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.

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.

"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.

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.

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.

Optically pumped lasing at 3 µm from compositionally graded GeSn with tin up to 22.3.

The recent demonstration of the GeSn laser opened a promising route towards the monolithic integration of light sources on the Si platform. A GeSn laser with higher Sn content is highly desirable to enhance the emission efficiency and to cover longer wavelength. This Letter reports optically pumped edge-emitting GeSn lasers operating at 3 µm, whose device structure featured Sn compositionally graded with a maximum Sn content of 22.3%. By using a 1950-nm laser pumping in comparison with a 1064-nm pumping, the local heating and quantum defect were effectively reduced, which improved laser performance in terms of higher maximum lasing temperature and lower threshold.

Study of direct bandgap type-I GeSn/GeSn double quantum well with improved carrier confinement.

The GeSn-based quantum wells (QWs) have been investigated recently for the development of efficient GeSn emitters. Although our previous study indicated that the direct bandgap well with type-I band alignment was achieved, the demonstrated QW still has insufficient carrier confinement. In this work, we report the systematic study of light emission from the Ge0.91Sn0.09/Ge0.85Sn0.15/Ge0.91Sn0.09 double QW structure. Two double QW samples, with the thicknesses of Ge0.85Sn0.15 well of 6 and 19 nm, were investigated. Band structure calculations revealed that both samples feature type-I band alignment. Compared with our previous study, by increasing the Sn composition in GeSn barrier and well, the QW layer featured increased energy separation between the indirect and direct bandgaps towards a better direct gap semiconductor. Moreover, the thicker well sample exhibited improved carrier confinement compared to the thinner well sample due to lowered first quantized energy level in the Γ valley. To identify the optical transition characteristics, photoluminescence (PL) study using three pump lasers with different penetration depths and photon energies was performed. The PL spectra confirmed the direct bandgap well feature and the improved carrier confinement, as significantly enhanced QW emission from the thicker well sample was observed.

Non-avalanche single photon detection without carrier transit-time delay through quantum capacitive coupling.

Searching for innovative approaches to detect single photons remains at the center of science and technology for decades. This paper proposes a zero transit-time, non-avalanche quantum capacitive photodetector to register single photons. In this detector, the absorption of a single photon changes the wave function of a single electron trapped in a quantum dot (QD), leading to a charge density redistribution nearby. This redistribution translates into a voltage signal through capacitive coupling between the QD and the measurement probe. Using InAs QD/AlAs barrier as a model system, the simulation shows that the output signal reaches ~4 mV per absorbed photon, promising for high-sensitivity, ps single-photon detection.

Study of a SiGeSn/GeSn/SiGeSn structure toward direct bandgap type-I quantum well for all group-IV optoelectronics.

A SiGeSn/GeSn/SiGeSn single quantum well structure was grown using an industry standard chemical vapor deposition reactor with low-cost commercially available precursors. The material characterization revealed the precisely controlled material growth process. Temperature-dependent photoluminescence spectra were correlated with band structure calculation for a structure accurately determined by high-resolution x-ray diffraction and transmission electron microscopy. Based on the result, a systematic study of SiGeSn and GeSn bandgap energy separation and barrier heights versus material compositions and strain was conducted, leading to a practical design of a type-I direct bandgap quantum well.

Systematic study of Si-based GeSn photodiodes with 2.6 µm detector cutoff for short-wave infrared detection.

Normal-incidence Ge1-xSnx photodiode detectors with Sn compositions of 7 and 10% have been demonstrated. Such detectors were based on Ge/Ge1-xSnx/Ge double heterostructures grown directly on a Si substrate via a chemical vapor deposition system. A temperature-dependence study of these detectors was conducted using both electrical and optical characterizations from 300 to 77 K. Spectral response up to 2.6 µm was achieved for a 10% Sn device at room temperature. The peak responsivity and specific detectivity (D*) were measured to be 0.3 A/W and 4 × 109 cmHz1/2W-1 at 1.55 µm, respectively. The spectral D* of a 7% Sn device at 77 K was only one order-of-magnitude lower than that of an extended-InGaAs photodiode operating in the same wavelength range, indicating the promising future of GeSn-based photodetectors.

Increased pertechnetate and radioiodine uptake in the thyroid gland with subacute thyroiditis and concurrent Graves' disease.

OBJECTIVE: A 61 years old woman presented with low grade fever and weight loss for a month. Thyroid function tests showed hyperthyroidism: increased technetium-99m pertechnetate ((99m)Tc O(-)4) and radioiodine ((131)I) uptake and elevated thyroid stimulating hormone receptor antibodies (TSHRAb). She also had high erythrocyte sedimentation rate. Fine-needle aspiration (FNA) biopsies of left thyroid lobe revealed subacute thyroiditis (SAT). Simultaneous occurrence of SAT and Graves' disease (GD) was diagnosed. The patient was in good physical condition after two doses of betamethasone and daily administration of low dose antithyroid drugs. CONCLUSION: This case indicated that the measurement of TSHRAb is useful in understanding the clinical course of patients with SAT when thyroid function tests including the (99m)Tc and (131)I uptake are not compatible with the diagnosis. In such cases, GD should be suspected. The mechanism of high (99m)Tc and/or (131)I uptake in patients with simultaneous SAT and GD may be due to the inflammatory process which was detected by FNA in a small part of the left thyroid lobe inducing the stimulating effects of elevated TSHRAb on the undamaged follicular cells.

Lipoprotein lipase activity is required for cardiac lipid droplet production.

The rodent heart accumulates TGs and lipid droplets during fasting. The sources of heart lipids could be either FFAs liberated from adipose tissue or FAs from lipoprotein-associated TGs via the action of lipoprotein lipase (LpL). Because circulating levels of FFAs increase during fasting, it has been assumed that albumin transported FFAs are the source of lipids within heart lipid droplets. We studied mice with three genetic mutations: peroxisomal proliferator-activated receptor α deficiency, cluster of differentiation 36 (CD36) deficiency, and heart-specific LpL deletion. All three genetically altered groups of mice had defective accumulation of lipid droplet TGs. Moreover, hearts from mice treated with poloxamer 407, an inhibitor of lipoprotein TG lipolysis, also failed to accumulate TGs, despite increased uptake of FFAs. TG storage did not impair maximal cardiac function as measured by stress echocardiography. Thus, LpL hydrolysis of circulating lipoproteins is required for the accumulation of lipids in the heart of fasting mice.

Nonhuman transferrin receptor 1 is an efficient cell entry receptor for Ocozocoautla de Espinosa virus.

Ocozocoautla de Espinosa virus (OCEV) is a novel, uncultured arenavirus. We found that the OCEV glycoprotein mediates entry into grivet and bat cells through transferrin receptor 1 (TfR1) binding but that OCEV glycoprotein precursor (GPC)-pseudotyped retroviruses poorly entered 53 human cancer cell lines. Interestingly, OCEV and Tacaribe virus could use bat, but not human, TfR1. Replacing three human TfR1 amino acids with their bat ortholog counterparts transformed human TfR1 into an efficient OCEV and Tacaribe virus receptor.

Temperature dependent spectral response and detectivity of GeSn photoconductors on silicon for short wave infrared detection.

The GeSn direct gap material system, with Si complementary-metal-oxide semiconductor (CMOS) compatibility, presents a promising solution for direct incorporation of focal plane arrays with short wave infrared detection on Si. A temperature dependence study of GeSn photoconductors with 0.9, 3.2, and 7.0% Sn was conducted using both electrical and optical characterizations from 300 to 77 K. The GeSn layers were grown on Si substrates using a commercially available chemical vapor deposition reactor in a Si CMOS compatible process. Carrier activation energies due to ionization and trap states are extracted from the temperature dependent dark I-V characteristics. The temperature dependent spectral response of each photoconductor was measured, and a maximum long wavelength response to 2.1 µm was observed for the 7.0% Sn sample. The DC responsivity measured at 1.55 µm showed around two orders of magnitude improvement at reduced temperatures for all samples compared to room temperature measurements. The noise current and temperature dependent specific detectivity (D*) were also measured for each sample at 1.55 µm, and a maximum D* value of 1 × 10(9) cm·âˆšHz/W was observed at 77 K.

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.

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.

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.

Ventricular assist device implantation corrects myocardial lipotoxicity, reverses insulin resistance, and normalizes cardiac metabolism in patients with advanced heart failure.

BACKGROUND: Heart failure is associated with impaired myocardial metabolism with a shift from fatty acids to glucose use for ATP generation. We hypothesized that cardiac accumulation of toxic lipid intermediates inhibits insulin signaling in advanced heart failure and that mechanical unloading of the failing myocardium corrects impaired cardiac metabolism. METHODS AND RESULTS: We analyzed the myocardium and serum of 61 patients with heart failure (body mass index, 26.5±5.1 kg/m(2); age, 51±12 years) obtained during left ventricular assist device implantation and at explantation (mean duration, 185±156 days) and from 9 control subjects. Systemic insulin resistance in heart failure was accompanied by decreased myocardial triglyceride and overall fatty acid content but increased toxic lipid intermediates, diacylglycerol, and ceramide. Increased membrane localization of protein kinase C isoforms, inhibitors of insulin signaling, and decreased activity of insulin signaling molecules Akt and Foxo were detectable in heart failure compared with control subjects. Left ventricular assist device implantation improved whole-body insulin resistance (homeostatic model of analysis-insulin resistance, 4.5±0.6-3.2±0.5; P<0.05) and decreased myocardial levels of diacylglycerol and ceramide, whereas triglyceride and fatty acid content remained unchanged. Improved activation of the insulin/phosphatidylinositol-3 kinase/Akt signaling cascade after left ventricular assist device implantation was confirmed by increased phosphorylation of Akt and Foxo, which was accompanied by decreased membrane localization of protein kinase C isoforms after left ventricular assist device implantation. CONCLUSIONS: Mechanical unloading after left ventricular assist device implantation corrects systemic and local metabolic derangements in advanced heart failure, leading to reduced myocardial levels of toxic lipid intermediates and improved cardiac insulin signaling.

Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride in optimal heart metabolism and function.

Hearts utilize fatty acids as a primary source of energy. The sources of those lipids include free fatty acids and lipoprotein triglycerides. Deletion of the primary triglyceride-hydrolyzing enzyme lipoprotein lipase (LPL) leads to cardiac dysfunction. Whether heart LPL-knockout (hLPL0) mice are compromised due a deficiency in energetic substrates is unknown. To test whether alternative sources of energy will prevent cardiac dysfunction in hLPL0 mice, two different models were used to supply nonlipid energy. 1) hLPL0 mice were crossed with mice transgenically expressing GLUT1 in cardiomyocytes to increase glucose uptake into the heart; this cross-corrected cardiac dysfunction, reduced cardiac hypertrophy, and increased myocardial ATP. 2) Mice were randomly assigned to a sedentary or training group (swimming) at 3 mo of age, which leads to increased skeletal muscle production of lactate. hLPL0 mice had greater expression of the lactate transporter monocarboxylate transporter-1 (MCT-1) and increased cardiac lactate uptake. Compared with hearts from sedentary hLPL0 mice, hearts from trained hLPL0 mice had adaptive hypertrophy and improved cardiac function. We conclude that defective energy intake and not the reduced uptake of fat-soluble vitamins or cholesterol is responsible for cardiac dysfunction in hLPL0 mice. In addition, our studies suggest that adaptations in cardiac metabolism contribute to the beneficial effects of exercise on the myocardium of patients with heart failure.

Fish oil selectively improves heart function in a mouse model of lipid-induced cardiomyopathy.

Fish oil (FO) supplementation may improve cardiac function in some patients with heart failure, especially those with diabetes. To determine why this occurs, we studied the effects of FO in mice with heart failure either due to transgenic expression of the lipid uptake protein acyl CoA synthetase 1 (ACS1) or overexpression of the transcription factor peroxisomal proliferator-activated receptor (PPAR) γ via the cardiac-specific myosin heavy chain (MHC) promoter. ACS1 mice and control littermates were fed 3 diets containing low-dose or high-dose FO or nonpurified diet (NPD) for 6 weeks. MHC-PPARγ mice were fed low-dose FO or NPD. Compared with control mice fed with NPD, ACS1, and MHC-PPARγ, mice fed with NPD had reduced cardiac function and survival with cardiac fibrosis. In contrast, ACS1 mice fed with high-dose FO had better cardiac function, survival, and less myocardial fibrosis. FO increased eicosapentaenoic and docosahexaenoic acids and reduced saturated fatty acids in cardiac diacylglycerols. This was associated with reduced protein kinase C alpha and beta activation. In contrast, low-dose FO reduced MHC-PPARγ mice survival with no change in protein kinase C activation or cardiac function. Thus, dietary FO reverses fibrosis and improves cardiac function and survival of ACS1 mice but does not benefit all forms of lipid-mediated cardiomyopathy.