bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteolysis Targeting Chimeras (PROTACs) Based on Imatinib Induced Degradation of BCR‐ABL in K562 Cells
Authors: Li Chuang , Zhang Peng , Chang Gaojie , Pan Mingyue , Lu Fengke , Huang Jiahao , Wang Yanzhi , Zhao Qingyan , Sun Bingxia , Cui Yuting , Sang Feng
Published: April 2023

The proteolysis targeting chimera (PROTAC) technology is widely explored in cancer research and utilized in the treatment of various tumors and malignancies. In the design and optimization of PROTAC, linker is not only critical to the degradation activity of PROTACs, but also greatly affects the membrane permeability, metabolic stability and drug availability. In this study, fifteen new PROTACs based on Imatinib were designed, synthesized, and assessed for their anticancer activity against K562 cells. The CCK‐8 assay results showed that a new PROTAC with a 2‐oxoethyl linker (PROTAC 1) exhibited significant antiproliferative activity against K562 (IC50=0.62±0.02 μM) cells. Western blot analysis showed that PROTAC 1 regulated the protein levels of BCR‐ABL in a dose‐dependent manner and induced degradation of BCR‐ABL in a ubiquitin‐proteasome‐dependent manner in K562 cells. This study provides further evidence for the importance of linker selection in PROTAC design.
A Molecularly Imprinted Polymer Based on Fe3O4@Au Nanoparticles for Detection of Aflatoxin B1 in Food Samples
Authors: Pezeshkpur Maryam , Tadayon Fariba , Sohrabi Mahmoud Reza
Published: April 2023

Based on molecular imprinting and nanotechnology, a molecular imprinted polymer (MIP) coupled with Fe3O4−Au nanocomposite adsorbent has been successfully developed for rapid quantification of aflatoxin B1 in foodstuff. The characterization of the prepared Fe3O4−Au and Fe3O4−Au‐MIP was studied by scanning electron microscopy (SEM), energy dispersive X‐ray spectroscopy (EDX), transmission electron microscopy (TEM), Fourier‐transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD), and vibrating sample magnetometer (VSM). The limit of detection (LOD) and limit of quantification (LOQ) were estimated to be 6.12 and 18.6 μg L−1, respectively. The adsorption capacity was 8.975 mg g−1 which revealed that the synthesized magnetic MIP (MMIP) presented high selective recognition property to AFB1. The selectivity adsorption experiments indicated that compared with three different competetive Aflatoxins, MMIP showed excellent affinity to AFB1. It was found that the adsorption capacity of MMIP for AFB1 remained essentially the same after 6 adsorption‐desorption cycle which shows the acceptable repeatability and reusability of the MMIP. The proposed method was successfully applied to the estimation of AFB1 in non‐alcoholic beer and barley samples with good recoveries (94.47–97.31 %). Also, the relative standard deviation (RSD %) values were lower than 3.7 %. The selectivity, stability and reproducibility of the proposed method were acceptable. The results revealed that Fe3O4−Au@MIP could be used as an efficient and reusable adsorbent for AFB1 in food samples. This study provides a simple, inexpensive, fast, accurate and environmentally‐friendly technique instead of expensive and time‐consuming procedures for determining AFB1 in food matrices.
Potassium t‐Butoxide‐Promoted Metal‐Free Synthesis of Pyrazino[1,2‐a]indoles via Direct Amidation and Intramolecular Hydroamination Reaction
Authors: Yazzaf Rozita , Adib Mehdi , Mahdavi Mohammad
Published: April 2023

A library of pyrazino[1,2‐a]indoles has been synthesized via direct amidation and alkyne hydroamination reactions of the molecule produced by indole‐2‐carboxylic acid and propargyl bromide. The noteworthy features of the present strategy are short reaction time, excellent yields and a broad substrate scope. This cascade reaction also occurred under transition metal‐free and ambient conditions as well as operational simplicity.
Ratiometric Nanothermometer Based on a Radical Excimer for In Vivo Sensing
Authors: Blasi Davide , Gonzalez‐Pato Nerea , Rodriguez Rodriguez Xavier , Diez‐Zabala Iñigo , Srinivasan Sumithra Yasaswini , Camarero Núria , Esquivias Oriol , Roldán Mònica , Guasch Judith , Laromaine Anna , Gorostiza Pau , Veciana Jaume , Ratera Imma
Published: April 2023

Ratiometric fluorescent nanothermometers with near‐infrared emission play an important role in in vivo sensing since they can be used as intracellular thermal sensing probes with high spatial resolution and high sensitivity, to investigate cellular functions of interest in diagnosis and therapy, where current approaches are not effective. Herein, the temperature‐dependent fluorescence of organic nanoparticles is designed, synthesized, and studied based on the dual emission, generated by monomer and excimer species, of the tris(2,4,6‐trichlorophenyl)methyl radical (TTM) doping organic nanoparticles (TTMd‐ONPs), made of optically neutral tris(2,4,6‐trichlorophenyl)methane (TTM‐αH), acting as a matrix. The excimer emission intensity of TTMd‐ONPs decreases with increasing temperatures whereas the monomer emission is almost independent and can be used as an internal reference. TTMd‐ONPs show a great temperature sensitivity (3.4% K−1 at 328 K) and a wide temperature response at ambient conditions with excellent reversibility and high colloidal stability. In addition, TTMd‐ONPs are not cytotoxic and their ratiometric outputs are unaffected by changes in the environment. Individual TTMd‐ONPs are able to sense temperature changes at the nano‐microscale. In vivo thermometry experiments in Caenorhabditis elegans (C. elegans) worms show that TTMd‐ONPs can locally monitor internal body temperature changes with spatio‐temporal resolution and high sensitivity, offering multiple applications in the biological nanothermometry field.
Laser CVD Growth of Uniquely <010>‐oriented β‐Ga2O3 Films on Quartz Substrate with Ultrafast Photoelectric Response
Authors: Tu Rong , Li Xinyu , Xu Qingfang , Gao Tenghua , Zhang Xian , Li Bao‐Wen , Zhang Song , Goto Takashi , Zhang Lianmeng
Published: April 2023

The oriented growth of β‐Ga2O3 films has triggered extensive interest due to the remarkable and complex anisotropy found in the β‐Ga2O3 bulks. Remarkable properties, including stronger solar‐blind ultraviolet (SBUV) absorption, better mobility, and higher thermal conductivity, are usually observed along <010> direction as compared to other low‐index axes. So far, <010>‐oriented β‐Ga2O3 film growth has been hindered by the lack of suitable substrates and higher surface energy of the (010) crystal plane. Herein, the first growth of uniquely <010>‐oriented β‐Ga2O3 films on quartz substrates by laser chemical vapor deposition (LCVD) are reported. By investigating the effects of deposition temperature (Tdep) and O2 flow rate (RO2) on the growth of β‐Ga2O3 films, it is found that the formation of <010> orientation is closely related to the higher stability of oxygen close‐packed planes under O‐rich condition. As a result, a grain size of up to ≈2 µm and a deposition rate of up to ≈ 40 µm h−1 are obtained. Metal‐semiconductor‐metal (MSM) type detector based on <010>‐oriented β‐Ga2O3 film exhibits ultra‐fast response speed, 1–2 orders of magnitude higher than those of most detectors based on β‐Ga2O3 films with other orientations.
Nanodrug Inducing Autophagy Inhibition and Mitochondria Dysfunction for Potentiating Tumor Photo‐Immunotherapy
Authors: Xiao Hong , Li Xiaoxia , Li Bo , Yang Shuguang , Qin Jingya , Han Shisong , Ren Jie , Shuai Xintao
Published: April 2023

Anticancer immunotherapy is hampered by the poor tumor immunogenicity and immunosuppressive tumor microenvironment (TME). Herein, a liposome nanodrug co‐encapsulating doxycycline hydrochloride (Doxy) and chlorin e6 (Ce6) to simultaneously induce autophagy inhibition and mitochondria dysfunction for potentiating tumor photo‐immunotherapy is developed. Under near infrared laser irradiation, Ce6 generates cytotoxic reactive oxygen species (ROS) and elicits robust photodynamic therapy (PDT)‐induced immunogenic cell death (ICD) for immunosuppressive TME remodeling. In addition, Doxy induced mitochondria dysfunction, which increases ROS generation and enhances PDT to exert more potent killing effect and more powerful ICD. Meanwhile, Doxy increases MHC‐I expression on tumor cells surface by efficient autophagy inhibition, leading to more efficient antigen presentation and CTLs recognition to increase tumor immunogenicity. The nanodrugs elicit remarkable antitumor therapy by combining Ce6‐mediated PDT and Doxy‐induced autophagy inhibition and mitochondria dysfunction. The developed nanodrugs represent a highly efficient strategy for improving cancer immunotherapy.
Lead‐Free, Luminescent Perovskite Nanocrystals Obtained through Ambient Condition Synthesis
Authors: Treber Fiona , Frank Kilian , Nickel Bert , Lampe Carola , Urban Alexander S.
Published: April 2023

Heterovalently substituting toxic lead is an increasingly popular design strategy to obtain environmentally sustainable variants of the exciting material class of halide perovskites. Perovskite nanocrystals (NCs) obtained through solution‐based methods exhibit exceedingly high optical quality. Unfortunately, most of these synthesis routes still require reaction under inert gas and at very high temperatures. Herein a novel synthesis routine for lead‐free double perovskite (LFDP) NCs is presented. An approach based upon the hot injection and ligand‐assisted reprecipitation (LARP) methods to achieve a low‐temperature and ambient atmosphere‐based synthesis for manganese‐doped Cs2NaBiCl6 NCs is presented. Mn incorporation is critical for the otherwise non‐emissive material, with a 9:1 Bi:Mn precursor ratio maximizing the bright orange photoluminescence (PL) and quantum yield (QY). Higher synthesis temperatures slightly increase the material's performance, yet NCs synthesized at room temperature are still emissive, highlighting the versatility of the synthetic approach. While the material's indirect bandgap limits its appeal for optoelectronics, this feature could benefit photocatalysis due to longer carrier lifetimes. Moreover, the developed synthesis is facile and can rapidly be adapted to other more viable material compositions and up‐scaled to realize applications directly.
Construction of Synchronous‐Deposition K Metal Anodes Via Modulation of Ion/Electron Transport Kinetics for High‐Rate and Low‐Temperature K Metal Batteries
Authors: Jiang Jinlong , Liu Yiqian , Liao Yalan , Li Wenrong , Xu Yi , Liu Xiaoyu , Jiang Yong , Zhang Jiujun , Zhao Bing
Published: April 2023

The construction of conductive scaffolds is demonstrated to be an ideal strategy to alleviate the volume expansion and dendrite growth of K metal anodes. Nevertheless, the heterogeneous top–bottom deposition behavior caused by incompatible electronic/ionic conductivity of three‐dimensional (3D) skeleton severely hinders its application. Here, a K2Se/Cu conducting layer is fabricated on the Cu foam so as to enhance ionic transport and weaken electronic conductivity of the skeleton. Then, an excellent simultaneous deposition behavior of K metal inside the host is obtained for the first time via tuning fast ionic transport and low electronic conductivity. The simultaneous deposition mode can not only utilize the entire 3D structure to accommodate the volume expansion during K deposition but also avoid the formation of K dendrites at high current and ultra‐low temperature. Consequently, the symmetric cells present a long cycle lifespan over 1000 h with a low deposition overpotential of 80 mV at 1 mA cm−2. Furthermore, the full cell matching with the perylene‐tetracarboxylic dianhydride (PTCDA) cathode presents an outstanding cycle lifespan over 600 cycles at 5 C at ‐20°C. The proposed simultaneous deposition strategy provides a new design direction for the construction of dendrite‐free K metal anodes.
Titanium Nitride Nanorods Array‐Decorated Graphite Felt as Highly Efficient Negative Electrode for Iron–Chromium Redox Flow Battery
Authors: Liu Yiyang , Xu Jiao , Lu Shanfu , Xiang Yan
Published: April 2023

Iron‐chromium redox flow batteries have attracted widespread attention because of their low cost. However, the performance of these batteries is still lower than that of vanadium redox flow batteries due to the poor electrochemical activity of Cr3+/Cr2+ redox couples on graphite felt electrodes. Herein, binder‐free TiN nanorods array—decorated 3D graphite felt composite electrode—is demonstrated. The dendrite‐like TiN nanorods array increases the specific surface area of the electrode. The nitrogen and oxygen elements on the surface provide more adsorption sites and electrochemically active sites for Cr3+/Cr2+. The contact resistance of the composite electrode is effectively reduced and its homogeneity and stability are improved by avoiding the use of a binder and mixing process. A battery prepared using the TiN nanorods array‐decorated 3D graphite felt electrode has enabled the maximum power density to be 427 mW·cm‐2, which is 74.0% higher than a battery assembled with TiN nanoparticles bonded to graphite felt. At a current density of 80 mA·cm‐2, the TiN nanorods battery exhibits the highest coulombic efficiency of 93.0%, voltage efficiency of 90.4%, and energy efficiency of 84.1%. Moreover, the battery efficiency and composite electrode structure remains stable during a redox flow battery cycle test.
Spin‐Lattice Coupled Metamagnetism in Frustrated van der Waals Magnet CrOCl
Authors: Zhang Minjie , Hu Qifeng , Huang Yuqiang , Hua Chenqiang , Cheng Man , Liu Zhou , Song Shijie , Wang Fanggui , Lu Hengzhe , He Pimo , Cao Guang‐Han , Xu Zhu‐An , Lu Yunhao , Yang Jinbo , Zheng Yi
Published: April 2023

The long‐range magnetic ordering in frustrated magnetic systems is stabilized by coupling magnetic moments to various degrees of freedom, for example, by enhancing magnetic anisotropy via lattice distortion. Here, the unconventional spin‐lattice coupled metamagnetic properties of atomically‐thin CrOCl, a van der Waals antiferromagnet with inherent magnetic frustration rooted in the staggered square lattice, are reported. Using temperature‐ and angle‐dependent tunneling magnetoconductance (TMC), in complementary with magnetic torque and first‐principles calculations, the antiferromagnetic (AFM)‐to‐ferrimagnetic (FiM) metamagnetic transitions (MTs) of few‐layer CrOCl are revealed to be triggered by collective magnetic moment flipping rather than the established spin‐flop mechanism, when external magnetic field (H) enforces a lattice reconstruction interlocked with the five‐fold periodicity of the FiM phase. The spin‐lattice coupled MTs are manifested by drastic jumps in TMC, which show anomalous upshifts at the transition thresholds and persist much higher above the AFM Néel temperature. While the MTs exhibit distinctive triaxial anisotropy, reflecting divergent magnetocrystalline anisotropy of thec‐axis AFM ground state, the resulting FiM phase has ana‐ceasy plane in which the magnetization axis is freely rotated byH. At the 2D limit, such a field‐tunable FiM phase may provide unique opportunities to explore exotic emergent phenomena and novel spintronics devices.
Custom‐Made Piezoelectric Solid Solution Material for Cancer Therapy
Authors: Lv Shanrong , Qiu Zhili , Yu Dehong , Wu Xiunan , Yan Xiang , Ren Yiping , Huang Yuqi , Jiang Guan , Gao Fenglei
Published: April 2023

Piezoelectric material‐mediated sonodynamic therapy (SDT) has received considerable research interest in cancer therapy. However, the simple applications of conventional piezoelectric materials do not realize the full potential of piezoelectric materials in medicine. Therefore, the energy band structure of a piezoelectric material is modulated in this study to meet the actual requirement for cancer treatment. Herein, an elaborate PEGylated piezoelectric solid solution 0.7BiFeO3‐0.3BaTiO3 nanoparticles (P‐BF‐BT NPs) is synthesized, and the resultant particles achieve excellent piezoelectric properties and their band structure is tuned via band engineering. The tuned band structure of P‐BF‐BT NPs is energetically favorable for the synchronous production of superoxide radicals (•O2−) and oxygen (O2) self‐supply via water splitting by the piezoelectric effect. Besides, the P‐BF‐BT NPs can initiate the Fenton reaction to generate hydroxyl radical (•OH), and thus, chemodynamic therapy (CDT) can be augmented by ultrasound. Detailed in vitro and in vivo research has verified the promising effects of multimodal imaging‐guided P‐BF‐BT NP‐mediated synergistic SDT/CDT by the piezo‐Fenton process in hypoxic tumor elimination, accompanied by high therapeutic biosafety. The current demonstrates a novel strategy for designing and synthesizing “custom‐made” piezoelectric materials for cancer therapy in the future.
Photosynthesis of Hydrogen Peroxide Based on g‑C3N4: The Road of a Cost‐Effective Clean Fuel Production
Authors: Xie Linxuan , Wang Xinyu , Zhang Zeyuan , Ma Yiyue , Du Ting , Wang Rong , Wang Jianlong
Published: April 2023

Emerging artificial photosynthesis promises to offer a competitive means for solar energy conversion and further solves the energy crisis facing the world. Hydrogen peroxide (H2O2), which is considered as a benign oxidant and a prospective liquid fuel, has received worldwide attention in the field of artificial photosynthesis on account of the source materials are just oxygen, water, and sunlight. Graphitic carbon nitride (g‐C3N4)‐based photocatalysts for H2O2 generation have attracted extensive research interest due to the intrinsic properties of g‐C3N4. In this review, research processes for H2O2 generation on the basis of g‐C3N4, including development, fabrication, merits, and disadvantages, and the state‐of‐the‐art methods to enhance the performance are summarized after a brief introduction and the mechanism analysis of an efficient catalytic system. Also, recent applications of g‐C3N4‐based photocatalysts for H2O2 production are reviewed, and the significance of active sites and synthetic pathways are highlighted from the view of reducing barriers. Finally, this paper ends with some concluding remarks to reveal the issues and opportunities of g‐C3N4‐based photocatalysts for producing H2O2 in a high yield.
Constructing exception handling chains for testing Java virtual machine implementations
Authors: Chen Bochuan , Guo Xiao , Chen Yuting , Yu Xiaofeng , Bu Lei
Published: April 2023

The Java virtual machine (JVM) is the cornerstone of the Java platforms. A JVM's exception handling implementation interrupts, when the objective application encounters an exception (or an error), the normal execution of the application and performs specific handling tasks. However, little research has been done in systematically validating JVMs' exception handling implementations—test programs or even applications need to be carefully designed for throwing/catching exceptions at runtime; a JVM's exception handling implementation is also complicated, making it challenging to design tests for testing all of its functionalities. Inspired by the recent success of fuzz testing of compilers and JVM implementations, we introduce EHCBuilder, the first technique for fuzzing JVMs' exception handling implementations. The key idea is to construct exception handling chains, each of which abstracts a program's execution into a sequence of exception throwings, catchings, and/or handlings. A classfile seed can then be mutated into test programs with diverse exception handling chains, enabling (1) exceptions to be continuously thrown and caught at runtime, and (2) JVMs' exception handling implementations to be much more thoroughly tested. We have implemented EHCBuilder and evaluated EHCBuilder on popular JVM implementations including OpenJDK's HotSpot, Eclipse's OpenJ9, Azul's Zulu, and Oracle's GraalVM. Our results show that EHCBuilder can generate programs with very intricate exception handling chains and reveal differences among JVMs' exception handling implementations: Up to thousands of lines of source code in HotSpot's exception handling implementation are covered more than the original benchmarks; during 39 K iterations, EHCBuilder generates exception handling chains of different lengths, revealing 258 runtime differences. We classify the differences into four categories, and reveal a fast throw issue confirmed by HotSpot developers and another initCause issue confirmed by the OpenJ9 community.
Using a handheld metal detector to detect ingested hooks and other metallic objects in freshwater turtles
Authors: Lane Vanessa R. , Gerdes Parker , Ridgdill Dalton G. , Ray Brittany L.
Published: April 2023

Turtles can be unintentionally hooked during recreational and commercial fishing operations. While hook ingestion is not always fatal, ingested hooks can harm or kill turtles by damaging soft tissues or affecting digestion. Detecting ingested hooks and other metallic debris in the field is a challenge. As such, we tested the efficacy of a handheld metal detector in detecting ingested fish hooks and incidental metallic debris in freshwater turtles in Georgia, USA. We captured 426 individual freshwater turtles representing 4 species and radiographed 106 yellow‐bellied sliders (Trachemys scripta scripta). Of 37 turtles that tested positive with a handheld metal detector, radiographs revealed 17 (46%) had ingested at least one hook, 15 (40%) had ingested an unidentifiable metal object or objects, and 5 (14%) showed no clear signs of hooks or other metallic objects. All 69 turtles that tested negative in the field and were radiographed showed no signs of metal ingestion. Accordingly, our proportion of false positives was 14% (5 of 37), false negatives (metal not detected in field but on follow‐up radiograph) were 0% (0 of 69), and our overall accuracy at detecting ingested metal with a handheld metal detector was 95% (101 of 106 radiographed turtles). Thus, handheld metal detectors may be a useful tool for detecting ingested hooks and other metallic objects in freshwater turtles.
Impact of needle size and distinct flow conditions on thermal performance of TiO2–MWCNTs hybrid nanofluid flow past thin needle using Casson fluid model
Authors: Prashar Preeti , Ojjela Odelu , Kambhatla Pravin Kashyap
Published: April 2023

Hybrid nanofluids comprising carbon nanotubes (CNTs) are finding applications in advanced heat exchange technologies due to the unusually high thermal conductivity and chemically inert nature of CNTs. The thermal performance of a hybrid nanofluid, comprising MWCNTs and TiO2 nanoparticles and flowing past a thin hot needle, is investigated in the present article. The Sakiadis and Blasius hybrid nanofluid flow scenarios around a parabolically shaped thin hot needle are modeled by using a non‐Newtonian Casson fluid model coupled with the energy equation. The governing equations are coupled non‐linear partial differential equations which are solved by the shooting method along with the 4th order Runge–Kutta method. The main aim of the study is to perform a comparative analysis among the base fluid (which is a 50:50 mixture of ethylene glycol [EG] and water), TiO2/EG–water nanofluid, and TiO2–MWCNTs/EG–water hybrid nanofluid and to analyze which fluid is the best transporter of heat. Apart from this, the impact of needle size and different flow conditions on heat transport is investigated. The numerical results reveal that the rate of heat transfer is maximum for TiO2–MWCNTs/EG–water hybrid nanofluid among the base fluid, nanofluid, and hybrid nanofluid. The magnitude of the Nusselt number is high for the case of the Blasius flow than for the Sakiadis flow.
Aerodynamic Parameter Estimation for Launch Vehicles
Authors: Jia Jian , Chen Weifeng , Wang Zixuan
Published: April 2023

Aerodynamic force plays an important role in the flight of space launch vehicles. Therefore, obtaining accurate aerodynamic characteristics is the basis and prerequisite for establishing an aerodynamic model and designing a vehicle with excellent characteristics.
1/L2 corrected soft photon theorem from a CFT3 Ward identity
Authors: Banerjee Nabamita , Fernandes Karan , Mitra Arpita
Published: April 2023

Abstract

Classical soft theorems applied to probe scattering processes on AdS4 spacetimes predict the existence of perturbative 1/L2 corrections to the soft photon and soft graviton factors of asymptotically flat spacetimes. In this paper, we establish that the 1/L2 corrected soft photon theorem can be derived from a large N CFT3 Ward identity. We derive a perturbed soft photon mode operator on a flat spacetime patch in global AdS4 in terms of an integrated expression of the boundary CFT current. Using the same in the CFT3 Ward identity, we recover the 1/L2 corrected soft photon factor derived from classical soft theorems.
A two-generational SU(7) model with extended weak sector: mass hierarchies, mixings, and the flavor non-universality
Authors: Chen Ning , Mao Ying-nan , Teng Zhaolong , Wang Bin , Zhao Xiangjun
Published: April 2023

Abstract

We study a possible gauge symmetry breaking pattern in an SU(7) grand unified theory, which describes the mass origins of all electrically charged SM fermions of the second and the third generations. Two intermediate gauge symmetries of $$ {\mathcal{G}}_{341}\equiv \textrm{SU}{(3)}_c\otimes \textrm{SU}{(4)}_W\otimes \textrm{U}{(1)}_{X_0} $$

G
341

≡
SU

3

c

⊗
SU

4

W

⊗
U

1

X
0

and $$ {\mathcal{G}}_{331}\equiv \textrm{SU}{(3)}_c\otimes \textrm{SU}{(4)}_W\otimes \textrm{U}{(1)}_{X_1} $$

G
331

≡
SU

3

c

⊗
SU

4

W

⊗
U

1

X
1

arise above the electroweak scale. SM fermion mass hierarchies between two generations can be obtained through a generalized seesaw mechanism. The mechanism can be achieved with suppressed symmetry breaking VEVs from multiple Higgs fields that are necessary to avoid tadpole terms in the Higgs potential. Some general features of the SU(7) fermion spectrum will be described, which include the existence of vectorlike fermions, the tree-level flavor changing weak currents between the SM fermions and heavy partner fermions, and the flavor non-universality between different SM generations from the extended weak sector.
Towards learning optimized kernels for complex Langevin
Authors: Alvestad Daniel , Larsen Rasmus , Rothkopf Alexander
Published: April 2023

Abstract

We present a novel strategy aimed at restoring correct convergence in complex Langevin simulations. The central idea is to incorporate system-specific prior knowledge into the simulations, in order to circumvent the NP-hard sign problem. In order to do so, we modify complex Langevin using kernels and propose the use of modern auto-differentiation methods to learn optimal kernel values. The optimization process is guided by functionals encoding relevant prior information, such as symmetries or Euclidean correlator data. Our approach recovers correct convergence in the non-interacting theory on the Schwinger-Keldysh contour for any real-time extent. For the strongly coupled quantum anharmonic oscillator we achieve correct convergence up to three-times the real-time extent of the previous benchmark study. An appendix sheds light on the fact that for correct convergence not only the absence of boundary terms, but in addition the correct Fokker-Plank spectrum is crucial.
On generalised D1-D5 near horizons and their spectra
Authors: Lima Mariana , Macpherson Niall T. , Melnikov Dmitry , Ypanaqué Luis
Published: April 2023

Abstract

There has been considerable recent interest in type II string compactifications on AdS3×S3×M4 due to both new progress in the AdS3/CFT2 correspondence and an independent search for new $$ \mathcal{N} $$
N
= (4, 0) supergravity solutions. In this work we report a new family of small $$ \mathcal{N} $$
N
= (4, 0) preserving warped AdS3×S3×CY2 compactifications of type IIB supergravity. The S3 in this family is non trivially fibered over the CY2. We show how these new solutions provide a IIB embedding of minimal ungauged d = 5 supergravity coupled to an Abelian vector multiplet. We also make a few initial steps towards the identification of dual CFT2 candidates. Specifically, we study the Kaluza-Klein spectrum of the spin two and certain vector fluctuations that are expected to be dual to the stress-energy tensor, SU(2) R current and several other BPS operator families in the dual CFT2.
Variant Nelson-Barr mechanism with minimal flavor violation
Authors: Bai Yang , Wojcik George N.
Published: April 2023

Abstract

Within the general framework of using spontaneous CP violation to solve the strong CP problem, we construct a variant Nelson-Barr model in which the Standard Model (SM) quark contribution to the strong CP phase is cancelled by new heavy QCD-charged fermions. This cancellation is ensured by choosing conjugate representations for the new colored states under the same global flavor symmetry of SM quarks. Choosing the global flavor symmetry to be that of minimal flavor violation, we suppress higher-order corrections to the strong CP phase to well below current experimental constraints. More than two dozen massless Goldstone bosons emerge from spontaneous flavor symmetry breaking, which yield strong astrophysical constraints on the symmetry breaking scale. In the early universe, the Goldstone bosons can be thermally produced from their interactions with the heavy colored fermions and contribute to ∆Neff at a measurable level. As a function of reheating temperature, the predicted ∆Neff shows an interesting plateau behavior we dub the “flavor stairway”, which encodes information about the SM quark flavor structure.
Graviton scattering in AdS5 × S5 at two loops
Authors: Huang Zhongjie , Yuan Ellis Ye
Published: April 2023

Abstract

We report a result for the third-order correction in 1/N expansion to the four-point correlator of the stress tensor multiplet in $$ \mathcal{N} $$
N
= 4 super Yang-Mills theory at large ’t Hooft coupling, which corresponds to the two-loop scattering of four gravitons in the dual AdS5 × S5 supergravity. This is obtained by bootstrapping an educated ansatz based on intuitions from the hidden 10-dimensional conformal symmetry.
Results from a first-in-human study of dersimelagon, an investigational oral selective MC1R agonist
Authors: Ogasawara Akihito , Ogawa Kei , Ide Ryosuke , Ikenaga Yuka , Fukunaga Chie , Nakayama Satoshi , Tsuda Minoru
Published: April 2023

Purpose

To describe outcomes from the first-in-human study of dersimelagon, an investigational oral selective MC1R agonist, under development for the treatment of erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP).

Methods

In this double-blind, placebo-controlled phase 1 study, the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral doses of dersimelagon in healthy participants were evaluated.

Results

Dersimelagon was generally well tolerated in healthy participants, with the most common TEAEs being lentigo (52.8%) and skin hyperpigmentation (50.0%) after multiple doses. Systemic exposure to dersimelagon in plasma (based on AUC0-∞ and Cmax) increased in a slightly more than dose-proportional manner over the 1- to 600-mg single-dose range. Following multiple doses, dersimelagon was rapidly absorbed (median Tmax ranging from 4 to 5 h postdose on days 1 and 14). Mean t1/2 ranged from 10.56 to 18.97 h on day 14, and the steady state of plasma concentration was generally reached by 5 days of multiple dosing. There were no observable effects of age or race on the PK profile of dersimelagon or its metabolite dersimelagon glucuronide. No treatment-related effects on melanin density (MD) were observed following single doses of dersimelagon; however, after multiple doses, increases in MD were observed in participants receiving 150 and 300 mg dersimelagon.

Conclusion

Our study results indicate that dersimelagon is generally well tolerated and demonstrates a generally consistent PK profile across diverse subgroups. Treatment-related increases in MD warrant further investigation in a larger study population and in patients with EPP and XLP.

Trial registration

A Study to Investigate the Safety, Tolerability and Pharmacokinetics of MT-7117 in Healthy Subjects, NCT02834442, https://clinicaltrials.gov/ct2/show/NCT02834442, registration began July 2016.
The ultrasound assessment of osteoarthritis: the current status
Authors: Nevalainen Mika T. , Uusimaa Antti-Pekka , Saarakkala Simo
Published: April 2023

Traditionally, osteoarthritis (OA) is diagnosed with the clinical examination supplemented by the conventional radiography (CR). In the research literature, the role of ultrasound (US) imaging in the diagnostics of OA has risen steadily during the last two decades. US imaging is cheap and globally widely available often already in primary healthcare. Here, we reviewed the most essential US literature focusing on OA diagnostics and progression prediction using the various search engines. Starting from the year 2000, our search provided 1 445 journal articles. After reviewing the abstracts, 89 articles were finally included. Most of the reviewed articles focused on the imaging of knee and hand OA, whereas only a minority dealt with the imaging of hip, ankle, midfoot, acromioclavicular, and temporomandibular joints. Overall, during the last 20 years, the use of US imaging for OA assessment has increased in the scientific literature. In knee and hand joints, US imaging has been reported to be a promising tool to evaluate OA changes. Furthermore, the reproducibility of US as well as its association to MRI findings are excellent. Importantly, US seems to even outperform CR in certain aspects, such as detection of osteophytes, joint inflammation, meniscus protrusion, and localized cartilage damage (especially at the medial femoral condyle and sulcus area). Based on the reviewed literature, US can be truly considered as a complementary tool to CR in the clinical setup for OA diagnostics. New technical developments may even enhance the diagnostic value of the US in the future.
Deep learning–based diagnosis of osteoblastic bone metastases and bone islands in computed tomograph images: a multicenter diagnostic study
Authors: Xiong Yuchao , Guo Wei , Liang Zhiping , Wu Li , Ye Guoxi , Liang Ying-ying , Wen Chao , Yang Feng , Chen Song , Zeng Xu-wen , Xu Fan
Published: April 2023

Objective

To develop and validate a deep learning (DL) model based on CT for differentiating bone islands and osteoblastic bone metastases.

Materials and methods

The patients with sclerosing bone lesions (SBLs) were retrospectively included in three hospitals. The images from site 1 were randomly assigned to the training (70%) and intrinsic verification (10%) datasets for developing the two-dimensional (2D) DL model (single-slice input) and “2.5-dimensional” (2.5D) DL model (three-slice input) and to the internal validation dataset (20%) for evaluating the performance of both models. The diagnostic performance was evaluated using the internal validation set from site 1 and additional external validation datasets from site 2 and site 3. And statistically analyze the performance of 2D and 2.5D DL models.

Results

In total, 1918 SBLs in 728 patients in site 1, 122 SBLs in 71 patients in site 2, and 71 SBLs in 47 patients in site 3 were used to develop and test the 2D and 2.5D DL models. The best performance was obtained using the 2.5D DL model, which achieved an AUC of 0.996 (95% confidence interval [CI], 0.995–0.996), 0.958 (95% CI, 0.958–0.960), and 0.952 (95% CI, 0.951–0.953) and accuracies of 0.950, 0.902, and 0.863 for the internal validation set, the external validation set from site 2 and site 3, respectively.

Conclusion

A DL model based on a three-slice CT image input (2.5D DL model) can improve the prediction of osteoblastic bone metastases, which can facilitate clinical decision-making.

Key Points

• This study investigated the value of deep learning models in identifying bone islands and osteoblastic bone metastases.

• Three-slice CT image input (2.5D DL model) outweighed the 2D model in the classification of sclerosing bone lesions.

• The 2.5D deep learning model showed excellent performance using the internal (AUC, 0.996) and two external (AUC, 0.958; AUC, 0.952) validation sets.
Heat stress in horses: a literature review
Authors: Kang Hyungsuk , Zsoldos Rebeka R. , Sole-Guitart Albert , Narayan Edward , Cawdell-Smith A. Judith , Gaughan John B.
Published: April 2023

Healthy adult horses can balance accumulation and dissipation of body heat to maintain their body temperature between 37.5 and 38.5 °C, when they are in their thermoneutral zone (5 to 25 °C). However, under some circumstances, such as following strenuous exercise under hot, or hot and humid conditions, the accumulation of body heat exceeds dissipation and horses can suffer from heat stress. Prolonged or severe heat stress can lead to anhidrosis, heat stroke, or brain damage in the horse. To ameliorate the negative effects of high heat load in the body, early detection of heat stress and immediate human intervention is required to reduce the horse’s elevated body temperature in a timely manner. Body temperature measurement and deviations from the normal range are used to detect heat stress. Rectal temperature is the most commonly used method to monitor body temperature in horses, but other body temperature monitoring technologies, percutaneous thermal sensing microchips or infrared thermometry, are currently being studied for routine monitoring of the body temperature of horses as a more practical alternative. When heat stress is detected, horses can be cooled down by cool water application, air movement over the horse (e.g., fans), or a combination of these. The early detection of heat stress and the use of the most effective cooling methods is important to improve the welfare of heat stressed horses.
The Lausanne Hospitality Model: a model integrating hospitality into supportive care
Authors: Lê Van Kim , Arditi Chantal , Terrier Lohyd , Ninane Françoise , Savoie Annie , Rochat Sylvie , Peytremann-Bridevaux Isabelle , Eicher Manuela , Schaad Béatrice
Published: April 2023

Purpose

Cancer care is undergoing a conceptual shift with the introduction of the principles of patient-centered care to support patients’ individual needs. These needs include those related to hospitality during cancer treatments. This paper aims to provide an extension of the supportive care framework by bringing in the hospitality approach inspired by the hotel industry.

Method

The “Lausanne Hospitality Model,” integrating hospitality into supportive care, was developed through an iterative process, combining expertise in supportive care and health services research, communication, and the hotel industry.

Results

This conceptual paper integrates hospitality and service sciences into the supportive care framework. The “Lausanne Hospitality Model” offers new insights into the notions of cancer journey, patient experience, services, and practices that may be involved when facilitating hospitality. While most concepts used in the model are based on prior research, they have not been combined previously. The model highlights the place of hospitality in the patient’s experience within cancer services and, by extension, its role in professional practice.

Conclusion

Practices involved in the delivery of cancer care need to reinforce the importance attributed to hospitality services, as they impact patients’ experiences. By integrating the hospitality perspective into healthcare delivery and supportive care, this paper addresses previously theoretically overlooked aspects that impact patients’ experiences during cancer care.
Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes
Authors: Herrera-Ramírez Piedad , Berger Sarah Alina , Josa Dana , Aguilà David , Caballero Ana B. , Fontova Pere , Soto-Cerrato Vanessa , Martínez Manuel , Gamez Patrick
Published: April 2023

Two ruthenium(II) polypyridyl complexes were prepared with the {Ru(phen)2}2+ moiety and a third sterically non-hindering bidentate ligand, namely 2,2′-dipyridylamine (dpa) and N-benzyl-2,2′-dipyridylamine (Bndpa). Hence, complexes [Ru(phen)2(dpa)](PF6)2 (1) and [Ru(phen)2(Bndpa)](PF6)2 (2) were characterized and their photochemical behaviour in solution (acetonitrile and water) was subsequently investigated. Compounds 1 and 2, which do not exhibit notably distorted octahedral coordination environments, contrarily to the homoleptic “parent” compound [Ru(phen)3](PF6)2, experience two-step photoejection of the dpa and Bndpa ligand upon irradiation (1050–430 nm) for several hours. DNA-binding studies revealed that compounds 1 and 2 affect the biomolecule differently upon irradiation; while 2 solely modifies its electrophoretic mobility, complex 1 is also capable of cleaving it. In vitro cytotoxicity studies with two cancer-cell lines, namely A549 (lung adenocarcinoma) and A375 (melanoma), showed that both 1 and 2 are not toxic in the dark, while only 1 is significantly cytotoxic if irradiated, 2 remaining non-toxic under these conditions.

Graphical abstract

Light irradiation of the complex cation [Ru(phen)2(dpa)]2+ leads to the generation of transient Ru species that is present in the solution medium for several hours, and that is significantly cytotoxic, ultimately producing non-toxic free dpa and [Ru(phen)(OH2)2]2+.
Augmented grocery shopping: fostering healthier food purchases through AR
Authors: Pini Valentina , Orso Valeria , Pluchino Patrik , Gamberini Luciano
Published: April 2023

Food choices are intimately related to individual health. Therefore, the food we buy should be carefully chosen. However, grocery shopping is typically done in noisy environments, and food products usually present cluttered labels with dense texts that make it hard to properly evaluate relevant nutritional data. Augmented reality (AR) allows a shopper to visualize digitally generated contents onto real objects and to interact with them. In this experiment, we investigated the effects of delivering nutritional information using AR technology on food choices. To this end, we ran a between-participants laboratory experiment in which participants were asked to choose among the products available. The experimental group received the food-related information via AR, while the control group had ordinary access to food packaging. We found that AR technology facilitated the choice of healthier food items. Additionally, participants in the experimental group reported that they based their decisions on nutritional information rather than on the appearance of the package. The present work highlights how AR can be exploited to bring to the foreground information that would otherwise be hard to spot, thereby increasing the consumer’s awareness of the overall characteristics of the product.
Nasotracheal Microbiota of Nestlings of Parent White storks with Different Foraging Habits in Spain
Authors: Abdullahi Idris Nasir , Juárez-Fernández Guillermo , Höfle Úrsula , Cardona-Cabrera Teresa , Mínguez David , Pineda-Pampliega Javier , Lozano Carmen , Zarazaga Myriam , Torres Carmen
Published: April 2023

Migratory storks could be vectors of transmission of bacteria of public health concern mediated by the colonization, persistence and excretion of such bacteria. This study aims to determine genera/species diversity, prevalence, and co-colonization indices of bacteria obtained from tracheal (T) and nasal (N) samples from storks in relation to exposure to point sources through foraging. One-hundred and thirty-six samples from 87 nestlings of colonies of parent white storks with different foraging habits (natural habitat and landfills) were obtained (84 T-samples and 52 N-samples) and processed. Morphologically distinct colonies (up to 12/sample) were randomly selected and identified by MALDI-TOF-MS. About 87.2% of the total 806 isolates recovered were identified: 398 from T-samples (56.6%) and 305 from N-samples (43.4%). Among identified isolates, 17 genera and 46 species of Gram-positive and Gram-negative bacteria were detected, Staphylococcus (58.0%) and Enterococcus (20.5%) being the most prevalent genera. S. sciuri was the most prevalent species from T (36.7%) and N (34.4%) cavities of total isolates, followed by E. faecalis (11.1% each from T and N), and S. aureus [T (6.5%), N (13.4%)]. Of N-samples, E. faecium was significantly associated with nestlings of parent storks foraging in landfills (p = 0.018). S. sciuri (p = 0.0034) and M. caseolyticus (p = 0.032) from T-samples were significantly higher among nestlings of parent storks foraging in natural habitats. More than 80% of bacterial species in the T and N cavities showed 1–10% co-colonization indices with one another, but few had ≥ 40% indices. S. sciuri and E. faecalis were the most frequent species identified in the stork nestlings. Moreover, they were highly colonized by other diverse and potentially pathogenic bacteria. Thus, storks could be sentinels of point sources and vehicles of bacterial transmission across the “One Health” ecosystems.
New Insights on the Palaeo-archaeological Potential of the Niokolo-Koba National Park, Senegal
Authors: Ndiaye Matar , Huysecom Eric , Douze Katja
Published: April 2023

The study of the Palaeolithic in Senegal has made considerable progress in the last decade and has provided a renewed vision of the behavioral evolution of prehistoric populations in West Africa. The cultural trajectories within the region seem to be highly variable and bear witness to strong behavioral dynamics, the mechanisms of which still need to be better understood. However, the number of reliable, dated, and stratified sites, as well as the palaeoenvironmental data providing a context for populations in their palaeolandscapes, is still scarce. In order to provide new and solid data, we conducted new archaeological survey in the Niokolo-Koba National Park in south-central Senegal, aiming at a preliminary identification of Pleistocene and early Holocene sedimentary deposits. Here, we report an overview of the newly discovered industries found in different contexts. Most of the 27 identified sites show surface and out-of-context assemblages, but other sites are stratified and have all the criteria to justify the development of a long-term archaeological, geochronological, geomorphological, and palaeobotanical project. The Niokolo-Koba National Park, through which the Gambia River flows, is characterized by an abundance of sources of knappable material and by well-preserved sedimentary sequences. Therefore, archaeological research in the Niokolo-Koba National Park has the potential to provide major milestones in our understanding of the evolutionary dynamics at work in West Africa during the early periods of occupation of the region.
General and patient-specific seizure classification using deep neural networks
Authors: Massoud Yasmin M. , Abdelzaher Mennatallah , Kuhlmann Levin , Abd El Ghany Mohamed A.
Published: April 2023

Seizure prediction algorithms have been central in the field of data analysis for the improvement of epileptic patients’ lives. The most recent advancements of which include the use of deep neural networks to present an optimized, accurate seizure prediction system. This work puts forth deep learning methods to automate the process of epileptic seizure detection with electroencephalogram (EEG) signals as input; both a patient-specific and general approach are followed. EEG signals are time structure series motivating the use of sequence algorithms such as temporal convolutional neural networks (TCNNs), and long short-term memory networks. We then compare this methodology to other prior pre-implemented structures, including our previous work for seizure prediction using machine learning approaches support vector machine and random under-sampling boost. Moreover, patient-specific and general seizure prediction approaches are used to evaluate the performance of the best algorithms. Area under curve (AUC) is used to select the best performing algorithm to account for the imbalanced dataset. The presented TCNN model showed the best patient-specific results than that of the general approach with, AUC of 0.73, while ML model had the best results for general classification with AUC of 0.75.