bluuebunny/crossref_metadata_2025 huggingface dataset:
NH3-detecting room temperature PANI-TiO2-based flexible gas sensor with EIS-validated sensing mechanism
Authors: Jain Aakanksha , Gautam Shivam Kumar , Panda Siddhartha
Published: July 2023

PANI-metal oxide nanocomposites have been studied extensively to improve sensor performance at room temperature. To date, researchers have utilized PANI-TiO2 for sensing NH3, but no elucidation of the sensing mechanism has been reported. In this research work, PANI-TiO2 nanocomposite-based flexible gas sensor for detecting NH3, operating at room temperature, has been investigated. The novelty lies in elucidating the sensing mechanism using electrochemical impedance spectroscopy (EIS) study. Effects of the operating temperature and different humidity levels of the CDA environment on the sensing parameters of the devices are also studied. PANI-TiO2 (10 wt% TiO2 with respect to aniline) device showed the best response of 9.88% against 2 ppm of NH3 at 21 °C. The sensor can detect NH3 as low as 2 ppm within 10 seconds. A low deviation of 3.5% in sensor response after 100 bending cycles was observed. Further, the sensor maintained a near-consistent response even after seven months of fabrication. Moreover, linearity was observed in the I-V analysis, providing further evidence that devices are ohmic. Furthermore, the contributions of the bulk, grain boundary, depletion region, and resistance between the electrode and the sensing film in the sensor response were identified by the EIS studies.
Dynamic survivability in oscillator systems
Authors: Sun Zhongkui , Wang Yuexin
Published: July 2023

Whether the dynamic systems can display normal performance or complete key mission is the hot spot in recent years. In accordance with this, dynamic survivability is defined for the first time and mission-completion-probability is given as an index in this study. Taking the behavior of diffusively coupled oscillator systems with Erdös-Rényi random graph and Barabási-Albert scale-free network structures as examples, we show the network structures, systems’ parameters and attack strategies exhibit a profound influence on the dynamic survivability. Erdös-Rényi random graph and Barabási-Albert scale-free systems display better or worse dynamic survivability under different attack strategies respectively. Our outcomes fill the gap in the survivability study and are helpful for enhancing the dynamic survivability of real systems.
Uncovering the attributes of Bi2O3-CdO-TeO2 glasses: examining their structural, optical, and gamma ray shielding properties
Authors: Al-Otaibi Jamelah S , Kumar Ashok , Mahmoud K G , Almuqrin Aljawhara H , Sayyed M I
Published: July 2023

The present work deals with the fabrication of Bi2O3-CdO-TeO2 glasses using the melt quenching technique. XRD determines the amorphous nature, while the FTIR technique provides information about the molecular vibrations present in a sample. To understand the optical properties of the glass, UV–Vis absorption spectra in the 200–800 nm range and Tauc’s plot method to determine the indirect allowed band gap energies are used. The band gap energy decreases as the concentration of Bi2O3 is increasing. Additionally, Monte Carlo (MC) simulation technique has been used to assess the linear attenuation coefficient (μ). The evaluation demonstrates an improvement in μ by 12% and 7%, respectively at 0.15 MeV and 0.662 MeV with increasing the Bi2O3 concentration from 45 mol% to 60 mol%. The half-value thickness (Δ0.5) and lead equivalent thickness (Δeq) of the fabricated samples marginally improved by the minor increase in μ in the mid-gamma energy region. The fabricated samples have applications in the field of gamma-ray shielding.
Aemulus ν: precise predictions for matter and biased tracer power spectra in the presence of neutrinos
Authors: DeRose Joseph , Kokron Nickolas , Banerjee Arka , Chen Shi-Fan , White Martin , Wechsler Risa , Storey-Fisher Kate , Tinker Jeremy , Zhai Zhongxu
Published: July 2023

We present the Aemulus
ν simulations: a suite of 150 (1.05 h-1 Gpc)3
N-body simulations with a mass resolution of 3.51 × 1010 Ω
cb
/0.3  h-1
M
⊙ in a wνCDM cosmological parameter space. The simulations have been explicitly designed to span a broad range in σ
8 to facilitate investigations of tension between large scale structure and cosmic microwave background cosmological probes. Neutrinos are treated as a second particle species to ensure accuracy to 0.5 eV, the maximum neutrino mass that we have simulated. By employing Zel'dovich control variates, we increase the effective volume of our simulations by factors of 10-105 depending on the statistic in question. As a first application of these simulations, we build new hybrid effective field theory and matter power spectrum surrogate models, demonstrating that they achieve ≤ 1% accuracy for k ≤ 1 hMpc-1 and 0 ≤ z ≤ 3, and ≤ 2% accuracy for k ≤ 4 hMpc-1 for the matter power spectrum. We publicly release the trained surrogate models, and estimates of the surrogate model errors in the hope that they will be broadly applicable to a range of cosmological analyses for many years to come.
Investigating the gamma-ray burst from decaying MeV-scale axion-like particles produced in supernova explosions
Authors: Müller Eike , Calore Francesca , Carenza Pierluca , Eckner Christopher , Marsh M.C. David
Published: July 2023

We investigate the characteristics of the gamma-ray signal following the decay of MeV-scale Axion-Like Particles (ALPs) coupled to photons which are produced in a Supernova (SN) explosion.
This analysis is the first to include the production of heavier ALPs through the photon coalescence process, enlarging the mass range of ALPs that could be observed in this way and giving a stronger bound from the observation of SN 1987A.
Furthermore, we present a new analytical method for calculating the predicted gamma-ray signal from ALP decays. With this method we can rigorously prove the validity of an approximation that has been used in some of the previous literature, which we show here to be valid only if all gamma rays arrive under extremely small observation angles (i.e. very close to the line of sight to the SN). However, it also shows where the approximation is not valid, and offers an efficient alternative to calculate the ALP-induced gamma-ray flux in a general setting when the observation angles are not guaranteed to be small.
We also estimate the sensitivity of the Fermi Large Area Telescope (Fermi-LAT) to this gamma-ray signal from a future nearby SN and show that in the case of a non-observation the current bounds on the ALP-photon coupling gaγ
are strengthened by about an order of magnitude.
In the case of an observation, we show that it may be possible to reconstruct the product gaγ

2
ma
, with ma
the mass of the ALP.
Ground-state phase diagram, symmetries, excitation spectra and finite-frequency scaling of the two-mode quantum Rabi model
Authors: Chen 陈 Yue 越 , Liu 刘 Maoxin 卯鑫 , Chen 陈 Xiaosong 晓松
Published: July 2023

We investigate the two-mode quantum Rabi model (QRM) describing the interaction between a two-level atom and a two-mode cavity field. The quantum phase transitions are found when the ratio η of transition frequency of atom to frequency of cavity field approaches infinity. We apply the Schrieffer–Wolff (SW) transformation to derive the low-energy effective Hamiltonian of the two-mode QRM, thus yielding the critical point and rich phase diagram of quantum phase transitions. The phase diagram consists of four regions: a normal phase, an electric superradiant phase, a magnetic superradiant phase and an electromagnetic superradiant phase. The quantum phase transition between the normal phase and the electric (magnetic) superradiant phase is of second order and associates with the breaking of the discrete Z
2 symmetry. On the other hand, the phase transition between the electric superradiant phase and the magnetic superradiant phase is of first order and relates to the breaking of the continuous U(1) symmetry. Several important physical quantities, for example the excitation energy and average photon number in the four phases, are derived. We find that the excitation spectra exhibit the Nambu–Goldstone mode. We calculate analytically the higher-order correction and finite-frequency exponents of relevant quantities. To confirm the validity of the low-energy effective Hamiltonians analytically derived by us, the finite-frequency scaling relation of the averaged photon numbers is calculated by numerically diagonalizing the two-mode quantum Rabi Hamiltonian.
Melting of electronic/excitonic crystals in 2D semiconductor moiré patterns: A perspective from the Lindemann criterion
Authors: Zhou 周 Jiyong 纪勇 , Tang 唐 Jianju 剑炬 , Yu 俞 Hongyi 弘毅
Published: July 2023

Using the Lindemann criterion, we analyzed the quantum and thermal melting of electronic/excitonic crystals recently discovered in two-dimensional (2D) semiconductor moiré patterns. We show that the finite 2D screening of the atomically thin material can suppress (enhance) the inter-site Coulomb (dipolar) interaction strength, thus inhibits (facilitates) the formation of the electronic (excitonic) crystal. Meanwhile, a strong enough moiré confinement is found to be essential for realizing the crystal phase with a wavelength near 10 nm or shorter. From the calculated Lindemann ratio which quantifies the fluctuation of the site displacement, we estimate that the crystal will melt into a liquid above a critical temperature ranging from several tens Kelvin to above 100 K (depending on the system parameters).
Bacterial turbulence in gradient confinement
Authors: Yan 颜 Ningzhe 宁哲 , Xie 谢 Chenliang 晨亮 , Luo 罗 Hao 昊 , Liu 刘 Yanan 亚楠 , Jing 经 Guangyin 光银
Published: July 2023

We investigate a novel form of non-uniform living turbulence at an extremely low Reynolds number using a bacterial suspension confined within a sessile droplet. This turbulence differs from homogeneous active turbulences in two or three-dimensional geometries. The heterogeneity arises from a gradient of bacterial activity due to oxygen depletion along the droplet’s radial direction. Motile bacteria inject energy at individual scales, resulting in local anisotropic energy fluctuations that collectively give rise to isotropic turbulence. We find that the total kinetic energy and enstrophy decrease as distance from the drop contact line increases, due to the weakening of bacterial activity caused by oxygen depletion. While the balance between kinetic energy and enstrophy establishes a characteristic vortex scale depending on the contact angle of the sessile drop. The energy spectrum exhibits diverse scaling behaviors at large wavenumber, ranging from k
−1/5 to k
−1, depending on the geometric confinement. Our findings demonstrate how spatial regulation of turbulence can be achieved by tuning the activity of driving units, offering insights into the dynamic behavior of living systems and the potential for controlling turbulence through gradient confinements.
Effect of resonant magnetic perturbations including toroidal sidebands on magnetic footprints and fast ion losses in HL-2M
Authors: Hao G.Z. , Dong G.Q. , Liu Y.Q. , Xu Y.H. , Zhao Y.F. , Wang S. , He H.D. , Xue M. , Li Z.J. , Li J.X. , Li C.Y. , Wang L. , Xu J.Q. , Chen W. , Cai L.J. , Zhong W.L. , Xu M. , Duan X.R.
Published: July 2023

Externally applied resonant magnetic perturbations (RMPs), generated by magnetic coils located outside the plasma (referred to as RMP coils), provide an effective way to control the edge localized mode (ELM) in tokamak devices. Due to the discrete nature of the toroidal distribution of these window-frame coils, toroidal sidebands always exist together with the fundamental harmonics designed for ELM control. In this work, the MARS-F code (Liu et al 2000 Phys. Plasmas
7 3681) is applied to investigate the detailed features of the RMP spectra considering both the dominant harmonic (n = 2) and the associated sideband (n = 6), and the impact of the combined fields on magnetic footprints as well as on the fast ion losses for a reference double-null scenario in the HL-2M device. It is found that the sum of the n = 2 and n = 6 RMP fields splits the footprint and widens the footprint area, as compared to the single-n (n = 2) harmonic case. The resistive plasma response breaks the up–down symmetry of the footprint pattern on the outer divertor plates, which is otherwise symmetric assuming vacuum RMP fields. Considering fast ion losses, a threshold value exists for the initially launched radial position of test particles, as well as for the RMP coil current, before the loss occurs. When the threshold criterion is satisfied, the combined n = 2 and n = 6 RMP fields enhance the fast ion loss rate by

∼

20
%

, as compared to that of the n = 2 component alone. These results illustrate the important role of the sideband of RMP fields on the magnetic footprints and fast ion losses in tokamak plasmas.
Development of Time Projection Chamber prototype integrated with UV laser tracks for the future circular e+e- collider
Authors: She X. , Qi H.R. , Chang Y. , Yu L.W. , Dai H.L. , Zhang J.X. , Zhang J. , Deng Z. , Wu L.H. , Li G. , Ruan M.Q. , Wang J.C. , Chen Y.B. , Yu C.X.
Published: July 2023

The Circular Electron Positron Collider (CEPC) has been proposed as a Higgs and a high luminosity Z factory in the last few years.
The baseline detector concept design consists of a Time Projection Chamber (TPC) as the main tracker detector, which needs the high precision spatial resolution of approximately 100 μm in rφ direction over the whole the drift length.
There will be no power-pulsing mode in the future circular colliders, the specific limitations of the detector requirements should be considered at the high luminosity Z pole.
Several critical issues remain regarding the TPC R&D.
The physics goals require particle identification (PID) resolution to be considered using the cluster counting method.
The updated simulation results of the PID resolution demonstrate the potential of TPC technology to fit Z-pole running at CEPC.
To meet the physics requirements for the tracker detector in CEPC, a TPC prototype integrated with an ultraviolet laser track system has been developed.
The prototype consists of several horizontal laser tracks around the TPC detector chamber with a drift length of 500 mm, the fast electronics readout of 1280 channels, a 20000 V field-cage, a double-layer GEM detector with 200 × 200 mm2 active area and a DAQ system.
The spatial resolution, dE/dx resolution, and drift velocity were studied and analyzed using the TPC prototype and the 266 nm UV laser tracks.
Some updated experimental results, including the spatial resolution, the laser track reconstruction, and dE/dx resolution have been obtained.
By using the pseudo full-length track to evaluate the full-size TPC with 220 layers at CEPC, the dE/dx resolution was estimated to be about 3.4%.
All results indicates that this TPC prototype integrated with UV laser tracks has been successfully developed to meet the updated CEPC physics requirements.
Cytocompatible and osteoinductive cotton cellulose nanofiber/chitosan nanobiocomposite scaffold for bone tissue engineering
Authors: Zanette Rafaella de Souza Salomão , Fayer Leonara , Vasconcellos Rebecca , de Oliveira Luiz Fernando Cappa , Maranduba Carlos Magno da Costa , de Alvarenga Érika Lorena Fonseca Costa , Martins Maria Alice , Brandão Humberto de Mello , Munk Michele
Published: July 2023

Natural polymeric nanobiocomposites hold promise in repairing damaged bone tissue in tissue engineering. These materials create an extracellular matrix (ECM)-like microenvironment that induces stem cell differentiation. In this study, we investigated a new cytocompatible nanobiocomposite made from cotton cellulose nanofibers (CNFs) combined with chitosan polymer to induce osteogenic stem cell differentiation. First, we characterized the chemical composition, nanotopography, swelling properties, and mechanical properties of the cotton CNF/chitosan nanobiocomposite scaffold. Then, we examined the biological characteristics of the nanocomposites to evaluate their cytocompatibility and osteogenic differentiation potential using human mesenchymal stem cells derived from exfoliated deciduous teeth. The results showed that the nanobiocomposite exhibited favorable cytocompatibility and promoted osteogenic differentiation of cells without the need for chemical inducers, as demonstrated by the increase in alkaline phosphatase activity and ECM mineralization. Therefore, the cotton CNF/chitosan nanobiocomposite scaffold holds great promise for bone tissue engineering applications.
Sufficiency in passenger transport and its potential for lowering energy demand
Authors: Arnz M , Krumm A
Published: July 2023

Prior research suggests that energy demand-side interventions have a large potential in climate change mitigation, connected to co-benefits in human well-being and several Sustainable Development Goals. However, it is challenging to translate such strategies into local and sectoral realities. We explore sufficiency futures for German passenger transport, a sector that is assumed to further grow in most studies, to analyse demand reduction potentials. In an interdisciplinary research design, we collect 133 diverse drivers of change of which we construct three sufficiency storylines. We translate them into parameters of the aggregated transport model quetzal_germany and quantify it through an expert survey. Results indicate that passenger transport energy demand can be lowered by up to 73%, while pointing at the various cultural, political, economic, technological, and organisational developments that are responsible for this change and show co-benefits for well-being. The comparison to global low energy demand studies suggests that our results lie between two boundaries: the absolute minimum for decent living standards and the most ambitious illustrative modelling pathway in the IPCC Sixth Assessment Report. This work bridges the gap between ambitious climate targets from a global perspective and corresponding system design requirements in the local context.
A metriplectic formulation of polarized radiative transfer
Authors: Bosboom V , Kraus M , Schlottbom M
Published: July 2023

We present a metriplectic formulation of the radiative transfer equation with polarization and varying refractive index and show that this formulation automatically satisfies the first two laws of thermodynamics. In particular, the derived antisymmetric bracket enjoys the Jacobi identity. To obtain this formulation we suitably transform the equation and show that important physical quantities derived from the solution remain invariant under such a transformation.
Injectable rBMSCs-laden hydrogel microspheres loaded with naringin for osteomyelitis treatment
Authors: Dong Minyi , Yang Xiaofu , Lu Jingyi , Siow Lixuen , He Huihui , Liu An , Wu Pengcheng , He Yong , Sun Miao , Yu Mengfei , Wang Huiming
Published: July 2023

Osteomyelitis, caused by purulent bacteria invading bone tissue, often occurs in long bones and seriously affects the physical and mental health and working ability of patients; it can even endanger life. However, due to bone cavity structure, osteomyelitis tends to occur inside the bone and thus lacks an effective treatment; anti-inflammatory treatment and repair of bone defects are necessary. Here, we developed injectable hydrogel microspheres loaded with naringin and bone marrow mesenchymal stem cells, which have anti-inflammatory and osteogenic properties. These homogeneous microspheres, ranging from 200 to 1000 μm, can be rapidly fabricated using an electro-assisted bio-fabrication method. Interestingly, it was found that microspheres with relatively small diameters (200 μm) were more conducive to the initial cell attachment, growth, spread, and later osteogenic differentiation. The developed microspheres can effectively treat tibial osteomyelitis in rats within six weeks, proving their prospects for clinical application.
Roadmap on structured waves
Authors: Bliokh Konstantin Y , Karimi Ebrahim , Padgett Miles J , Alonso Miguel A , Dennis Mark R , Dudley Angela , Forbes Andrew , Zahedpour Sina , Hancock Scott W , Milchberg Howard M , Rotter Stefan , Nori Franco , Özdemir Şahin K , Bender Nicholas , Cao Hui , Corkum Paul B , Hernández-García Carlos , Ren Haoran , Kivshar Yuri , Silveirinha Mário G , Engheta Nader , Rauschenbeutel Arno , Schneeweiss Philipp , Volz Jürgen , Leykam Daniel , Smirnova Daria A , Rong Kexiu , Wang Bo , Hasman Erez , Picardi Michela F , Zayats Anatoly V , Rodríguez-Fortuño Francisco J , Yang Chenwen , Ren Jie , Khanikaev Alexander B , Alù Andrea , Brasselet Etienne , Shats Michael , Verbeeck Jo , Schattschneider Peter , Sarenac Dusan , Cory David G , Pushin Dmitry A , Birk Michael , Gorlach Alexey , Kaminer Ido , Cardano Filippo , Marrucci Lorenzo , Krenn Mario , Marquardt Florian
Published: July 2023

Structured waves are ubiquitous for all areas of wave physics, both classical and quantum, where the wavefields are inhomogeneous and cannot be approximated by a single plane wave. Even the interference of two plane waves, or of a single inhomogeneous (evanescent) wave, provides a number of nontrivial phenomena and additional functionalities as compared to a single plane wave. Complex wavefields with inhomogeneities in the amplitude, phase, and polarization, including topological structures and singularities, underpin modern nanooptics and photonics, yet they are equally important, e.g. for quantum matter waves, acoustics, water waves, etc. Structured waves are crucial in optical and electron microscopy, wave propagation and scattering, imaging, communications, quantum optics, topological and non-Hermitian wave systems, quantum condensed-matter systems, optomechanics, plasmonics and metamaterials, optical and acoustic manipulation, and so forth. This Roadmap is written collectively by prominent researchers and aims to survey the role of structured waves in various areas of wave physics. Providing background, current research, and anticipating future developments, it will be of interest to a wide cross-disciplinary audience.
Understanding the interplay of solution and process parameters on the physico-chemical properties of ZnO nanofibers synthesized by sol-gel electrospinning
Authors: Prabhu Niranjan N , Rajendra B V , Anandhan S , Murthy Krishna , Jagadeesh Chandra R B , George Gibin , Sachin Kumar B , Shivamurthy B
Published: July 2023

Aging populations and the increase in chronic diseases worldwide demand efficient healthcare tools for simple, rapid, and accurate diagnosis and monitoring the human health. In this context, gas sensors are used to analyze the type of gas in the breath to diagnose chronic diseases. Metal oxide and ceramic nanofibers (NFs) produced by the electrospinning (ES) method have been investigated for potential use as gas sensors in the engineering and medical sectors. The material and process parameters are the main influencing factors on the functional performance of electrospun metal oxide NFs. Zinc oxide (ZnO) based NFs are used in various gas sensors due to the wide band gap (3.37eV), large exciton binding energy, and high mobility of charge carriers of ZnO. In this research, we made an attempt to study the effect of poly(vinyl alcohol) (PVA) and zinc acetate dihydrate (ZnAc2) concentrations and feed rate, voltage, spinneret tip-to-collector distance (TCD), and pyrolysis temperature on the physical properties of ZnO NFs. An average fiber diameter of 119 nm was obtained after pyrolysis at 600 °C of electrospun fiber produced from an aqueous PVA solution of concentration 15 w% with 7.5 w% ZnAc2 based on the weight of PVA. The grain size, transmittance, structural defects, and band gap energy of NFs were found to increase as a function of the pyrolysis temperature, which could be beneficial for the functional applications of these NFs.
Dynamical systems of correspondences on the projective line I: Moduli spaces and multiplier maps
Authors: Gotou Rin
Published: July 2023

We consider moduli spaces of dynamical systems of correspondences over the projective line as a generalization of moduli spaces of dynamical systems of endomorphisms on the projective line. We define the moduli space

D
y

n

d
,
e

Dyn_{d,e}

of degree

(
d
,
e
)

(d,e)

correspondences. We construct a family

ρ
c

:
D
y

n

d
,
e

⇢
D
y

n

1
,
d
+
e
−
1

\rho _c : Dyn_{d,e} \dashrightarrow Dyn_{1,d+e-1}

of rational maps representation-theoretically. Here we note that

D
y

n

1
,
d
+
e
−
1

Dyn_{1,d+e-1}

is identical to the moduli space of the usual dynamical systems of degree

d
+
e
−
1

d+e-1

. We show that the moduli space

D
y

n

d
,
e

Dyn_{d,e}

is rational by using

ρ
c

\rho _c

. Moreover, the multiplier maps for the fixed points factor through

ρ
c

\rho _c

. Furthermore, we show the Woods Hole formulae for correspondences of different degrees are also related by

ρ
c

\rho _c

and obtain another representation-theoretically simplified form of the formula.
Kleinian sphere packings, reflection groups, and arithmeticity
Authors: Bogachev Nikolay , Kolpakov Alexander , Kontorovich Alex
Published: July 2023

In this paper we study crystallographic sphere packings and Kleinian sphere packings, introduced first by Kontorovich and Nakamura in 2017 and then studied further by Kapovich and Kontorovich in 2021. In particular, we solve the problem of existence of crystallographic sphere packings in certain higher dimensions posed by Kontorovich and Nakamura. In addition, we present a geometric doubling procedure allowing to obtain sphere packings from some Coxeter polyhedra without isolated roots, and study “properly integral” packings (that is, ones which are integral but not superintegral). Our techniques rely extensively on computations with Lorentzian quadratic forms, their orthogonal groups, and associated higher–dimensional hyperbolic polyhedra.
On the constants in abstract inverse theorems of approximation theory
Authors: Vinogradov O.
Published: July 2023

In the classical inverse theorems of constructive function theory, structural characteristics of an approximated function are estimated in terms of its best approximations. Most of the known proofs of the inverse theorems utilize Bernstein’s idea to expand the function in polynomials of its best approximation. In the present paper, Bernstein’s proof is modified by using integrals instead of sums. With this modification, it turns out that desired inequalities are based on identities similar to Frullani integrals. The considerations here are quite general, which allows one to obtain analogs of the inverse theorems for functionals in abstract Banach or even seminormed spaces. Then these abstract results are specified and inverse theorems in concrete spaces of functions are deduced, including weighted spaces, with explicit constants.
General elementary solution of a 𝑞-sided convolution type homogeneous equation
Authors: Saranchuk Yu. , Shishkin A.
Published: July 2023

Exponential polynomials satisfying a homogeneous equation of convolution type are called its elementary solutions. The article is devoted to convolution-type operators in the complex domain that generalize the well-known operators of

q
q

-sided convolution and

π
\pi

-convolution. The properties of such operators are investigated and the general form of elementary solutions (general elementary solution) of a homogeneous equation of

q
q

-sided convolution type is described.
DISCOVERY OF A CYNOMOLGUS MONKEY-CROSS-REACTIVE ANTI-HUMAN CD3 MAB FOR T CELL ENGAGERS
Authors: Mei Qin , Wang George , Liu Jieying , Chen Yunying , Gu Jijie , Nie Siwei
Published: July 2023

Background

Anti-CD3 based T cell engager antibodies can redirect cytotoxic activity of T cells in a non-MHC restricted fashion to kill tumor cells effectively. Therefore, the discovery of an anti-CD3 antibody capable of activating T cells in the presence of tumor cells is highly desirable. Recently, many anti-CD3 bispecific antibodies (bsAbs) entered clinical trials. Despite the promising efficacy of anti-CD3 bsAbs, safety issues arose and establishing a proper therapeutic window between efficacy and safety became a challenge. One of the safety concerns for anti-CD3 bsAbs is the cytokine release syndrome due to T-cell activation. Recent studies have shown that this safety challenge can be mitigated by selecting an anti-CD3 antibody with the appropriate binding epitope, CD3 affinity and binding kinetics (on and off rate).

Methods

by using WuXi Biologics’ state-of-the-art hybridoma platform, an anti-CD3 Ab was discovered through a combination of immunization and screening strategies.

Results

the selected anti-CD3 Ab demonstrates moderate affinity and fast-on fast-off binding kinetics against both human and cynomolgus CD3 molecules. Once constructed into T cell engagers (TCEs) using this anti-CD3 Ab with TAA binding arms in WuXiBody® format, the obtained TCEs mediated efficient anti-tumor activity, but induced low levels of cytokine production by T cells.

Conclusions

WuXi Biologics has discovered an anti-CD3 Ab with desired binding properties to human CD3. As shown in two showcases, the TCEs constructed using this anti-CD3 Ab can elicit efficient T cell cytotoxicity against tumor cells but low levels of cytokine release. The cross-reactivity of the anti-CD3 Ab enables preclinical assessments of toxicity in NHP.
JSKN003, A NOVEL BIPARATOPIC ANTI-HER2 ANTIBODY-DRUG CONJUGATE, EXHIBITS POTENT ANTITUMOR EFFICACY
Authors: Wang Pilin , Guo Kangping , Peng Jianjian , Sun Jie , Xu Ting
Published: July 2023

In human advanced solid tumors, expression of HER2 protein has been reported in various tumor tissues and a variety of cultured tumor cell lines including breast cancer, gastric cancer, pancreatic cancer, lung cancer, colorectal cancer, and ovarian cancer. Due to the critical roles of HER2 in carcinogenesis, two main targeted therapies have been developed in the past two decades to block the HER2-driven pathways, which include small molecule compounds that inhibit the tyrosine kinase activity of the intracellular domain, and mono-antibodies (mAbs) that target the extracellular domain (ECD) of the receptors. JSKN003 is an antibody-drug conjugate (ADC) comprised of a recombinant, humanized anti-human epidermal growth factor receptor 2 (HER2) bispecific antibody conjugated to a topoisomerase I inhibitor via a dibenzocyclooctyne tetrapeptide linker. The anti-HER2 component, KN026, is a recombinant, humanized bispecific antibody that targets both extra-cellular domains II (pertuzumab binding site) and IV (trastuzumab binding site) of HER2. JSKN003 showed high affinity binding to human HER2 with KDs of 2.209 E-10M, which is comparable to its parental antibody KN026 and bound to NCI-N87 and BxPC-3 cells in a concentration-dependent manner. At the same time JSKN003 showed more extensive and faster internalization than DS8201 on NCI-N87 cells. As expected, JSKN003 showed directly inhibits growth by targeting HER2 positive tumor model (NCI-N87 and BT474 cell models). The single dose and multiple dose pharmacokinetics study in cynomolgus monkey indicated that JSKN003, total antibody and DXd had general linear dynamic characteristics, and pharmacokinetics parameters showed no significant differences between males and females in the range 0.3-30 mg/kg. The HNSTD (highest non-severely toxic dose) of JSKN003 was determined as 30mg/kg in cynomolgus monkeys. These preclinical data suggest that JSKN003 could potentially benefit patients with tumors co-expressing HER2 through improved drug selectivity and efficacy. JSKN003’s safety, tolerability and preliminary anti-tumor activity are currently being evaluated in a first-in-human phase I study in advanced stage solid tumors in Australia (NCT05494918) using a BOIN design. This ADC is targeted on the subjects who has HER2 expression and/or HER2-gene mutation and may address an unmet medical need for these patients.
POTENT AND SELECTIVE A2AR MONOCLONAL ANTIBODY ANTAGONIST FOR THE TREATMENT OF CANCER
Authors: Hu Changyun , Wang Yanyan , Lan Xiqian , Zhang Jiandong , Zhao Xinyan
Published: July 2023

Background and significance

The presence of adenosine at abnormally high concentrations in tumor microenvironment leads to the activation of adenosine receptor 2A (A2aR) and represents one of the mechanisms for cancer patients to be resistance to immune checkpoint blockade therapies. CD39 and CD73 play an important role in converting ATP to adenosine. Currently antibodies or small molecule inhibitors (SMIs) targeting CD39 and CD73, as well as SMIs targeting adenosine receptors, are under preclinical investigation and early clinical development. However, effective biologics targeting adenosine receptors has not been reported. Here we demonstrated that humanized anti-A2aR antibodies represent promising novel therapeutic candidates for developing immunotherapy to restore anti-tumor responses in solid tumors that only partially respond or are completely resistance to ICB therapies.

Methods

Humanized anti-human A2aR monoclonal antibodies (mAbs) were generated from mouse hybridoma antibody via classic CDR grafting method. The A2aR binding and non-human primate cross-reactivity were measured by FACS using human A2aR-expressing HEK293 cells as well as human and cynomolgus monkey PBMCs. Internalizing properties were determined by FACS and immunofluorescent method. The cellular potency of these mAbs was assessed by their capability of inhibiting cAMP production induced by A2aR agonist adenosine and NECA in hA2aR-overexpressing HEK293 cells. The ability of lead candidates to reverse adenosine-mediated suppression of human effector cell function was determined using standard CD3/CD28 activation conditions in the presence of A2aR agonist NECA.

Results and Conclusion

We successfully humanized anti-A2aR antibody discovered via hybridoma technology. Humanized anti-A2aR antibodies maintain binding, cross-reactivity to human and cynomolgus monkey A2aR, as well as internalizing property and A2aR-antagonizing potency, in comparison with parental antibody. Humanized antibodies are 5~10 fold more potent than clinical stage small molecule inhibitors CPI-444 and AB928 in inhibiting cAMP production. Blockade of A2aR with humanized antibody can restore activation and cytokine production of human T and NK cells suppressed by A2aR agonist adenosine or NECA. Thus, antibody-mediated blockade of A2aR pathway represents a novel strategy to mitigate adenosine-mediated tumor resistance to immune checkpoint blockade therapies.
Exploring the natural and treatment history of vitiligo: perceptions of patients and healthcare professionals from the global VALIANT study
Authors: Hamzavi Iltefat H , Bibeau Kristen , Grimes Pearl , Harris John E , van Geel Nanja , Parsad Davinder , Tulpule Mukta , Gardner Jackie , Valle Yan , Tlhong Matewa Gaone , LaFiura Christine , Ren Haobo , Ezzedine Khaled
Published: July 2023

Background

Vitiligo is a chronic autoimmune disease affecting melanocytes, resulting in skin depigmentation. Patients with vitiligo often have reduced quality of life and comorbid autoimmune conditions and have reported a lack of available treatments for their vitiligo.

Objectives

The Vitiligo and Life Impact Among International Communities (VALIANT) study is the first global survey to explore the natural history and management of vitiligo from the perspectives of patients and healthcare professionals (HCPs).

Methods

The survey recruited adults (≥ 18 years) diagnosed with vitiligo and HCPs treating patients with vitiligo via an online panel in 17 countries. Patients were queried regarding clinical characteristics and vitiligo treatment. HCPs were queried regarding diagnosis and management of patients with vitiligo.

Results

Included in the analysis were 3541 patients and 1203 HCPs. Nearly half (45.2%) of the patients had > 5% affected body surface area; 57.1% reported family history. Patients obtained formal diagnosis after a mean (SD) of 2.4 (4.1) years; 44.9% reported previous misdiagnosis. Many patients (56.7%) reported being told that vitiligo could not be treated; 53.9% of HCPs believed patients who never treated their vitiligo had been told that vitiligo could not be treated. One-quarter of HCPs (26.3%) did not believe that an effective therapy for vitiligo exists; 44.6% of patients reported giving up on finding an effective therapy. Top treatment goals for patients and HCPs, respectively, were reduction or cessation of spread (24.7% and 18.5%) and repigmentation (22.5% and 37.2%). Patient perception of effective care was similar for treatment by dermatologists (66.9%) and primary care HCPs (67.0%).

Conclusions

Patients with vitiligo and HCPs reported similar treatment goals and expressed frustration with the lack of effective therapies. Patients reported high rates of initial misdiagnosis; many ceased seeking healthcare because they perceived that vitiligo could not be treated. The findings highlight the need for earlier diagnosis and improved disease management for vitiligo.
Comparative analysis of immune-related adverse events among patients with melanoma on immune checkpoint inhibitors: a retrospective cohort study
Authors: Pan Catherina X , Kim Daniel Y , Lau Charles B , Lau William C , Rowley Rachael , Kanwar Ruhi , LeBoeuf Nicole R , Nambudiri Vinod E
Published: July 2023

In a large, multi-institutional cohort of 672 patients with melanoma, we examined the comparative incidence and severity of immune-related adverse events among patients receiving first-line immune checkpoint inhibitors. Comparing PD-1 inhibitors, nivolumab was associated with significantly lower risk of high-grade toxicity onset compared with pembrolizumab on unadjusted logistic regression analysis. Compared with pembrolizumab, use of the CTLA-4 inhibitor ipilimumab was associated with a significant increase in risk of gastrointestinal, but not endocrine and cutaneous toxicities.
Artificial intelligence-assisted publishing in five prominent dermatology journals: a quantitative study of recent publications
Authors: Heerfordt Ida M
Published: July 2023

The potential applications of artificial intelligence (AI) in dermatology literature are discussed, and AI-generated content within abstracts of five prominent dermatology journals is investigated. Using validated AI detection software, the study categorized 57 abstracts and found none to be possibly or likely AI-generated. A highlighted limitation was the reliability of the software in detecting AI-generated content.
Athena: Specialty Certificate Examination case for dermatopathology
Authors: Wolinska Anna , Murray Gregg , Rizkalla Hala , Collins Sinead
Published: July 2023

A 48-year-old woman presented with a 2-year history of a lesion arising from the umbilicus. The lesion exuded a cyclical serosanguinous fluid with menses. Histology demonstrated a dermal lesion of glandular structures lined by endometrial-type epithelial cells.
Temporal characteristics of gamma rhythm constrain properties of noise in an inhibition-stabilized network model
Authors: Krishnakumaran R , Ray Supratim
Published: July 2023

Gamma rhythm refers to oscillatory neural activity between 30 and 80 Hz, induced in visual cortex by stimuli such as iso-luminant hues or gratings. The power and peak frequency of gamma depend on the properties of the stimulus such as size and contrast. Gamma waveform is typically arch-shaped, with narrow troughs and broad peaks, and can be replicated in a self-oscillating Wilson–Cowan (WC) model operating in an appropriate regime. However, oscillations in this model are infinitely long, unlike physiological gamma that occurs in short bursts. Further, unlike the model, gamma is faster after stimulus onset and slows down over time. Here, we first characterized gamma burst duration in local field potential data recorded from two monkeys as they viewed full screen iso-luminant hues. We then added different types of noise in the inputs to the WC model and tested how that affected duration and temporal dynamics of gamma. While the model failed with the often-used Poisson noise, Ornstein–Uhlenbeck noise applied to both the excitatory and the inhibitory populations replicated the duration and slowing of gamma and replicated the shape and stimulus dependencies. Thus, the temporal dynamics of gamma oscillations put constraints on the type and properties of underlying neural noise.
Moisture and soil type are primary drivers of Helicoverpa zea (Lepidoptera: Noctuidae) pupation
Authors: Dillard DeShae , Reisig Dominic D , Schug Hayden T , Burrack Hannah J
Published: July 2023

Studies in the lab have demonstrated that evaluating the effect of soil moisture and other variables is essential for understanding the importance of environmental factors influencing the Heliothinae pupal stage, but simulated field studies are conducted infrequently. We compared the pupation of Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) under saturated and unsaturated conditions across 3 distinct soil types (coarse sand, high organic muck, and fine-textured clay) and observed adult emergence, as well as pupal depth and weight. The interaction between soil type and moisture had a significant effect on adult emergence. Fewer adults emerged from dry fine-textured clay soil than from dry coarse sand and high organic muck. However, there was no effect of soil type and no interaction between soil and moisture on pupal depth. Soil moisture was the primary driver of pupal depth, suggesting prepupae use moisture to mediate their position within the pupal chamber. In addition, pupal weight was unrelated to soil type, moisture, or their interaction. Our study demonstrates that soil moisture can be a greater driver of H. zea pupation than soil type, but additional observations are necessary to understand the mechanism by which moisture impacts pupation.
Maternal behavioral thermoregulation facilitated evolutionary transitions from egg laying to live birth
Authors: Pettersen Amanda K , Feiner Nathalie , Noble Daniel W A , While Geoffrey M , Uller Tobias , Cornwallis Charlie K
Published: July 2023

Live birth is a key innovation that has evolved from egg-laying ancestors over 100 times in reptiles. However, egg-laying lizards and snakes can have preferred body temperatures that are lethal to developing embryos, which should select against prolonged egg retention. Here, we demonstrate that thermal mismatches between mothers and offspring are widespread across the squamate phylogeny. This mismatch is resolved by gravid females adjusting their body temperature towards the thermal optimum of their embryos. We find that the same response occurs in both live-bearing and egg-laying species, despite the latter only retaining embryos during the early stages of development. Importantly, phylogenetic reconstructions suggest this thermoregulatory behavior in gravid females evolved in egg-laying species prior to the evolution of live birth. Maternal thermoregulatory behavior, therefore, bypasses the constraints imposed by a slowly evolving thermal physiology and has likely been a key facilitator in the repeated transition to live birth.
Do China’s Foreign Economic Ties Lead to Influence Abroad? New Evidence from Recent Events
Authors: Wang Guan , Pearson Margaret M , Kastner Scott L
Published: July 2023

Do China’s growing foreign economic ties translate into political influence abroad? We identify issues about which China cares deeply, and assess whether increased economic ties correlate with greater expressed support for Chinese activities on these issues. We collect new data to measure how countries have responded to China’s implementation of a National Security Law for Hong Kong, and recent policies in Xinjiang. We find that countries with closer economic linkages to China were less likely to criticize—and in some cases more likely to support—China’s actions in Hong Kong and Xinjiang, but the strength and significance of this effect vary considerably depending on the context and type of economic ties. Interestingly, the effects of China’s foreign economic ties are substantively smaller than levels of democracy and development. The findings call into question simple assumptions about the translation of economic ties into political influence, and suggest directions for future study.
Identity-by-descent-based estimation of the X chromosome effective population size with application to sex-specific demographic history
Authors: Cai Ruoyi , Browning Brian L , Browning Sharon R
Published: July 2023

The effective size of a population (Ne) in the recent past can be estimated through analysis of identity-by-descent (IBD) segments. Several methods have been developed for estimating Ne from autosomal IBD segments, but no such effort has been made with X chromosome IBD segments. In this work, we propose a method to estimate the X chromosome effective population size from X chromosome IBD segments. We show how to use the estimated autosome Ne and X chromosome Ne to estimate the female and male effective population sizes. We demonstrate the accuracy of our autosome and X chromosome Ne estimation with simulated data. We find that the estimated female and male effective population sizes generally reflect the simulated sex-specific effective population sizes across the past 100 generations but that short-term differences between the estimated sex-specific Ne across tens of generations may not reliably indicate true sex-specific differences. We analyzed the effective size of populations represented by samples of sequenced UK White British and UK Indian individuals from the UK Biobank.
A graph approach for fast dense array inter-station phase delay interpretation
Authors: Lecointre A , Roux P , Bouttier P-A , Picard C , Louvet V
Published: July 2023

We present a phase-delay detection procedure adapted for seismic arrays composed of a large number of stations. We use graph formalism to introduce a direct method to compute station phase delays starting from inter-station phase differences deduced from noise cross-correlation functions. We focus this study on surface wave main arrival as phase-difference evaluation at each station requires high coherence level. Then, we perform numerical experiments with synthetic data computed as a realistic and dense network of 79 stations in a 400 by $400\, \mathrm{km^2}$ square box. For one of the 79 stations, we simulate a phase difference of 15 per cent of the signal period. Further, we evaluate the accuracy and precision of phase-delay estimation at each station with regard to the quality of the cross-correlation functions (i.e. the signal-to-noise ratio). When the inter-station coherence levels are larger than 0.6 (i.e. a high-quality signal), we show good agreement between the phase-delay estimation and its expected value of 15 per cent of the signal period. We introduce a coherence-weighted estimate of phase delay and show that applying this weighting allows us to be less vulnerable to phase-delay underestimation for intermediate-quality signals. Then, the method is applied to experimental data recorded by a high density nodal array with 923 vertical geophones with 19 d of continuous records, centred on the 600 by $600\, \mathrm{m^2}$ damage zone of the Clark branch of the San Jacinto Fault Zone, Southern California (USA). We verify that the San Jacinto network is well synchronized, as most of the estimated phase delays are less than 2 per cent of the central period of the signal, and they are associated with high levels of inter-station coherence. More surprisingly, the spatial features of the estimated phase delays show deterministic geographical patterns that are related to topography and that exhibit similarities with phase velocity maps at $4.5\, \mathrm{Hz}$ from previous 3-D velocity inversions. This suggests that the topographic effect may be accounted for to estimate accurate phase delays. Also, we note that the temporal variability of the estimated phase delays in the case of the San Jacinto data set are related to atmospheric forcing. Our direct method for estimating phase delays is applicable to structure-oriented monitoring studies, and it opens perspectives in the monitoring of seismic velocity variations.