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Metallic glass offers several advantages, including high strength, corrosion resistance, and low coercivity. In precision machining fields like optical devices, medical devices, and micro-electromechanical systems, Ti-based metallic glass offers more advantages than Fe- and Zr-based metallic glass. However, its current machinability poses a challenge in meeting the requirements of precision metallic glass parts. To obtain the best machining performance, a thermophysical model of the EDM drilling process was established to simulate the temperature distribution on the surface of metal glass workpiece during EDM drilling. In addition, a new systematic method is utilized to calculate the characteristics of important machining holes, such as inlet and outlet overcut and inlet and outlet edge deviation. In this investigation, the maximum relative overcut and edge deviation are 8.59% and 7.23%, respectively, relative to the electrode radius. To improve the machining quality and machining stability, the slit width should be kept at an ideal value. Therefore, the recommended discharge current is 4–5 A, pulse duration is 50 μ s, and pulse duty ratio is 0.2 - 0.3 when EDM drilling of amorphous alloy. Based on this, the EDM drilling analysis method by numerical and experimental investigation for titanium-based metallic glass is put forward, which provides scientific theoretical guidance for the EDM of drilling it. [ABSTRACT FROM AUTHOR]

Owing to its attractive optical and electronic properties, silicon carbide is an emerging platform for integrated photonics. However an integral component of the platform is missing—an electro-optic modulator, a device which encodes electrical signals onto light. As a non-centrosymmetric crystal, silicon carbide exhibits the Pockels effect, yet a modulator has not been realized since the discovery of this effect more than three decades ago. Here we design, fabricate, and demonstrate a Pockels modulator in silicon carbide. Specifically, we realize a waveguide-integrated, small form-factor, gigahertz-bandwidth modulator that operates using complementary metal-oxide-semiconductor (CMOS)-level voltages on a thin film of silicon carbide on insulator. Our device is fabricated using a CMOS foundry compatible fabrication process and features no signal degradation, no presence of photorefractive effects, and stable operation at high optical intensities (913 kW/mm2), allowing for high optical signal-to-noise ratios for modern communications. Our work unites Pockels electro-optics with a CMOS foundry compatible platform in silicon carbide. Electro-optic modulator is used to encode electrical signals onto light. Here the authors demonstrate an electro-optic modulator, based on Silicon Carbide, which can be useful for quantum and optical communications. [ABSTRACT FROM AUTHOR]

We present a novel workflow for forecasting production in unconventional reservoirs using reduced-order models and machine-learning. Our physics-informed machine-learning workflow addresses the challenges to real-time reservoir management in unconventionals, namely the lack of data (i.e., the time-frame for which the wells have been producing), and the significant computational expense of high-fidelity modeling. We do this by applying the machine-learning paradigm of transfer learning, where we combine fast, but less accurate reduced-order models with slow, but accurate high-fidelity models. We use the Patzek model (Proc Natl Acad Sci 11:19731–19736, https://doi.org/10.1073/pnas.1313380110, 2013) as the reduced-order model to generate synthetic production data and supplement this data with synthetic production data obtained from high-fidelity discrete fracture network simulations of the site of interest. Our results demonstrate that training with low-fidelity models is not sufficient for accurate forecasting, but transfer learning is able to augment the knowledge and perform well once trained with the small set of results from the high-fidelity model. Such a physics-informed machine-learning (PIML) workflow, grounded in physics, is a viable candidate for real-time history matching and production forecasting in a fractured shale gas reservoir. [ABSTRACT FROM AUTHOR]

The Ras-like GTPases RalA and RalB are important drivers of tumour growth and metastasis. Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here we used protein structure analysis and virtual screening to identify drug-like molecules that bind to a site on the GDP-bound form of Ral. The compounds RBC6, RBC8 and RBC10 inhibited the binding of Ral to its effector RALBP1, as well as inhibiting Ral-mediated cell spreading of murine embryonic fibroblasts and anchorage-independent growth of human cancer cell lines. The binding of the RBC8 derivative BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasmon resonance and 1H-15N transverse relaxation-optimized spectroscopy (TROSY) NMR spectroscopy. RBC8 and BQU57 show selectivity for Ral relative to the GTPases Ras and RhoA and inhibit tumour xenograft growth to a similar extent to the depletion of Ral using RNA interference. Our results show the utility of structure-based discovery for the development of therapeutics for Ral-dependent cancers. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) can impact viral infections by binding to sequences with partial complementarity on viral RNA transcripts, usually resulting in the repression of virus replication. In the present study, we identified a potential binding site for miR-130 in the 5′ untranslated region (bps 155-162) of the porcine reproductive and respiratory syndrome virus (PRRSV) genome. We found that the delivery of multiple miR-130 family mimics, especially miR-130b, resulted in inhibition of PRRSV replication in vitro. miR-130 was effective in inhibiting the replication of multiple type 2 PRRSV strains, but not against vSHE, a classical type 1 strain. miR-130 over-expression did not induce IFN-α or TNF-α expression in either uninfected or PRRSV-infected porcine alveolar macrophages. Results from luciferase reporter assays indicated that miR-130 directly targeted the PRRSV 5′ UTR. Intranasal inoculation of piglets with miR-130b exhibited antiviral activity in vivo and partially protected piglets from an otherwise lethal challenge with HP-PRRSV strain vJX143. Overall, these results demonstrate the importance of the miR-130 family in modulating PRRSV replication and also provide a scientific basis for using cellular miRNAs in anti-PRRSV therapies. [ABSTRACT FROM AUTHOR]