bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase separation vs aggregation behavior for model disordered proteins
Authors: Rana Ushnish , Brangwynne Clifford P. , Panagiotopoulos Athanassios Z.
Published: September 2021

Liquid–liquid phase separation (LLPS) is widely utilized by the cell to organize and regulate various biochemical processes. Although the LLPS of proteins is known to occur in a sequence-dependent manner, it is unclear how sequence properties dictate the nature of the phase transition and thereby influence condensed phase morphology. In this work, we have utilized grand canonical Monte Carlo simulations for a simple coarse-grained model of disordered proteins to systematically investigate how sequence distribution, sticker fraction, and chain length impact the formation of finite-size aggregates, which can preempt macroscopic phase separation for some sequences. We demonstrate that a normalized sequence charge decoration (SCD) parameter establishes a “soft” predictive criterion for distinguishing when a model protein undergoes macroscopic phase separation vs finite aggregation. Additionally, we find that this order parameter is strongly correlated with the critical density for phase separation, highlighting an unambiguous connection between sequence distribution and condensed phase density. Results obtained from an analysis of the order parameter reveal that at sufficiently long chain lengths, the vast majority of sequences are likely to phase separate. Our results suggest that classical LLPS should be the primary phase transition for disordered proteins when short-ranged attractive interactions dominate and suggest a possible reason behind recent findings of widespread phase separation throughout living cells.
Optimizing the intensity and purity of a Zeeman-decelerated beam
Authors: Mohamed Omar , Wu Lok Yiu , Tsikritea Andriana , Heazlewood Brianna R.
Published: September 2021

A pure, state-selected beam of gas-phase radicals is an important tool for the precise study of radical reactions that are astrochemically and atmospherically relevant. Generating such a beam has proven to be an ongoing challenge for the scientific community. Using evolutionary algorithms to optimize the variable experimental parameters, the passage of state- and velocity-selected hydrogen atoms can be optimized as they travel through a 12-stage Zeeman decelerator and a magnetic guide. Only H atoms traveling at the target velocity are present in the beam that reaches the detection region, from a source containing a mixture of different species. All other species—including seed gases, precursor molecules, other dissociation products, and H atoms traveling outside the target velocity—are removed from the beam. The fully optimized parameters yield a pure H-atom beam containing twice as many target particles and a narrower velocity distribution compared to beams produced when only the Zeeman decelerator is optimized. These significant improvements highlight the importance of considering the passage of all target particles in the beam as they pass through all elements of the experimental apparatus.
Limitations of perturbative coupled-cluster approximations for highly accurate investigations of Rb2+
Authors: Schnabel Jan , Cheng Lan , Köhn Andreas
Published: September 2021

We reveal limitations of several standard coupled-cluster (CC) methods with perturbation-theory based noniterative or approximate iterative treatments of triple excitations when applied to the determination of highly accurate potential energy curves (PECs) of ionic dimers, such as the XΣg+2 electronic ground state of Rb2+. Such computations are of current interest for the understanding of ion–atom interactions in the ultracold regime. We demonstrate that these CC methods lead to an unphysical long-range barrier for the Rb2+ system. The barrier is small but spoils the long-range behavior of the PEC. The effect is also found for other X2+ systems, such as X = Li, Na, and K. Calculations using a flexible framework for obtaining leading perturbative triples corrections derived using an analytic CC singles and doubles energy derivative formulation demonstrate that the origin of this problem lies in the use of T̂3 amplitudes obtained from approximate CC singles, doubles, and triples amplitude equations. It is shown that the unphysical barrier is related to a symmetry instability of the underlying Hartree–Fock mean-field solution, leading to orbitals representing two +0.5-fold charged ions in the limit of separated fragments. This, in turn, leads to a wrong 1/R asymptote of the interaction potential computed by perturbation-based CC approximations. Physically meaningful perturbative corrections in the long-range tail of the PEC may instead be obtained using symmetry-broken reference determinants.
Bright and dark modes of exchange-coupled ferromagnetic bilayers in a microwave cavity
Authors: Zhan Xingxing , Zhang Ying , Yan Xiaohong , Xiao Yang
Published: September 2021

In recent experiments, cavity-mediated bright and dark magnon modes have been observed in cavities containing two separated ferromagnetic materials. Motivated by these results, we study the bright and dark magnon modes of an exchange-coupled ferromagnetic bilayer in which both cavity-mediated and direct interlayer exchange coupling are present. Our results show that the occurrence of a magnon dark mode in the absence of interlayer coupling requires equal frequencies for the two magnon modes. With direct magnon–magnon coupling, the magnon dark mode is determined by both magnon frequencies, as well as by the magnon–photon and direct magnon–magnon coupling strengths. Our results may be useful for future cavity magnonic experiments involving ferromagnetic bilayers.
Precise and accurate control of the ellipticity of THz radiation using a photoconductive pixel array
Authors: Mosley C. D. W. , Deveikis J. , Lloyd-Hughes J.
Published: September 2021

Full control of the ellipticity of broadband pulses of THz radiation, from linear to left- or right-handed circular polarization, was demonstrated via a four-pixel photoconductive emitter with an integrated achromatic waveplate. Excellent polarization purity and accuracy were achieved, with Stokes parameters exceeding 97% for linear and circular polarization, via a robust scheme that corrected electrically for polarization changes caused by imperfect optical elements. Furthermore, to assess the speed and precision of measurements of the THz polarization, we introduced a figure of merit, the standard error after one second of measurement, found to be 0.047° for the polarization angle.
An 8-nm-thick Sn-doped polycrystalline
β
-Ga2O3 MOSFET with a “normally off” operation
Authors: Yoon Youngbin , Kim Min Ju , Cho Byung Jin , Shin Myunghun , Hwang Wan Sik
Published: September 2021

Monoclinic gallium oxide (β-Ga2O3) has attracted the interest of the scientific community due to its application in power electronics. Power electronics that need to handle a high voltage often uses a “normally off” device with a positive threshold voltage due to its fail-safe operation and its simple system architecture. In this work, 8-nm-thick Sn-doped polycrystalline β-Ga2O3 thin films were investigated as a channel material for power electronics, and their properties were characterized. The optical bandgap of the 8-nm-thick Sn-doped β-Ga2O3 was determined to be 5.77 eV, which is larger than that of 100-nm-thick Sn-doped β-Ga2O3 due to the quantum confinement effect. The developed back-gated device demonstrated normally off behavior and exhibited a voltage handling capacity as high as 224 V (2.88 MV/cm). This ultrathin β-Ga2O3 layer could also be applied to fields other than power electronics, including displays, optical sensors, photocatalytic sensors, and solar cells.
Growth of highly conductive Al-rich AlGaN:Si with low group-III vacancy concentration
Authors: Almogbel Abdullah S. , Zollner Christian J. , Saifaddin Burhan K. , Iza Michael , Wang Jianfeng , Yao Yifan , Wang Michael , Foronda Humberto , Prozheev Igor , Tuomisto Filip , Albadri Abdulrahman , Nakamura Shuji , DenBaars Steven P. , Speck James S.
Published: September 2021

The impact of AlGaN growth conditions on AlGaN:Si resistivity and surface morphology has been investigated using metalorganic chemical vapor deposition. Growth parameters including growth temperature, growth rate, and trimethylindium (TMI) flow have been systematically studied to minimize the resistivity of AlGaN:Si. We observed a strong anticorrelation between AlGaN:Si conductivity and growth temperature, suggesting increased silicon donor compensation at elevated temperatures. Secondary ion mass spectrometry and positron annihilation spectroscopy ruled out compensation by common impurities or group-III monovacancies as a reason for the observed phenomenon, in contrast to theoretical predictions. The underlying reason for AlGaN:Si resistivity dependence on growth temperature is discussed based on the possibility of silicon acting as a DX center in Al0.65Ga0.35N at high growth temperatures. We also show remarkable enhancement of AlGaN:Si conductivity by introducing TMI flow during growth. A minimum resistivity of 7.5 mΩ cm was obtained for n-type Al0.65Ga0.35N, which is among the lowest reported resistivity for this composition.
The Modular Breeding Program Simulator (MoBPS) allows efficient simulation of complex breeding programs
Authors: Pook Torsten , Reimer Christian , Freudenberg Alexander , Büttgen Lisa , Geibel Johannes , Ganesan Amudha , Ha Ngoc-Thuy , Schlather Martin , Mikkelsen Lars Friis , Simianer Henner
Published: September 2021

Context Breeding programs aim at improving the genetic characteristics of livestock populations with respect to productivity, fitness and adaptation, while controlling negative effects such as inbreeding or health and welfare issues. As breeding is affected by a variety of interdependent factors, the analysis of the effect of certain breeding actions and the optimisation of a breeding program are highly complex tasks. Aims This study was conducted to display the potential of using stochastic simulation to analyse, evaluate and compare breeding programs and to show how the Modular Breeding Program Simulator (MoBPS) simulation framework can further enhance this. Methods In this study, a simplified version of the breeding program of Göttingen Minipigs was simulated to analyse the impact of genotyping and optimum contribution selection in regard to both genetic gain and diversity. The software MoBPS was used as the backend simulation software and was extended to allow for a more realistic modelling of pig breeding programs. Among others, extensions include the simulation of phenotypes with discrete observations (e.g. teat count), variable litter sizes, and a breeding value estimation in the associated R-package miraculix that utilises a graphics processing unit. Key results Genotyping with the subsequent use of genomic best linear unbiased prediction (GBLUP) led to substantial increases in genetic gain (15.3%) compared with a pedigree-based BLUP, while reducing the increase of inbreeding by 24.8%. The additional use of optimum genetic selection was shown to be favourable compared with the plain selection of top boars. The use of graphics processing unit-based breeding value estimation with known heritability was ~100 times faster than the state-of-the-art R-package rrBLUP. Conclusions The results regarding the effect of both genotyping and optimal contribution selection are in line with well established results. Paired with additional new features such as the modelling of discrete phenotypes and adaptable litter sizes, this confirms MoBPS to be a unique tool for the realistic modelling of modern breeding programs. Implications The MoBPS framework provides a powerful tool for scientists and breeders to perform stochastic simulations to optimise the practical design of modern breeding programs to secure standardised breeding of high-quality animals and answer associated research questions.
Single-cell-type transcriptomic analysis reveals distinct gene expression profiles in wheat guard cells in response to abscisic acid
Authors: Wang Junbin , Li Yang , Wu Tianwen , Miao Chen , Xie Meijuan , Ding Bo , Li Ming , Bao Shuguang , Chen Xiaoqiang , Hu Zhaorong , Xie Xiaodong
Published: September 2021

Stomatal closure, driven by shrinking guard cells in response to the accumulation of abscisic acid (ABA) under drought stress, has a great impact on plant growth and environmental acclimation. However, the molecular regulatory mechanism underlying the turgor alteration of guard cells remains elusive, especially in cereal grasses. Here, we develop a modified enzyme digestion-based approach for the isolation of wheat (Triticum aestivum L.) guard cells. With this approach, we can remove mesophyll, pavement cells and subsidiary cells successively from the epidermis of the trichomeless coleoptile in wheat and preserve guard cells on the cuticle layers in an intact and physiologically active conditions. Using a robust single-cell-type RNA sequencing analysis, we discovered 9829 differentially expressed genes (DEGs) as significantly up- or down-regulated in guard cells in response to ABA treatment. Transcriptome analysis revealed a large percent of DEGs encoding multiple phytohormone signalling pathways, transporters, calcium signalling components, protein kinases and other ABA signalling-related proteins, which are primarily involved in key signalling pathways in ABA-regulated stomatal control and stress response. Our findings provide valuable resource for investigating the transcriptional regulatory mechanism underlying wheat guard cells in response to ABA.
Globalization mitigates the risk of conflict caused by strategic territory
Authors: Gallea Quentin , Rohner Dominic
Published: September 2021

Significance

In an era where global trade is under pressure, it is heatedly debated whether a more integrated, globalized world is fueling or appeasing conflicts. Past studies have focused on how trade links impact interstate wars, but the effects of globalization on domestic conflict have been severely understudied. Our dataset of the strategic importance of each point of the globe allows us to shed light on this controversy. This algorithm-based measure is constructed by using exclusively natural terrain features, thereby avoiding common methodological pitfalls confounding results. We find that while strategic locations may often be the object of armed competition, periods of international trade booms increase the incentives to protect trade routes and attenuate the conflict risk at strategically important locations.
Interprotomer disulfide-stabilized variants of the human metapneumovirus fusion glycoprotein induce high titer-neutralizing responses
Authors: Stewart-Jones Guillaume B. E. , Gorman Jason , Ou Li , Zhang Baoshan , Joyce M. Gordon , Yang Lijuan , Cheng Cheng , Chuang Gwo-Yu , Foulds Kathryn E. , Kong Wing-Pui , Olia Adam S. , Sastry Mallika , Shen Chen-Hsiang , Todd John-Paul , Tsybovsky Yaroslav , Verardi Raffaello , Yang Yongping , Collins Peter L. , Corti Davide , Lanzavecchia Antonio , Scorpio Diana G. , Mascola John R. , Buchholz Ursula J. , Kwong Peter D.
Published: September 2021

Significance

Type I fusion machines rearrange from prefusion to postfusion conformations to induce viral-cell entry, with structure-based stabilization of the metastable prefusion forms of these machines yielding promising vaccine candidates. However, with human metapneumovirus (HMPV), both prefusion and postfusion forms of the fusion (F) glycoprotein yield equivalent titers. We therefore tried an alternative strategy, the creation of interprotomer disulfides (IP-DSs) linking together each of the three protomers of the F trimer. In mice, IP-DS stabilization induced significantly higher titers than non–IP-DS–stabilized trimers. In macaques, improvement was more modest; nonetheless, IP-DS–stabilized trimers, in either prefusion or postfusion forms, could induce neutralizing titers many times the average titer observed in a healthy human cohort, suggesting their utility as vaccine immunogens.
Metalinguistic tactics in the Hong Kong protest movement
Authors: Jones Rodney H. , Chau Dennis
Published: September 2021

This paper explores the metalinguistic tactics used by Hong Kong protesters in 2014 and 2019 and how they reflected and exploited a range of dominant ideologies about language in the city. These tactics are considered both in terms of their rhetorical utility in the “message war” between protesters and authorities, and their significance in the broader sociolinguistic context of Hong Kong. The analysis reveals how such tactics entailed both opportunities and risks, allowing protesters to create shareable discursive artifacts that spread quickly over social media and to promote in-group solidarity and distrust of their political opponents, but also limiting their ability to broaden the appeal of their messages to certain segments of the population and implicating them in upholding language ideologies that promote exclusion and marginalization.
Be happy when your stomach is
Authors: Hoffmann Dorothea
Published: September 2021

In this paper I provide a description of the role of body-part terms in expressions of emotion and other semantic extensions in MalakMalak, a non-Pama-Nyungan language of the Daly River area. Body-based expressions denote events, emotions, personality traits, significant places and people and are used to refer to times and number. Particularly central in the language aremen‘stomach’,pundu‘head’ andtjewurr‘ear’ associated respectively with basic emotions, states of mind and reason. The figurative extensions of these body parts are discussed systematically, and compared with what is known for other languages of the Daly River region. The article also explores the grammatical make up of body-based emotional collocations, and in particular the role of noun incorporation. In MalakMalak, noun incorporation is a central part of forming predicates with body parts, but uncommon in any other semantic domain of the language and only lexemes denoting basic emotions may also incorporate closed-class adjectives.
Topological aspects of antiferromagnets
Authors: Bonbien V , Zhuo Fengjun , Salimath A , Ly O , Abbout A , Manchon A
Published: September 2021

The long fascination that antiferromagnetic materials has exerted on the scientific community over about a century has been entirely renewed recently with the discovery of several unexpected phenomena, including various classes of anomalous spin and charge Hall effects and unconventional magnonic transport, and also homochiral magnetic entities such as skyrmions. With these breakthroughs, antiferromagnets stand out as a rich playground for the investigation of novel topological behavior, and as promising candidate materials for disruptive low-power microelectronic applications. Remarkably, the newly discovered phenomena are all related to the topology of the magnetic, electronic or magnonic ground state of the antiferromagnets. This review exposes how non-trivial topology emerges at different levels in antiferromagnets and explores the novel mechanisms that have been discovered recently. We also discuss how novel classes of quantum magnets could enrich the currently expanding field of antiferromagnetic spintronics and how spin transport can in turn favor a better understanding of exotic quantum excitations.
Effects of metallic underlayer on SERS performance of a metal film over nanosphere metasurface
Authors: Nguyen T V , Pham L T , Khuyen B X , Duong D C , Nghiem L H T , Nguyen N T , Vu D , Hoa D Q , Lam V D , Nguyen H M
Published: September 2021

Metal film over nanosphere (MFON) metasurfaces have numerous applications, specifically as nanosensors for bio and chemical detection. Additionally, their interesting optical properties have also attracted the attention of many research groups. In this work, we study the influence of the metallic underlayer on the surface-enhanced Raman scattering (SERS) effect of the MFON structure. Two sets of MFON on silicon and mirror substrates were prepared for SERS measurement with rhodamine 6G. Experimental results show that the mirror layer boosts the SERS signal by two to five times. Finite difference time domain simulation was performed to gain insights into this improvement. Numerical results show that metallic underlayer helps to increase the concentration of the electric field at the hot spots. Moreover, it reflects the Raman signal via the extraordinary optical transmission channel of the MFON structure, improving the back-scattered Raman signal collection efficiency. Both of these effects can contribute to the increase of the SERS signal in agreement with the experimental results. More importantly, it provides an additional tool to tailor the optical properties of MFON metasurfaces.
Analysis of strength properties of 3D printed lightweight structures made of AlSi10Mg material
Authors: Andronov V , Šimota J , Pelikán L , Beránek L , Novák V
Published: September 2021

The main aim of this article is to compare two approaches to decreasing the overall weight of components by using additive manufacturing from AlSi10Mg alloy. This optimization is advantageous as it lessens both the production time of parts (components) and overall costs, in key industries such as aviation. The first method used to reduce the weight of a structure is the implementation of lattice structures, which replace filled parts with selected structures of different shapes, while maintaining key properties of the original structure. The other method to decrease weight is the topological optimization of prepared samples. In this article, these two options have been compared. The specially designed sample was first optimized topologically. Subsequently, it was lightened using selected structures (Octet truss and Rhombic dodecahedron) in SW Magics with different lattice parameters. These samples were then printed using DMLS technology from AlSi10Mg on the ConceptLaser M2 Cusing system. The material used was analysed by SEM, and a particle size distribution was also performed. Furthermore, a three-point bending test was performed on the bodies produced in this way. The results of this test were analysed and evaluated in terms of load (bending force), depending on the type of sample and the volume/weight saved.
Effects of the process parameters on the formation of the Zn-enriched surface layer of Mg by thermochemical treatment in a medium containing ZnCl2
Authors: Bucki T , Konieczny M
Published: September 2021

The fabrication of the Zn-enriched surface layer of Mg involved annealing of the Mg specimens in a contact with the paste containing ZnCl2. Annealing of the specimen at 440 °C for 120 min resulted in the formation of a surface layer with a complex structure. In the outer zone, dendrites of a solid solution of Zn in Mg were observed at a eutectoid matrix (an MgZn intermetallic phase and a solution of Zn in Mg). The inner, transition zone, which was located at the interface adjacent to Mg substrate, was composed of a solid solution of Zn in Mg. The use of various period of annealing time (30, 60, 90 and 120 min) showed that increasing the annealing time leads to an increase in the thickness of the layer. A similar structure of the layer was observed for each variant of the annealing time. The analysis for the specimen fabricated at 410 °C for 120 min showed that the use of lower temperature resulted in a formation of a thin layer, eutectoid in structure. When higher annealing temperature (470 °C) was used, the thick surface layer with an uneven thickness and containing macroscopic unevenness was produced on the specimen surface.
Comparison of laser and electron beam weldability of high-strength steels
Authors: Capek J , Kec J , Nemecek S , Trojan K , Ganev N , Cerny I
Published: September 2021

Pressure vessels made of high-strength steels are usually welded by arc methods. The paper deals with the development of laser and electron thick-walled beam welding technology for the mentioned applications. The mechanical and structural properties of laser and electron beam welds of plates with a thickness of 5–20 mm are compared both with and without additional filling material. The study is completed with a detailed analysis of residual stresses and their relation not only to the used welding technology but also to the results in the weld area. Laser and electron beam welds achieve high mechanical values and sufficient fatigue life. Therefore, the technology has been verified and applied for welding the test pressure vessel.
Microstructure changes occurring in heat-resistant steels during severe plastic deformation and subsequent creep
Authors: Kral P , Dvorak J , Sklenicka V , Horita Z , Takizawa Y , Tang Y , Kucharova K , Kvapilova M , Svobodova M
Published: September 2021

This work investigates creep and microstructure characteristics in P92 martensitic and 304L austenitic stainless steel after the imposing of large value of plastic strain. The as-received coarse-grained steels were strongly deformed at room temperature (RT) before tensile creep testing. The flat specimens were tested at 873 K and 923 K under different applied stresses. Microstructures were analysed by means of scanning electron microscope with EBSD (electron back-scatter diffraction) camera and transmission electron microscope. It was observed that application of severe plastic deformation (SPD) techniques at RT significantly reduces grain size and changes phase structure of 304L austenitic steel. The microstructure investigations revealed that the growth of new phases is enhanced in plastically deformed P92 martensitic and 304L austenitic stainless steels compared to their undeformed states. Creep results showed that the mean grain size of SPD-processed steels is still near ultrafine-grained region even after long-term creep testing and the coarsening of microstructure is predominantly influenced by creep time and strain.
Evaluation of the usefulness of rotors for aluminium refining
Authors: Kuglin K. , Kalisz D
Published: September 2021

Refining of liquid aluminium by blowing with an inert gas is one of the most effective methods of purifying liquid metal from hydrogen and non-metallic inclusions. In order to improve the efficiency of this process, it is necessary to develop a rotor design. The study compares rotors designed and their usefulness. For this purpose, the theoretical number of nozzles, the amount of gas per nozzle and the gas bubble radius were calculated.
Comparison of high temperature corrosion resistance of NiCr-based coatings applied by High Velocity Oxygen Fuel and Twin Arc Spray processes
Authors: Lencová K. , Mušálek R. , Lukáč F. , Vostřák M. , Česánek Z.
Published: September 2021

High temperature corrosion in a molten sodium sulfate salt environment is a serious problem of coal-fired boiler components. The promising possibility for surface protection is to apply thermally sprayed coatings. However, the key to success is to choose the optimal material and the proper spraying technology for a given application. Therefore, this study is aimed at a comparison of the high temperature behaviour of two protecting NiCr-based coatings sprayed by different technologies on 1.4903 (W.nr.) chrome-molybdenum steel. NiCrMoWFe was deposited by High Velocity Oxygen Fuel technology (HVOF). Twin wire arc spray technology (TWAS) was used to deposit multi-layered “multicoat” consisting of NiCrMoNbTa and NiCrTi with ceramic overlay Armaguard coated by brush. Chrome-molybdenum steel 1.7715 (W.nr.) commonly used in coal-fired boiler was also exposed to the high temperature corrosion test to evaluate the potential benefit of the coating. Coated as well as the uncoated specimens were exposed to the molten salt environment 18% Na2SO4 and 82% Fe2(SO4)3 at 690 °C under cyclic condition. The thermogravimetric approach was used to determine kinetics of corrosion. The X-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS) techniques were used to analyze the corrosion products and determine the corrosion mechanism. The results of high temperature corrosion resistance show that NiCrMoWFe coated by HVOF and multicoat sprayed by TWAS was comparable.
Direct comparison between Co-28Cr-6Mo alloy prepared by Selective Laser Melting and traditional investment casting
Authors: Roudnicka M , Bigas J , Sreibr V , Palousek D , Vojtech D
Published: September 2021

Thanks to high mechanical properties stable at elevated temperatures, high abrasion resistance, suitable corrosion resistance and biocompatibility, ternary cobalt alloy Co-28Cr-6Mo is a widely used material in the field of aviation industry and medical implants production. Due to the difficult formability and machinability of this alloy in combination with complex shapes of produced parts, investment casting is the mostly employed production process. However, additive manufacturing provides new processing opportunities. E.g. Selective Laser Melting (SLM) technology fusing metallic powders by precisely focused and controlled laser beam enables the production of highly complex parts with high precision. In this contribution, we bring a direct comparison between the microstructures and mechanical properties of Co-28Cr-6Mo alloy prepared by SLM and investment casting. Due to significant differences in microstructure fineness and phase composition, SLM is revealed to increase not only material strength and hardness but concurrently plasticity. As a result of rapid solidification during SLM, very fine cellular microstructure with Mo microsegregation at cell walls is formed without the occurrence of any secondary phases. The distinctive microstructure of the additively manufactured alloy can be expected to be the cause of many other variances in the material behaviour.
Neural stem cell delivery using brain-derived tissue-specific bioink for recovering from traumatic brain injury
Authors: Bae Mihyeon , Hwang Do Won , Ko Min Kyung , Jin Yeona , Shin Woo Jung , Park Wonbin , Chae Suhun , Lee Hong Jun , Jang Jinah , Yi Hee-Gyeong , Lee Dong Soo , Cho Dong-Woo
Published: September 2021

Traumatic brain injury is one of the leading causes of accidental death and disability. The loss of parts in a severely injured brain induces edema, neuronal apoptosis, and neuroinflammation. Recently, stem cell transplantation demonstrated regenerative efficacy in an injured brain. However, the efficacy of current stem cell therapy needs improvement to resolve issues such as low survival of implanted stem cells and low efficacy of differentiation into respective cells. We developed brain-derived decellularized extracellular matrix (BdECM) bioink that is printable and has native brain-like stiffness. This study aimed to fabricate injured cavity-fit scaffold with BdECM bioink and assessed the utility of BdECM bioink for stem cell delivery to a traumatically injured brain. Our BdECM bioink had shear thinning property for three-dimensional (3D)-cell-printing and physical properties and fiber structures comparable to those of the native brain, which is important for tissue integration after implantation. The human neural stem cells (NSCs) (F3 cells) laden with BdECM bioink were found to be fully differentiated to neurons; the levels of markers for mature differentiated neurons were higher than those observed with collagen bioink in vitro. Moreover, the BdECM bioink demonstrated potential in defect-fit carrier fabrication with 3D cell-printing, based on the rheological properties and shape fidelity of the material. As F3 cell-laden BdECM bioink was transplanted into the motor cortex of a rat brain, high efficacy of differentiation into mature neurons was observed in the transplanted NSCs; notably increased level of MAP2, a marker of neuronal differentiation, was observed. Furthermore, the transplanted-cell bioink suppressed reactive astrogliosis and microglial activation that may impede regeneration of the injured brain. The brain-specific material reported here is favorable for NSC differentiation and suppression of neuroinflammation and is expected to successfully support regeneration of a traumatically injured brain.
The Hilbert-Kunz function of some quadratic quotients of the Rees algebra
Authors: Strazzanti Francesco , Zarzuela Armengou Santiago
Published: September 2021

Given a commutative local ring

(
R
,

m

)

(R,\mathfrak m)

and an ideal

I
I

of

R
R

, a family of quotients of the Rees algebra

R
[
I
t
]

R[It]

has been recently studied as a unified approach to the Nagata’s idealization and the amalgamated duplication and as a way to construct interesting examples, especially integral domains. When

R
R

is noetherian of prime characteristic, we compute the Hilbert-Kunz function of the members of this family and, provided that either

I
I

is

m

\mathfrak {m}

-primary or

R
R

is regular and F-finite, we also find their Hilbert-Kunz multiplicity. Some consequences and examples are explored.
On regularity of symbolic Rees algebras and symbolic powers of vertex cover ideals of graphs
Authors: Nanduri Ramakrishna
Published: September 2021

In this work, we study the bigraded regularities of the symbolic Rees algebras

R
s

(
J
(
G
)
)
,

R
s

(
I
(
G
)
)

R_s(J(G)), R_s(I(G))

, of the vertex cover ideal

J
(
G
)

J(G)

and the edge ideal

I
(
G
)

I(G)

, of a graph

G
G

respectively. We give combinatorial upper bounds for the

(
1
,
0
)

(1,0)

-regularities of

R
s

(
J
(
G
)
)

R_s(J(G))

and

R
s

(
I
(
G
)
)

R_s(I(G))

. By using this upper bounds, we give general linear upper bounds for
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="r e g left-parenthesis upper J left-parenthesis upper G right-parenthesis Superscript left-parenthesis k right-parenthesis Baseline right-parenthesis comma r e g left-parenthesis upper I left-parenthesis upper G right-parenthesis Superscript left-parenthesis k right-parenthesis Baseline right-parenthesis">

r
e
g
(
J
(
G

)

(
k
)

)
,
r
e
g
(
I
(
G

)

(
k
)

)

reg(J(G)^{(k)}), reg(I(G)^{(k)})

for any

k
≥
1

k\geq 1

. Let

G
G

be a graph on

n
n

vertices and

deg
⁡
(
J
(
G
)
)

\deg (J(G))

be the maximum degree of minimal generators of

J
(
G
)

J(G)

. We show that if

G
G

is a non-bipartite graph, then
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="k degree left-parenthesis upper J left-parenthesis upper G right-parenthesis right-parenthesis less-than-or-equal-to r e g left-parenthesis upper J left-parenthesis upper G right-parenthesis Superscript left-parenthesis k right-parenthesis Baseline right-parenthesis less-than-or-equal-to k degree left-parenthesis upper J left-parenthesis upper G right-parenthesis right-parenthesis plus alpha 0 left-parenthesis upper G right-parenthesis minus 1 plus StartAbsoluteValue upper A 0 union StartSet x Subscript i 1 Baseline comma ellipsis comma x Subscript i Sub Subscript r Subscript Baseline EndSet EndAbsoluteValue minus r comma">

k
deg
⁡
(
J
(
G
)
)

≤

r
e
g
(
J
(
G

)

(
k
)

)

≤

k
deg
⁡
(
J
(
G
)
)
+

α
0

(
G
)
−
1
+

|

A
0

∪
{

x

i
1

,
…
,

x

i
r

}

|

−
r
,

\begin{equation*} k \deg (J(G)) \!\leq \! reg(J(G)^{(k)})\!\leq \! k \deg (J(G))+ \alpha _0(G)-1+|A_0\cup \{x_{i_1}, \ldots , x_{i_r}\}|-r, \end{equation*}

for all

k
≥
1

k \geq 1

, where

α
0

(
G
)

\alpha _0(G)

denotes the vertex cover number of

G
G

,

A
0

A_0

is a maximal independent set in

G
G

of maximal cardinality, and

r
r

is the number of

0
0

-covers that are present in an irreducible representation of the affine cone associated with the irreducible covers of

G
G

. Also if

G
G

is a non-bipartite perfect graph, then

2
k
≤
r
e
g
(
I
(
G

)

(
k
)

)
≤
2
k
+
n
−
r
+
1
,

\begin{equation*} 2k \leq reg(I(G)^{(k)})\leq 2k+n-r+1, \end{equation*}

for all

k
≥
1

k \geq 1

, where

r
r

is the number of

0
0

-covers of

Γ
(
G
)

\Gamma (G)

that are present in an irreducible representation of the affine cone associated with the irreducible covers of

Γ
(
G
)

\Gamma (G)

.
Uniform annihilators of systems of parameters
Authors: Quy Pham
Published: September 2021

In this paper we give uniform annihilators for some relations of all systems of parameters in a local ring. Our results provide simple proofs for some classical results.
Elliptic equations in divergence form with drifts in 𝐿²
Authors: Kwon Hyunwoo
Published: September 2021

We consider the Dirichlet problem for second-order linear elliptic equations in divergence form

−
d
i
v
(
A
∇
u
)
+

b

⋅
∇
u
+
λ
u
=
f
+
d
i
v

F

in 
Ω

and

u
=
0

on 
∂
Ω
,

\begin{equation*} -div(A\nabla u)+\mathbf {b} \cdot \nabla u+\lambda u=f+div\mathbf {F}\quad \text {in } \Omega \quad \text {and}\quad u=0\quad \text {on } \partial \Omega , \end{equation*}

in bounded Lipschitz domain

Ω
\Omega

in

R

2

\mathbb {R}^2

, where

A
:

R

2

→

R

2
2

A:\mathbb {R}^2\rightarrow \mathbb {R}^{2^2}

,

b

:
Ω
→

R

2

\mathbf {b} : \Omega \rightarrow \mathbb {R}^2

, and

λ
≥
0

\lambda \geq 0

are given. If

2
>
p
>
∞

2>p>\infty

and

A
A

has a small mean oscillation in small balls,

Ω
\Omega

has small Lipschitz constant, and

d
i
v
A
,

b

∈

L

2

(
Ω
;

R

2

)

divA,\,\mathbf {b} \in L^{2}(\Omega ;\mathbb {R}^2)

, then we prove existence and uniqueness of weak solutions in

W
0

1
,
p

(
Ω
)

W^{1,p}_0(\Omega )

of the problem. Similar result also holds for the dual problem.
Euler characteristic of the space of real multivariate irreducible polynomials
Authors: Hyde Trevor
Published: September 2021

We compute the compactly supported Euler characteristic of the space of degree

d
d

irreducible polynomials in

n
n

variables with real coefficients and show that the values are given by the digits in the so-called balanced binary expansion of the number of variables

n
n

.
Estimating the Complier Average Causal Effect in a Meta-Analysis of Randomized Clinical Trials With Binary Outcomes Accounting for Noncompliance: A Generalized Linear Latent and Mixed Model Approach
Authors: Zhou Ting , Zhou Jincheng , Hodges James S , Lin Lifeng , Chen Yong , Cole Stephen R , Chu Haitao
Published: September 2021

Noncompliance, a common problem in randomized clinical trials (RCTs), can bias estimation of the effect of treatment receipt using a standard intention-to-treat analysis. The complier average causal effect (CACE) measures the effect of an intervention in the latent subpopulation that would comply with their assigned treatment. Although several methods have been developed to estimate the CACE in analyzing a single RCT, methods for estimating the CACE in a meta-analysis of RCTs with noncompliance await further development. This article reviews the assumptions needed to estimate the CACE in a single RCT and proposes a frequentist alternative for estimating the CACE in a meta-analysis, using a generalized linear latent and mixed model with SAS software (SAS Institute, Inc.). The method accounts for between-study heterogeneity using random effects. We implement the methods and describe an illustrative example of a meta-analysis of 10 RCTs evaluating the effect of receiving epidural analgesia in labor on cesarean delivery, where noncompliance varies dramatically between studies. Simulation studies are used to evaluate the performance of the proposed method.
Prediction of whole-cell transcriptional response with machine learning
Authors: Eslami Mohammed , Borujeni Amin Espah , Eramian Hamed , Weston Mark , Zheng George , Urrutia Joshua , Corbet Carolyn , Becker Diveena , Maschhoff Paul , Clowers Katie , Cristofaro Alexander , Hosseini Hamid Doost , Gordon D Benjamin , Dorfan Yuval , Singer Jedediah , Vaughn Matthew , Gaffney Niall , Fonner John , Stubbs Joe , Voigt Christopher A , Yeung Enoch
Published: September 2021

Motivation

Applications in synthetic and systems biology can benefit from measuring whole-cell response to biochemical perturbations. Execution of experiments to cover all possible combinations of perturbations is infeasible. In this paper, we present the host response model (HRM), a machine learning approach that maps response of single perturbations to transcriptional response of the combination of perturbations.

Results

The HRM combines high-throughput sequencing with machine learning to infer links between experimental context, prior knowledge of cell regulatory networks, and RNASeq data to predict a gene’s dysregulation. We find that the HRM can predict the directionality of dysregulation to a combination of inducers with an accuracy of >90% using data from single inducers. We further find that the use of prior, known cell regulatory networks doubles the predictive performance of the HRM (an R2 from 0.3 to 0.65). The model was validated in two organisms, Escherichia coli and Bacillus subtilis, using new experiments conducted after training. Finally, while the HRM is trained with gene expression data, the direct prediction of differential expression makes it possible to also conduct enrichment analyses using its predictions. We show that the HRM can accurately classify >95% of the pathway regulations. The HRM reduces the number of RNASeq experiments needed as responses can be tested in silico prior to the experiment.

Availability and implementation

The HRM software and tutorial are available at https://github.com/sd2e/CDM and the configurable differential expression analysis tools and tutorials are available at https://github.com/SD2E/omics_tools.

Supplementary information

Supplementary data are available at Bioinformatics online.
Phase 2 Randomized Study of Oral Ibrexafungerp Versus Fluconazole in Vulvovaginal Candidiasis
Authors: Nyirjesy Paul , Schwebke Jane R , Angulo David A , Harriott Itzel A , Azie Nkechi E , Sobel Jack D
Published: September 2021

Background

Vulvovaginal candidiasis affects approximately 75% of women in their lifetime. Approved treatment options are limited to oral or topical azoles. Ibrexafungerp, a novel, first-in-class oral triterpenoid glucan synthase inhibitor, has demonstrated broad fungicidal Candida activity and a favorable tolerability profile. The primary objective of this dose-finding study was to identify the optimal dose of oral ibrexafungerp in patients with acute vulvovaginal candidiasis.

Methods

Patients with vulvovaginal signs and symptoms score ≥7 were randomized equally to 6 treatments groups: 5 treatment doses of oral ibrexafungerp or oral fluconazole 150 mg. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms) at the test-of-cure visit (day 10).

Results

Overall, 186 patients were randomized into the 6 treatment groups. Results, using the modified intent-to-treat population (baseline positive culture), are reported for ibrexafungerp 300 mg twice daily (BID) for 1 day (n = 27), which was the dose selected for phase 3 studies, and fluconazole 150 mg for 1 day (n = 24). At day 10, the clinical cure rates for ibrexafungerp and fluconazole were 51.9% and 58.3%, respectively; at day 25, patients with no signs or symptoms were 70.4% and 50.0%, respectively. During the study ibrexafungerp patients required less antifungal rescue medications compared with fluconazole (3.7% vs 29.2%, respectively). Ibrexafungerp was well tolerated, with the most common treatment-related adverse events being mild gastrointestinal events.

Conclusions

Ibrexafungerp is a well-tolerated novel antifungal with comparable efficacy to fluconazole in the treatment of acute vulvovaginal candidiasis.

Clinical Trials Registration

NCT03253094
Silent Inflammatory Bowel Disease
Authors: Coates Matthew D , Binion David G
Published: September 2021

Inflammatory bowel disease (IBD) is frequently associated with a variety of problematic symptoms, including abdominal pain and bowel habit changes, which are associated with poor patient quality of life and significant healthcare expenditure. Interestingly, silent IBD, a condition where patients demonstrate reduced perception and/or reporting of symptoms in the setting of active inflammation, may be as clinically consequential. This condition has been associated with serious complications leading to more costly interventions. It is by its nature an under-recognized phenomenon that affects substantial portions of patients with either Crohn’s disease or ulcerative colitis. At the present time, although there are a variety of theories relating to the underlying causes and contributors, little is known about why this phenomenon occurs. As a result, there is a lack of cost-effective, reliable diagnostic methods to identify and manage “at-risk” patients. However, it is significantly likely that further study and an improved understanding of this condition will lead to improved approaches for the diagnosis and treatment of patients with silent IBD as well as other gastrointestinal disorders associated with alterations in symptomatic perception. In this article, we critically review studies that have investigated silent IBD. Specifically, we discuss the following: (1) the methods for defining silent IBD, (2) the known epidemiology of silent IBD, (3) potential causes of and contributors to this clinical entity, (4) current diagnostic modalities available to identify it, and (5) gaps in our understanding as well as potential novel diagnostic and therapeutic applications that could be developed with further study of this condition.
Cell Type-Specific Membrane Potential Changes in Dorsolateral Striatum Accompanying Reward-Based Sensorimotor Learning
Authors: Sippy Tanya , Chaimowitz Corryn , Crochet Sylvain , Petersen Carl C H
Published: September 2021

The striatum integrates sensorimotor and motivational signals, likely playing a key role in reward-based learning of goal-directed behavior. However, cell type-specific mechanisms underlying reinforcement learning remain to be precisely determined. Here, we investigated changes in membrane potential dynamics of dorsolateral striatal neurons comparing naïve mice and expert mice trained to lick a reward spout in response to whisker deflection. We recorded from three distinct cell types: (i) direct pathway striatonigral neurons, which express type 1 dopamine receptors; (ii) indirect pathway striatopallidal neurons, which express type 2 dopamine receptors; and (iii) tonically active, putative cholinergic, striatal neurons. Task learning was accompanied by cell type-specific changes in the membrane potential dynamics evoked by the whisker deflection and licking in successfully-performed trials. Both striatonigral and striatopallidal types of striatal projection neurons showed enhanced task-related depolarization across learning. Striatonigral neurons showed a prominent increase in a short latency sensory-evoked depolarization in expert compared to naïve mice. In contrast, the putative cholinergic striatal neurons developed a hyperpolarizing response across learning, driving a pause in their firing. Our results reveal cell type-specific changes in striatal membrane potential dynamics across the learning of a simple goal-directed sensorimotor transformation, helpful for furthering the understanding of the various potential roles of different basal ganglia circuits.