bluuebunny/crossref_metadata_2025 huggingface dataset:
Lithium acetate modified PU/graphene composites as separator for advanced Li‐ion batteries
Authors: Jiang Yong , Lu Cai , Liu Xing , Jiang Yunhong , Ding Yanhuai
Published: December 2019

Here lithium acetate modified PU/graphene composites were prepared from a simple electrospun method. The electrochemical properties, thermal stability, and mechanical properties of polyurethane (PU) separator have been improved remarkably by the addition of lithium acetate and graphene. The composite separator can maintain the dimension size even after being treated at 170°C for 1 h. High ionic conductivity of 2.47 mS·cm−1 can be reached. The results show that the as‐prepared lithium acetate modified PU/graphene separator is a promising candidate for commercial polyolefin separators.
Synthesis of ω‐Bi2O3 micropyramids with excellent photocatalytic properties
Authors: Xu Zezhong , Han Chengliang , Xie Jinsong
Published: December 2019

Novel triclinic bismuth oxide (ω‐Bi2O3) microcrystals with a pyramid‐like shape were successfully synthesised by a facile hydrothermal method. The effects of potassium sodium tartrate (KNaC4H4O6 ·4H2 O) concentration and the reaction time on the morphology were investigated, respectively. The experimental results showed that the tartrate (C4H4O6 2–) ions were responsible for the crystal growth of pyramid‐like ω‐Bi2O3 at the same reaction time. The photocatalytic activity of ω‐Bi2O3 pyramids was evaluated by degrading methyl orange under the visible‐light irradiation, revealing the ω‐Bi2O3 pyramids exhibited outstanding photocatalytic activity due to its suitable bandgap energy.
Preparation of ball‐flower‐like MoS2 as a superior electrode for pseudocapacitor
Authors: Luo Shiting , Wang Xiaolang , Chen Meifeng , Xu Limei , Zhou Xiaoping , Ma Lin
Published: December 2019

A sodium polyacrylate‐mediated strategy was employed to prepare well‐defined MoS2 ball‐flower‐like nanomaterials. It was found that the polyacrylate acted as a morphology‐directing agent to promote MoS2 nanosheets to self‐assemble into ball‐flowers with 3D hierarchical structures. Moreover, as an electrode applied in a supercapacitor, the ball‐flower‐like MoS2 exhibited a remarkable pseudocapacitive performance such as a high specific capacitance and superior cycling durability.
An empirical metallicity tracer in CEMP and C-normal stars
Authors: Singh D. , Hansen C. J. , Byrgesen J. S. , Reichert M. , Reggiani H. M.
Published: December 2019

Context. Deriving the metallicity, [Fe/H], in low-resolution spectra of carbon-enhanced metal-poor (CEMP) stars is a tedious task that, owing to the large number of line blends, often leads to uncertainties on [Fe/H] exceeding 0.25 dex. The CEMP stars increase in number with decreasing [Fe/H] and some of these are known to be bona fide second generation halo stars. Hence, knowing their [Fe/H] is important for tracing the formation and chemical evolution of the Galaxy.

Aims. Here, we aim to improve the [Fe/H] measurements in low-resolution spectra by avoiding issues related to blends. In turn, we improve our chemical tagging in such spectra at low metallicities.

Methods. We developed an empirical way of deriving [Fe/H] in CEMP (and C-normal) stars that relates the equivalent width (EW) of strong lines, which remain detectable in lower resolution, metal-poor spectra, such as X-shooter spectra to [Fe/H].

Results. The best [Fe/H] tracers are found to be Cr I and Ni I, which both show strong transitions in spectral regions that are free of molecular bands (between ~5200−6800Å, a region accessible to most surveys). We derive different relations for dwarfs and giants. The relations are valid in the ranges ~ − 3 < [Fe/H] < −0.5 and 10 < EW < 800 m Å (Cr) or [Fe/H] > −3.2 and EW > 5 m Å (Ni), depending on the trace element and line as well as the stellar evolutionary stage.

Conclusions. The empirical relations are valid for both CEMP and C-normal stars and have been proven to be accurate tracers in a sample of ~400 stars (mainly giants). The metallicities are accurate to within ± ~0.2 dex depending on the sample and resolution, and the empirical relations are robust to within 0.05–0.1 dex. Our relations will improve the metallicity determination in future surveys, which will encounter a large number of CEMP stars, and will greatly speed up the process of determining [Fe/H] as the EWs only need to be measured in two or three lines in relatively clean regions compared to dealing with numerous blended Fe lines.
The Nuker model for galactic nuclei
Authors: Baes Maarten
Published: December 2019

The Nuker profile, characterised by an inner and outer power-law profile smoothly merged around a break radius, is a very popular model to describe the surface brightness profile of galactic nuclei. A disadvantage of this model for dynamical studies is that the spatial density distribution that corresponds to this surface brightness profile cannot be written in terms of elementary or regular special functions. We derive a compact and elegant analytical expression for the density of the Nuker model, based the Mellin integral transform method. We use this expression to discuss the general behaviour and asymptotic expansion of the density. We also discuss the special subclass of Nuker models with an infinitely sharp break and demonstrate that these models are always characterised by non-monotonous and hence unphysical density profile. We extend our study to the dynamical structure of spherical isotropic galactic nuclei with a Nuker surface brightness profile. Based on this analysis, we extend and refine the classification of spherical isotropic galactic nuclei introduced by Tremaine et al. (1994, AJ, 107, 634). We demonstrate that both the inner density slope and the sharpness of the break between the inner and outer profiles critically determine the consistency and stability of the Nuker models.
Idiopathic Hypertrophic Spinal Pachymeningitis: A Diagnostic Challenge: A Case Report and Review of the Literature
Authors: Alsulaiman Abdulla
Published: December 2019

Idiopathic hypertrophic pachymeningitis (IHP) can resemble other disorders associated with spinal compression. It is a rare inflammatory fibrosing disease of the dura of unidentified etiology and is considered a diagnosis of exclusion. We present a case of idiopathic hypertrophic spinal pachymeningitis occupying a long segment of cervical dura. This is a case of 38-year-old female patient, who suffered progressive neck pain for 2-year duration. Examination revealed spasticity in all four limbs, plus three symmetric reflexes all over, and the sensory level at T4. Magnetic resonance imaging showed spinal cord compression by a thickened anterior and posterior dura adjacent to the cord from C2 to C7. The diagnosis of spinal IHP was confirmed through biopsy. The patient improved after treatment with corticosteroids. Early surgical intervention with postoperative corticosteroid therapy is a known treatment for this disease, as a way to prevent irreversible neurological damage.
Neurologic Assessment and Management of the Multiple Ligament Injured Knee: A Review and Synthesis of Current Evidence
Authors: Hoit Graeme , Farag Jordan , Whelan Daniel B.
Published: December 2019

Knee dislocations are rare but devastating injuries that can often be associated with concomitant nerve injury, most often of the common peroneal nerve. Prompt diagnosis, investigation, and appropriate treatment are important in this subset of patients. This article provides an overview of relevant injury demographics, anatomy, diagnosis, and prognosis, and suggests a treatment algorithm for nerve injury associated with multiligament knee injury.
Factors Associated with Knee Arthroplasty in a Knee Osteoarthritis Patient Cohort Treated with Intra-articular Injections of Hylan G-F 20
Authors: Ong Kevin , Lau Edmund , Runa Maria , Daley William , Altman Roy
Published: December 2019

Hylan G-F 20 viscosupplementation can be used to treat knee osteoarthritis pain. This study evaluated time to knee arthroplasty (KA), KA risk factors, and health care resource utilization in patients aged ≥18 years with claims in the Optum Clinformatics Data Mart database (2006–2016) for knee osteoarthritis treated with at least one course of hylan G-F 20. Kaplan–Meier analysis estimated KA risk from osteoarthritis diagnosis and first hylan G-F 20 treatment. KA risk factors were determined using multivariate Cox regression. Among 62,033 patients treated with hylan G-F 20 and/or hylan G-F 20 single intra-articular injection, 60 to 64% did not undergo KA 8 years following first injection. KA risk factors from time of osteoarthritis diagnosis and first hylan G-F 20 treatment were similar: increased age, fewer comorbidities, fewer hylan G-F 20 treatments, female sex, and no ultrasound/fluoroscopy for injection guidance. Patients who underwent KA versus those who did not had more office visits and claims for opioids, nonsteroidal anti-inflammatory drugs, and physical therapy. Patients less likely to undergo KA were younger (<40 years), had more comorbidities, received more courses of hylan G-F 20, were males, or received ultrasound/fluoroscopic injection guidance. Patients who did not receive KA versus those who did used fewer health care resources.
Room temperature exchange bias in antiferromagnetic composite BiFeO3-TbMnO3
Authors: Gupta Prince K. , Ghosh Surajit , Kumar Shiv , Pal Arkadeb , Singh Prajyoti , Alam Mohd , Singh Abhishek , Roy Somnath , Singh Rahul , Singh Bheeshma Pratap , Naveen Kumar N. , Schwier Eike F. , Sawada Masahiro , Matsumura Takeshi , Shimada Kenya , Lin Hong-Ji , Chin Yi-Ying , Ghosh A. K. , Chatterjee Sandip
Published: December 2019

The magnetic property of a 0.7BiFeO3-0.3TbMnO3 composite has been studied in detail and compared with that of 0.8BiFeO3-0.2TbMnO3. The magnetic properties in 0.7BiFeO3-0.3TbMnO3 are improved in manifold compared to BiFeO3. An exchange bias (HEB) is observed in both the compositions of these antiferromagnetic composites, which varies between 5 and 180 Oe with a maximum at ∼275 K. Isothermal remanent magnetization measurements at room temperature indicate the presence of an interfacial layer of a 2-dimensional dilute uniaxial antiferromagnet in a uniform magnetic field (2D DAFF). The presence of exchange bias can be explained on the basis of a strong strain-mediated magnetoelectric coupling induced exchange interaction and the creation of a 2D DAFF layer at the interface. The properties of this layer are defined by canting and pinning of BiFeO3 spins at the interface with TbMnO3 due to Fe and Mn interaction. X-ray magnetic circular dichroism confirms the presence of canted antiferromagnetic ordering of BiFeO3, charge transfer between Mn ions, and different magnetically coupled layers that play a vital role in the exchange bias.
Surface reconstruction based on CAD model driven priori templates
Authors: Hao Long , Huang Xiang , Li ShuangGao
Published: December 2019

In this paper, a method of reconstructing 3D (three dimensional) models from the original scanned point cloud using priori templates is proposed. Different from previous reconstruction methods that triangulate and fit the original scanning point cloud directly, we construct a priori template based on the CAD (computer aided design) model and guide the reconstruction of the original scanning point cloud with the priori template. Given a CAD model, the basic geometric elements are used as the basic units to extract the set elements of 3D shapes. Then the geometric elements are meshed, and the normal vectors at the mesh nodes are extracted. The corresponding point cloud data of each basic element are extracted from the original point cloud. The point cloud data near the normal of the guide point are searched, and the Gaussian weighted average value of the searched point represents the actual geometric parameters of the part at the guide point. Finally, the geometric elements of the basic unit are reconstructed locally by Non-Uniform Rational B-Splines surface fitting, and the complete reconstruction model is obtained by integrating the local reconstruction. Experiments show that our method can solve the problems of high quality reconstruction, sharp feature preservation, and detail recovery in surface reconstruction.
Phase-space resolved rates in driven multidimensional chemical reactions
Authors: Feldmaier Matthias , Bardakcioglu Robin , Reiff Johannes , Main Jörg , Hernandez Rigoberto
Published: December 2019

Chemical reactions in multidimensional driven systems are typically described by a time-dependent rank-1 saddle associated with one reaction and several orthogonal coordinates (including the solvent bath). To investigate reactions in such systems, we develop a fast and robust method—viz., local manifold analysis (LMA)—for computing the instantaneous decay rate of reactants. Specifically, it computes the instantaneous decay rates along saddle-bound trajectories near the activated complex by exploiting local properties of the stable and unstable manifold associated with the normally hyperbolic invariant manifold (NHIM). The LMA method offers substantial reduction in numerical effort and increased reliability in comparison with direct ensemble integration. It provides an instantaneous flux that can be assigned to every point on the NHIM and which is associated with a trajectory—regardless of whether it is periodic, quasiperiodic, or chaotic—that is bound on the NHIM. The time average of these fluxes in the driven system corresponds to the average rate through a given local section containing the corresponding point on the NHIM. We find good agreement between the results of the LMA and direct ensemble integration obtained using numerically constructed, recrossing-free dividing surfaces.
Chips-on-a-plate device for monitoring cellular migration in a microchannel-based intestinal follicle-associated epithelium model
Authors: Lee Young , Kim Soo Jee , Park Je-Kyun
Published: December 2019

This paper describes a chips-on-a-plate (COP) device for monitoring the migration of Raji cells in the Caco-2/Raji coculture. To generate a model of the human intestinal follicle-associated epithelium (FAE), the coculture method using a conventional Transwell cell culture insert was established. Due to the structural limitations of the Transwell insert, live-cell tracking studies have not been performed previously using the existing FAE model. In this study, we designed a COP device to conduct long-term live-cell tracking of Raji cell migration using a microchannel-based FAE model. The COP device incorporates microfluidic chips integrated on a standard well plate, consistent humidity control to allow live-cell microscopy for 2 days, and microchannels connecting the two cell culture chambers of the COP device, which serve as a monitoring area for cellular migration. Using the COP device, we provide the first analysis of various migratory characteristics of Raji cells, including their chemotactic index in the microchannel-based FAE model. We showed that the migration of Raji cells could be controlled by modulating the geometry of the connecting microchannels. Cellular treatments with cytokines revealed that the cytokines increased the permeability of an FAE model with a detachment of Caco-2 cells. Live-cell monitoring of Raji cells treated with a fluorescent reagent also indicated exocytosis as a key agent of the Caco-2/Raji interaction. The COP device allows live-cell tracking analyses of cocultured cells in the microchannel-based FAE model, providing a promising tool for investigating cellular behavior associated with the recruitment of Raji to Caco-2 cells.
Viscoelastic second normal stress difference dominated multiple-stream particle focusing in microfluidic channels
Authors: Feng Haidong , Magda Jules John , Gale Bruce Kent
Published: December 2019

Particle focusing in viscoelastic fluid flow is a promising approach for inducing particle separations in microfluidic devices. The results from theoretical studies indicated that multiple stream particle focusing can be realized with a large magnitude of the elastic second normal stress difference (N2). For dilute polymer solutions, theoretical and experimental studies show that the magnitude of N2 is never large, no matter how large the polymer molecular weight nor how high the shear rate. However, for concentrated entangled polymer solutions, the magnitude of N2 becomes large at high shear rates. Therefore, in order to test the hypothesis that N2 can be used to induce multiple particle stream focusing behavior, we perform the systematic study of the effects of increasing carrier fluid polymer concentrations in a microchannel containing fluorescent particles. In a dilute polymer solution, multiple particle stream focusing is not observed, even at high shear rates and large dimensionless Weissenberg number values (Wi ≈ 30) at which the elastic first normal stress difference (N1) and the viscosity shear-thinning should be very large, while in a concentrated entangled polymer solution, we observe that particle streams focused upon the channel centerline bifurcate to form two symmetric off-channel particle streams at higher shear rates. This particle focusing behavior is different from previous multiple-stream focusing phenomena, and that we attribute to the influence of the second normal stress difference N2. This N2 induced multiple stream focusing phenomenon provides a different approach for manipulating the particle trajectory and separation in a microchannel.
The first-order magnetoelastic transition in Eu2In: A 151Eu Mössbauer study
Authors: Ryan D. H. , Paudyal Durga , Guillou Francois , Mudryk Yaroslav , Pathak Arjun K. , Pecharsky Vitalij K.
Published: December 2019

Our 151Eu Mössbauer investigation of Eu2In and Eu2Sn shows that the europium in both materials is fully divalent. We confirm the distinct thermodynamic orders of the magnetic transitions and reveal a remarkable difference between the magnetic environments of the europium atoms in the two compounds. Possible structural and electronic origins for these differences are discussed using DFT calculations.
Integration of Tb/Co multilayers within optically switchable perpendicular magnetic tunnel junctions
Authors: Avilés-Félix L. , Álvaro-Gómez L. , Li G. , Davies C. S. , Olivier A. , Rubio-Roy M. , Auffret S. , Kirilyuk A. , Kimel A. V. , Rasing Th. , Buda-Prejbeanu L. D. , Sousa R. C. , Dieny B. , Prejbeanu I. L.
Published: December 2019

This work reports the development of perpendicular magnetic tunnel junctions, based on a multilayered stack of [Tb/Co] nanolayers, in which the magnetization can be reliably toggled using a single optical pulse. The helicity-independent single-shot switching of the magnetization in the Tb/Co multilayered stack was achieved using either 60 fs-long or 5 ps laser pulses with incident fluences down to 4.7 mJ/cm2. The magnetic switching was achieved for a Co-rich composition window of the multilayer corresponding to layer thickness ratios tCo/tTb between 1.3-1.5. This was confirmed for the multilayer alone as well as for the multilayer coupled to aCoFeB electrode, with a structure consisting of CoFeB/Ta/[Tb/Co]N. The optical switching is preserved even after annealing at 250°C in magnetic tunnel junctions (MTJ) electrodes, exhibiting a tunnel magnetoresistance (TMR) of 41% and RxA value of 150 Ωμm after its integration, measured on unpatterned MTJ stacks. These results represent the first step towards the development of hybrid spintronic photonic systems with fJ switching energies.
Optical control and manipulation of diamagnetically levitated pyrolytic graphite
Authors: Young Jared , Biggs Harrison , Yee Steven , ElBidweihy Hatem
Published: December 2019

When levitating above an alternating-pole permanent magnet array, pyrolytic graphite can be displaced by asymmetric diamagnetic forces resulting from optically-induced, localized temperature changes and the thermal dependence of pyrolytic graphite’s magnetic susceptibility. In this paper, we present methods for addressable, automated position control of levitating pyrolytic graphite samples acting as milli-robots for small-scale assembly and manipulation applications using optical actuation and machine vision techniques. A simple control method is presented that harnesses interactions between complex magnetic fields and small-scale thermomagnetic and optical material properties. A user may dictate arbitrary desired milli-robot positions to a closed loop control system, which automatically detects and actuates milli-robots to the desired positions and works to maintain them there. Hardware requirements and considerations are discussed along with software calibration, image processing, and control methodologies. Results from experiments demonstrating automated position control of pyrolytic graphite milli-robots of various sizes levitating over various permanent magnet array configurations are presented. Sequential control of multiple milli-robots in close proximity without work surface segmentation is also demonstrated successfully. The observed effect of milli-robot size to magnet array grid spacing ratio on milli-robot in-plane motion is discussed, concluding that larger ratios result in smoother and faster motion control due to relative decreases in magnetic barrier forces on the pyrolytic graphite milli-robot and minimized separation between minimum free energy positions.
Stability of spin XOR gate operation in silicon based lateral spin device with large variations in spin transport parameters
Authors: Ishihara Ryoma , Lee Soobeom , Ando Yuichiro , Ohshima Ryo , Goto Minori , Miwa Shinji , Suzuki Yoshishige , Koike Hayato , Shiraishi Masashi
Published: December 2019

We investigate stability of the spin exclusive or (XOR) gate operation in silicon(Si) -based lateral spin devices whose spin transport properties have large variations. The optimum charge current, I0, for the spin XOR gate operation is calculated by using the one dimensional spin-drift-diffusion model with variable spin polarization, interface resistance of the ferromagnetic contact, channel length and channel conductivity. I0 is strongly modulated by changing the spin transport parameters particularly under the condition with small spin polarization and short channel length. In contrast, I0 shows constant value irrespective of the interface resistance of one ferromagnetic contact under spin extraction condition. Our results provide a device design guideline for the robust spin XOR gate operation.
Low temperature superspin glass behavior in a Co/Ag multilayer
Authors: Navarro E. , Alonso M. , Ruiz A. , Magen C. , Urdiroz U. , Cebollada F. , Balcells Ll. , Martínez B. , Palomares F. J. , González J. M.
Published: December 2019

We report on the low temperature magnetic behavior of an epitaxially grown multilayer formed by 32 repetitions of a nominal period corresponding to 1 monolayer (ML) Co and 16 ML Ag. The study of the magnetic properties was based on the measurement of the temperature dependencies of the dc magnetization upon field cooling (FC) and zero field cooling (ZFC) and of the ac field real and imaginary parts of the susceptibility. From our results we conclude about the occurrence of i) a well-defined bilayers stacking sequence matching the nominal one, ii) a discontinuous growth in the Co layers resulting on close-to-monodisperse, spherical Co nanoparticles having an average diameter of 1.6 nm, iii) a frequency dependent peak in the temperature dependence of the real part of the ac susceptibility exhibiting a per decade relative temperature variation of 4.5 x 10−2, iv) an applied dc field, Hdc, variation of the temperature at which the irreversibility is detected in the FC/ZFC curves corresponding to the Almeida-Thouless prediction, and v) a critical behavior characterized by a glass-transition temperature slightly below the peak temperatures observed at low frequency in the temperature dependence of the ac susceptibility and a dynamic scaling exponent in the range of the values usually obtained for spin glass systems. From our results we conclude that i) our sample experiences a superspin-glass/paramagnetic phase transition, ii) the interactions mediating the spin glass freezing process are the dipolar ones taking place among the Co particles (creating fields at the average interparticle distance of the order of 8 x 105 A/m) which provide competitiveness that combined with the reduced amount of disorder built-in the Co layers results on frustration.
Tensile control of the thermal flow in plasmonic heaters realized on flexible substrates
Authors: Lio Giuseppe Emanuele , Palermo Giovanna , De Luca Antonio , Caputo Roberto
Published: December 2019

In this paper, we present a simple and robust numerical method capable of predicting, with high accuracy, the thermal effects occurring for different gold nanoparticle arrangements under externally applied strain. The physical system is numerically implemented in the COMSOL Multiphysics simulation platform. The photothermal response of different arrangements of gold nanoparticles, resonantly excited by linearly polarized light, is considered with the system at rest and under the action of mechanical stress. The generation of heat at the nanoscale is analyzed by considering how this is affected by the variation of the extinction cross section. We describe the peculiar conditions under which mechanically controlled gold nanoparticle arrangements can significantly increase the local temperature due to the formation of localized photothermal hot spots. The resulting systems are envisioned in applications as optomechanically tunable plasmonic heaters.
Molecular dynamics investigation of wetting-dewetting behavior of model carbon material by 1-butyl-3-methylimidazolium acetate ionic liquid nanodroplet
Authors: Dhattarwal Harender S. , Kashyap Hemant K.
Published: December 2019

In order to comprehend the wetting-dewetting behavior of a solid surface by a liquid, it is crucial to contemplate both the surface flexibility and the interactions involved. Herein, by employing molecular dynamics simulations, we aim to understand the structural changes in 1-butyl-3-methylimidazolium acetate ([bmim][Ac]) ionic liquid (IL) nanodroplets on model carbon sheets with varying IL-sheet interaction potentials along with the flexibility of the carbon sheet. The extent of the wetting is estimated by computing the average contact angle formed by [bmim][Ac] nanodroplets on the sheet surface. We observe that the wetting-dewetting behavior of the sheet and its affinity toward [bmim]+ and [Ac]− depend not only on the IL-sheet interaction but also on its flexibility or rigidity. The extent of wetting is observed to be consistently greater for the rigid surface in the entire range of IL-sheet interaction potentials studied herein. Although in the adlayer, [bmim]+ rings and [Ac]− anions prefer to be parallel to the carbon surface, the ordering of the [bmim]+ rings is highly affected by the introduction of flexibility in the carbon surface. Enhanced structural and orientational ordering of imidazolium rings of [bmim]+ cations in the adlayer of the rigid surface is observed, supporting the comprehension of greater wetting extent of the rigid surface by the IL droplet.
OsmiR528 regulates rice-pollen intine formation by targeting an uclacyanin to influence flavonoid metabolism
Authors: Zhang Yu-Chan , He Rui-Rui , Lian Jian-Ping , Zhou Yan-Fei , Zhang Fan , Li Quan-Feng , Yu Yang , Feng Yan-Zhao , Yang Yu-Wei , Lei Meng-Qi , He Huang , Zhang Zhi , Chen Yue-Qin
Published: December 2019

Significance

The intine layer of pollen is essential for pollen grain maturation and pollen tube germination. Abnormal intine development causes pollen sterility and affects seed-setting; therefore, the identification of regulators of intine formation is important for elucidating the mechanisms of pollen formation and function, especially for crop breeding. Here, we report a microRNA, OsmiR528, which regulates pollen intine formation and male fertility in rice (
Oryza sativa
). OsmiR528 directly targets the uclacyanin family member
OsUCL23
to regulate flavonoid metabolism and pollen intine development. This study revealed the function of OsmiR528 and an uclacyanin in pollen development.
CRISPR-mediated modeling and functional validation of candidate tumor suppressor genes in small cell lung cancer
Authors: Ng Sheng Rong , Rideout William M. , Akama-Garren Elliot H. , Bhutkar Arjun , Mercer Kim L. , Schenkel Jason M. , Bronson Roderick T. , Jacks Tyler
Published: December 2019

Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer that remains among the most lethal of solid tumor malignancies. Recent genomic sequencing studies have identified many recurrently mutated genes in human SCLC tumors. However, the functional roles of most of these genes remain to be validated. Here, we have adapted the CRISPR-Cas9 system to a well-established murine model of SCLC to rapidly model loss-of-function mutations in candidate genes identified from SCLC sequencing studies. We show that loss of the gene
p107
significantly accelerates tumor progression. Notably, compared with loss of the closely related gene
p130
, loss of
p107
results in fewer but larger tumors as well as earlier metastatic spread. In addition, we observe differences in proliferation and apoptosis as well as altered distribution of initiated tumors in the lung, resulting from loss of
p107
or
p130
. Collectively, these data demonstrate the feasibility of using the CRISPR-Cas9 system to model loss of candidate tumor suppressor genes in SCLC, and we anticipate that this approach will facilitate efforts to investigate mechanisms driving tumor progression in this deadly disease.
Nonhuman primate models of hippocampal development and dysfunction
Authors: Bachevalier Jocelyne
Published: December 2019

Nonhuman primates provide highly valuable animal models that have significantly advanced our understanding of numerous behavioral and biological phenomena in humans. Here, we reviewed a series of developmental neuropsychological studies that informed us on the timing of development of the hippocampus and of hippocampal-dependent cognitive functions in primates. Data indicate that, in primates, the emergence of adult-like proficiency on behavioral tasks sensitive to hippocampal dysfunction is a stepwise process and reflects the gradual maturation of different hippocampal circuits and their connections with other neural structures. Profound and persistent memory loss resulting from insult to the hippocampus in infancy was absent in early infancy but became evident later in childhood and persisted in adulthood, indicating very little sparing or recovery of function. Finally, the early hippocampal insult resulted in both adaptive and maladaptive neuroplasticity: i.e., sparing contextual memory, but affecting working memory processes as well as emotional reactivity and hypothalamic–pituitary–adrenal (HPA) axis functioning. The results provide significant information on the emergence of hippocampal-dependent functions in humans, on the time course of memory impairment in human cases with early hippocampal insult, and on the clinical implication of the hippocampus in developmental neuropsychiatric disorders.
Experiments in macaque monkeys provide critical insights into age-associated changes in cognitive and sensory function
Authors: Gray Daniel T. , Barnes Carol A.
Published: December 2019

The use of animal models in brain aging research has led to numerous fundamental insights into the neurobiological processes that underlie changes in brain function associated with normative aging. Macaque monkeys have become the predominant nonhuman primate model system in brain aging research due to their striking similarities to humans in their behavioral capacities, sensory processing abilities, and brain architecture. Recent public concern about nonhuman primate research has made it imperative to attempt to clearly articulate the potential benefits to human health that this model enables. The present review will highlight how nonhuman primates provide a critical bridge between experiments conducted in rodents and development of therapeutics for humans. Several studies discussed here exemplify how nonhuman primate research has enriched our understanding of cognitive and sensory decline in the aging brain, as well as how this work has been important for translating mechanistic implications derived from experiments conducted in rodents to human brain aging research.
Multiple neuronal circuits for variable object–action choices based on short- and long-term memories
Authors: Hikosaka Okihide , Yasuda Masaharu , Nakamura Kae , Isoda Masaki , Kim Hyoung F. , Terao Yasuo , Amita Hidetoshi , Maeda Kazutaka
Published: December 2019

At each time in our life, we choose one or few behaviors, while suppressing many other behaviors. This is the basic mechanism in the basal ganglia, which is done by tonic inhibition and selective disinhibition. Dysfunctions of the basal ganglia then cause 2 types of disorders (difficulty in initiating necessary actions and difficulty in suppressing unnecessary actions) that occur in Parkinson’s disease. The basal ganglia generate such opposite outcomes through parallel circuits: The direct pathway for initiation and indirect pathway for suppression. Importantly, the direct pathway processes good information and the indirect pathway processes bad information, which enables the choice of good behavior and the rejection of bad behavior. This is mainly enabled by dopaminergic inputs to these circuits. However, the value judgment is complex because the world is complex. Sometimes, the value must be based on recent events, thus is based on short-term memories. Or, the value must be based on historical events, thus is based on long-term memories. Such memory-based value judgment is generated by another parallel circuit originating from the caudate head and caudate tail. These circuit-information mechanisms allow other brain areas (e.g., prefrontal cortex) to contribute to decisions by sending information to these basal ganglia circuits. Moreover, the basal ganglia mechanisms (i.e., what to choose) are associated with cerebellum mechanisms (i.e., when to choose). Overall, multiple levels of parallel circuits in and around the basal ganglia are essential for coordinated behaviors. Understanding these circuits is useful for creating clinical treatments of disorders resulting from the failure of these circuits.
From bed to bench side: Reverse translation to optimize neuromodulation for mood disorders
Authors: Rudebeck Peter H. , Rich Erin L. , Mayberg Helen S.
Published: December 2019

The advent of neuroimaging has provided foundational insights into the neural basis of psychiatric conditions, such as major depression. Across countless studies, dysfunction has been localized to distinct parts of the limbic system. Specific knowledge about affected locations has led to the development of circuit modulation therapies to correct dysfunction, notably deep brain stimulation (DBS). This and other emerging neuromodulation approaches have shown great promise, but their refinement has been slow and fundamental questions about their mechanisms of action remain. Here, we argue that their continued development requires reverse translation to animal models with close homology to humans, namely, nonhuman primates. With a particular focus on DBS approaches for depression, we highlight the parts of the brain that have been targeted by neuromodulation in humans, their efficacy, and why nonhuman primates are the most suitable model in which to conduct their refinement. We finish by highlighting key gaps in our knowledge that need to be filled to allow more rapid progress toward effective therapies in patients for whom all other treatment attempts have failed.
Why we need nonhuman primates to study the role of ventromedial prefrontal cortex in the regulation of threat- and reward-elicited responses
Authors: Roberts Angela C. , Clarke Hannah F.
Published: December 2019

The ventromedial prefrontal cortex (vmPFC) is consistently implicated in the cognitive and emotional symptoms of many psychiatric disorders, but the causal mechanisms of its involvement remain unknown. In part, this is because of the poor characterization of the disorders and their symptoms, and the focus of experimental studies in animals on subcortical (rather than cortical) dysregulation. Moreover, even in those experimental studies that have focused on the vmPFC, the preferred animal model for such research has been the rodent, in which there are marked differences in the organization of this region to that seen in humans, and thus the extent of functional homology is unclear. There is also a paucity of well-defined behavioral paradigms suitable for translating disorder-relevant findings across species. With these considerations in mind, we discuss the value of nonhuman primates (NHPs) in bridging the translational gap between human and rodent studies. We focus on recent investigations into the involvement in reward and threat processing of 2 major regions of the vmPFC, areas 25 and 32 in NHPs and their anatomical homologs, the infralimbic and prelimbic cortex, in rodents. We highlight potential similarities, but also differences between species, and consider them in light of the extent to which anatomical homology reflects functional homology, the expansion of the PFC in human and NHPs, and most importantly how they can guide future studies to improve the translatability of findings from preclinical animal studies into the clinic.
Distributed processing of movement signaling
Authors: Kennedy Scott D. , Schwartz Andrew B.
Published: December 2019

Basic neurophysiological research with monkeys has shown how neurons in the motor cortex have firing rates tuned to movement direction. This original finding would have been difficult to uncover without the use of a behaving primate paradigm in which subjects grasped a handle and moved purposefully to targets in different directions. Subsequent research, again using behaving primate models, extended these findings to continuous drawing and to arm and hand movements encompassing action across multiple joints. This research also led to robust extraction algorithms in which information from neuronal populations is used to decode movement intent. The ability to decode intended movement provided the foundation for neural prosthetics in which brain-controlled interfaces are used by paralyzed human subjects to control computer cursors or high-performance motorized prosthetic arms and hands. This translation of neurophysiological laboratory findings to therapy is a clear example of why using nonhuman primates for basic research is valuable for advancing treatment of neurological disorders. Recent research emphasizes the distribution of intention signaling through neuronal populations and shows how many movement parameters are encoded simultaneously. In addition to direction and velocity, the arm’s impedance has now been found to be encoded as well. The ability to decode motion and force from neural populations will make it possible to extend neural prosthetic paradigms to precise interaction with objects, enabling paralyzed individuals to perform many tasks of daily living.
Oligomeric Aβ in the monkey brain impacts synaptic integrity and induces accelerated cortical aging
Authors: Beckman Danielle , Ott Sean , Donis-Cox Kristine , Janssen William G. , Bliss-Moreau Eliza , Rudebeck Peter H. , Baxter Mark G. , Morrison John H.
Published: December 2019

As the average age of the population continues to rise, the number of individuals affected with age-related cognitive decline and Alzheimer’s disease (AD) has increased and is projected to cost more than $290 billion in the United States in 2019. Despite significant investment in research over the last decades, there is no effective treatment to prevent or delay AD progression. There is a translational gap in AD research, with promising drugs based on work in rodent models failing in clinical trials. Aging is the leading risk factor for developing AD and understanding neurobiological changes that affect synaptic integrity with aging will help clarify why the aged brain is vulnerable to AD. We describe here the development of a rhesus monkey model of AD using soluble oligomers of the amyloid beta (Aβ) peptide (AβOs). AβOs infused into the monkey brain target a specific population of spines in the prefrontal cortex, induce neuroinflammation, and increase AD biomarkers in the cerebrospinal fluid to similar levels observed in patients with AD. Importantly, AβOs lead to similar dendritic spine loss to that observed in normal aging in monkeys, but so far without detection of amyloid plaques or tau pathology. Understanding the basis of synaptic impairment is the most effective route to early intervention and prevention or postponement of age-related cognitive decline and transition to AD. These initial findings support the use of monkeys as a platform to understand age-related vulnerabilities of the primate brain and may help develop effective disease-modifying therapies for treatment of AD and related dementias.
Dorsoventral decoupling of Hox gene expression underpins the diversification of molluscs
Authors: Huan Pin , Wang Qian , Tan Sujian , Liu Baozhong
Published: December 2019

In contrast to the Hox genes in arthropods and vertebrates, those in molluscs show diverse expression patterns with differences reported among lineages. Here, we investigate 2 phylogenetically distant molluscs, a gastropod and a polyplacophoran, and show that the Hox expression in both species can be divided into 2 categories. The Hox expression in the ventral ectoderm generally shows a canonical staggered pattern comparable to the patterns of other bilaterians and likely contributes to ventral patterning, such as neurogenesis. The other category of Hox expression on the dorsal side is strongly correlated with shell formation and exhibits lineage-specific characteristics in each class of mollusc. This generalized model of decoupled dorsoventral Hox expression is compatible with known Hox expression data from other molluscan lineages and may represent a key characteristic of molluscan Hox expression. These results support the concept of widespread staggered Hox expression in Mollusca and reveal aspects that may be related to the evolutionary diversification of molluscs. We propose that dorsoventral decoupling of Hox expression allowed lineage-specific dorsal and ventral patterning, which may have facilitated the evolution of diverse body plans in different molluscan lineages.
The neurology clinic needs monkey research
Authors: Goldberg Michael E.
Published: December 2019

This report discusses how a number of currently incurable diseases might be treated by advances developed as the result of current ongoing research on monkeys. The diseases discussed include Parkinson's disease, amyotrophic lateral sclerosis, spinal cord injury, peripheral neuropathy, and stroke. Finally, the report discusses the devastating effect the animal rights movement and adverse publicity can have on basic neurobiological research on monkeys.
Drivers of change in China’s energy-related CO2emissions
Authors: Zheng Xiaoqi , Lu Yonglong , Yuan Jingjing , Baninla Yvette , Zhang Sheng , Stenseth Nils Chr. , Hessen Dag O. , Tian Hanqin , Obersteiner Michael , Chen Deliang
Published: December 2019

CO2emissions are of global concern because of climate change. China has become the largest CO2emitter in the world and presently accounts for 30% of global emissions. Here, we analyze the major drivers of energy-related CO2emissions in China from 1978 when the reform and opening-up policy was launched. We find that 1) there has been a 6-fold increase in energy-related CO2emissions, which was driven primarily (176%) by economic growth followed by population growth (16%), while the effects of energy intensity (−79%) and carbon intensity (−13%) slowed the growth of carbon emissions over most of this period; 2) energy-related CO2emissions are positively related to per capita gross domestic product (GDP), population growth rate, carbon intensity, and energy intensity; and 3) a portfolio of command-and-control policies affecting the drivers has altered the total emission trend. However, given the major role of China in global climate change mitigation, significant future reductions in China’s CO2emissions will require transformation toward low-carbon energy systems.
Microsecond-timescale simulations suggest 5-HT–mediated preactivation of the 5-HT3Aserotonin receptor
Authors: Guros Nicholas B. , Balijepalli Arvind , Klauda Jeffery B.
Published: December 2019

Significance

The pentameric ligand-gated ion channel 5-HT3Aexhibits a transient preactive state that provides valuable insight into its binding and activation mechanisms. In this preactive state, the allosteric regulation of the channel structure, and thereby function, upon ligand binding occur at timescales that are too fast to be measured experimentally. This study demonstrates the power of microsecond-timescale MD simulations in detecting these transitional preactive states upon ligand binding and describing their effects on channel function at the molecular scale. Such a mechanistic understanding of the channel function is a critical element in the design of therapeutics for the regulation of 5-HT3A, which are needed to reverse the effects of numerous pathological conditions.
An inhibitor of complement C5 provides structural insights into activation
Authors: Reichhardt Martin P. , Johnson Steven , Tang Terence , Morgan Thomas , Tebeka Nchimunya , Popitsch Niko , Deme Justin C. , Jore Matthijs M. , Lea Susan M.
Published: December 2019

The complement system is a crucial part of innate immune defenses against invading pathogens. The blood-meal of the tickRhipicephalus pulchelluslasts for days, and the tick must therefore rely on inhibitors to counter complement activation. We have identified a class of inhibitors from tick saliva, the CirpT family, and generated detailed structural data revealing their mechanism of action. We show direct binding of a CirpT to complement C5 and have determined the structure of the C5–CirpT complex by cryoelectron microscopy. This reveals an interaction with the peripheral macro globulin domain 4 (C5_MG4) of C5. To achieve higher resolution detail, the structure of the C5_MG4–CirpT complex was solved by X-ray crystallography (at 2.7 Å). We thus present the fold of the CirpT protein family, and provide detailed mechanistic insights into its inhibitory function. Analysis of the binding interface reveals a mechanism of C5 inhibition, and provides information to expand our biological understanding of the activation of C5, and thus the terminal complement pathway.