bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical anti‐angiogenic and anti‐cancer activities of BAY1143269 in glioblastoma via targeting oncogenic protein expression
Authors: Wan Weifeng , Zhang Xin , Huang Changren , Chen Ligang , Yang Xiaobo , Bao Kunyang , Peng Tangming 
Published: July 2022

AbstractGlioblastoma angiogenesis is critical for tumor growth, making it an appealing target for treatment development. BAY1143269 is a novel inhibitor of mitogen‐activated protein kinase interacting serine/threonine‐protein kinase 1 (MKN1) and has potent anti‐cancer activity. We identified BAY1143269 as an angiogenesis inhibitor, by in vitro and in vivo glioblastoma angiogenesis models. BAY1143269 inhibited the capillary network formation of glioblastoma microvascular endothelial cells (GMECs), particularly the early stage of tubular structure formation. It also inhibited migration and proliferation, and induced apoptosis of GMECs isolated from glioblastoma patients. We found that BAY1143269 acted on GMECs by suppressing the eukaryotic translation initiation factor 4E (eIF4E) and eIF4E‐mediated expression of oncogenic proteins, including those involved in cell cycle, epithelial‐mesenchymal transition (EMT), and pro‐survival. In addition, BAY1143269 suppressed eIF4E phosphorylation, inhibited proliferation, and induced apoptosis of glioblastoma cells. Interestingly, it reduced vascular endothelial growth factor (VEGF) level in tumor cells and culturing medium, demonstrating the inhibitory effect of BAY1143269 on tumor proangiogenic microenvironment. We finally challenged BAY1143269 on the glioblastoma xenograft mice model and observed a significant tumor growth reduction without toxicity in mice receiving oral BAY1143269. Immunoblotting analysis demonstrated significantly less phosphorylated‐eIF4E (p‐eIF4E), cluster of differentiation 31 (CD31) (microvascular endothelial cell marker), and VEGF in tumors from drug‐treated mice. In summary, the inhibition of glioblastoma angiogenesis with BAY1143269 may provide an alternative approach for anti‐glioblastoma therapy.
A Wiener degradation process with drift‐based approach of determining target reliability index of concrete structures
Authors: Zhang Zhenhao , Liang Gaoming , Niu Qinglei , Wang Fuming , Chen Jigong , Zhao Bing , Ke Lu 
Published: July 2022

AbstractIn this paper, a novel approach is proposed to determine target reliability index based on modeling performance degradation of concrete structures as a stochastic process. First, the Wiener process with drift is used to simulate the degradation process of relative dynamic elastic modulus of concrete, and the drift coefficient and diffusion coefficient of Wiener process are estimated according to the experimental data of degradation of relative dynamic elastic modulus. Then, based on the relations between concrete compressive strength, dynamic elastic modulus, and relative dynamic elastic modulus, the relationship between compressive strength and the amount of degradation of relative dynamic elastic modulus are deduced, and then, the statistical parameters of concrete compressive strength under different service time can be calculated. Finally, based on the established limit state equation of flexural capacity of the weak section and the statistical parameters of compressive strength at different times, the reliability index of a structure under different service life is calculated. On the other hand, according to the drift Wiener process model of relative dynamic elastic modulus degradation of concrete, the time‐varying failure probability of structural durability degradation is calculated based on the first‐passage failure probability formula of drift Wiener process. Taking a concrete plant structure as an example, the time‐varying reliability index calculated based on the limit state equation and the time‐varying failure probability obtained based on the first‐passage failure probability analysis of drift Wiener process are compared, and then the recommended values of target reliability index of structural bearing capacity are comprehensively determined.
Investigation of SGS alloys CoNbMnZ (Z = As, Sb) suitable for dissipationless spintronic devices and thermoelectric technology
Authors: Seh Ab Quyoom , Gupta Dinesh C. 
Published: July 2022

AbstractThe current study examines two quaternary Heusler alloys, CoNbMnZ (Z = As, Sb). The structural optimization displays a Y2‐type structure with a ferromagnetic feature as a stable state. Mechanical characteristics, cohesive, and formation energies further support the stability of these materials. The generalized gradient method band structure depicts the metallic character of both alloys. Upon integrating the modified Becke–Johnson potential to the generalized gradient method, the alloys signify a spin gapless semiconducting nature (SGS). The origin of the spin gapless property is explained using constituent hybridization through schematic representation. Since SGS alloys have zero spin‐flip energy, both holes and electrons display 100% spin polarization, making them ideal candidates for spintronics applications, which is a unique property of these alloys. Both alloys have a magnetic moment 2μB following the Slater–Pauling rule MT = ZT − 24. Furthermore, the computed thermoelectric properties suggest that these alloys are thermo‐efficient, might generate thermoelectric power, and act as green energy materials.
18‐Crown‐6 Additive to Enhance Performance and Durability in Solution‐Processed Halide Perovskite Electronics
Authors: Sim Kihyung , Nakao Takuya , Sasase Masato , Iimura Soshi , Kim Junghwan , Hosono Hideo 
Published: July 2022

AbstractRecently, an “interlayer” has been often adopted in organic–inorganic hybrid perovskite light‐emitting diodes (PeLEDs). The term “interlayer” infers that the layer function is not clear, but it improves electroluminescence (EL) performance. In this respect, it is of interest to determine the exact role of the interlayer and how it works in PeLEDs. In this study, the interlayer is determined to play a crucial role in suppressing the chemical reaction between the metal oxide and hybrid perovskite layers. Nevertheless, the use of an interlayer, a wide gap insulator, does not guarantee the best PeLED performance because it hinders charge injection into the emission layer. Here, a method is proposed that does not apply an “interlayer” but enables simultaneous attainment of high EL performance and outstanding device stability. 18‐crown 6‐ether (18C6) additive (2.5 mg mL−1) is found to fully suppress the chemical reaction between the metal oxide and hybrid perovskite layers. With the 18C6 additive, an 82‐fold longer device lifetime and very low operating voltage (3.2 V at 10 000 cd m−2) are demonstrated in a PeLED.
Rationally Designed Heptamethine Cyanine Photosensitizers that Amplify Tumor‐Specific Endoplasmic Reticulum Stress and Boost Antitumor Immunity
Authors: Huang Xie , Gao Mingquan , Xing Haiyan , Du Zaizhi , Wu Zifei , Liu Jing , Li Tao , Cao Jiang , Yang Xiaochao , Li Rong , Wang Weidong , Wang Junping , Luo Shenglin 
Published: July 2022

AbstractCancer phototherapy activates immunogenic cell death (ICD) and elicits a systemic antitumor immune response, which is an emerging approach for tumor treatment. Most available photosensitizers require a combination of immune adjuvants or checkpoint inhibitors to trigger antitumor immunity because of the immunosuppressive tumor microenvironment and the limited phototherapeutic effect. A class of tumor‐targeting heptamethine cyanine photosensitizers modified with an endoplasmic reticulum (ER)‐targeting group (benzenesulfonamide) are synthesized. Phototherapy of tumor cells markedly amplifies ER stress and promotes tumor antigen release, as the ER is required for protein synthesis, secretion, and transport. More importantly, different electron‐donating or ‐withdrawing substitutions are introduced into benzenesulfonamide to modulate the nonradiative decay pathways through intramolecular charge transfer, including singlet–triplet intersystem crossing (photodynamic effect) and internal thermal conversion (photothermal effect). Thus, a heptamethine cyanine photosensitizer containing a binitro‐substituted benzenesulfonamide (ER‐Cy‐poNO2) is identified that preferentially accumulates in the ER of tumor cells. It significantly enhances the phototherapeutic effect by inducing excessive ER stress and robust ICD. Consequently, this small molecular photosensitizer triggers a sufficient antitumor immune response and effectively suppresses the growth of both primary and distant metastatic tumors, whereas no apparent toxicity is observed. This heptamethine cyanine photosensitizer has the potential to enhance cancer‐targeted immunotherapy.
Robust Heterostructures in Two‐Dimensional Perovskites by Threshold‐Dominating Anion Exchange
Authors: He Chengyu , Li Jing , Bao Yanan , Li Jianliang , Wang Hengshan , Zhang Mingqun , Li HuaFeng , Tang Huayi , Sun Zhiguang , Zhang Qi , Fang Yurui , Xu Jiao , Yang Yiming 
Published: July 2022

AbstractHeterostructures play an irreplaceable role in high‐performance optoelectronic devices. However, the preparation of robust perovskite heterostructures is challenging due to spontaneous interdiffusion of halogen anions. Herein, a vapor‐phase anion exchange method universally suitable for the preparation of robust 2D Ruddlesden–Popper perovskite (RPP) heterostructures is developed. A variety of heterostructures are fabricated based on exfoliated RPP microplates (MPs). Depending on the specific organic cations, the heterostructures can be either sharp and uniform, or broad and gradient, suggesting a new anion diffusion behavior different from that in 3D perovskites. Further experimental studies reveal that the lateral transport of anions follows a threshold‐dominating mechanism, while the vertical transport can be partially or completely suppressed by organic cations. Subsequently, quantitative investigation of anion diffusion in 2D perovskites is conducted. The lateral diffusion coefficient of halogen anions is calculated to be 6 to 7 orders of magnitude larger than the vertical coefficient, consistent with the observed highly anisotropic anion diffusion. In addition, it is shown that the anion exchange threshold can also enhance the thermodynamic stability of the heterostructures at elevated temperature. These results provide a general method to fabricate robust lateral RPP heterostructures, and offer important insights into anion behavior in low‐dimensional perovskites.
Effect of different exposure conditions on the self‐healing capacity of engineered cementitious composites with crystalline admixture
Authors: Mahmoodi Sina , Sadeghian Pedram 
Published: July 2022

AbstractIn this study, the effect of different exposure conditions of ambient air, tap water, and seawater on two levels of crack widths in engineered cementitious composites (ECC) were investigated. Crystalline admixture (CA) was implemented in the ECC mix to promote self‐healing capacity. Flexural testing on prism specimens (100 × 100 × 350 mm) was conducted to evaluate self‐healing by recovering the stiffness in the specimens with crack widths below 200 μm. Water permeability test was also carried out to assess the crack‐filling capability of ECC disk specimens (100‐mm diameter × 50‐mm thickness) with single crack widths over 1 mm. Digital image correlation technique was used to monitor crack propagation patterns and crack widths. To analyze the microstructure of the healing products, X‐ray diffraction test was conducted on groups of tap water and seawater exposures. Concluding results proved seawater to be a promising environmental condition for the self‐healing process in ECC specimens incorporating CA, in terms of recovery of mechanical and transport properties. Brucite was found to be formed as the additional healing agent that promoted self‐healing in this condition. These results can be applied for coastal concrete structures.
In Vitro Selection of Deoxyribozymes for the Detection of RNA Modifications
Authors: Liaqat Anam , Sednev Maksim V. , Höbartner Claudia 
Published: July 2022

AbstractDeoxyribozymes are artificially evolved DNA molecules with catalytic abilities. RNA-cleaving deoxyribozymes have been recognized as an efficient tool for detection of modifications in target RNAs and provide an alternative to traditional and modern methods for detection of ribose or nucleobase methylation. However, there are only few examples of DNA enzymes that specifically reveal the presence of a certain type of modification, including N6-methyladenosine, and the knowledge about how DNA enzymes recognize modified RNAs is still extremely limited. Therefore, DNA enzymes cannot be easily engineered for the analysis of desired RNA modifications, but are instead identified by in vitro selection from random DNA libraries using synthetic modified RNA substrates. This protocol describes a general in vitro selection stagtegy to evolve new RNA-cleaving DNA enzymes that can efficiently differentiate modified RNA substrates from their unmodified counterpart.
Non-radioactive In Vivo Labeling of RNA with 4-Thiouracil
Authors: Braun Christina , Knüppel Robert , Perez-Fernandez Jorge , Ferreira-Cerca Sébastien 
Published: July 2022

AbstractRNA molecules and their expression dynamics play essential roles in the establishment of complex cellular phenotypes and/or in the rapid cellular adaption to environmental changes. Accordingly, analyzing RNA expression remains an important step to understand the molecular basis controlling the formation of cellular phenotypes, cellular homeostasis or disease progression. Steady-state RNA levels in the cells are controlled by the sum of highly dynamic molecular processes contributing to RNA expression and can be classified in transcription, maturation and degradation. The main goal of analyzing RNA dynamics is to disentangle the individual contribution of these molecular processes to the life cycle of a given RNA under different physiological conditions. In the recent years, the use of nonradioactive nucleotide/nucleoside analogs and improved chemistry, in combination with time-dependent and high-throughput analysis, have greatly expanded our understanding of RNA metabolism across various cell types, organisms, and growth conditions.In this chapter, we describe a step-by-step protocol allowing pulse labeling of RNA with the nonradioactive nucleotide analog, 4-thiouracil, in the eukaryotic model organism Saccharomyces cerevisiae and the model archaeon Haloferax volcanii.
Translation Phases in Eukaryotes
Authors: Blanchet Sandra , Ranjan Namit 
Published: July 2022

AbstractProtein synthesis in eukaryotes is carried out by 80S ribosomes with the help of many specific translation factors. Translation comprises four major steps: initiation, elongation, termination, and ribosome recycling. In this review, we provide a comprehensive list of translation factors required for protein synthesis in yeast and higher eukaryotes and summarize the mechanisms of each individual phase of eukaryotic translation.
Thermofluor-Based Analysis of Protein Integrity and Ligand Interactions
Authors: Pinz Sophia , Doskocil Eva , Seufert Wolfgang 
Published: July 2022

AbstractThermofluor is a fluorescence-based thermal shift assay, which measures temperature-induced protein unfolding and thereby yields valuable information about the integrity of a purified recombinant protein. Analysis of ligand binding to a protein is another popular application of this assay. Thermofluor requires neither protein labeling nor highly specialized equipment, and can be performed in a regular real-time PCR instrument. Thus, for a typical molecular biology laboratory, Thermofluor is a convenient method for the routine assessment of protein quality. Here, we provide Thermofluor protocols using the example of Cdc123. This ATP-grasp protein is an essential assembly chaperone of the eukaryotic translation initiation factor eIF2. We also report on a destabilized mutant protein version and on the ATP-mediated thermal stabilization of wild-type Cdc123 illustrating protein integrity assessment and ligand binding analysis as two major applications of the Thermofluor assay.
Establishment and Maintenance of Open Ribosomal RNA Gene Chromatin States in Eukaryotes
Authors: Schächner Christopher , Merkl Philipp E. , Pilsl Michael , Schwank Katrin , Hergert Kristin , Kruse Sebastian , Milkereit Philipp , Tschochner Herbert , Griesenbeck Joachim 
Published: July 2022

AbstractIn growing eukaryotic cells, nuclear ribosomal (r)RNA synthesis by RNA polymerase (RNAP) I accounts for the vast majority of cellular transcription. This high output is achieved by the presence of multiple copies of rRNA genes in eukaryotic genomes transcribed at a high rate. In contrast to most of the other transcribed genomic loci, actively transcribed rRNA genes are largely devoid of nucleosomes adapting a characteristic “open” chromatin state, whereas a significant fraction of rRNA genes resides in a transcriptionally inactive nucleosomal “closed” chromatin state. Here, we review our current knowledge about the nature of open rRNA gene chromatin and discuss how this state may be established.
Eukaryotic Ribosome assembly and Nucleocytoplasmic Transport
Authors: Oborská-Oplová Michaela , Fischer Ute , Altvater Martin , Panse Vikram Govind 
Published: July 2022

AbstractThe process of eukaryotic ribosome assembly stretches across the nucleolus, the nucleoplasm and the cytoplasm, and therefore relies on efficient nucleocytoplasmic transport. In yeast, the import machinery delivers ~140,000 ribosomal proteins every minute to the nucleus for ribosome assembly. At the same time, the export machinery facilitates translocation of ~2000 pre-ribosomal particles every minute through ~200 nuclear pore complexes (NPC) into the cytoplasm. Eukaryotic ribosome assembly also requires >200 conserved assembly factors, which transiently associate with pre-ribosomal particles. Their site(s) of action on maturing pre-ribosomes are beginning to be elucidated. In this chapter, we outline protocols that enable rapid biochemical isolation of pre-ribosomal particles for single particle cryo-electron microscopy (cryo-EM) and in vitro reconstitution of nuclear transport processes. We discuss cell-biological and genetic approaches to investigate how the ribosome assembly and the nucleocytoplasmic transport machineries collaborate to produce functional ribosomes.
Medicine, the Holocaust, and Human Dignity: Lessons from Human Rights
Authors: Wasserman Jason Adam , Navin Mark Christopher 
Published: July 2022

AbstractThe development of bioethics in the late Twentieth Century parallels the development of human rights discourses. Both intellectual movements have ideological roots in a reckoning with the tragedy of the Holocaust and both invoke conceptions of human dignity that have sometimes been accused of being vague or empty and therefore useless. However, despite its ambiguity, human dignity plays an important role in both discourses. In particular, we argue that bioethics scholars can learn from how advocates of human rights have balanced their idealized and abstract conceptions of dignity (and other values) with a focus on how real-world personal and institutional moral failures can inform efforts to promote human rights. We argue that a reengagement with the horrors of the Holocaust can supplement and motivate a critical, real-world bioethics, one that is responsive to the personal and institutional failures of our time and which provides practical guidance undernon-idealconditions.
The Physician’s Role: Patient v. Population
Authors: Urion David K. 
Published: July 2022

AbstractThere is always a tension between Public health and individual medical care. The former seeks, by one ethical optic, a fundamentally consequentialist goal: the greatest good for the greatest number of individuals. The latter has, at its moral base, an encounter between a medical provider and a patient, and its ethical goal is to optimize the outcome that the patient desires. While this dichotomy of intent and effort must be nuanced, setting it out in these terms helps us understand the tensions that we see between Public health initiatives and individual medical care. This chapter will suggest that by examining two movements that attempted to insert larger community concerns into the individual patient encounter, we might gain insight into what happens in the moral space of the patient encounter when the provider is compelled to consider these larger concerns. The Eugenics movement of the late nineteenth and early twentieth centuries, and the population health movement of the late twentieth and early twenty-first centuries will be considered as two examples of attempts to alter the individual patient encounter through the lens of larger societal concerns.
Ultralight millicharged dark matter via misalignment
Authors: Bogorad Zachary , Toro Natalia 
Published: July 2022

Abstract
We explore the cosmology and phenomenology of millicharged and millicharge-like dark matter with masses from 1 eV to 10 keV and charges of 10−18 to 10−14. Dark matter in this mass range cannot be thermally produced, but can arise from non-thermal mechanisms. We propose a concrete model employing a spontaneously broken approximate global symmetry, in which millicharged dark matter is produced via the misalignment mechanism. We show that this production mechanism is cosmologically consistent and compatible with the observed dark matter abundance. This model can be implemented using either fundamental scalars or hidden-sector quarks, and coupled either to the Standard Model photon or to a hidden photon. We then consider the phenomenology of light millicharged dark matter, regardless of its cosmological origin, and determine the parameter space consistent with existing experiments and observations. A significant part of the new parameter space we consider may be accessible in the near future through direct deflection experiments, measurements of the cosmic microwave background blackbody spectrum, and future constraints on plasma instabilities due to dark matter self-interaction.
Complementary signals of lepton flavor violation at a high-energy muon collider
Authors: Homiller Samuel , Lu Qianshu , Reece Matthew 
Published: July 2022

AbstractA muon collider would be a powerful probe of flavor violation in new physics. There is a strong complementary case for collider measurements and precision low-energy probes of lepton flavor violation (as well as CP violation). We illustrate this by studying the collider reach in a supersymmetric scenario with flavor-violating slepton mixing. We find that the collider could discover sleptons and measure the slepton and neutralino masses with high precision, enabling event reconstruction that could cleanly separate flavor-violating new physics signals from Standard Model backgrounds. The discovery reach of a high-energy muon collider would cover a comparably large, and overlapping, range of parameter space to futureμ → econversion and electron EDM experiments, and unlike precision experiments could immediately shed light on the nature of new physics responsible for flavor violation. This complementarity strengthens the case that a muon collider could be an ideal energy-frontier laboratory in the search for physics beyond the Standard Model.
Primitive ideals in affinoid enveloping algebras of semisimple Lie algebras
Authors: Stanciu Ioan 
Published: July 2022

AbstractFor a semisimple Lie algebra defined over a discrete valuation ring with field of fractions K, we prove that any primitive ideal with rational central character in the affinoid enveloping algebra, $$\widehat{U({\mathfrak {g}})_{K}}$$

U

(
g
)

K

^

, is the annihilator of an affinoid highest weight module. In the case $$n>0$$

n
>
0

, we characterise all the primitive ideals in the affinoid algebra $$\widehat{U(\mathfrak {{g}})_{n,K}}$$

U

(
g
)

n
,
K

^

.