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The photoisomerization reaction of a fluorescent protein chromophore occurs on the ultrafast timescale. The structural dynamics that result from femtosecond optical excitation have contributions from vibrational and electronic processes and from reaction dynamics that involve the crossing through a conical intersection. The creation and progression of the ultrafast structural dynamics strongly depends on optical and molecular parameters. When using X-ray crystallography as a probe of ultrafast dynamics, the origin of the observed nuclear motions is not known. Now, high-resolution pump-probe X-ray crystallography reveals complex sub-ångström, ultrafast motions and hydrogen-bonding rearrangements in the active site of a fluorescent protein. However, we demonstrate that the measured motions are not part of the photoisomerization reaction but instead arise from impulsively driven coherent vibrational processes in the electronic ground state. A coherent-control experiment using a two-colour and two-pulse optical excitation strongly amplifies the X-ray crystallographic difference density, while it fully depletes the photoisomerization process. A coherent control mechanism was tested and confirmed the wave packets assignment.

In-vessel retention through external reactor vessel cooling (IVR-ERVC) is a severe accident management (SAM) strategy that has been adopted and used in many nuclear reactors such as AP1000, APR1400, and light water reactor etc. Some reactor accidents have raised concerns about nuclear reactors among residents, leading to a decrease in residents' acceptability and many studies on SAM are being conducted. Experiments on IVR-ERVC are almost impossible due to its specificity, so fluid characteristics are analyzed through BALI experiments with similar condition. In this study, computational fluid dynamics (CFD) via Reynolds-averaged Navier-Stokes (RANS) and large eddy simulation (LES) for BALI experiments were performed. Steady-state CFD analysis was performed on three turbulence models, and SST k-ω model was in good agreement with the experimental measurement temperature within the maximum error range of 1.9%. LES CFD analysis was performed based on the RANS analysis results and it was confirmed that the temperature and wall heat flux for depth was consistent within an error range of 1.0% with BALI experiment. The LES CFD analysis results were compared with those of the Lagrangian-based solver. LES matched the temperature distribution better than SOPHIA, but SOPHIA calculated the position of boundary between stratified layer and convective layer more accurately. On the other hand, Lagrangian-based solver predicted several small eddy behaviors of the convective layer and LES predicted large vortex behavior. The vibration characteristics near the cooling part of the BALI experimental device were confirmed through Fast Fourier Transform (FFT) investigation. It was found that the power spectral density for pressure at least 10 times higher near the side cooling than near the top cooling.

Anisotropic materials with chirality or birefringence can be used to manipulate the polarization states of electromagnetic waves. However, the comparatively low anisotropy of natural materials hinders the miniaturization of optical components and devices at terahertz frequencies. In this study, we experimentally demonstrate that the relative phase retardation of a THz wave can be electrically controlled by integrating patterned mono- and bilayer graphene onto an otherwise isotropic metasurface. Specifically, we show that a refractive index for one of the orthogonal polarization states can be electrically controlled by modulating graphene’s conductivity, thereby weakening the capacitive coupling between adjacent meta-atoms in an anisotropic manner. With monolayer graphene, phase retardation of 15° to 81° between two orthogonal polarization states can be achieved. Maximum phase retardation of 90° through a metasurface with bilayer graphene suggests its use as a tunable quarter-wave plate. Continuous control from linear- to circular-polarization states may provide a wide range of opportunities for the development of compact THz polarization devices and polarization-sensitive THz technology.

Abstract Angiotensin-converting enzyme 2 (ACE2) is an important factor in coronavirus disease (COVID-19) interactions. Losartan (LOS) belongs to the angiotensin receptor blocker (ARB) family. Additionally, the protective role of ACE2 restored by LOS has been suggested and clinically examined in the treatment of COVID-19 patients. Furthermore, clinical trials with LOS have been conducted. However, the mechanism through which LOS enhances ACE2 expression remains unclear. In addition, the response of ACE2 to LOS differs among patients. Our LOS-treated patient data revealed a correlated mechanism of ACE2 with components of the renin-angiotensinogen system. We observed a significant positive regulation of MAS1 and ACE2 expression. In the context of LOS treatment of COVID-19, ACE2 expression could depend on LOS regulated MAS1. Thus, MAS1 expression could predict the COVID-19 treatment response of LOS.

Understanding the interplay between charge, nematic, and structural ordering tendencies in cuprate superconductors is critical to unraveling their complex phase diagram. Using pump-probe time-resolved resonant X-ray scattering on the (0 0 1) Bragg peak at the Cu L3 and O K resonances, we investigate nonequilibrium dynamics of Qa = Qb = 0 nematic order and its association with both charge density wave (CDW) order and lattice dynamics in La1.65Eu0.2Sr0.15CuO4. The orbital selectivity of the resonant X-ray scattering cross-section allows nematicity dynamics associated with the planar O 2p and Cu 3d states to be distinguished from the response of anisotropic lattice distortions. A direct time-domain comparison of CDW translational symmetry breaking and nematic rotational-symmetry breaking reveals that these broken symmetries remain closely linked in the photoexcited state, consistent with the stability of CDW topological defects in the investigated pump fluence regime. [ABSTRACT FROM AUTHOR]

Background Currently, several antibody (Ab)-based therapies have shown excellent therapeutic effects in the clinic. Nonetheless, Ab penetration into tumor tissues is limited due to abnormal vasculature, tumor interstitial pressure, and excessive extracellular matrix (ECM) accumulation, thus demanding novel strategies to overcome these barriers.Methods The intratumoral distribution of therapeutic Abs were detected by fluorescence microscopy or positron emission tomography in both human gastric xenograft and syngeneic pancreatic hamster tumor models. The antitumor efficacy by combination of oncolytic adenovirus (Ad), which coexpresses relaxin (RLX), interleukin (IL)-12, and granulocyte macrophage colony-stimulating factor (GM-CSF) (oAd/IL12/GM-RLX) and antibody against the programmed cell death protein 1 (αPD-1) was examined in hamster subcutaneous and orthotopic pancreatic tumor models. The immunological aspects of these combination therapy regimen were assessed by flow cytometry or immunohistochemistry in subcutaneous hamster tumor models.Results Relaxin-expressing oncolytic Ad effectively degraded tumor ECM and enhanced the tumor penetration of trastuzumab in comparison with trastuzumab monotherapy. Based on these results, an oAd/IL12/GM-RLX was used to enhance the potency of immune checkpoint blockade. The combination of the oAd/IL12/GM-RLX and αPD-1 promoted a concomitant degradation of the tumor ECM and amelioration of the immunosuppressive tumor niches, ultimately enhanced intratumoral infiltration of both αPD-1 and activated T cells. Of note, the combination therapy was able to elicit a potent and durable antitumor immune response against cold tumors that were refractory to immune checkpoint inhibitor monotherapy.Conclusions Our findings are the first to demonstrate that expression of four genes (IL-12p35, IL-12p40, GM-CSF, and RLX) mediated by a single oncolytic Ad vector can promote remodeling of both physical and immunological aspects of the tumor niches to overcome the major limitations of Ab-based therapies that have emerged in recent clinical trials.

Abstract Background Chemotherapy-induced alopecia has been well documented as a cause of distress to patients undergoing cancer treatment. Almost all traditional chemotherapeutic agents cause severe alopecia. Despite advances in the treatment of chemotherapy-induced alopecia, there is no effective treatment for preventing chemotherapy-induced alopecia. Methods In the present study, we investigated the potential role of a multi-target iron chelator, M30 in protecting against cyclophosphamide-induced alopecia in C57BL/6 mice implanted with an osmotic pump. M30 enhanced hair growth and prevented cyclophosphamide-induced abnormal hair in the mice. Furthermore, we examined the gene expression profiles derived from skin biopsy specimens of normal mice, cyclophosphamide-treated mice, and cyclophosphamide treated mice with M30 supplement. Results The top genes namely Tnfrsf19, Ercc2, Lama5, Ctsl, and Per1 were identified by microarray analysis. These genes were found to be involved in the biological processes of hair cycle, hair cycle phase, hair cycle process, hair follicle development, hair follicle maturation, hair follicle morphogenesis, regulation of hair cycle. Conclusion Our study demonstrates that M30 treatment is a promising therapy for cyclophosphamide-induced alopecia and suggests that the top five genes have unique preventive effects in cyclophosphamide-induced transformation.