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The positive transcription elongation factor b (P-TEFb) is an essential factor that induces transcription elongation and is also negatively regulated by the cellular factor HEXIM1. Previously, the chimeric protein HEXIM1-Tat (HT) was demonstrated to inhibit human immunodeficiency virus-1 (HIV)-1 transcription. In this study, we attempted to develop an improved antiviral protein that specifically binds viral RNA (vRNA) by fusing HT to HIV-1 nucleocapsid (NC). Thus, we synthesized NC-HEXIM1-Tat (NHT) and HEXIM1-Tat-NC (HTN). NHT and HTN inhibited virus proliferation more effectively than HT, and they did not attenuate the function of HT. Notably, NHT and HTN inhibited the infectivity of the progeny virus, whereas HT had no such effect. NHT and HTN selectively and effectively interacted with vRNA and inhibited the proper packaging of the HIV-1 genome. Taken together, our results illustrated that the novel NC-fused chimeric proteins NHT and HTN display novel mechanisms of anti-HIV effects by inhibiting both HIV-1 transcription and packaging.

Background: The treatment options for basal ganglia intracerebral hemorrhage (ICH), either surgical or conservative, remain controversial. A previous study developed “A new modified ICH (MICH) score” that suggests which treatment option will be better for basal ganglia ICH. According to this scoring system, a MICH score of 0 or 1 indicates that conservative treatment is better than surgical treatment. The purpose of this study was to determine whether conservative treatment is still a better option for a basal ganglia hemorrhage in patients with MICH scores of 0 and 1, with initial poor motor grades. Methods: This retrospective study was comprised of 41 patients with a spontaneous basal ganglia hemorrhage. These patient groups had no previous brain lesions, their initial MICH score was 0 or 1, and the manual muscle test (MMT) of their hand was grade 2+ or lower in the initial evaluation. All patients were transferred to the Department of Rehabilitation Medicine and received rehabilitation treatment. Ten patients had an operative intervention, which was burr-hole aspiration or craniotomy with hematoma removal. The control group included 31 patients who underwent conservative treatment. Outcome evaluations used the Berg Balance Scale (BBS), Modified Barthel Index (MBI), and Brunnstrom recovery stage (BRS) which were evaluated at initial and regular follow-ups after 1, 3, and 6 months. We defined an improvement state if the BRS of their hand became 4 or more in 6 months, which means an escape from the synergic pattern. Results: Demographic characteristics showed no significant differences in age, sex, hemiplegic side, initial GCS score, presence of IVH and hydrocephalus, or distribution of MICH scores 0 and 1. There was only a significant difference in the distribution of hematoma volume between groups of less than 20 mL and groups from 21 to 50 mL (p = 0.049). There were no significant differences in MBI values in 1 month or improvement of BRS of their hand in 6 months between the two groups. Conclusions: Even in the group classified as predominantly conservative in basal ganglia hemorrhage patients, if the initial muscle strength is low, it is necessary to reconsider whether conservative treatment is superior to surgical treatment in terms of functional improvement.

Metal additive manufacturing (AM) is an innovative manufacturing technology that uses a high-power laser for the layer-by-layer production of metal components. Despite many achievements in the field of AM, few studies have focused on the nondestructive characterization of microstructures, such as grain size and porosity. In this study, various microstructures of additively manufactured metal components were characterized non-destructively using linear/nonlinear ultrasonic techniques. The contributions of this study are as follows: (1) presenting correlation analyses of various microstructures (grain size and texture, lack of fusion, and porosity) and ultrasonic properties (ultrasonic velocity, attenuation, and nonlinearity parameters), (2) development of nondestructive microstructural characterization techniques for additively manufactured components; and (3) exploring the potential for the online monitoring of AM processes owing to the nondestructive nature of the proposed technique. The performance of the proposed technique was validated using additively manufactured samples under varying laser beam speed conditions. The characteristics of the target microstructures characterized using the proposed technique were consistent with the results obtained using destructive optical microscopy and electron back-scattered diffraction methods.

The absolute acoustic nonlinearity parameter β is defined by the displacement amplitudes of the fundamental and second-order harmonic frequency components of the ultrasonic wave propagating through the material. As β is a sensitive index for the micro-damage interior of industrial components at early stages, its measurement methods have been actively investigated. This study proposes a laser-ultrasonic detection method to measure β. This method provides (1) the β measurement in a noncontact and nondestructive manner, (2) inspection ability of different materials without complex calibration owing to direct ultrasonic displacement detection, and (3) applicability for the general milling machined surfaces of components owing to the use of a laser interferometer based on two-wave mixing in the photorefractive crystal. The performance of the proposed method is validated using copper and 6061 aluminum alloy specimens with sub-micrometer surface roughness. The experimental results demonstrated that the β values measured by the proposed method for the two specimens were consistent with those obtained by the conventional piezoelectric detection method and the range of previously published values.

Abstract In this study we examined the anti-leukemia activity of a small molecule inhibitor of Hsp70 proteins, apoptozole (Az), and hybrids in which it is linked to an inhibitor of either Hsp90 (geldanamycin) or Abl kinase (imatinib). The results of NMR studies revealed that Az associates with an ATPase domain of Hsc70 and thus blocks ATP binding to the protein. Observations made in the cell study indicated that Az treatment promotes leukemia cell death by activating caspase-dependent apoptosis without affecting the caspase-independent apoptotic pathway. Importantly, the hybrids composed of Az and geldanamycin, which have high inhibitory activities towards both Hsp70 and Hsp90, exhibit enhanced anti-leukemia activity relative to the individual inhibitors. However, the Az and imatinib hybrids have weak inhibitory activities towards Hsp70 and Abl, and display lower cytotoxicity against leukemia cells compared to those of the individual constituents. The results of a mechanistic study showed that the active hybrid molecules promote leukemia cell death through a caspase-dependent apoptotic pathway. Taken together, the findings suggest that Hsp70 inhibitors as well as their hybrids can serve as potential anti-leukemia agents.

Ultrasonic testing (UT) has been actively studied to evaluate the porosity of additively manufactured parts. Currently, ultrasonic measurements of as-deposited parts with a rough surface remain problematic because the surface lowers the signal-to-noise ratio (SNR) of ultrasonic signals, which degrades the UT performance. In this study, various deep learning (DL) techniques that can effectively extract the features of defects, even from signals with a low SNR, were applied to UT, and their performance in terms of the porosity evaluation of additively manufactured parts with rough surfaces was investigated. Experimentally, the effects of the processing conditions of additive manufacturing on the resulting porosity were first analyzed using both optical and scanning acoustic microscopy. Second, convolutional neural network (CNN), deep neural network, and multi-layer perceptron models were trained using time-domain ultrasonic signals obtained from additively manufactured specimens with various levels of porosity and surface roughness. The experimental results showed that all the models could evaluate porosity accurately, even that of the as-deposited specimens. In particular, the CNN delivered the best performance at 94.5%. However, conventional UT could not be applied because of the low SNR. The generalization performance when using newly manufactured as-deposited specimens was high at 90%.

Electroactive polymer (EAP) is a polymer that reacts to electrical stimuli, such as voltage, and can be divided into electronic and ionic EAP by an electrical energy transfer mechanism within the polymer. The mechanism of ionic EAP is the movement of the positive ions inducing voltage change in the polymer membrane. Among the ionic EAPs, an ionic polymer–metal composite (IPMC) is composed of a metal electrode on the surface of the polymer membrane. A common material for the polymer membrane of IPMC is Nafion containing hydrogen ions, and platinum, gold, and silver are commonly used for the electrode. As a result, IPMC has advantages, such as low voltage requirements, large bending displacement, and bidirectional actuation. Manufacturing of IPMC is composed of preparing the polymer membrane and plating electrode. Preparation methods for the membrane include solution casting, hot pressing, and 3D printing. Meanwhile, electrode formation methods include electroless plating, electroplating, direct assembly process, and sputtering deposition. The manufactured IPMC is widely demonstrated in applications such as grippers, micro-pumps, biomedical, biomimetics, bending sensors, flow sensors, energy harvesters, biosensors, and humidity sensors. This paper will review the overall field of IPMC by demonstrating the categorization, principle, materials, and manufacturing method of IPMC and its applications.

Previous numerical simulations of double-peaked Type IIb supernova (SN IIb) light curves have demonstrated that the radius and mass of the hydrogen-rich envelope of the progenitor star can significantly influence the brightness and timescale of the early-time light curve around the first peak. In this study, we investigate how Thomson scattering and chemical mixing in the SN ejecta affect the optical light curves during the early stages of the SNe IIb using radiation hydrodynamics simulations. By comparing the results from two different numerical codes (i.e., STELLA and SNEC ), we find that the optical brightness of the first peak can be reduced by more than a factor of 3 as a result of the effect of Thomson scattering that causes the thermalization depth to be located below the Rosseland mean photosphere, compared to the corresponding case where this effect is ignored. We also observe a short-lived plateau-like feature lasting for a few days in the early-time optical light curves of our models, in contrast to typical observed SNe IIb that show a quasi-linear decrease in optical magnitudes after the first peak. A significant degree of chemical mixing between the hydrogen-rich envelope and the helium core in SN ejecta is required to reconcile this discrepancy between the model prediction and observation. Meanwhile, to properly reproduce the first peak, a significant mixing of ^56 Ni into the hydrogen-rich outermost layers should be restricted. Our findings indicate that inferring the SN IIb progenitor structure from a simplified approach that ignores these two factors may introduce substantial uncertainty.

We present near-infrared (NIR) and optical observations of the Type Ic supernova (SN Ic) SN 2021krf obtained between days 13 and 259 at several ground-based telescopes. The NIR spectrum at day 68 exhibits a rising K -band continuum flux density longward of ∼2.0 μ m, and a late-time optical spectrum at day 259 shows strong [O i ] 6300 and 6364 Å emission-line asymmetry, both indicating the presence of dust, likely formed in the SN ejecta. We estimate a carbon-grain dust mass of ∼2 × 10 ^−5 M _⊙ and a dust temperature of ∼900–1200 K associated with this rising continuum and suggest the dust has formed in SN ejecta. Utilizing the one-dimensional multigroup radiation-hydrodynamics code STELLA, we present two degenerate progenitor solutions for SN 2021krf, characterized by C–O star masses of 3.93 and 5.74 M _⊙ , but with the same best-fit ^56 Ni mass of 0.11 M _⊙ for early times (0–70 days). At late times (70–300 days), optical light curves of SN 2021krf decline substantially more slowly than those expected from ^56 Co radioactive decay. Lack of H and He lines in the late-time SN spectrum suggests the absence of significant interaction of the ejecta with the circumstellar medium. We reproduce the entire bolometric light curve with a combination of radioactive decay and an additional powering source in the form of a central engine of a millisecond pulsar with a magnetic field smaller than that of a typical magnetar.

We investigate the dynamics of a non-linear network with noise, periodic forcing and delayed feedback. Our model reveals that there exist forcing regimes—called persistent entrainment regimes—in which the system displays oscillatory responses that outlast the termination of the forcing. Our analysis shows that in presence of delays, periodic forcing can selectively excite components of an infinite reservoir of intrinsic modes and hence display a wide range of damped frequencies. Mean-field and linear stability analysis allows a characterization of the magnitude and duration of these persistent oscillations, as well as their dependence on noise intensity and time delay. These results provide new perspectives on the control of non-linear delayed system using periodic forcing.