromosome segregation will present new opportunities to design strategies to limit bacterial diseases.
Modular and coordinated activity of AAA+ active sites in the double-ring ClpA unfoldase of the ClpAP protease
Authors: Zuromski Kristin L. , Sauer Robert T. , Baker Tania A.
Published: October 2020

Significance

Understanding of how ClpA and other double-ring AAA+ enzymes perform mechanical work is limited. Using site-specific cross-linking and mutagenesis, we introduced ATPase-inactive AAA+ modules at alternating positions in individual ClpA rings, or in both rings, to investigate potential active-site coordination during ClpAP degradation. ClpA variants containing alternating active/inactive ATPase modules processively unfolded, translocated, and supported ClpP degradation of protein substrates with energetic efficiencies similar to, or higher than, completely active ClpA. These results impact current models describing the mechanisms of AAA+ family enzymes. The cross-linking/mutagenesis method we employed will also be useful for answering other structure-function questions about ClpA and related double-ring enzymes.
A study of the structural and magnetic properties of nitrides of iron and nickel (XN; X = Fe, Ni) using density functional theory approach
Authors: Atsue T , Ogunniranye I B , Oyewande O E
Published: October 2020

Transition metal nitrides possess important properties of interest such as superconductivity, high hardness, optical, electronic and magnetic among others which are relevant for technological applications. In this study, structural and magnetic properties of nitrides of iron and nickel have been investigated using generalized gradient approximation of Perdew–Burke–Ernzerhof revised for solids (GGA-PBEsol) as implemented in Quantum Espresso, a density functional theory based computational software package. The compounds were considered in the zinc blende face centered cubic (FCC), hexagonal closed packed (HCP) and primitive tetragonal structures and the results revealed that FeN and NiN energetically prefer zinc blende FCC structure. The results of spin polarized calculation indicated that FeN exhibited non-magnetic properties only in the zinc blende FCC structure and a magnetic moment of 2.17 μ
B and 3.18 μ
B per formula units in the HCP and primitive tetragonal structures respectively, whereas NiN was non-magnetic for the three crystal structures.
High-order phase reduction for coupled oscillators
Authors: Gengel Erik , Teichmann Erik , Rosenblum Michael , Pikovsky Arkady
Published: October 2020

We explore the phase reduction in networks of coupled oscillators in the higher orders of the coupling parameter. For coupled Stuart–Landau oscillators, where the phase can be introduced explicitly, we develop an analytic perturbation procedure to explicitly obtain the higher-order approximation. We demonstrate this by deriving the second-order phase equations for a network of three Stuart–Landau oscillators. For systems where explicit expressions of the phase are not available, we present a numerical procedure that constructs the phase dynamics equations for a small network of coupled units. We apply this approach to a network of three van der Pol oscillators and reveal components in the coupling with different scaling in the interaction strength.
Fourier transform as a triangular matrix
Authors: Lusztig G.
Published: October 2020

Let

V
V

be a finite dimensional vector space over the field with two elements with a given nondegenerate symplectic form. Let

[
V
]

[V]

be the vector space of complex valued functions on

V
V

, and let

[
V

]

Z

[V]_{\mathbf {Z}}

be the subgroup of

[
V
]

[V]

consisting of integer valued functions. We show that there exists a

Z

\mathbf {Z}

-basis of

[
V

]

Z

[V]_{\mathbf {Z}}

consisting of characteristic functions of certain isotropic subspaces of

V
V

and such that the matrix of the Fourier transform from

[
V
]

[V]

to

[
V
]

[V]

with respect to this basis is triangular. We show that this is a special case of a result which holds for any two-sided cell in a Weyl group.
Taylor’s theorem for functionals on BMO with application to BMO local minimizers
Authors: Spector Daniel , Spector Scott
Published: October 2020

In this note two results are established for energy functionals that are given by the integral of

W
(

x

,
∇

u

(

x

)
)

W({\mathbf x},\nabla {\mathbf u}({\mathbf x}))

over

Ω
⊂

R

n

\Omega \subset {\mathbb R}^n

with

∇

u

∈

B
M
O

(
Ω
;

R

N
×
n

)

\nabla {\mathbf u}\in \mathrm {BMO}(\Omega ;{\mathbb R}^{N\times n})

, the space of functions of Bounded Mean Oscillation of John and Nirenberg. A version of Taylor’s theorem is first shown to be valid provided the integrand

W
W

has polynomial growth. This result is then used to demonstrate that every Lipschitz-continuous solution of the corresponding Euler-Lagrange equations at which the second variation of the energy is uniformly positive is a strict local minimizer of the energy in

W

1
,

B
M
O

(
Ω
;

R

N

)

W^{1,\mathrm {BMO}}(\Omega ;{\mathbb R}^N)

, the subspace of the Sobolev space

W

1
,
1

(
Ω
;

R

N

)

W^{1,1}(\Omega ;{\mathbb R}^N)

for which the weak derivative

∇

u

∈

B
M
O

(
Ω
;

R

N
×
n

)

\nabla {\mathbf u}\in \mathrm {BMO}(\Omega ;{\mathbb R}^{N\times n})

.
Paving the translational ageing research pathway—training the next generation of researchers
Authors: Tullo Ellen , Dodds Richard M , Birkbeck Matthew , Habiballa Leena , Sayer Avan Aihie
Published: October 2020

Ageing is an archetypal translational research topic, spanning a breadth of academic disciplines. This poses challenges for researchers aiming to act upon laboratory findings to develop and implement interventions that directly benefit older people. Divisions between distinct academic research cultures present barriers to collaborative working. We present potential strategies to improve the translation of ageing research with examples of successful projects working across disciplines. Researchers and clinicians in ageing should be supported to develop a translational interest and receive specific training about translational research.
Care homes and COVID-19 in Hong Kong: how the lessons from SARS were used to good effect
Authors: Chow Lina
Published: October 2020

In Hong Kong, about 15% of older people (aged 80 and above) live in care homes, one of the highest proportions in the world. During the spread of severe acute respiratory syndrome in 2003, the crude fatality rate for older people in care homes that were infected was 72%. After taking the advice of a team of international experts, the Hong Kong Government implemented comprehensive preventive measures to cope with the future epidemics. This commentary evaluates the effectiveness of these measures in coping with both influenza outbreaks and COVID-19 and suggests the lessons learnt are relevant to both developed and less developed countries? Lockdown in care homes is very effective under two conditions. Healthcare workers must wear surgical masks in the care home. Hospitals must adopt a strict policy to prevent virus transmission by discharged patients. Care homes situated within high-rise residential towers are particularly vulnerable to COVID-19 transmission; their residents can more easily be infected by asymptomatic carriers from the community. Airborne virus can also be transmitted more swiftly in care homes with open-plan layouts. Lockdown had been shown to significantly reduce influenza outbreaks in care homes. On the other hand, lockdown causes loneliness to residents. Care homes allow residents to move freely within the care home though with the risk of spreading the virus by resident who is an asymptomatic carrier. Finally, lockdown may cause family members to have guilty feelings. Family members can only make video call or window visit to residents.
MDeePred: novel multi-channel protein featurization for deep learning-based binding affinity prediction in drug discovery
Authors: Rifaioglu A S , Cetin Atalay R , Cansen Kahraman D , Doğan T , Martin M , Atalay V
Published: October 2020

Motivation

Identification of interactions between bioactive small molecules and target proteins is crucial for novel drug discovery, drug repurposing and uncovering off-target effects. Due to the tremendous size of the chemical space, experimental bioactivity screening efforts require the aid of computational approaches. Although deep learning models have been successful in predicting bioactive compounds, effective and comprehensive featurization of proteins, to be given as input to deep neural networks, remains a challenge.

Results

Here, we present a novel protein featurization approach to be used in deep learning-based compound–target protein binding affinity prediction. In the proposed method, multiple types of protein features such as sequence, structural, evolutionary and physicochemical properties are incorporated within multiple 2D vectors, which is then fed to state-of-the-art pairwise input hybrid deep neural networks to predict the real-valued compound–target protein interactions. The method adopts the proteochemometric approach, where both the compound and target protein features are used at the input level to model their interaction. The whole system is called MDeePred and it is a new method to be used for the purposes of computational drug discovery and repositioning. We evaluated MDeePred on well-known benchmark datasets and compared its performance with the state-of-the-art methods. We also performed in vitro comparative analysis of MDeePred predictions with selected kinase inhibitors’ action on cancer cells. MDeePred is a scalable method with sufficiently high predictive performance. The featurization approach proposed here can also be utilized for other protein-related predictive tasks.

Availability and implementation

The source code, datasets, additional information and user instructions of MDeePred are available at https://github.com/cansyl/MDeePred.

Supplementary information

Supplementary data are available at Bioinformatics online.
UNRES-Dock—protein–protein and peptide–protein docking by coarse-grained replica-exchange MD simulations
Authors: Krupa Paweł , Karczyńska Agnieszka S , Mozolewska Magdalena A , Liwo Adam , Czaplewski Cezary
Published: October 2020

Motivation

The majority of the proteins in living organisms occur as homo- or hetero-multimeric structures. Although there are many tools to predict the structures of single-chain proteins or protein complexes with small ligands, peptide–protein and protein–protein docking is more challenging. In this work, we utilized multiplexed replica-exchange molecular dynamics (MREMD) simulations with the physics-based heavily coarse-grained UNRES model, which provides more than a 1000-fold simulation speed-up compared with all-atom approaches to predict structures of protein complexes.

Results

We present a new protein–protein and peptide–protein docking functionality of the UNRES package, which includes a variable degree of conformational flexibility. UNRES-Dock protocol was tested on a set of 55 complexes with size from 43 to 587 amino-acid residues, showing that structures of the complexes can be predicted with good quality, if the sampling of the conformational space is sufficient, especially for flexible peptide–protein systems. The developed automatized protocol has been implemented in the standalone UNRES package and in the UNRES server.

Availability and implementation

UNRES server: http://unres-server.chem.ug.edu.pl; UNRES package and data used in testing of UNRES-Dock: http://unres.pl.

Supplementary information

Supplementary data are available at Bioinformatics online.
A pseudotemporal causality approach to identifying miRNA–mRNA interactions during biological processes
Authors: Cifuentes-Bernal Andres M , Pham Vu Vh , Li Xiaomei , Liu Lin , Li Jiuyong , Le Thuc Duy
Published: October 2020

Motivation

microRNAs (miRNAs) are important gene regulators and they are involved in many biological processes, including cancer progression. Therefore, correctly identifying miRNA–mRNA interactions is a crucial task. To this end, a huge number of computational methods has been developed, but they mainly use the data at one snapshot and ignore the dynamics of a biological process. The recent development of single cell data and the booming of the exploration of cell trajectories using ‘pseudotime’ concept have inspired us to develop a pseudotime-based method to infer the miRNA–mRNA relationships characterizing a biological process by taking into account the temporal aspect of the process.

Results

We have developed a novel approach, called pseudotime causality, to find the causal relationships between miRNAs and mRNAs during a biological process. We have applied the proposed method to both single cell and bulk sequencing datasets for Epithelia to Mesenchymal Transition, a key process in cancer metastasis. The evaluation results show that our method significantly outperforms existing methods in finding miRNA–mRNA interactions in both single cell and bulk data. The results suggest that utilizing the pseudotemporal information from the data helps reveal the gene regulation in a biological process much better than using the static information.

Availability and implementation

R scripts and datasets can be found at https://github.com/AndresMCB/PTC.

Supplementary information

Supplementary data are available at Bioinformatics online.
VirPreNet: a weighted ensemble convolutional neural network for the virulence prediction of influenza A virus using all eight segments
Authors: Yin Rui , Luo Zihan , Zhuang Pei , Lin Zhuoyi , Kwoh Chee Keong
Published: October 2020

Motivation

Influenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. Previous work has been investigated to reveal the determinants of virulence of the influenza A virus. To further facilitate flu surveillance, explicit detection of influenza virulence is crucial to protect public health from potential future pandemics.

Results

In this article, we propose a weighted ensemble convolutional neural network (CNN) for the virulence prediction of influenza A viruses named VirPreNet that uses all eight segments. Firstly, mouse lethal dose 50 is exerted to label the virulence of infections into two classes, namely avirulent and virulent. A numerical representation of amino acids named ProtVec is applied to the eight-segments in a distributed manner to encode the biological sequences. After splittings and embeddings of influenza strains, the ensemble CNN is constructed as the base model on the influenza dataset of each segment, which serves as the VirPreNet’s main part. Followed by a linear layer, the initial predictive outcomes are integrated and assigned with different weights for the final prediction. The experimental results on the collected influenza dataset indicate that VirPreNet achieves state-of-the-art performance combining ProtVec with our proposed architecture. It outperforms baseline methods on the independent testing data. Moreover, our proposed model reveals the importance of PB2 and HA segments on the virulence prediction. We believe that our model may provide new insights into the investigation of influenza virulence.

Availability and implementation

Codes and data to generate the VirPreNet are publicly available at https://github.com/Rayin-saber/VirPreNet.

Supplementary information

Supplementary data are available at Bioinformatics online.
Therapeutic applications oftrans-splicing
Authors: Hong Elizabeth M , Ingemarsdotter Carin K , Lever Andrew M L
Published: October 2020

Background

RNA trans-splicing joins exons from different pre-mRNA transcripts to generate a chimeric product. Trans-splicing can also occur at the protein level, with split inteins mediating the ligation of separate gene products to generate a mature protein.

Sources of data

Comprehensive literature search of published research papers and reviews using Pubmed.

Areas of agreement

Trans-splicing techniques have been used to target a wide range of diseases in both in vitro and in vivo models, resulting in RNA, protein and functional correction.

Areas of controversy

Off-target effects can lead to therapeutically undesirable consequences. In vivo efficacy is typically low, and delivery issues remain a challenge.

Growing points

Trans-splicing provides a promising avenue for developing novel therapeutic approaches. However, much more research needs to be done before developing towards preclinical studies.

Areas timely for developing research

Increasing trans-splicing efficacy and specificity by rational design, screening and competitive inhibition of endogenous cis-splicing.