bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Brachial Plexus Birth Palsies: The Stanford Experience
Authors: Park Eugene , Fox Paige M. , Curtin Catherine , Hentz Vincent R.
Published: March 2023

The start of Stanford's brachial plexus birth palsy (BPBP) experience dates back to 1983, when Dr. Vincent Rod Hentz visited Dr. Alain Gilbert on sabbatical. Since then, our principles of care for patients with BPBP have evolved based on our group's longitudinal experience caring for children with the entire spectrum of sequelae that arise in children with BPBP. We base our clinical decision making on frequent serial examinations and use intraoperative evoked potentials to guide surgical decisions. Here, we discuss our current principles on surgical indications, timing of surgery, and preferred techniques for secondary surgery in patients with BPBP.
Simulations of plasmas driven by laser wavelengths in the 1.064—10.6
μ
m range for their characterization as future extreme ultraviolet light sources
Authors: Hemminga D. J. , Versolato O. O. , Sheil J.
Published: March 2023

We characterize the properties of extreme ultraviolet (EUV) light source plasmas driven by laser wavelengths in the λ laser = 1.064 − 10.6   μ m range and laser intensities of I laser = 0.5 − 5 × 10 11 W cm−2 for λ laser = 1.064   μ m. Detailed numerical simulations of laser-irradiated spherical tin microdroplet targets reveal a strong laser-wavelength dependence on laser absorptivity and the conversion efficiency of generating in-band EUV radiation. For λ laser = 1.064   μ m irradiation, the increase in in-band radiation with increasing laser intensity is offset by only a minor reduction in conversion efficiency. Radiative losses are found to dominate the power balance for all laser wavelengths and intensities, and a clear shift from kinetic to in-band radiative losses with increasing laser wavelength is identified. Yet, with increasing laser intensity, such a shift is absent. We find that the existence of a maximum conversion efficiency, near λ laser = 4   μ m, originates from the interplay between the optical depths of the laser light and the in-band EUV photons for this specific droplet-target geometry.
The criterion of planar instability in alloy solidification under varying conditions: A viewpoint from free energy
Authors: Yu Fengyi
Published: March 2023

In alloy solidification, the transport processes of heat and solute result in morphological instability of the interface, forming different patterns of the solidification structure and determining the mechanical properties of components. As the first observable phenomenon of morphological instabilities, planar instability influences the subsequent stages significantly, deserving in-depth investigations. In this paper, the planar instability in alloy solidification under varying conditions is studied. First, the dynamical evolution of the planar instability is performed by the theoretical model and the phase-field model, respectively. Second, to represent the history-dependence of solidification, varying parameters are adopted in the simulations. Then, the criterion of planar instability under varying conditions is discussed. This paper considers that the critical parameters of planar instability are the excess free energy at the interface and the corresponding interfacial energy. Finally, to validate the criterion, comparisons between the phase-field and theoretical models are carried out, showing good consistency. Moreover, solidification processes with different preferred crystallographic orientations are performed, demonstrating the effect mechanism of the excess free energy and interfacial energy on planar instability. The idea of the interfacial energy influencing the planar instability could be applied to investigating other patterns induced by interfacial instability.
Regularity of weak solutions for the stationary Ericksen–Leslie and MHD systems
Authors: Jarrín Oscar
Published: March 2023

We consider two elliptic coupled systems of relevance in the fluid dynamics. These systems are posed on the whole space R3, and they consider the action of external forces. The first system deals with the simplified Ericksen–Leslie (SEL) system, which describes the dynamics of liquid crystal flows. The second system is the time-independent magneto-hydrodynamic (MHD) equations. For the SEL system, we obtain a new criterion to improve the regularity of weak solutions, provided that they belong to some homogeneous Morrey space. As a bi-product, we also obtain some new regularity criterion for the stationary Navier–Stokes equations and for a nonlinear harmonic map flow. This new regularity criterion also holds true for the MHD equations. Furthermore, for this last system, we are able to use the Gevrey class to prove that all finite energy weak solutions are analytic functions, provided that the external forces belong to some Gevrey class.
Local uniqueness of multi-peak solutions to a class of Schrödinger equations with competing potential
Authors: Niu Yahui , Tian Shuying , Yang Pingping
Published: March 2023

In this paper, we consider the nonlinear Schrödinger equations. Let A(x)≔[V(x)]pp−2−N2[K(x)]−2p−2. Under some conditions on A, we show the local uniqueness of positive multi-peak solutions concentrating near k(k ≥ 2) distinct non-degenerate critical points of A by using the local Pohozaev identity. We generalize Cao–Li–Luo’s results to the competing potential cases and show how these two potentials impact the uniqueness of concentrated solutions.
Parametric investigation of azimuthal instabilities and electron transport in a radial-azimuthal E × B plasma configuration
Authors: Reza M. , Faraji F. , Knoll A.
Published: March 2023

Partially magnetized low-temperature plasmas (LTP) in an E × B configuration, where the applied magnetic field is perpendicular to the self-consistent electric field, have become increasingly relevant in industrial applications. Hall thrusters, a type of electrostatic plasma propulsion, are one of the main LTP technologies whose advancement is hindered by the not-fully-understood underlying physics of operation, particularly, with respect to the plasma instabilities and the associated electron cross field transport. The development of Hall thrusters with unconventional magnetic field topologies has imposed further questions regarding the instabilities' characteristics and the electrons' dynamics in these modern cross field configurations. Accordingly, we present in this effort a detailed parametric study of the influence of three factors on the plasma processes in the radial-azimuthal coordinates of a Hall thruster, namely, the magnetic field gradient, secondary electron emission, and plasma number density. The studies are carried out using the reduced-order particle-in-cell code developed by the authors. The setup of the radial-azimuthal simulations largely follows a well-defined benchmark case from the literature in which the magnetic field is oriented along the radius, and a constant axial electric field is applied perpendicular to the simulation plane. The salient finding from our investigations is that, in the studied cases corresponding to elevated plasma densities, a long-wavelength azimuthal mode with the frequency of about 1 MHz is developed. Moreover, in the presence of strong magnetic field gradients, this mode results from an inverse energy cascade and induces a significant electron cross field transport as well as a notable heating of the ions.
A spectroscopic study of the mechanism of Au(III) (hydro-)oxides in promoting plasmon-mediated photoelectrochemical water-oxidation
Authors: Wu Li-Wen , Liu Chiyan , Han Yong , Yu Yi , Liu Zhi , Huang Yi-Fan
Published: March 2023

To understand the roles of Au(III) (hydro-)oxides in promoting plasmon-mediated photoelectrochemical (PMPEC) water-oxidation, we employed in situ microphotoelectrochemical surface-enhanced Raman spectroscopy and ambient-pressure x-ray photoelectron spectroscopy to elucidate the correlations between the amount of surface Au(III) (hydro-)oxides and the photocurrent of PMPEC water-oxidation on Au. By applying preoxidation potentials, we made surface Au(III) (hydro-)oxides on a plasmonic Au photoanode. According to the charge of reductively stripping surface oxygenated species before and after PMPEC water-oxidation, we found that a negative shift of an onset potential, increase in photocurrent, and much less growth of surface (hydro-)oxides were correlated with each other as a result of the increase in the coverage of Au (III) (hydro-)oxides. These results suggest that the surface Au(III) (hydro-)oxides kinetically promoted water-oxidation by restricting the growth of surface (hydro-)oxides.
Simulation of non-spherical particles in curved microfluidic channels
Authors: Hafemann T. , Fröhlich J.
Published: March 2023

The paper analyzes the migration of non-spherical particles in curved micro-channels. Inertial migration combined with Dean drag results in a reduced set of stable focusing positions in specific regions of the cross section of the channel. These are studied using fully resolved transient simulations of particulate flows in rectangular curved ducts with oblate and prolate particles at a bulk Reynolds number of 100 and dilute particle concentrations. The simulations were conducted with four particles in a periodic domain, instead of only one, as common practice, to investigate the particle interaction. It is observed that the focusing positions are different for the non-spherical particles compared to those obtained with spherical ones. Not only non-spherical particles focus closer to the upper and lower walls, but also their focusing position is closer to the half width of the channel. Furthermore, the migration velocity along the cross section is compared between particle shapes. Results show that all shapes lead to a significant change in migration velocity between outer and inner halves of the channel. This effect is substantially more pronounced for non-spherical particles and is observed for the first time here. It offers an independent possibility for particle separation according to shape.
Thermal conductivity of 2D diamond superstructures in interlayer-bonded twisted bilayer graphene
Authors: Mostafa Afnan , Ramasubramaniam Ashwin , Maroudas Dimitrios
Published: March 2023

We report results from a systematic analysis of thermal transport in 2D diamond superstructures in interlayer-bonded twisted bilayer graphene (IB-TBG) based on molecular-dynamics simulations. We find that the introduction of interlayer C–C bonds in these bilayer structures causes an abrupt drop in the thermal conductivity of pristine, non-interlayer-bonded bilayer graphene, while further increase in the interlayer C–C bond density (2D diamond fraction) leads to a monotonic increase in the thermal conductivity of the resulting superstructures with increasing 2D diamond fraction toward the high thermal conductivity of 2D diamond (diamane). We also find that a similar trend is exhibited in the thermal conductivity of interlayer-bonded graphene bilayers with randomly distributed individual interlayer C–C bonds (RD-IBGs) as a function of interlayer C–C bond density, but with the thermal conductivity of the IB-TBG 2D diamond superstructures consistently exceeding that of RD-IBGs at a given interlayer bond density. We analyze the simulation results employing effective medium and percolation theories and explain the predicted thermal conductivity dependence on interlayer bond density on the basis of lattice distortions induced in the bilayer structures as a result of interlayer bonding. Our findings demonstrate that the thermal conductivity of IB-TBG 2D diamond superstructures and RD-IBGs can be precisely tuned by controlling interlayer C–C bond density and have important implications for the thermal management applications of interlayer-bonded few-layer graphene derivatives.
Observation of coherently coupled cation spin dynamics in an insulating ferrimagnetic oxide
Authors: Klewe C. , Shafer P. , Shoup J. E. , Kons C. , Pogoryelov Y. , Knut R. , Gray B. A. , Jeon H.-M. , Howe B. M. , Karis O. , Suzuki Y. , Arenholz E. , Arena D. A. , Emori S.
Published: March 2023

Many technologically useful magnetic oxides are ferrimagnetic insulators, which consist of chemically distinct cations. Here, we examine the spin dynamics of different magnetic cations in ferrimagnetic NiZnAl-ferrite (Ni0.65Zn0.35Al0.8Fe1.2O4) under continuous microwave excitation. Specifically, we employ time-resolved x-ray ferromagnetic resonance to separately probe Fe2+/3+ and Ni2+ cations on different sublattice sites. Our results show that the precessing cation moments retain a rigid, collinear configuration to within ≈2°. Moreover, the effective spin relaxation is identical to within <10% for all magnetic cations in the ferrite. Thus, we validate the oft-assumed “ferromagnetic-like” dynamics in the resonantly driven ferrimagnetic oxide: the magnetic moments from different cations precess as a coherent, collective magnetization, despite the high contents of nonmagnetic Zn2+ and Al3+ diluting the exchange interactions.
Lifetime of photoexcited carriers in space-controlled Si nanopillar/SiGe composite films investigated by a laser heterodyne photothermal displacement method
Authors: Harada Tomoki , Ohori Daisuke , Endo Kazuhiko , Samukawa Seiji , Ikari Tetsuo , Fukuyama Atsuhiko
Published: March 2023

Thermal management has become more critical as semiconductor devices are miniaturized. In metal–oxide–semiconductor field-effect transistors, the problem is the reduction in electron mobility in the channel layer owing to the temperature rise caused by heat generation near the channel-drain region. Focusing on the mean free paths of phonons and electrons in Si, nanostructures of a few 10 nm may only hinder heat propagation without affecting electron transportation. Therefore, inserting nanostructures into the channel layer may prevent a temperature rise and maintain a higher electron mobility. To discuss the relationship between the spacing between the nanopillars (NPs) and the heat generation and carrier behavior of the Si-NP/SiGe composite film, samples with NP spacings of 13, 27, or 47 nm were prepared. We previously confirmed that the thermal conductivity of the Si-NP/SiGe composite film decreased as NP spacing narrowed. The NPs scattered phonon propagation and suppressed heat propagation. However, carrier transport properties such as electrical conductivity, carrier mobility, and carrier lifetime have never been discussed. The laser heterodyne photothermal displacement method was used to examine the effect of nanostructures on carrier mobility and carrier lifetime of Si-NP/SiGe composite films. We observed that the carrier lifetime became longer when the NP spacing was comparable to the electron mean-free path of approximately 27 nm.
Influences of semi-circular, square, and triangular grooves on mixing behavior of an axisymmetric supersonic jet
Authors: Mali Amit Krishnat , Jana Tamal , Kaushik Mrinal , Mishra Debi Prasad
Published: March 2023

The length of the supersonic jet ejected from the military aircraft must be reduced in order to decrease its heat signature and aeroacoustic noise and thereby to enhance its stealth capability. The reduction or manipulation of the supersonic core can be achieved through various passive control techniques. Considering this, the present study explores the mixing characteristics of supersonic jets with and without passive controls. Passive controls in the form of grooves configured at the exit of a Mach 1.73 convergent–divergent nozzle are investigated computationally. Particularly, the supersonic jet decay characteristics and flow development for a plain nozzle and a nozzle with semi-circular, square, and triangular grooves are presented. In addition, the study explores different turbulence models, namely, Spalart–Allmaras, realizable k-ε, std k-ω, shear stress transport (SST) k-ω, and SST transition. The realizable k-ε turbulence model is found to be the most effective one in capturing the supersonic jet structure. It is observed that the grooves produce large distortions in the jet structure, accompanied by significant mass entrainment and lateral spread. Interestingly, semi-circular grooves are proven to be most effective in all cases of expansion level than square and triangular grooves. For the semi-circular grooves, a maximum of 48.5% reduction in the supersonic core length of the correctly expanded jet at nozzle pressure ratio (NPR) of 5 is achieved. The reduction in the supersonic core length for semi-circular grooves is 31% for the overexpanded jet at NPR 4 and 29% for the underexpanded jet at NPR 7.
International agreements and the plant genetics research community: A guide to practice
Authors: Marden Emily , Sackville Hamilton Ruaraidh , Halewood Michael , McCouch Susan
Published: March 2023

Plant genetic resources (PGR), including collections held in national and international gene banks, provide access to a wide array of genetic diversity and are critical to genomics research, conservation efforts, and applied breeding. Yet, there is a general lack of awareness in the research community about the rules and treaties that govern the use of PGR, about access and benefit sharing obligations contained in international treaties and/or national laws, and about how best to comply with potentially applicable requirements. This article provides a brief history and overview of three key international agreements, namely the Convention on Biological Diversity, the Nagoya Protocol, and the International Treaty on Plant Genetic Resources for Food and Agriculture, which collectively address responsibilities and obligations related to the use of much of the world’s PGR. By highlighting the coverage and key considerations of each agreement, the article provides a guide for those who use PGR in plant genetics research to better understand when and how international agreements apply, and—where the rules are unclear—to suggest best practices for compliance with existing agreements.
Genomics-driven breeding for local adaptation of durum wheat is enhanced by farmers’ traditional knowledge
Authors: Gesesse Cherinet Alem , Nigir Bogale , de Sousa Kauê , Gianfranceschi Luca , Gallo Guido Roberto , Poland Jesse , Kidane Yosef Gebrehawaryat , Abate Desta Ermias , Fadda Carlo , Pè Mario Enrico , Dell’Acqua Matteo
Published: March 2023

In the smallholder, low-input farming systems widespread in sub-Saharan Africa, farmers select and propagate crop varieties based on their traditional knowledge and experience. A data-driven integration of their knowledge into breeding pipelines may support the sustainable intensification of local farming. Here, we combine genomics with participatory research to tap into traditional knowledge in smallholder farming systems, using durum wheat (Triticum durumDesf.) in Ethiopia as a case study. We developed and genotyped a large multiparental population, called the Ethiopian NAM (EtNAM), that recombines an elite international breeding line with Ethiopian traditional varieties maintained by local farmers. A total of 1,200 EtNAM lines were evaluated for agronomic performance and farmers’ appreciation in three locations in Ethiopia, finding that women and men farmers could skillfully identify the worth of wheat genotypes and their potential for local adaptation. We then trained a genomic selection (GS) model using farmer appreciation scores and found that its prediction accuracy over grain yield (GY) was higher than that of a benchmark GS model trained on GY. Finally, we used forward genetics approaches to identify marker–trait associations for agronomic traits and farmer appreciation scores. We produced genetic maps for individual EtNAM families and used them to support the characterization of genomic loci of breeding relevance with pleiotropic effects on phenology, yield, and farmer preference. Our data show that farmers’ traditional knowledge can be integrated in genomics-driven breeding to support the selection of best allelic combinations for local adaptation.
Destabilizing effect of climate change on the persistence of a short-lived primate
Authors: Ozgul Arpat , Fichtel Claudia , Paniw Maria , Kappeler Peter M.
Published: March 2023

Seasonal tropical environments are among those regions that are the most affected by shifts in temperature and rainfall regimes under climate change, with potentially severe consequences for wildlife population persistence. This persistence is ultimately determined by complex demographic responses to multiple climatic drivers, yet these complexities have been little explored in tropical mammals. We use long-term, individual-based demographic data (1994 to 2020) from a short-lived primate in western Madagascar, the gray mouse lemur (
Microcebus murinus
), to investigate the demographic drivers of population persistence under observed shifts in seasonal temperature and rainfall. While rainfall during the wet season has been declining over the years, dry season temperatures have been increasing, with these trends projected to continue. These environmental changes resulted in lower survival and higher recruitment rates over time for gray mouse lemurs. Although the contrasting changes have prevented the study population from collapsing, the resulting increase in life-history speed has destabilized an otherwise stable population. Population projections under more recent rainfall and temperature levels predict an increase in population fluctuations and a corresponding increase in the extinction risk over the next five decades. Our analyses show that a relatively short-lived mammal with high reproductive output, representing a life history that is expected to closely track changes in its environment, can nonetheless be threatened by climate change.
Robust ring-opening reaction via asymmetrically coordinated Fe single atoms scaffolded by spoke-like mesoporous carbon nanospheres
Authors: Li Zhimin , Yan Yan , Liu Minjie , Qu Zehua , Yue Yongcheng , Mao Tong , Zhao Shuang , Liu Mingkai , Lin Zhiqun
Published: March 2023

The ability to construct metal single-atom catalysts (SACs) asymmetrically coordinated with organic heteroatoms represents an important endeavor toward developing high-performance catalysts over symmetrically coordinated counterparts. Moreover, it is of key importance in creating supporting matrix with porous architecture for situating SACs as it greatly impacts the mass diffusion and transport of electrolyte. Herein, we report the crafting of Fe single atoms with asymmetrically coordinated nitrogen (N) and phosphorus (P) atoms scaffolded by rationally designed mesoporous carbon nanospheres (MCNs) with spoke-like nanochannels for boosting ring-opening reaction of epoxide to produce an array of pharmacologically important 
β
-amino alcohols. Notably, interfacial defects in MCN derived from the use of sacrificial template create abundant unpaired electrons, thereby stably anchoring N and P atoms and in turn Fe atoms on MCN. Importantly, the introduction of P atom promotes the symmetry-breaking of common four N-coordinated Fe sites, resulting in the Fe-N
3
P sites on MCN (denoted Fe-N
3
P-MCN) with an asymmetric electronic configuration and thus superior catalytic capability. As such, the Fe-N
3
P-MCN catalysts manifest a high catalytic activity for ring-opening reaction of epoxide (97% yield) over the Fe-N
3
P docked on nonporous carbon surface (91%) as well as the sole Fe-N
4
 SACs grounded on the same MCN support (89%). Density functional theory calculations reveal that Fe-N
3
P SAC lowers the activation barrier for the C–O bond cleavage and the C–N bond formation, thus accelerating the ring-opening of epoxide. Our study provides fundamental and practical insights into developing advanced catalysts in a simple and controllable manner for multistep organic reactions.
Tonic-signaling chimeric antigen receptors drive human regulatory T cell exhaustion
Authors: Lamarche Caroline , Ward-Hartstonge Kirsten , Mi Tian , Lin David T. S. , Huang Qing , Brown Andrew , Edwards Karlie , Novakovsky Gherman E. , Qi Christopher N. , Kobor Michael S. , Zebley Caitlin C. , Weber Evan W. , Mackall Crystal L. , Levings Megan K
Published: March 2023

Regulatory T cell (Treg) therapy is a promising approach to improve outcomes in transplantation and autoimmunity. In conventional T cell therapy, chronic stimulation can result in poor in vivo function, a phenomenon termed exhaustion. Whether or not Tregs are also susceptible to exhaustion, and if so, if this would limit their therapeutic effect, was unknown. To “benchmark” exhaustion in human Tregs, we used a method known to induce exhaustion in conventional T cells: expression of a tonic-signaling chimeric antigen receptor (TS-CAR). We found that TS-CAR-expressing Tregs rapidly acquired a phenotype that resembled exhaustion and had major changes in their transcriptome, metabolism, and epigenome. Similar to conventional T cells, TS-CAR Tregs upregulated expression of inhibitory receptors and transcription factors such as PD-1, TIM3, TOX and BLIMP1, and displayed a global increase in chromatin accessibility-enriched AP-1 family transcription factor binding sites. However, they also displayed Treg-specific changes such as high expression of 4-1BB, LAP, and GARP. DNA methylation analysis and comparison to a CD8
+
T cell-based multipotency index showed that Tregs naturally exist in a relatively differentiated state, with further TS-CAR-induced changes. Functionally, TS-CAR Tregs remained stable and suppressive in vitro but were nonfunctional in vivo, as tested in a model of xenogeneic graft-versus-host disease. These data are the first comprehensive investigation of exhaustion in Tregs and reveal key similarities and differences with exhausted conventional T cells. The finding that human Tregs are susceptible to chronic stimulation–driven dysfunction has important implications for the design of CAR Treg adoptive immunotherapy strategies.
Allosteric inactivation of an engineered optogenetic GTPase
Authors: Jain Abha , Dokholyan Nikolay V. , Lee Andrew L.
Published: March 2023

Optogenetics is a technique for establishing direct spatiotemporal control over molecular function within living cells using light. Light application induces conformational changes within targeted proteins that produce changes in function. One of the applications of optogenetic tools is an allosteric control of proteins via light-sensing domain (LOV2), which allows direct and robust control of protein function. Computational studies supported by cellular imaging demonstrated that application of light allosterically inhibited signaling proteins Vav2, ITSN, and Rac1, but the structural and dynamic basis of such control has yet to be elucidated by experiment. Here, using NMR spectroscopy, we discover principles of action of allosteric control of cell division control protein 42 (CDC42), a small GTPase involved in cell signaling. Both LOV2 and Cdc42 employ flexibility in their function to switch between “dark”/“lit” or active/inactive states, respectively. By conjoining Cdc42 and phototropin1 LOV2 domains into the bi-switchable fusion Cdc42Lov, application of light—or alternatively, mutation in LOV2 to mimic light absorption—allosterically inhibits Cdc42 downstream signaling. The flow and patterning of allosteric transduction in this flexible system are well suited to observation by NMR. Close monitoring of the structural and dynamic properties of dark versus “lit” states of Cdc42Lov revealed lit-induced allosteric perturbations that extend to Cdc42’s downstream effector binding site. Chemical shift perturbations for lit mimic, I539E, have distinct regions of sensitivity, and both the domains are coupled together, leading to bidirectional interdomain signaling. Insights gained from this optoallosteric design will increase our ability to control response sensitivity in future designs.
Stomatal patchiness and cellular computing
Authors: Peak David , Hogan Matthew T. , Mott Keith A.
Published: March 2023

Control of carbon dioxide and water vapor exchange between a leaf’s interior and the surrounding air is accomplished by variations in the turgor pressures in the small epidermal and guard cells that cover the leaf’s surface. These pressures respond to changes in light intensity and wavelength, temperature, CO
2
concentration, and air humidity. The dynamical equations that describe such processes are formally identical to those that define computation in a two-layer, adaptive, cellular nonlinear network. This exact identification suggests that leaf gas-exchange processes can be understood as analog computation and that exploiting the output of two-layer, adaptive, cellular nonlinear networks might provide new tools in applied plant research.
Statins enhance the efficacy of HER2-targeting radioligand therapy in drug-resistant gastric cancers
Authors: Rao Yi , Samuels Zachary , Carter Lukas M. , Monette Sebastien , Panikar Sandeep Surendra , Pereira Patricia M. R. , Lewis Jason S.
Published: March 2023

Human epidermal growth factor receptor 2 (HER2) is overexpressed in various cancer types. HER2-targeting trastuzumab plus chemotherapy is used as first-line therapy for HER2-positive recurrent or primary metastatic gastric cancer, but intrinsic and acquired trastuzumab resistance inevitably develop over time. To overcome gastric cancer resistance to HER2-targeted therapies, we have conjugated trastuzumab with a beta-emitting therapeutic isotope, lutetium-177, to deliver radiation locally to gastric tumors with minimal toxicity. Because trastuzumab-based targeted radioligand therapy (RLT) requires only the extramembrane domain binding of membrane-bound HER2 receptors, HER2-targeting RLT can bypass any resistance mechanisms that occur downstream of HER2 binding. Leveraging our previous discoveries that statins, a class of cholesterol-lowering drugs, can enhance the cell surface-bound HER2 to achieve effective drug delivery in tumors, we proposed that the combination of statins and [
177
Lu]Lu-trastuzumab-based RLT can enhance the therapeutic efficacy of HER2-targeted RLT in drug-resistant gastric cancers. We demonstrate that lovastatin elevates cell surface HER2 levels and increases the tumor-absorbed radiation dose of [
177
Lu]Lu-DOTA-trastuzumab. Furthermore, lovastatin-modulated [
177
Lu]Lu-DOTA-trastuzumab RLT durably inhibits tumor growth and prolongs overall survival in mice bearing NCI-N87 gastric tumors and HER2-positive patient-derived xenografts (PDXs) of known clinical resistance to trastuzumab therapy. Statins also exhibit a radioprotective effect, reducing radiotoxicity in a mice cohort given the combination of statins and [
177
Lu]Lu-DOTA-trastuzumab. Since statins are commonly prescribed to patients, our results strongly support the feasibility of clinical studies that combine lovastatin with HER2-targeted RLT in HER2-postive patients and trastuzumab-resistant HER2-positive patients.
Immunoglobulin G subclasses confer protection against
Staphylococcus aureus
bloodstream dissemination through distinct mechanisms in mouse models
Authors: Chen Xinhai , Gula Haley , Pius Tonu , Ou Chong , Gomozkova Margaryta , Wang Lai-Xi , Schneewind Olaf , Missiakas Dominique
Published: March 2023

Antibodies bind target molecules with exquisite specificity. The removal of these targets is mediated by the effector functions of antibodies. We reported earlier that the monoclonal antibody (mAb) 3F6 promotes opsonophagocytic killing of
Staphylococcus aureus
in blood and reduces bacterial replication in animals. Here, we generated mouse immunoglobulin G (mIgG) subclass variants and observed a hierarchy in protective efficacy 3F6-mIgG2a > 3F6-mIgG1 ≥ 3F6-mIgG2b >> 3F6-mIgG3 following bloodstream challenge of C57BL/6J mice. This hierarchy was not observed in BALB/cJ mice: All IgG subclasses conferred similar protection. IgG subclasses differ in their ability to activate complement and interact with Fcγ receptors (FcγR) on immune cells. 3F6-mIgG2a-dependent protection was lost in FcγR-deficient, but not in complement-deficient C57BL/6J animals. Measurements of the relative ratio of FcγRIV over complement receptor 3 (CR3) on neutrophils suggest the preferential expression of FcγRIV in C57BL/6 mice and of CR3 in BALB/cJ mice. To determine the physiological significance of these differing ratios, blocking antibodies against FcγRIV or CR3 were administered to animals before challenge. Correlating with the relative abundance of each receptor, 3F6-mIgG2a-dependent protection in C57BL/6J mice showed a greater reliance for FcγRIV while protection in BALB/cJ mice was only impaired upon neutralization of CR3. Thus, 3F6-based clearance of
S. aureus
in mice relies on a strain-specific contribution of variable FcγR- and complement-dependent pathways. We surmise that these variabilities are the result of genetic polymorphism(s) that may be encountered in other mammals including humans and may have clinical implications in predicting the efficacy of mAb-based therapies.
PRL-1/2 phosphatases control TRPM7 magnesium-dependent function to regulate cellular bioenergetics
Authors: Hardy Serge , Zolotarov Yevgen , Coleman Jacob , Roitman Simon , Khursheed Hira , Aubry Isabelle , Uetani Noriko , Tremblay Michel L.
Published: March 2023

Phosphatases of regenerating liver (PRL-1, PRL-2, PRL-3; also known as PTP4A1, PTP4A2, PTP4A3, respectively) control intracellular magnesium levels by interacting with the CNNM magnesium transport regulators. Still, the exact mechanism governing magnesium transport by this protein complex is not well understood. Herein, we have developed a genetically encoded intracellular magnesium-specific reporter and demonstrate that the CNNM family inhibits the function of the TRPM7 magnesium channel. We show that the small GTPase ARL15 increases CNNM3/TRPM7 protein complex formation to reduce TRPM7 activity. Conversely, PRL-2 overexpression counteracts ARL15 binding to CNNM3 and enhances the function of TRPM7 by preventing the interaction between CNNM3 and TRPM7. Moreover, while TRPM7-induced cell signaling is promoted by PRL-1/2, it is reduced when CNNM3 is overexpressed. Lowering cellular magnesium levels reduces the interaction of CNNM3 with TRPM7 in a PRL-dependent manner, whereby knockdown of PRL-1/2 restores the protein complex formation. Cotargeting of TRPM7 and PRL-1/2 alters mitochondrial function and sensitizes cells to metabolic stress induced by magnesium depletion. These findings reveal the dynamic regulation of TRPM7 function in response to PRL-1/2 levels, to coordinate magnesium transport and reprogram cellular metabolism.
Treg cells require Izumo1R to regulate γδT cell-driven inflammation in the skin
Authors: Zarin Payam , Shwartz Yulia , Ortiz-Lopez Adriana , Hanna Bola S. , Sassone-Corsi Martina , Hsu Ya-chieh , Mathis Diane , Benoist Christophe
Published: March 2023

Izumo1R is a pseudo-folate receptor with an essential role in mediating tight oocyte/spermatozoa contacts during fertilization. Intriguingly, it is also expressed in CD4
+
T lymphocytes, in particular Treg cells under the control of Foxp3. To understand Izumo1R function in Treg cells, we analyzed mice with Treg-specific
Izumo1r
deficiency (Iz1rTrKO). Treg differentiation and homeostasis were largely normal, with no overt autoimmunity and only marginal increases in PD1
+
and CD44
hi
Treg phenotypes. pTreg differentiation was also unaffected. Iz1rTrKO mice proved uniquely susceptible to imiquimod-induced, γδT cell-dependent, skin disease, contrasting with normal responses to several inflammatory or tumor challenges, including other models of skin inflammation. Analysis of Iz1rTrKO skin revealed a subclinical inflammation that presaged IMQ-induced changes, with an imbalance of Rorγ+ γδT cells. Immunostaining of normal mouse skin revealed the expression of Izumo1, the ligand for Izumo1R, electively in dermal γδT cells. We propose that Izumo1R on Tregs enables tight contacts with γδT cells, thereby controlling a particular path of skin inflammation.
Numerical and experimental investigation of probeless friction stir spot welding of a multilayer aluminium alloy compound
Authors: Contuzzi Nicola , Rashkovets Mariia , Casalino Giuseppe
Published: March 2023

This paper presents the experimental and numerical results of the influence of dwell time (30, 60, 90 s), down force (2450, 4900, 7350 N), and rotational speed (1000, 1500, 2000 RPM) on microstructure, microhardness, and material ﬂow during solid-state welding. Probeless friction stir spot welding (P-FSSW) with a flat tool shoulder was assisted to form a metal compound of AA2024, AA6082, and AA5754 aluminium plates with different thicknesses in lap configuration. The analysis of the experimental data and numerical results showed that down force had a significant influence on the material flow and the quality of the welds. High friction energy, and subsequent intensive material flow, promoted the vortexes formation, which improve metals mixing and grain refinements.
Soft shadow images
Authors: Grebe-Ellis Johannes , Quick Thomas
Published: March 2023

In traditional optics education, shadows are often regarded as a mere triviality, namely as silhouettes of obstacles to the propagation of light. However, by examining a series of shadow phenomena from an embedded perspective, we challenge this view and demonstrate how in general both the shape of the object and light source have significant impact on the resulting soft shadow images. Through experimental and mathematical analysis of the imaging properties of inverse objects, we develop a generalized concept of shadow images as complementary phenomena. Shadow images are instructive examples of optical convolution and provide an opportunity to learn about the power of embedded perspective for the study of optical phenomena in the classroom. Additionally, we introduce the less-known phenomenon of the bright shadow.
Reconstruction of smooth shape defects in waveguides using locally resonant frequencies
Authors: Niclas Angèle , Seppecher Laurent
Published: March 2023

This article aims to present a new method to reconstruct slowly varying width defects in 2D waveguides using locally resonant frequencies. At these frequencies, locally resonant modes propagate in the waveguide under the form of Airy functions depending on a parameter called the locally resonant point. In this particular point, the local width of the waveguide is known and its location can be recovered from boundary measurements of the wavefield. Using the same process for different frequencies, we produce a good approximation of the width in all the waveguide. Given multi-frequency measurements taken at the surface of the waveguide, we provide a

L

∞

-stable explicit method to reconstruct the width of the waveguide. We finally validate our method on numerical data, and we discuss its applications and limits.
A mixed element scheme for the Helmholtz transmission eigenvalue problem for anisotropic media
Authors: Liu Qing , Li Tiexiang , Zhang Shuo
Published: March 2023

In this paper, we study the Helmholtz transmission eigenvalue problem for inhomogeneous anisotropic media with the index of refraction

n
(
x
)
≡
1

in two and three dimensions. Starting with the nonlinear fourth-order formulation established by Cakoni et al 2009 J. Integral Equ. Appl.
21 203–27, we present an equivalent mixed formulation for this problem with auxiliary variables, followed by finite element discretization. Using the proposed scheme, we rigorously show that the optimal convergence rate for the transmission eigenvalues on both convex and nonconvex domains can be expected. With this scheme, we obtain a sparse generalized eigenvalue problem whose size is too demanding, even with a coarse mesh that its smallest few real eigenvalues fail to be solved by the shift and invert method. We partially overcome this critical issue by deflating nearly all of the

∞

eigenvalues with huge multiplicity, resulting in a marked reduction in the matrix size without deteriorating the sparsity. Extensive numerical examples are reported to demonstrate the effectiveness and efficiency of the proposed scheme.
Probing onset of nuclear vaporisation in heavy-ion collisions
Authors: Dhillon Navjot K , Rana Rajat , Sucheta  , Gautam Sakshi , Puri Rajeev K
Published: March 2023

The onset of nuclear vaporisation in heavy-ion collisions is examined in the present study. For this, we perform quantum molecular dynamics (QMD) model calculations supplemented with a clusterisation algorithm for fragment identification, namely the Simulated Annealing Clusterization algorithm (SACA) approach. Our results with the very sophisticated SACA method show a good agreement with the experimental findings of vaporisation (predicted by the asymptotic behaviour of the average fragment charge) in 16O + 80Br and 16O + 107Ag collisions. Further, we predicted the energy of the onset of vaporisation for 40Ca + 40Ca, 84Kr + 84Kr, 132Xe + 132Xe and 197Au + 197Au collisions by investigating the gas/liquid content and probability of vaporisation (and its derivative) versus the incident energy behaviour. These two observables probe the critical point of nuclear vaporisation in an extremely sophisticated manner, relative to an average fragment charge. Our findings on these two novel variables to predict the energy of the onset of vaporisation is verifiable in experiments. The influence of the colliding geometry as well as the role of Coulomb interactions are also studied to understand the system size effects on nuclear vaporisation.
Polaron induced local spin texture and anomalous Hall effect in the quadrilateral prism-shaped nanotube with Rashba and Dresselhaus spin–orbit coupling
Authors: Zhang Longlong , Pan Deng , Zhu Shilei , Li Shiqi
Published: March 2023

We theoretically study the spin-texture dynamics and the transverse asymmetric charge deflection induced by the polaron in a quadrilateral prism-shaped nanotube with the Rashba and Dresselhaus spin–orbit coupling (SOC). We reveal the polaron gives rise to the nontrivial local spin textures in the nanotube within the cross section plane. The spins demonstrate oscillations and the oscillating patterns are dependent on the SOC type. For the nanotube containing a segment of the ferromagnetic domain, the sizable asymmetric charge deflections could additionally take place, namely, the anomalous Hall effect. The amount of the deflected charges is determined by the strength and orientations of the ferromagnetic magnetization as well as the SOC type. The work provides a valuable insight of the coherent transport of polaron through a quasi-one-dimensional nanotube with Rashba and Dresselhaus SOC and open avenues for the potential device applications.
Stability of DNA and RNA hairpins: a comparative study based on ox-DNA
Authors: Yang Chao , Song Xiaoya , Feng Yuyu , Zhao Guangju , Liu Yanhui
Published: March 2023

Advances in single-molecule experiments on macromolecular crowding urgently need an efficient simulation method to resolve their discrepancies quantitatively. Ox-DNA model has been since reworked to treat the thermodynamics and mechanical properties of DNA/RNA hairpin at a stretching force. In hopping experiments, the critical forces of RNA hairpins at different temperatures are greater than those of DNA hairpins, in addition, the Gibbs free energy at a fixed temperature required to convert an RNA hairpin into a single-stranded molecule at zero force is obviously greater than that of DNA hairpin and gradually decreases by increasing the temperature. As far as force-ramping experiments are concerned, the first-rupture forces of RNA/DNA hairpins corresponding to the maximum probability density linearly pertain to the force-loading rate, with those of RNA hairpins being greater. The extended ox-DNA model could potentially identify the interaction between biologically inert polymer and RNA/DNA hairpins in crowded environments.
Global solutions to the free boundary value problem of a chemotaxis-Navier–Stokes system
Authors: Hou Qianqian
Published: March 2023

In this paper, we investigate the global solvability of the chemotaxis-Navier–Stokes system on a three-dimensional moving domain of finite depth, bounded below by a rigid flat bottom and bounded above by the free surface. Completing the system with physical boundary conditions on the free surface that match the boundary descriptions in the experiments and numerical simulations, we establish the global existence and uniqueness of solutions near a constant state

(
0
,

c
ˆ

,
0
)

, where

c
ˆ

is the saturation value of the oxygen on the free surface. To the best of our knowledge, this is the first analytical work for the well-posedness of chemotaxis-Navier–Stokes system on a time-dependent domain.
The rigid unit mode model: review of ideas and applications
Authors: Tan Lei , Heine Volker , Li Gong , Dove Martin T
Published: March 2023

We review a set of ideas concerning the flexibility of network materials, broadly defined as structures in which atoms form small polyhedral units that are connected at corners. One clear example is represented by the family of silica polymorphs, with structures composed of corner-linked SiO4 tetrahedra. The rigid unit mode (RUM) is defined as any normal mode in which the structural polyhedra can translate and/or rotate without distortion, and since forces associated with changing the size and shape of the polyhedra are much stronger than those associated with rotations of two polyhedra around a shared vertex, the RUMs might be expected to have low frequencies compared to all other phonon modes. In this paper we discuss the flexibility of network structures, and how RUMs can arise in such structures, both in principle and in a number of specific examples of real systems. We also discuss applications of the RUM model, particularly for our understanding of phenomena such as displacive phase transitions and negative thermal expansion in network materials.
In-field strain and temperature measurements in a (RE)Ba2Cu3O7−x coil via Rayleigh-backscattering interrogated optical fibers
Authors: Scurti F , Velez C , Kelly A , Ishmael S , Schwartz J
Published: March 2023

(RE)Ba2Cu3O7-x (REBCO) conductors have overcome technical challenges related to manufacturing quality, length homogeneity, scale-up of piece-length, and joints. There is one remaining technical challenge, however, which is common to all high temperature superconductors and lies in effective detection of failure to prevent material degradation. An innovative technique based on optical fibers interrogated by Rayleigh backscattering has been shown to have advantages over voltage taps at detecting incipient faults. Prior work has experimentally demonstrated the technique in several implementation scenarios, including direct integration of optical fibers into superconducting conductors and cables to create a class of ‘SMART’ conductors and cables that are able to monitor their own health. In this paper, the magnet monitoring technique based on Rayleigh backscattering interrogated optical fibers has been experimentally studied in a model coil subject to external magnetic field, where different fiber integration methods are used to increase selectivity of the fiber sensor to temperature. Results show that the spectral shift displays different features during strain and thermal transients. The implications of the results in terms of potential and limitations of each sensor as well as strain-temperature decoupling are discussed.
Engineering non-Markovianity from defect-phonon interactions
Authors: González Francisco J , Tancara Diego , Dinani Hossein T , Coto Raúl , Norambuena Ariel
Published: March 2023

Understanding defect-phonon interactions in solid-state devices is crucial for improving our current knowledge of quantum platforms. In this work, we develop first-principles calculations for a defect composed of two spin-

1

/

2

particles that interact with phonon modes in a one-dimensional lattice. We follow a bottom-up approach that begins with a dipolar magnetic interaction to ultimately derive the spectral density function and time-local master equation that describes the open dynamics of the defect. We provide theoretical and numerical analysis for the non-Markovian (NM) features of the defect-phonon dynamics induced by a pure dephasing channel acting on the Bell basis. Finally, we analyze two measures of NM based on the canonical rates and Coherence, shedding more light on the role of the spectral density function and temperature; and envisioning experimental realizations.