Browse Articles

Repeated 5-aminolevulinic acid mediated sonodynamic therapy using magnetic resonance guided focused ultrasound in rat brain tumour models

AbstractSonodynamic therapy is an emerging therapeutic approach against brain tumours. However, the treatment scheme and ultrasound parameters have yet to be explored for clinical translation. Our study aimed to optimize ultrasound parameters for sonodynamic therapy (SDT) with 5-ALA as a sonosensitizing agent and to evaluate its therapeutic outcome on the rodent 9L gliosarcoma and the human U87 glioblastoma models. We stereotactically implanted brain tumour cells in rats and monitored tumour volume via MRI. SDT was conducted weekly using a 60 mg/kg dose of 5-ALA, injected intravenously 6 h before sonication. We used a driving frequency of 580 kHz with 0.75 MPa and evaluated the effect of different burst lengths to optimize ultrasound parameters. We also tested SDT against advanced-stage brain tumours to verify its efficacy further. Our results showed that a longer burst length could improve therapeutic outcomes. Tumour growth inhibition was established only in the first three weeks with 10 ms and 50 ms burst length sonication, but 86 ms burst length greatly improved the survival outcome. Therefore, the therapeutic efficacy is proportionate to the burst length and, thus, the total delivered energy. Repeated SDT using multiple targets to cover the entire tumour volume with optimal ultrasound parameters can achieve significant anti-tumour effects in both 9L and U87 models. Lastly, our results on late-stage tumour treatments showed that SDT can still provide prolonged survival. These promising findings demonstrate that repeated SDT using transcranial-focused ultrasound together with 5-ALA can optimize anti-tumour effects and even lead to complete clearance of the tumours. This weekly treatment with pulsed ultrasound sonication strategy is practical for future clinical translation.

Roof renewal disparities widen the equity gap in residential wildfire protection

Abstract Wildfires are having disproportionate impacts on U.S. households. Notably, in California, over half of wildfire-destroyed homes (54%) are in low-income areas. We investigate the relationship between social vulnerability and wildfire community preparedness using building permits from 16 counties in California with 2.9 million buildings (2013–2021) and the U.S. government’s designation of disadvantaged communities (DACs), which classifies a census tract as a DAC if it meets a threshold for certain burdens, such as climate, environmental, and socio-economic. Homes located in DACs are 29% more likely to be destroyed by wildfires within 30 years, partly driven by a gap in roof renewals, one of several important home hardening actions. Homes in DACs have 28% fewer roof renewals than non-DACs and post-wildfire, non-DAC homes have more than twice the increase in renewals (+17%) compared to DAC homes (+7%). Our research offers policy insights for narrowing this equity gap in renewals for wildfire-prone areas. We recommend increasing financial support for roof renewals and targeted awareness campaigns for existing programs which are not sufficiently emphasized in wildfire strategies, particularly in DACs.

Study of the recrystallization behaviors induced by annealing and irradiation on amorphous SiC

Silicon carbide and its derivatives are promising materials with potential applications in various types of nuclear reactors. To better understand their characteristics, this paper investigates the recrystallization behavior of amorphous SiC prepared through pre-irradiation using 800 keV Kr2+. Following different annealing processes, Raman spectra revealed that recrystallization happened beyond 873 K, and nearly complete recrystallization of the amorphous layer occurs at 1423 K. Afterward, in situ annealing and He+ irradiation experiments were conducted. The results indicate that the recrystallization progress is a layer-by-layer epitaxial regrowth on the amorphous–crystal interface under 873 K annealing, and the epitaxial recrystallization would slow down mainly due to the accumulation of defects and Kr atoms. However, under 30 keV He+ irradiation at 873 K, the interface continues to move. Moreover, when the irradiation dose rises, nanocrystals and helium bubbles appear simultaneously, growing in both size and density. The different recrystallization behaviors caused by irradiation and non-irradiation conditions could be explained by radiation-enhanced atomic diffusion, and helium bubbles are likely to be the by-products of nanocrystal formation. A possible explanation is proposed. This study provides insights into the practical application of amorphous silicon carbide in reactors and other irradiation environments.

E3 ligase RNF128 restricts A. alternata-induced ILC2 activation and type 2 immune response in the murine lung

DNA methylation modulates nucleosome retention in sperm and H3K4 methylation deposition in early mouse embryos

Abstract In the germ line and during early embryogenesis, DNA methylation (DNAme) undergoes global erasure and re-establishment to support germ cell and embryonic development. While DNAme acquisition during male germ cell development is essential for setting genomic DNA methylation imprints, other intergenerational roles for paternal DNAme in defining embryonic chromatin are unknown. Through conditional gene deletion of the de novo DNA methyltransferases Dnmt3a and/or Dnmt3b , we observe that DNMT3A primarily safeguards against DNA hypomethylation in undifferentiated spermatogonia, while DNMT3B catalyzes de novo DNAme during spermatogonial differentiation. Failing de novo DNAme in Dnmt3a / Dnmt3b double deficient spermatogonia is associated with increased nucleosome occupancy in mature sperm, preferentially at sites with higher CpG content, supporting the model that DNAme modulates nucleosome retention in sperm. To assess the impact of altered sperm chromatin in formatting embryonic chromatin, we measure H3K4me3 occupancy at paternal and maternal alleles in 2-cell embryos using a transposon-based tagging approach. Our data show that reduced DNAme in sperm renders paternal alleles permissive for H3K4me3 establishment in early embryos, independently of possible paternal inheritance of sperm born H3K4me3. Together, this study provides evidence that paternally inherited DNAme directs chromatin formation during early embryonic development.

Temperature dependent thermoelectric transport in PEDOT–PSS conducting polymer: The effect of additives

We report on both the electrical and thermoelectric transport properties as a function of temperature in poly(3,4-ethylene dioxythiophene) (PEDOT)–poly(styrene sulfonate) conducting polymers for a wide range of dimethyl sulfoxide (DMSO) additives. Whereas an insulating-like electrical behavior is found over the whole temperature range, a metallic-like thermopower is mainly observed. We show that the resistivity appears to be governed by a three-dimensional variable range hopping mechanism due to disordered regions with a decreasing localization temperature T0 and an increasing scaling factor ρ0 as a function of the DMSO ratio. The correlation between T0 and ρ0 demonstrates that they are both controlled by the localization length ξ0, which is strongly enhanced by the DMSO in agreement with the morphological evolution of the PEDOT chains with the additive. On the other hand, the high-T positive metallic-like thermopower seems rather unaffected by the additive in contrast to its low-T counterpart, which appears negative below a characteristic temperature Tswitch. By showing that the latter is closely related to the localization temperature, we propose to ascribe this sign switch to the thermoelectric contribution originating from disordered regions, which competes with the metallic ones due to ordered domains. While still controlled by the localization temperature, this negative contribution appears to be consistent with a phonon-drag component with a scaling behavior as T0T−3. These analyses allow us to discuss the overall temperature dependent thermoelectric properties in a consistent way by considering a heterogeneous structure with both ordered and disordered domains. By relating explicitly the electrical resistivity to the thermopower, our results do not only reconcile these transport coefficients, but they also provide a unified picture of the properties of the conducting polymers.

The role of a vaccine booster for a fractional order model of the dynamic of COVID-19: a case study in Thailand

Embracing plant plasticity or robustness as a means of ensuring food security

Voltage controlled light states in a spatially pseudo-random bit sequence encoded optical lattice

We have demonstrated reconfigurable light states in an optical lattice utilizing the electro-optic Pockels effect in a LiNbO3 slab through altering the transverse refractive index profile of the lattice by pseudo-random bit sequence (PRBS). By modifying the PRBS equivalent voltage range, different light states (ballistic, superdiffusive, diffusive, subdiffusive, and localized) are achieved within the completely disordered lattice. Furthermore, altering the maximum length size and number of periods of the PRBS creates lattices with different pseudo-random refractive index patterns. This provides a broader range of voltage control for switching from superdiffusive state to diffusive state than completely disorder lattice, allowing for precise voltage control over spatial profile for specific applications. This reconfigurable light states in this PRBS controlled lattice hold significant promise for various uses within a single integrated platform even after fabrication.

Rapid detection of drug abuse via tear analysis using surface enhanced Raman spectroscopy and machine learning

Inferring effects of mutations on SARS-CoV-2 transmission from genomic surveillance data

AbstractNew and more transmissible variants of SARS-CoV-2 have arisen multiple times over the course of the pandemic. Rapidly identifying mutations that affect transmission could improve our understanding of viral biology and highlight new variants that warrant further study. Here we develop a generic, analytical epidemiological model to infer the transmission effects of mutations from genomic surveillance data. Applying our model to SARS-CoV-2 data across many regions, we find multiple mutations that substantially affect the transmission rate, both within and outside the Spike protein. The mutations that we infer to have the largest effects on transmission are strongly supported by experimental evidence from prior studies. Importantly, our model detects lineages with increased transmission even at low frequencies. As an example, we infer significant transmission advantages for the Alpha, Delta, and Omicron variants shortly after their appearances in regional data, when they comprised only around 1-2% of sample sequences. Our model thus facilitates the rapid identification of variants and mutations that affect transmission from genomic surveillance data.

Tuning the superconducting dome in granular aluminum thin films

The peculiar superconducting properties of granular aluminum, which consists of nanometer-sized aluminum grains separated by aluminum oxide, are attractive for applications in quantum circuitry, and they are interesting from a fundamental materials physics view. The phase diagram of granular aluminum as a function of normal-state resistivity features a superconducting dome with a maximum critical temperature Tc well above the Tc=1.2K of pure aluminum. Here, we show how the maximum Tc of this superconducting dome grows if the substrate temperature during deposition is lowered from 300 K to cooling with liquid nitrogen (150 and 100 K) and liquid helium (25 K). The highest Tc that we observe is 3.27 K. These results highlight that granular aluminum is a model system for complex phase diagrams of superconductors and demonstrate its potential in the context of high kinetic inductance applications. This is augmented by our observation of comparably sharp superconducting transitions of high-resistivity samples grown at cryogenic temperatures and by a thickness dependence even for films substantially thicker than the grain size.

Genomic evidence of improved fertility and adaptation in Iranian domestic sheep attributed to introgression from Asiatic Mouflon and urial

Dentate gyrus norepinephrine ramping facilitates aversive contextual processing

Microtubules Sequester Acetylated YAP in the Cytoplasm and Inhibit Heart Regeneration

BACKGROUND: The Hippo pathway effector YAP (Yes-associated protein) plays an essential role in cardiomyocyte proliferation and heart regeneration. In response to physiological changes, YAP moves in and out of the nucleus. The pathophysiological mechanisms regulating YAP subcellular localization after myocardial infarction remain poorly defined. METHODS: We identified YAP acetylation at site K265 by in vitro acetylation followed by mass spectrometry analysis. We used adeno-associated virus to express YAP-containing mutations that either abolished acetylation (YAP-K265R) or mimicked acetylation (YAP-K265Q) and studied how acetylation regulates YAP subcellular localization in mouse hearts. We generated a cell line with YAP-K265R mutation and investigated the protein-protein interactors by YAP immunoprecipitation followed by mass spectrometry, then validated the YAP interaction in neonatal rat ventricular myocytes. We examined colocalization of YAP and TUBA4A (tubulin α 4A) by superresolution imaging. Furthermore, we developed YAP-K265R and αMHC-MerCreMer (MCM); Yap-loxP/K265R mutant mice to examine the pathophysiological role of YAP acetylation in cardiomyocytes during cardiac regeneration. RESULTS: We found that YAP is acetylated at K265 by CBP (CREB-binding protein)/P300 (E1A-binding protein P300) and is deacetylated by nicotinamide phosphoribosyltransferase/nicotinamide adenine dinucleotide/sirtuins axis in cardiomyocytes. After myocardial infarction, YAP acetylation is increased, which promotes YAP cytoplasmic localization. Compared with controls, mice that were genetically engineered to express a K265R mutation that prevents YAP K265 acetylation showed improved cardiac regenerative ability and increased YAP nuclear localization. Mechanistically, YAP acetylation facilitates its interaction with TUBA4A, a component of the microtubule network that sequesters acetylated YAP in the cytoplasm. After myocardial infarction, the microtubule network increased in cardiomyocytes, resulting in the accumulation of YAP in the cytoplasm. CONCLUSIONS: After myocardial infarction, decreased sirtuin activity enriches YAP acetylation at K265. The growing TUBA4A network sequesters acetylated YAP within the cytoplasm, which is detrimental to cardiac regeneration.

Temperature-independent zero–zero-birefringence polymer using <i>N</i>-substituted maleimide and styrene

To date, the orientational birefringence and the photoelastic birefringence of alternating copolymers have not been studied in detail. We focused on N-substituted maleimide (RMI) and styrene (St) as alternating copolymers and analyzed the birefringence, refractive index, and glass transition temperature (Tg) of the alternating copolymers. It was found that the photoelastic coefficient and Tg exhibit a nonlinear relationship with the composition ratio of RMI and St. It is considered that the alternating copolymerization of RMI and St confirms that the conformation is inhibited by interacting with each other. A zero–zero-birefringence polymer that exhibits no birefringence was obtained by using N-ethylmaleimide and St and adjusting the composition ratio. This polymer showed a high Tg, low haze, and a low temperature dependence of birefringence.

Different temperatures leakage mechanisms of (Al2O3)x(HfO2)1−x gate Dielectrics deposited by atomic layer deposition

BrCF2CN for photocatalytic cyanodifluoromethylation

40th Anniversary of the TIMI Study Group

Experimental observation of mutual coupling in resonator array on thin-metal-film

We present the experimental observation of electromagnetic mutual coupling in an array of ring-shaped resonators (meta-atoms) fabricated on a free-standing thin metal film using a maskless direct laser ablation technique. The transmission spectra of various resonator configurations were measured via terahertz time-domain spectroscopy and a vector network analysis. Numerical modeling of periodically arranged resonators, employing multipole decomposition, revealed a clear dependence of inter-element coupling on the number of meta-atoms in the array. Theoretical analysis of electric and magnetic dipoles and quadrupoles elucidates the nature of resonance peak splitting and broadening, resulting in a reduction in the quality factor as the number of meta-atoms increases. We anticipate that observed inter-element coupling behavior along with multipole mode analysis could advance the development of multi-pixel emitters, 2D plasmonic THz sources, sensors, electro-optical modulators, and resonators for subwavelength photonic and plasmonic applications.