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Hydration and carbonation reactions within the Earth cause an increase in solid volume by up to several tens of vol%, which can induce stress and rock fracture. Observations of naturally hydrated and carbonated peridotite suggest that permeability and fluid flow are enhanced by reaction-induced fracturing. However, permeability enhancement during solid-volume-increasing reactions has not been achieved in the laboratory, and the mechanisms of reaction-accelerated fluid flow remain largely unknown. Here, we present experimental evidence of significant permeability enhancement by volume-increasing reactions under confining pressure. The hydromechanical behavior of hydration of sintered periclase [MgO + H2O â Mg(OH)2] depends mainly on the initial pore-fluid connectivity. Permeability increased by three orders of magnitude for low-connectivity samples, whereas it decreased by two orders of magnitude for high-connectivity samples. Permeability enhancement was caused by hierarchical fracturing of the reacting materials, whereas a decrease was associated with homogeneous pore clogging by the reaction products. These behaviors suggest that the fluid flow rate, relative to reaction rate, is the main control on hydromechanical evolution during volume-increasing reactions. We suggest that an extremely high reaction rate and low pore-fluid connectivity lead to local stress perturbations and are essential for reaction-induced fracturing and accelerated fluid flow during hydration/carbonation.
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Measurement-device-independent quantum key distribution (MDI-QKD) has been proven to protect legitimate users from attacks against measurement devices. The MDI-QKD requires that the two photons arriving at the instrument be indistinguishable. Precise time control is required to eliminate the distinguishability due to differences in photon arrival times. In the conventional methods, the time difference between photons is measured at a measuring instrument (Charlie), and a control signal is transmitted to the users (Alice and Bob). However, this method requires a long feedback loop, and the control may become unstable for long-distance transmission. This article proposes a method in which the photon arrival time difference is detected and controlled at Charlie. The reference signal for the time control is generated by an optical frequency comb in synchronization with the quantum signal. Therefore, the quantum signal photons can also be synchronized by synchronizing the reference signal pulses. A proof-of-principle experiment confirmed that the time synchronization accuracy required for protocol execution could be obtained. This proposal simplifies the implementation of the MDI-QKD.
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Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP+ Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3+CD4+ T cells in the TME and exhibited remarkable anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.
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Anticuerpos Monoclonales/inmunología , Proteínas de la Membrana/inmunología , Neoplasias/inmunología , Linfocitos T Reguladores/inmunología , Animales , Femenino , Humanos , Tolerancia Inmunológica/inmunología , Inmunidad/inmunología , Inmunoterapia/métodos , Leucocitos Mononucleares/inmunología , Ratones , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Microambiente Tumoral/inmunologíaRESUMEN
To realize simplified cost-efficient optical networks with routing flexibility and scaling potential, a spatial-light-modulator-based optical-fiber joint switch for few-mode multicore fibers is proposed herein, which can route all spatial channels together as a unit. Numerical simulations and experiments were performed, and the results show that the signal paths for a 6-mode 19-core fiber can be simultaneously switched to the target output ports using the proposed method, and the mode-field patterns of the diffracted light can be maintained after joint switching. Further, the maximum port crosstalk can be reduced considerably from -11.6 to -25.1â dB by changing the position of the output port in the proposed method.
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Security certification of quantum key distribution systems with a practical device is essential for their social deployment. Considering the transmitter, we investigate quantum state generation affected by degraded electrical signals from practical bandwidth-limited devices on high-speed phase-encoding BB84 quantum key distribution systems. The state preparation flaw caused by this degradation undesirably enhances the distinguishability between the two bases for the BB84 protocol and decreases the key generation rate. We propose the state preparation with a dual parallel modulator for increasing the robustness to signal degradation. To verify the effectiveness of the dual parallel modulator, we characterize the generated states using state tomography and estimate the key generation rate based on the Gottesman-Lo-Lütkenhaus-Preskill theory with fidelity derived from the estimated density matrices. Simulation results show that the key generation rate remains unaffected by modulation voltage shifts up to 20%.
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G protein-coupled receptors (GPCRs) can form homodimers, heterodimers, or higher-order molecular complexes (oligomers). The reports on the change of functions through the oligomerization have been accumulated. Inhibition of GPCR oligomerization without affecting the protomer's overall structure would clarify the oligomer-specific functions although inhibition experiments are costly and require accurate information about the interface location. Unfortunately, the number of experimentally determined interfaces is limited. The precise prediction of the oligomerization interfaces is, therefore, useful for inhibition experiments to examine the oligomer-specific functions, which would accelerate investigations of the GPCR signaling. However, interface prediction for GPCR oligomerization is difficult because different GPCR subtypes belonging to the same subfamily often use different structural regions as their interfaces. We previously developed a high-performance method to predict the interfaces for GPCR oligomerization, by identifying the conserved surfaces with the sequence and structure information. Then, the structural characteristic of a GPCR structure is regarded to be a thick-tube like conformation that is approximately perpendicular to the membrane plane. Our method had successfully predicted all of the interfaces available on that day. We had launched a web server for our interface prediction of GPCRs (GRIP). We have improved the previous version of GRIP server and enhanced its usability. First, we discarded the approximation of the GPCR structure as the thick-tube-like conformation. This improvement increased the number of structures for the prediction. Second, the FUGUE-based template recommendation service was introduced to facilitate the choice of an appropriate structure for the prediction. The new prediction server is available at http://grip.b.dendai.ac.jp/â¼grip/.
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Bases de Datos Genéticas , Internet , Conformación Proteica , Receptores Acoplados a Proteínas G/ultraestructura , Humanos , Modelos Moleculares , Conformación Molecular , Multimerización de Proteína , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/clasificación , Receptores Acoplados a Proteínas G/genéticaRESUMEN
Nanopillar structure processing has been performed on condensation surfaces to control wettability and achieve a high heat transfer coefficient via dropwise condensation and jumping droplets. Modified dry etching was performed using gold (Au) nanoparticles generated by annealing Au as a mask. High-aspect-ratio nanopillar processing was also performed to produce uniform pillar surfaces and novel hierarchical pillar surfaces. A uniform nanopillar surface with pillars having diameters of 20-850 nm and a hierarchical pillar surface with thick pillars having diameters ranging from 100 to 860 nm and thin pillars with diameters ranging from 20 to 40 nm were mixed and fabricated. Condensation experiments were performed using the noncoated nanopillar surfaces, and the condensation behaviors on the silicon (Si) surfaces were observed from above using a microscope and from the side using a high-speed camera. On the uniform surface US-3 and the hierarchical surfaces HS-1 and HS-2, droplet jumps were observed frequently in the droplet size range of 20-50 µm. In contrast, as the droplet size increased to 50 µm or more, the number of jumps observed decreased as the droplet size increased. The frequency of droplet jumps on the hierarchical surfaces from the start of condensation to approximately 2 min was higher than that on the uniform surfaces, although the density of droplet formation on the hierarchical surfaces was not relatively large. On the basis of the observation of droplet behavior from the side surface, we identified that the primary jump was due to the coalescence of droplets adhering to the surface and that the subsequent jump was caused by the droplet coalescence when the jump droplets were reattached. The primary jump occurrence rate was high on all pillar surfaces.
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A wavefront superposition (WS) method is proposed for accurate and efficient mode conversion in mode-division multiplexing transmission. The WS method converts an input beam to the WS state, which is composed of the conversion target and radiation modes of a few-mode fiber. The appropriate weighting for the modal component of the WS state enables more efficient conversion than the conventional method in which the output beam consists only of the conversion target. Further, since the components of the radiation modes in the output are eliminated by the mode-filtering property of the few-mode fiber, no modal crosstalk occurs in the WS method. We examine the conversion performance of the WS method by a numerical simulation for the mode-multiplexing numbers 3, 6, 10, and 15. The WS method shows a 2.4 dB higher efficiency than the conventional method, while maintaining an extremely low modal crosstalk (less than -80 dB), even when the number of multiplexed modes is 15.
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Prions are infectious proteins that cause fatal neurodegenerative disorders including Creutzfeldt-Jakob and bovine spongiform encephalopathy (mad cow) diseases. The yeast [PSI+] prion is formed by the translation-termination factor Sup35, is the best-studied prion, and provides a useful model system for studying such diseases. However, despite recent progress in the understanding of prion diseases, the cellular defense mechanism against prions has not been elucidated. Here, we report that proteolytic cleavage of Sup35 suppresses spontaneous de novo generation of the [PSI+] prion. We found that during yeast growth in glucose media, a maximum of 40% of Sup35 is cleaved at its N-terminal prion domain. This cleavage requires the vacuolar proteases PrA-PrB. Cleavage occurs in a manner dependent on translation but independently of autophagy between the glutamine/asparagine-rich (Q/N-rich) stretch critical for prion formation and the oligopeptide-repeat region required for prion maintenance, resulting in the removal of the Q/N-rich stretch from the Sup35 N terminus. The complete inhibition of Sup35 cleavage, by knocking out either PrA (pep4Δ) or PrB (prb1Δ), increased the rate of de novo formation of [PSI+] prion up to â¼5-fold, whereas the activation of Sup35 cleavage, by overproducing PrB, inhibited [PSI+] formation. On the other hand, activation of the PrB pathway neither cleaved the amyloid conformers of Sup35 in [PSI+] strains nor eliminated preexisting [PSI+]. These findings point to a mechanism antagonizing prion generation in yeast. Our results underscore the usefulness of the yeast [PSI+] prion as a model system to investigate defense mechanisms against prion diseases and other amyloidoses.
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Proteínas Fúngicas/metabolismo , Factores de Terminación de Péptidos/metabolismo , Proteínas Priónicas/metabolismo , Priones/antagonistas & inhibidores , Proteolisis , Proteínas de Saccharomyces cerevisiae/metabolismo , Péptido Hidrolasas/metabolismo , Priones/metabolismo , Vacuolas/enzimología , Levaduras/metabolismoRESUMEN
We propose a virtual phase conjugation (VPC) based optical tomography (VPC-OT) for realizing single-shot optical tomographic imaging systems. Using a computer-based numerical beam propagation, the VPC combines pre-modulation and post-demodulation of the probe beam's wavefront, which provides an optical sectioning capability for resolving the depth coordinates. In VPC-OT, the physical optical microscope system and VPC are coupled using digital holography. Therefore, in contrast to conventional optical tomographic imaging (OTI) systems, this method does not require additional elements such as low-coherence light sources or confocal pinholes. It is challenging to obtain single-shot three-dimensional (3D) tomographic images using a conventional OTI system; however, this can be achieved using VPC-OT, which employs both digital holography and computer based numerical beam propagation. In addition, taking into account that VPC-OT is based on a complex amplitude detection using digital holography, this method allows us to simultaneously obtain quantitative phase contrast images. Using an objective lens with a numerical aperture (NA) of 0.8, we demonstrate a single-shot 3D imaging of frog blood cells with a depth resolution of 0.94 µm.
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Volume holographic demultiplexers (VHDMs) provide spatial mode demultiplexing using simple optical systems. However, applying VHDM to practical optical communication systems is difficult, as typical holographic media have no sensitivity in the infrared region, which includes optical transmission bands. In this paper, we propose a VHDM scheme combined with a dual-wavelength method (DWM). Using the DWM, VHDMs are able to perform mode demultiplexing in the optical transmission bands. We experimentally demonstrated the basic operation of our proposal using experiments performed at an 850-nm wavelength. In addition, we performed numerical simulations to investigate the application of VHDM to the C-band.
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Security certification of quantum key distribution (QKD) systems under practical conditions is necessary for social deployment. This article focused on the transmitter, and, in particular, investigated the intensity fluctuation of the optical pulses emitted by a gain-switched semiconductor laser used in QKD systems implementing decoy-BB84 protocol. A large intensity fluctuation was observed for low excitation, showing strong negative correlation between the adjacent pulses, which would affect the final key rate. The fluctuation decreased and the correlation disappeared as excitation increased. Simulation with rate equations successfully reproduced the experimental results and revealed that the large fluctuation originates from an intrinsic instability of gain-switched lasers driven periodically at a rate comparable to the inverse of carrier lifetime, as in GHz-clock QKD systems. Methods for further reduction of the intensity fluctuation were also discussed.
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To implement fault-tolerant quantum computation with continuous variables, Gottesman-Kitaev-Preskill (GKP) qubits have been recognized as an important technological element. However, the analog outcome of GKP qubits, which includes beneficial information to improve the error tolerance, has been wasted, because the GKP qubits have been treated as only discrete variables. In this Letter, we propose a hybrid quantum error correction approach that combines digital information with the analog information of the GKP qubits using a maximum-likelihood method. As an example, we demonstrate that the three-qubit bit-flip code can correct double errors, whereas the conventional method based on majority voting on the binary measurement outcome can correct only a single error. As another example, we show that a concatenated code known as Knill's C_{4}/C_{6} code can achieve the hashing bound for the quantum capacity of the Gaussian quantum channel (GQC). To the best of our knowledge, this approach is the first attempt to draw both digital and analog information to improve quantum error correction performance and achieve the hashing bound for the quantum capacity of the GQC.
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We propose a virtual interferogram-generation algorithm using two interferograms. This algorithm can measure a complex amplitude of a signal beam with high accuracy even when its intensity is greater than the intensity of a reference beam. Unlike the conventional algorithm that uses two interferograms, our algorithm can compute measurements when the phase shift of interferograms in not equal to π/2. Our method generates two phase-shifted holograms in a computer by capturing the intensities of two signal beams, two reference beams, and two interferograms. The complex amplitude of a signal beam is calculated by four interference patterns, two holograms, and two interferograms. The proposed algorithm can drastically suppress the calculation error caused by the smaller value between the intensity of the reference beam and can choose the most suitable phase shift.
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To obtain a phase distribution without the use of an optical path besides an object beam, a reference-free holographic diversity interferometry (RF-HDI) has been proposed. Although the RF-HDI can generate an internal reference beam from the object beam, the method has a problem of measurement accuracy due to insufficient power of the internal reference beam. To solve the problem, we newly propose a RF-HDI via iterative measurements. Our method improves the measurement accuracy by utilizing iterative measurements and feedback of each obtained phase image to the measurement system. In the experiment, the phase image, which has a random pattern, can be measured as an object beam with a higher accuracy than in the conventional RF-HDI. To support this result, we also evaluated the wavefront accuracy and optical power efficiency of an internal reference beam in this method. As a result, we verified that our method enables us to generate an internal reference beam that has the wavefront of a near single plane wave and a higher power efficiency than the conventional RF-HDI. In addition, our method can be applied to measurement for the modal content in an optical fiber, atmosphere turbulence, etc., where it is difficult to prepare an external reference beam with a high coherency.
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BACKGROUND: Adenosine A2b receptor (ADORA2B) encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. Little is known about the relevance of ADORA2B to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of ADORA2B in OSCC. METHODS: The ADORA2B expression levels in nine OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using an ADORA2B knockdown model, we assessed cellular proliferation and expression of hypoxia-inducible factor1α (HIF-1α). We examined the adenosine receptor expression profile under both normoxic and hypoxic conditions in the OSCC-derived cells. In addition to in vitro data, the clinical correlation between the ADORA2B expression levels in primary OSCCs (n = 100 patients) and the clinicopathological status by immunohistochemistry (IHC) also was evaluated. RESULTS: ADORA2B mRNA and protein were up-regulated significantly (p < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. Suppression of ADORA2B expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells. HIF-1α also was down-regulated in ADORA2B knockdown OSCC cells. During hypoxia, ADORA2B expression was induced significantly (p < 0.05) in the mRNA and protein after 24 hours of incubation in OSCC-derived cells. IHC showed that ADORA2B expression in primary OSCCs was significantly (p < 0.05) greater than in the normal oral counterparts and that ADORA2B-positive OSCCs were correlated closely (p < 0.05) with tumoral size. CONCLUSION: Our results suggested that ADORA2B controls cellular proliferation via HIF-1α activation, indicating that ADORA2B may be a key regulator of tumoral progression in OSCCs.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Receptor de Adenosina A2B/genética , Anciano , Carcinoma de Células Escamosas/metabolismo , Hipoxia de la Célula , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Receptor de Adenosina A2B/metabolismo , Regulación hacia ArribaRESUMEN
We propose a two-channel holographic diversity interferometer (2ch-HDI) system for single-shot and highly accurate measurements of complex amplitude fields with a simple optical setup. In this method, two phase-shifted interference patterns are generated, without requiring a phase-shifting device, by entering a circularly polarized reference beam into a polarizing beam splitter, and the resulting patterns are captured simultaneously using two image sensors. However, differences in the intensity distributions of the two image sensors may lead to serious measurement errors. Thus, we also develop a two-channel algorithm optimized for the 2ch-HDI to compensate for these differences. Simulation results show that this algorithm can compensate for such differences in the intensity distributions in the two image sensors. Experimental results confirm that the combination of the 2ch-HDI and the calculation algorithm significantly enhances measurement accuracy.
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Two methods are proposed to improve the readout quality of signals in self-referential holographic data storage (SR-HDS), in which no reference beam is required to record and read digital data holographically: the off-the-focus (OtF) method and the oversampling additional pattern (OsAP) method. The focal point is located outside of the recording medium in the OtF method, and the signal pattern is recorded with an additional pattern that possesses a higher spatial frequency than the signal pattern in the OsAP method. Experimental results show that both methods are effective for drastically improving the signal-to-noise ratio (SNR). In addition, through numerical simulation, it can be observed that the readout quality is improved by the achievement of homogeneous hologram distribution.
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We propose a spatial cross modulation method using a random diffuser and a phase-only spatial light modulator (SLM), by which arbitrary complex-amplitude fields can be generated with higher spatial resolution and diffraction efficiency than off-axis and double-phase computer-generated holograms. Our method encodes the original complex object as a phase-only diffusion image by scattering the complex object using a random diffuser. In addition, all incoming light to the SLM is consumed for a single diffraction order, making a diffraction efficiency of more than 90% possible. This method can be applied for holographic data storage, three-dimensional displays, and other such applications.
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In a conventional digital phase conjugation system, only the phase of an input light is time-reversed. This deteriorates phase conjugation fidelity and restricts application fields to specific cases only when the input light has uniformly-distributed scattered wavefront. To overcome these difficulties, we present a digital phase conjugate mirror based on parallel alignment of two phase-only spatial light modulators (SLMs), in which both amplitude and phase of the input light can be time-reversed. Experimental result showed that, in the phase conjugation through a holographic diffuser with diffusion angle of 0.5 degree, background noises decrease to 65% by our digital phase conjugation mirror.