Influence of Pre- and Post-Contouring Strategies to Downskin Sloped Surfaces in Laser Powder-Bed Fusion (L-PBF) Additive Manufacturing.

Among various metal additive manufacturing (AM) technologies, L-PBF is known for fabricating intricate components. However, due to step edges and powder particle attachments, attaining a good surface finish is challenging, especially on downskin surfaces. Contour scanning has potential to improve surface quality because such scanning may dominate the surface formation of sloped features. This study evaluates the effects of pre- and post-contouring strategies on the sloped downskin surfaces fabricated using a commercial L-PBF system with Ti6Al4V powder. L-PBF parts printed at inclination angles 30°, 45° and 60° were investigated. A double-contouring approach with varying processing conditions was employed and surface characteristics were analyzed using data acquired by white light interferometry. The average surface roughness, Sa, surface skewness, Ssk, and percentage area of powder particles attached onto surfaces were statistically evaluated. The lowest Sa obtained for pre- and post-contoured samples is 14.08 µm and 18.88 µm, respectively. For both strategies, the combination of a low laser power and a high scan speed on the interface of downskin surface and underneath powder results in smoother surfaces. However, while comparing both strategies, pre-contouring gives better surface finish for samples built at similar processing conditions, with a difference of nearly 5 µm in Sa.

Halorubrum pleomorphic virus-6 Membrane Fusion Is Triggered by an S-Layer Component of Its Haloarchaeal Host.

(1) Background: Haloarchaea comprise extremely halophilic organisms of the Archaea domain. They are single-cell organisms with distinctive membrane lipids and a protein-based cell wall or surface layer (S-layer) formed by a glycoprotein array. Pleolipoviruses, which infect haloarchaeal cells, have an envelope analogous to eukaryotic enveloped viruses. One such member, Halorubrum pleomorphic virus 6 (HRPV-6), has been shown to enter host cells through virus-cell membrane fusion. The HRPV-6 fusion activity was attributed to its VP4-like spike protein, but the physiological trigger required to induce membrane fusion remains yet unknown. (2) Methods: We used SDS-PAGE mass spectroscopy to characterize the S-layer extract, established a proteoliposome system, and used R18-fluorescence dequenching to measure membrane fusion. (3) Results: We show that the S-layer extraction by Mg2+ chelating from the HRPV-6 host, Halorubrum sp. SS7-4, abrogates HRPV-6 membrane fusion. When we in turn reconstituted the S-layer extract from Hrr. sp. SS7-4 onto liposomes in the presence of Mg2+, HRPV-6 membrane fusion with the proteoliposomes could be readily observed. This was not the case with liposomes alone or with proteoliposomes carrying the S-layer extract from other haloarchaea, such as Haloferax volcanii. (4) Conclusions: The S-layer extract from the host, Hrr. sp. SS7-4, corresponds to the physiological fusion trigger of HRPV-6.

Transient Laser Energy Absorption, Co-axial Melt Pool Monitoring, and Relationship to Melt Pool Morphology.

Melt pool monitoring (MPM) is a technique used in laser powder bed fusion (LPBF) to extract features from insitu sensor signals that correlate to defect formation or general part fabrication quality. Various melt pool phenomena have been shown to relate to measured transient absorption of the laser energy, which in turn, can be relatable to the melt pool emission measured in MPM systems. This paper describes use of a reflectometer-based instrument to measure the dynamic laser energy absorption during single-line laser scans. Scans are conducted on bare metal and single powder layer of nickel alloy 625 (IN625) at a range of laser powers. In addition, a photodetector aligned co-axially with the laser, often found in commercial LPBF monitoring systems, synchronously measured of the incandescent emission from the melt pool with the dynamic laser absorption. Relationships between the dynamic laser absorption, co-axial MPM, and surface features on the tracks are observed, providing illustration of the melt pool dynamics that formed these features. Time-integrated measurements of laser absorption are shown to correlate well with MPM signal, as well as indicate the transition between conduction and keyhole mode. This transition is corroborated by metallographic cross-section measurement, as well as topographic measurements of the solidified tracks. Ultimately, this paper exemplifies the utility of dynamic laser absorption measurements to inform both the physical nature of the melt pool dynamics, as well as interpretation of process monitoring signals.

A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model.

People living with HIV (PLWH) have expressed concern about the life-long burden and stigma associated with taking pills daily and can experience medication fatigue that might lead to suboptimal treatment adherence and the emergence of drug-resistant viral variants, thereby limiting future treatment options1-3. As such, there is strong interest in long-acting antiretroviral (ARV) agents that can be administered less frequently4. Herein, we report GS-CA1, a new archetypal small-molecule HIV capsid inhibitor with exceptional potency against HIV-2 and all major HIV-1 types, including viral variants resistant to the ARVs currently in clinical use. Mechanism-of-action studies indicate that GS-CA1 binds directly to the HIV-1 capsid and interferes with capsid-mediated nuclear import of viral DNA, HIV particle production and ordered capsid assembly. GS-CA1 selects in vitro for unfit GS-CA1-resistant capsid variants that remain fully susceptible to other classes of ARVs. Its high metabolic stability and low solubility enabled sustained drug release in mice following a single subcutaneous dosing. GS-CA1 showed high antiviral efficacy as a long-acting injectable monotherapy in a humanized mouse model of HIV-1 infection, outperforming long-acting rilpivirine. Collectively, these results demonstrate the potential of ultrapotent capsid inhibitors as new long-acting agents for the treatment of HIV-1 infection.

Entanglement of bosonic modes through an engineered exchange interaction.

Quantum computation presents a powerful new paradigm for information processing. A robust universal quantum computer can be realized with any well controlled quantum system, but a successful platform will ultimately require the combination of highly coherent, error-correctable quantum elements with at least one entangling operation between them1,2. Quantum information stored in a continuous-variable system-for example, a harmonic oscillator-can take advantage of hardware-efficient quantum error correction protocols that encode information in the large available Hilbert space of each element3-5. However, such encoded states typically have no controllable direct couplings, making deterministic entangling operations between them particularly challenging. Here we develop an efficient implementation of the exponential-SWAP operation6 and present its experimental realization between bosonic qubits stored in two superconducting microwave cavities. This engineered operation is analogous to the exchange interaction between discrete spin systems, but acts within any encoded subspace of the continuous-variable modes. Based on a control rotation, the operation produces a coherent superposition of identity and SWAP operations between arbitrary states of two harmonic oscillator modes and can be used to enact a deterministic entangling gate within quantum error correction codes. These results provide a valuable building block for universal quantum computation using bosonic modes.

4-Hydroxybenzoic acid serves as an endogenous ring precursor for antroquinonol biosynthesis in Antrodia cinnamomea.

Antrodia cinnamomea, an endemic fungus species of Taiwan, has long been used as a luxurious dietary supplement to enhance liver functions and as a remedy for various cancers. Antroquinonol (AQ), identified from the mycelium of A. cinnamomea, is currently in phase II clinical trials in the USA and Taiwan for the treatment of non-small-cell lung cancer. In the previous studies, we have demonstrated that AQ and 4-acetylantroquinonol B (4-AAQB) utilize orsellinic acid, via polyketide pathway, as the ring precursor, and their biosynthetic sequences are similar to those of coenzyme Q. In order to test 4-hydroxybenzoic acid (4-HBA), synthesized via shikimate pathway, is the ring precursor of AQ analogs, the strategy of metabolic labeling with stable isotopes was applied in this study. Here we have confirmed that 4-HBA serves as the ring precursor for AQ but not a precursor of 4-AAQB. Experimental results indicated that A. cinnamomea preferentially utilizes endogenous 4-HBA via shikimate pathway for AQ biosynthesis. Exogenous tyrosine and phenylalanine can be utilized for AQ biosynthesis when shikimate pathway is blocked by glyphosate. The benzoquinone ring of 4-AAQB is synthesized only via polyketide pathway, but that of AQ is synthesized via both polyketide pathway and shikimate pathway. The precursor-products relationships diagram of AQ and 4-AAQB in A. cinnamomea are proposed based on the experimental findings.

On thermal properties of metallic powder in laser powder bed fusion additive manufacturing.

Powder thermal properties play a critical role in laser powder-bed fusion (LPBF) additive manufacturing, specifically, the reduced effective thermal conductivity compared to that of the solid significantly affects heat conduction, which can influence the melt pool characteristics, and consequently, the part mechanical properties. This study intends to indirectly measure the thermal conductivity of metallic powder, nickel-based super alloy 625 (IN625) and Ti-6Al-4V (Ti64), in LPBF using a combined approach that consists of laser flash analysis, finite element (FE) heat transfer modeling and a multivariate inverse method. The test specimens were designed and fabricated by a LPBF system to encapsulate powder in a hollow disk to imitate powder-bed conditions. The as-built specimens were then subjected to laser flash testing to measure the transient thermal response. Next, an FE model replicate the hollow disk samples and laser flash testing was developed. A multi-point optimization algorithm was used to inversely extract the thermal conductivity of LPBF powder from the FE model based on the measured transient thermal response. The results indicate that the thermal conductivity of IN625 powder used in LPBF ranges from 0.65 W/(m·K) to 1.02 W/(m·K) at 100 °C and 500 °C, respectively, showing a linear relationship with the temperature. On the other hand, Ti64 powder has a lower thermal conductivity than IN625 powder, about 35% to 40% smaller. However, the thermal conductivity ratio of the powder to the respective solid counterpart is quite similar between the two materials, about 4.2% to 6.9% for IN625 and 3.4% to 5.2% for Ti64.

Deterministic teleportation of a quantum gate between two logical qubits.

A quantum computer has the potential to efficiently solve problems that are intractable for classical computers. However, constructing a large-scale quantum processor is challenging because of the errors and noise that are inherent in real-world quantum systems. One approach to addressing this challenge is to utilize modularity-a strategy used frequently in nature and engineering to build complex systems robustly. Such an approach manages complexity and uncertainty by assembling small, specialized components into a larger architecture. These considerations have motivated the development of a quantum modular architecture, in which separate quantum systems are connected into a quantum network via communication channels1,2. In this architecture, an essential tool for universal quantum computation is the teleportation of an entangling quantum gate3-5, but such teleportation has hitherto not been realized as a deterministic operation. Here we experimentally demonstrate the teleportation of a controlled-NOT (CNOT) gate, which we make deterministic by using real-time adaptive control. In addition, we take a crucial step towards implementing robust, error-correctable modules by enacting the gate between two logical qubits, encoding quantum information redundantly in the states of superconducting cavities6. By using such an error-correctable encoding, our teleported gate achieves a process fidelity of 79 per cent. Teleported gates have implications for fault-tolerant quantum computation3, and when realized within a network can have broad applications in quantum communication, metrology and simulations1,2,7. Our results illustrate a compelling approach for implementing multi-qubit operations on logical qubits and, if integrated with quantum error-correction protocols, indicate a promising path towards fault-tolerant quantum computation using a modular architecture.

A Combined Experimental-Numerical Method to Evaluate Powder Thermal Properties in Laser Powder Bed Fusion.

Powder bed metal additive manufacturing (AM) utilizes a high-energy heat source scanning at the surface of a powder layer in a predefined area to be melted and solidified to fabricate parts layer by layer. It is known that powder bed metal AM is primarily a thermal process, and further, heat conduction is the dominant heat transfer mode in the process. Hence, understanding the powder bed thermal conductivity is crucial to process temperature predictions, because powder thermal conductivity could be substantially different from its solid counterpart. On the other hand, measuring the powder thermal conductivity is a challenging task. The objective of this study is to investigate the powder thermal conductivity using a method that combines a thermal diffusivity measurement technique and a numerical heat transfer model. In the experimental aspect, disk-shaped samples, with powder inside, made by a laser powder bed fusion (LPBF) system, are measured using a laser flash system to obtain the thermal diffusivity and the normalized temperature history during testing. In parallel, a finite element (FE) model is developed to simulate the transient heat transfer of the laser flash process. The numerical model was first validated using reference material testing. Then, the model is extended to incorporate powder enclosed in an LPBF sample with thermal properties to be determined using an inverse method to approximate the simulation results to the thermal data from the experiments. In order to include the powder particles' contribution in the measurement, an improved model geometry, which improves the contact condition between powder particles and the sample solid shell, has been tested. A multipoint optimization inverse heat transfer method is used to calculate the powder thermal conductivity. From this study, the thermal conductivity of a nickel alloy 625 powder in powder bed conditions is estimated to be 1.01 W/m K at 500°C. [DOI: 10.1115/1.4040877].

Laboratory measurements of dusty surface charging in plasma.

A novel method is developed to study the charging of a conducting surface covered by a thin dust layer in plasma. The potential profile in the dust layer and the floating potential of the surface underneath are measured directly by embedding conducting wires in the dust and connecting the wires to a measurement plate outside the vacuum chamber, where a Trek non-contacting electrostatic voltmeter measures the floating potential of the measurement plate. Laboratory experiments are carried out to study plasma charging of a conducting plate covered by lunar dust simulant, JSC-1A. The results show that the plate potential is dependent on both the ambient plasma condition and the dust layer thickness. The current balance condition controls the floating potential of the dust surface while the dust layer acts as a capacitor and controls the potential of the plate with respect to the dust surface. Hence, a dust covered conducting plate will be charged more negatively than a clean plate.

Biosynthesis of Antroquinonol and 4-Acetylantroquinonol B via a Polyketide Pathway Using Orsellinic Acid as a Ring Precursor in Antrodia cinnamomea.

Antroquinonol (AQ) and 4-acetylantroquinonol B (4-AAQB), isolated from the mycelium of Antrodia cinnamomea, have a similar chemical backbone to coenzyme Q (CoQ). Based on the postulation that biosynthesis of both AQ and 4-AAQB in A. cinnamomea starts from the polyketide pathway, we cultivated this fungus in a culture medium containing [U-13C]oleic acid, and then we analyzed the crude extracts of the mycelium using UHPLC-MS. We found that AQ and 4-AAQB follow similar biosynthetic sequences as CoQ. Obvious [13C2] fragments on the ring backbone were detected in the mass spectrum for [13C2]AQ, [13C2]4-AAQB, and their [13C2] intermediates found in this study. The orsellinic acid, formed from acetyl-CoA and malonyl-CoA via the polyketide pathway, was found to be a novel benzoquinone ring precursor for AQ and 4-AAQB. The identification of endogenously synthesized farnesylated intermediates allows us to postulate the routes of AQ and 4-AAQB biosynthesis in A. cinnamomea.

A Schrödinger cat living in two boxes.

Quantum superpositions of distinct coherent states in a single-mode harmonic oscillator, known as "cat states," have been an elegant demonstration of Schrödinger's famous cat paradox. Here, we realize a two-mode cat state of electromagnetic fields in two microwave cavities bridged by a superconducting artificial atom, which can also be viewed as an entangled pair of single-cavity cat states. We present full quantum state tomography of this complex cat state over a Hilbert space exceeding 100 dimensions via quantum nondemolition measurements of the joint photon number parity. The ability to manipulate such multicavity quantum states paves the way for logical operations between redundantly encoded qubits for fault-tolerant quantum computation and communication.

Protection of the intestinal mucosa by intraepithelial gamma delta T cells.

gammadelta intraepithelial T lymphocytes (IEL) represent a major T cell population within the intestine of unclear functional relevance. The role of intestinal gammadelta IEL was evaluated in the dextran sodium sulfate (DSS) induced mouse colitis model system. Large numbers of gammadelta T cells, but not alphabeta T cells, were localized at sites of DSS-induced epithelial cell damage. gammadelta IEL in DSS treated mice expressed keratinocyte growth factor (KGF), a potent intestinal epithelial cell mitogen. gammadelta cell-deficient mice (TCRdelta(-/-)) and KGF-deficient mice (KGF(-/-)), but not alphabeta cell-deficient mice (TCRalpha(-/-)), were more prone than wild-type mice to DSS-induced mucosal injury and demonstrated delayed tissue repair after termination of DSS treatment. Termination of DSS treatment resulted in vigorous epithelial cell proliferation in wild-type mice but not in TCRdelta(-/-) mice or KGF(-/-) mice. These results suggest that gammadelta IEL help preserve the integrity of damaged epithelial surfaces by providing the localized delivery of an epithelial cell growth factor.