Algorithm-Based Linearly Graded Compositions of GeSn on GaAs (001) via Molecular Beam Epitaxy.

The growth of high-composition GeSn films in the future will likely be guided by algorithms. In this study, we show how a logarithmic-based algorithm can be used to obtain high-quality GeSn compositions up to 16% on GaAs (001) substrates via molecular beam epitaxy. Herein, we use composition targeting and logarithmic Sn cell temperature control to achieve linearly graded pseudomorph Ge1-xSnx compositions up to 10% before partial relaxation of the structure and a continued gradient up to 16% GeSn. In this report, we use X-ray diffraction, simulation, secondary ion mass spectrometry, and atomic force microscopy to analyze and demonstrate some of the possible growths that can be produced with the enclosed algorithm. This methodology of growth is a major step forward in the field of GeSn development and the first ever demonstration of algorithmically driven, linearly graded GeSn films.

The growth of Ge and direct bandgap Ge1-xSnx on GaAs (001) by molecular beam epitaxy.

Germanium tin (GeSn) is a tuneable narrow bandgap material, which has shown remarkable promise for the industry of near- and mid-infrared technologies for high efficiency photodetectors and laser devices. Its synthesis is challenged by the lattice mismatch between the GeSn alloy and the substrate on which it is grown, sensitively affecting its crystalline and optical qualities. In this article, we investigate the growth of Ge and GeSn on GaAs (001) substrates using two different buffer layers consisting of Ge/GaAs and Ge/AlAs via molecular beam epitaxy. The quality of the Ge layers was compared using X-ray diffraction, atomic force microscopy, reflection high-energy electron diffraction, and photoluminescence. The characterization techniques demonstrate high-quality Ge layers, including atomic steps, when grown on either GaAs or AlAs at a growth temperature between 500-600 °C. The photoluminescence from the Ge layers was similar in relative intensity and linewidth to that of bulk Ge. The Ge growth was followed by the growth of GeSn using a Sn composition gradient and substrate gradient approach to achieve GeSn films with 9 to 10% Sn composition. Characterization of the GeSn films also indicates high-quality gradients based on X-ray diffraction, photoluminescence, and energy-dispersive X-ray spectroscopy measurements. Finally, we were able to demonstrate temperature-dependent PL results showing that for the growth on Ge/GaAs buffer, the direct transition has shifted past the indirect transition to a longer wavelength/lower energy suggesting a direct bandgap GeSn material.

Recurrent MECR R258W causes adult-onset optic atrophy: A case report.

MECR-related neurologic disorder, also known as mitochondrial enoyl CoA reductase protein-associated neurodegeneration (MEPAN) or dystonia with optic atrophy and basal ganglia abnormalities in childhood (MIM: #617282), is an autosomal recessive inherited disease characterized by a progressive childhood-onset movement disorder and optic atrophy. Here we report a 19-year-old male, presented with progressive visual failure, nystagmus, and right orbital pain, with no history of movement or eye disorder in his childhood. His visual decline started at age 18 years, whereas nystagmus emerged seven months later. Analysis of whole-exome sequencing (WES) revealed a homozygous recurrent variant (NM_016011.5:c.772C > T, p.Arg258Trp) in MECR. These findings suggest phenotypic heterogeneity in MECR-related neurologic disorder, thus, more relevant case screening, will help to delineate the genotype-phenotype correlation of the MECR gene.

Study of all-group-IV SiGeSn mid-IR lasers with dual wavelength emission.

Direct band gap GeSn alloys have recently emerged as promising lasing source materials for monolithic integration on Si substrate. In this work, optically pumped mid-infrared GeSn lasers were studied with the observation of dual-wavelength lasing at 2187 nm and 2460 nm. Two simultaneous lasing regions include a GeSn buffer layer (bulk) and a SiGeSn/GeSn multiple quantum well structure that were grown seamlessly using a chemical vapor deposition reactor. The onset of dual lasing occurs at 420 kW/cm2. The wider bandgap SiGeSn partitioning barrier enables the independent operation of two gain regions. While the better performance device in terms of lower threshold may be obtained by using two MQW regions design, the preliminary results and discussions in this work paves a way towards all-group-IV dual wavelength lasers monolithically integrated on Si substrate.

"GeSn Rule-23"-The Performance Limit of GeSn Infrared Photodiodes.

Group-IV GeSn photodetectors (PDs) compatible with standard complementary metal-oxide-semiconductor (CMOS) processing have emerged as a new and non-toxic infrared detection technology to enable a wide range of infrared applications. The performance of GeSn PDs is highly dependent on the Sn composition and operation temperature. Here, we develop theoretical models to establish a simple rule of thumb, namely "GeSn-rule 23", to describe GeSn PDs' dark current density in terms of operation temperature, cutoff wavelength, and Sn composition. In addition, analysis of GeSn PDs' performance shows that the responsivity, detectivity, and bandwidth are highly dependent on operation temperature. This rule provides a simple and convenient indicator for device developers to estimate the device performance at various conditions for practical applications.

Anti-Nipah Virus Enzyme-Linked Immunosorbent Assays with Non-human Primate and Hamster Serum.

Enzyme-linked Immunosorbent assays or ELISAs are a versatile method for detecting various immunological ligands of interest. As the name suggests, ELISAs rely on the interaction between a ligand and an antibody to produce results. In the study of infectious disease, ELISAs are commonly used to determine if a pathogen-specific immune response has occurred in a host organism. These assays can be performed in serosurveys as part of epidemiological investigations during, or following, an infectious disease outbreak. In the research environment, ELISAs are used to quantify the humoral immune response following infection or vaccination of a host organism. Data from these assays can be used to determine the type of immune response elicited (e.g. IgG1 vs IgG2) and the robustness of the response. Here, we describe ELISAs that were developed for the study of either hamsters or non-human primates vaccinated against Nipah virus infection, or infected with Nipah virus. The ELISAs described include assays for both IgG and IgM in the hamster and non-human primate models for Nipah virus-induced disease. An assay was also developed for the detection of IgA in bronchoalveolar lavage from non-human primates.

Investigation of the cap layer for improved GeSn multiple quantum well laser performance.

The study of all-group-IV SiGeSn lasers has opened a new avenue to Si-based light sources. SiGeSn heterostructure and quantum well lasers have been successfully demonstrated in the past few years. It has been reported that, for multiple quantum well lasers, the optical confinement factor plays an important role in the net modal gain. In previous studies, adding a cap layer was proposed to increase the optical mode overlap with the active region and thereby improve the optical confinement factor of Fabry-Perot cavity lasers. In this work, SiGeSn/GeSn multiple quantum well (4-well) devices with various cap layer thicknesses, i.e., 0 (no cap), 190, 250, and 290 nm, are grown using a chemical vapor deposition reactor and characterized via optical pumping. While no-cap and thinner-cap devices only show spontaneous emission, the two thicker-cap devices exhibit lasing up to 77 K, with an emission peak at 2440 nm and a threshold of 214 kW/cm2 (250 nm cap device). The clear trend in device performance disclosed in this work provides guidance in device design for electrically injected SiGeSn quantum well lasers.

Multivalent viral particles elicit safe and efficient immunoprotection against Nipah Hendra and Ebola viruses.

Experimental vaccines for the deadly zoonotic Nipah (NiV), Hendra (HeV), and Ebola (EBOV) viruses have focused on targeting individual viruses, although their geographical and bat reservoir host overlaps warrant creation of multivalent vaccines. Here we explored whether replication-incompetent pseudotyped vesicular stomatitis virus (VSV) virions or NiV-based virus-like particles (VLPs) were suitable multivalent vaccine platforms by co-incorporating multiple surface glycoproteins from NiV, HeV, and EBOV onto these virions. We then enhanced the vaccines' thermotolerance using carbohydrates to enhance applicability in global regions that lack cold-chain infrastructure. Excitingly, in a Syrian hamster model of disease, the VSV multivalent vaccine elicited safe, strong, and protective neutralizing antibody responses against challenge with NiV, HeV, or EBOV. Our study provides proof-of-principle evidence that replication-incompetent multivalent viral particle vaccines are sufficient to provide protection against multiple zoonotic deadly viruses with high pandemic potential.

Primate hemorrhagic fever-causing arteriviruses are poised for spillover to humans.

Simian arteriviruses are endemic in some African primates and can cause fatal hemorrhagic fevers when they cross into primate hosts of new species. We find that CD163 acts as an intracellular receptor for simian hemorrhagic fever virus (SHFV; a simian arterivirus), a rare mode of virus entry that is shared with other hemorrhagic fever-causing viruses (e.g., Ebola and Lassa viruses). Further, SHFV enters and replicates in human monocytes, indicating full functionality of all of the human cellular proteins required for viral replication. Thus, simian arteriviruses in nature may not require major adaptations to the human host. Given that at least three distinct simian arteriviruses have caused fatal infections in captive macaques after host-switching, and that humans are immunologically naive to this family of viruses, development of serology tests for human surveillance should be a priority.

Development of LTCC-packaged optocouplers as optical galvanic isolation for high-temperature applications.

This paper reports high-temperature optocouplers for signal galvanic isolation. Low temperature co-fired ceramic (LTCC) technology was used in the design and fabrication of the high-temperature optocoupler package. The optimal coupling behaviors, driving capabilities and response speed of the optocouplers were concentrated and investigated in this paper. Emitters and detectors with different emission and spectral wavelengths were studied to achieve optimal coupling behaviors. Relatively high coupling efficiency is achieved with emitters and detectors of emission and spectral wavelength in the red spectrum (i.e., 620-750 nm), leading to higher current transfer ratios (CTR). To further enhance the electrical performance, optocouplers with multiple detectors in parallel were designed and fabricated. CTR, leakage current and response speed (i.e., propagation delay, rise time and fall time) of the optocouplers were characterized over a range of temperatures from 25 to 250 °C. The CTR degrades at high temperatures, while the leakage current and response speed show little degradation with varying temperatures. Furthermore, the behaviors of the optocouplers with varying temperatures are modeled and analyzed.

Duplex One-Step RT-qPCR Assays for Simultaneous Detection of Genomic and Subgenomic RNAs of SARS-CoV-2 Variants.

A hallmark of severe acute respiratory syndrome virus (SARS-CoV-2) replication is the discontinuous transcription of open reading frames (ORFs) encoding structural virus proteins. Real-time reverse transcription PCR (RT-qPCR) assays in previous publications used either single or multiplex assays for SARS-CoV-2 genomic RNA detection and a singleplex approach for subgenomic RNA detection. Although multiplex approaches often target multiple genomic RNA segments, an assay that concurrently detects genomic and subgenomic targets has been lacking. To bridge this gap, we developed two duplex one-step RT-qPCR assays that detect SARS-CoV-2 genomic ORF1a and either subgenomic spike or subgenomic ORF3a RNAs. All primers and probes for our assays were designed to bind to variants of SARS-CoV-2. In this study, our assays successfully detected SARS-CoV-2 Washington strain and delta variant isolates at various time points during the course of live virus infection in vitro. The ability to quantify subgenomic SARS-CoV-2 RNA is important, as it may indicate the presence of active replication, particularly in samples collected longitudinally. Furthermore, specific detection of genomic and subgenomic RNAs simultaneously in a single reaction increases assay efficiency, potentially leading to expedited lucidity about viral replication and pathogenesis of any variant of SARS-CoV-2.

Biocontrol and Action Mechanism of Bacillus subtilis Lipopeptides' Fengycins Against Alternaria solani in Potato as Assessed by a Transcriptome Analysis.

Alternaria solani is an airborne fungus and the primary causal agent of potato early blight worldwide. No available fungicides that are both effective and environmentally friendly are usable to control this fungus. Therefore, biological control is a potential approach for its suppression. In this study, Bacillus subtilis strain ZD01's fermentation broth strongly reduced A. solani pathogenicity under greenhouse conditions. The effects of strain ZD01's secondary metabolites on A. solani were investigated. The exposure of A. solani hyphae to the supernatant resulted in swelling and swollen sacs, and the ZD01 supernatant reduced A. solani conidial germination significantly. Matrix-assisted laser desorption/ionization time of flight mass spectrometry and pure product tests revealed that fengycins were the main antifungal lipopeptide substances. To elucidate the molecular mechanism of the fengycins' biological control, RNA sequencing analyses were performed. A transcriptome analysis revealed that 304 and 522 genes in A. solani were differentially expressed after 2-h and 6-h fengycin treatments, respectively. These genes were respectively mapped to 53 and 57 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In addition, the most enriched KEGG pathway analysis indicated that the inhibitory mechanisms of fengycins against A. solani regulated the expression of genes related to cell wall, cell membrane, transport, energy process, protein synthesis and genetic information. In particular, cell wall and cell membrane metabolism were the main processes affected by fengycin stress. Scanning and transmission electron microscope results revealed hyphal enlargement and a wide range of abnormalities in A. solani cells after exposure to fengycins. Furthermore, fengycins induced chitin synthesis in treated cells, and also caused the capture of cellular fluorescent green labeling and the release of adenosine triphosphate (ATP) from outer membranes of A. solani cells, which may enhance the fengycins ability to alter cell membrane permeability. Thus, this study increases the transcriptome data resources available and supplies a molecular framework for B. subtilis ZD01 inhibition of A. solani HWC-168 through various mechanisms, especially damaging A. solani cell walls and membranes. The transcriptomic insights may lead to an effective control strategy for potato early blight.

3D Nanoscale Mapping of Short-Range Order in GeSn Alloys.

GeSn on Si has attracted much research interest due to its tunable direct bandgap for mid-infrared applications. Recently, short-range order (SRO) in GeSn alloys has been theoretically predicted, which profoundly impacts the band structure. However, characterizing SRO in GeSn is challenging. Guided by physics-informed Poisson statistical analyses of k-nearest neighbors (KNN) in atom probe tomography (APT), a new approach is demonstrated here for 3D nanoscale SRO mapping and semi-quantitative strain mapping in GeSn. For GeSn with ≈14 at. % Sn, the SRO parameters of Sn-Sn 1NN in 10 × 10 × 10 nm3 nanocubes can deviate from that of the random alloys by ±15 %. The relatively large fluctuation of the SRO parameters contributes to band-edge softening observed optically. Sn-Sn 1NN also tends to be more favored toward the surface, less favored under strain relaxation or tensile strain, while almost independent of local Sn composition. An algorithm based on least square fit of atomic positions further verifies this Poisson-KNN statistical method. Compared to existing macroscopic spectroscopy or electron microscopy techniques, this new APT statistical analysis uniquely offers 3D SRO mapping at nanoscale resolution in a relatively large volume with millions of atoms. It can also be extended to investigate SRO in other alloy systems.

Design and optimization of high temperature optocouplers as galvanic isolation.

The commercial InGaN-based (blue and green) and AlGaInP-based (red) multiple quantum well (MQW) lighting emitting diodes (LEDs) were studied in a wide range of temperatures up to 800 K for their light emission and detection (i.e., LEDs operated under reverse bias as photodiodes (PDs)) characteristics. The results indicate the feasibility of integrating a pair of selected LEDs to fabricate high temperature (HT) optocouplers, which can be utilized as galvanic isolation to replace the bulky isolation transforms in the high-density power modules. A detailed study on LEDs and PDs were performed. The external quantum efficiency (EQE) of the LED and PDs were calculated. Higher relative external quantum efficiency (EQE) and lower efficiency droops with temperatures are obtained from the blue and green LEDs for display compared with the blue one for lighting and red LED for display. The blue for lighting and red for display devices show superior responsivity, specific detectivity (D*), and EQE compared with blue and green for display when operated as PDs. The results suggest that red LED devices for display can be used to optimize HT optocouplers due to the highest wavelength overlapping compared with others.

High-temperature analysis of optical coupling using AlGaAs/GaAs LEDs for high-density integrated power modules.

A low-temperature co-fired ceramic (LTCC)-based optocoupler design is demonstrated as a possible solution for optical isolation in high-density integrated power modules. The design and fabrication of LTCC based package are discussed. Commercially available aluminum gallium arsenide/gallium arsenide (AlGaAs/GaAs) double heterostructure is used both as emitter and photodetector in the proposed optocoupler. A detailed study on the electroluminescence and spectral response of the AlGaAs/GaAs structure is conducted at elevated temperatures. The material figure of merit parameter, D*, is calculated in the temperature range 77-800 K. The fabricated optocoupler is tested at elevated temperatures, and the results are presented.

Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties.

Sangivamycin is a nucleoside analog that is well tolerated by humans and broadly active against phylogenetically distinct viruses, including arenaviruses, filoviruses, and orthopoxviruses. Here, we show that sangivamycin is a potent antiviral against multiple variants of replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with half-maximal inhibitory concentration in the nanomolar range in several cell types. Sangivamycin suppressed SARS-CoV-2 replication with greater efficacy than remdesivir (another broad-spectrum nucleoside analog). When we investigated sangivamycin's potential for clinical administration, pharmacokinetic; absorption, distribution, metabolism, and excretion (ADME); and toxicity properties were found to be favorable. When tested in combination with remdesivir, efficacy was additive rather than competitive against SARS-CoV-2. The proven safety in humans, long half-life, potent antiviral activity (compared to remdesivir), and combinatorial potential suggest that sangivamycin is likely to be efficacious alone or in combination therapy to suppress viremia in patients. Sangivamycin may also have the ability to help combat drug-resistant or vaccine-escaping SARS-CoV-2 variants since it is antivirally active against several tested variants. Our results support the pursuit of sangivamycin for further preclinical and clinical development as a potential coronavirus disease 2019 therapeutic.

Growth of Pseudomorphic GeSn at Low Pressure with Sn Composition of 16.7.

Group-IV alloy GeSn holds great promise for the high-performance optoelectronic devices that can be monolithically integrated on Si for near- and mid-infrared applications. Growth of GeSn using chemical vapor deposition technique with various Sn and Ge precursors has been investigated worldwide. To achieve relatively high Sn incorporation, the use of higher pressure and/or higher order Ge hydrides precursors were reported. In this work, we successfully demonstrated the growth of high-quality GeSn with Sn composition of 16.7% at low pressure of 12 Torr. The alloy was grown using the commercially available GeH4 and SnCl4 precursors via a chemical vapor deposition reactor. Material and optical characterizations were performed to confirm the Sn incorporation and to study the optical properties. The demonstrated growth results reveal a low-pressure growth window to achieve high-quality and high Sn alloys for future device applications.

Investigation of SiGeSn/GeSn/SiGeSn single quantum well with enhanced well emission.

In this work, a SiGeSn/GeSn/SiGeSn single quantum well was grown and characterized. The sample has a thicker GeSn well of 22nm compared to a previously reported 9nm well configuration. The thicker well leads to: (i) lowered ground energy level in Γ valley offering more bandgap directness; (ii) increased carrier density in the well; and (iii) improved carrier collection due to increased barrier height. As a result, significantly enhanced emission from the quantum well was observed. The strong photoluminescence (PL) signal allows for the estimation of quantum efficiency (QE), which was unattainable in previous studies. Using pumping-power-dependent PL spectra at 20K, the peak spontaneous QE and external QE were measured as 37.9% and 1.45%, respectively.

Impact of nonlinear effects in Si towards integrated microwave-photonic applications.

As one of major integrated microwave photonics (IMWP) platforms, Si photonics exhibits the intensity-dependent Kerr effect and two-photon absorption (TPA) with associated free carrier effects (FCE). At the commonly used 1.55 µm, TPA losses and the associated FCE would eventually limit the dynamic range of Si photonic links. Resonating structures such as ring resonators (RRs) experience enhanced nonlinear effects due to significant intensity buildup. According to the bandgap characteristics of Si, TPA can be eliminated at and beyond 2.2 µm. In this work, a systemic simulation of straight waveguides and RRs is performed at wavelengths from 1.55 to 2.2 µm where the wavelength-dependent TPA loss is investigated. Moreover, the Kerr effect leads to unwanted change of refractive index, which shifts the RR resonant wavelength at both 1.55 and 2.2 µm, thus needing shift compensation. Compensated RRs operating at 2.2 µm could open a new venue for Si photonics towards IMWP applications.

On-Demand Patient-Specific Phenotype-to-Genotype Ebola Virus Characterization.

Biosafety, biosecurity, logistical, political, and technical considerations can delay or prevent the wide dissemination of source material containing viable virus from the geographic origin of an outbreak to laboratories involved in developing medical countermeasures (MCMs). However, once virus genome sequence information is available from clinical samples, reverse-genetics systems can be used to generate virus stocks de novo to initiate MCM development. In this study, we developed a reverse-genetics system for natural isolates of Ebola virus (EBOV) variants Makona, Tumba, and Ituri, which have been challenging to obtain. These systems were generated starting solely with in silico genome sequence information and have been used successfully to produce recombinant stocks of each of the viruses for use in MCM testing. The antiviral activity of MCMs targeting viral entry varied depending on the recombinant virus isolate used. Collectively, selecting and synthetically engineering emerging EBOV variants and demonstrating their efficacy against available MCMs will be crucial for answering pressing public health and biosecurity concerns during Ebola disease (EBOD) outbreaks.