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Interband cascade lasers (ICLs) are efficient and compact mid-infrared (3-5 µm) light sources with many applications. By enhancing the coupling coefficient and using a type-I ICL wafer, single-mode ICLs were demonstrated based on V-coupled cavity with significantly extended tuning range and with a side mode suppression ratio (SMSR) exceeding 35 dB in continuous wave operation near 3 µm. A V-coupled cavity ICL exhibited a wavelength tuning up to 67 nm at a fixed temperature, and the total tuning range exceeds 210 nm when the heat sink temperature is adjusted from 80 to 180 K. The realization of single-mode in such a wide temperature range with a tuning range exceeding 210 nm verified the advantage of V-coupled cavity ICLs for effective detection of multiple gas species. This is very different from the conventional distributed feedback (DFB) laser where the single-mode operation is restricted to a narrow temperature range, in which the match between the gain peak and the DFB grating period determined wavelength is required. Another V-coupled cavity ICL is tuned over 120 nm from 2997.56 nm to 3117.50 nm with the heat-sink temperature varied from 210 K to 240 K, over 100 K higher than the previously reported maximum operating temperature for V-coupled cavity ICLs.

 

Recent deep learning models that predict the Hi-C contact map from DNA sequence achieve promising accuracy but cannot generalize to new cell types and or even capture differences among training cell types. We propose Epiphany, a neural network to predict cell-type-specific Hi-C contact maps from widely available epigenomic tracks. Epiphany uses bidirectional long short-term memory layers to capture long-range dependencies and optionally a generative adversarial network architecture to encourage contact map realism. Epiphany shows excellent generalization to held-out chromosomes within and across cell types, yields accurate TAD and interaction calls, and predicts structural changes caused by perturbations of epigenomic signals.

 

Abstract Interband cascade lasers (ICLs) based on the type-II quantum well (QW) active region have attracted much attention for a range of practical applications in the mid-infrared due, in part, to their low power consumption. However, extending the operating wavelength of these ICLs into the long-wave infrared region presents several challenges including the reduced thermal conductivity of the optical cladding layers and the diminished wavefunction overlap in the type-II QW. One solution to alleviate the former concern is to use InAs-based ICLs. To solve the latter problem, InAs 0.5 P 0.5 barriers are introduced in the active region, which lowers the electronic energy level and allows for the InAs well width to be reduced at longer emission wavelengths. Here the advancement of long wavelength ICLs, made from four new InAs-based ICL wafers grown by molecular beam epitaxy, is reported. These ICLs lased in the wavelength range from 10 to 13 µ m and showed significantly improved performance compared with previous ICLs, including the first demonstration of broad-area devices operating in continuous wave mode beyond 12 µ m. These ICLs exhibited substantially increased output powers with reduced threshold voltages ( V th ) and current densities ( J th ). They operated at temperatures up to 40 K higher than previous ICLs at similar wavelengths. 

Osteoporosis is a common bone and metabolic disease that is characterized by bone density loss and microstructural degeneration. Human bone marrow-derived mesenchymal stem cells (hMSCs) are multipotent progenitor cells with the potential to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes, which have been utilized extensively in the field of bone tissue engineering and cell-based therapy. Although fluid shear stress plays an important role in bone osteogenic differentiation, the cellular and molecular mechanisms underlying this effect remain poorly understood. Here, a locked nucleic acid (LNA)/DNA nanobiosensor was exploited to monitor mRNA gene expression of hMSCs that were exposed to physiologically relevant fluid shear stress to examine the regulatory role of Notch signaling during osteogenic differentiation. First, the effects of fluid shear stress on cell viability, proliferation, morphology, and osteogenic differentiation were investigated and compared. Our results showed shear stress modulates hMSCs morphology and osteogenic differentiation depending on the applied shear and duration. By incorporating this LNA/DNA nanobiosensor and alkaline phosphatase (ALP) staining, we further investigated the role of Notch signaling in regulating osteogenic differentiation. Pharmacological treatment is applied to disrupt Notch signaling to investigate the mechanisms that govern shear stress induced osteogenic differentiation. Our experimental results provide convincing evidence supporting that physiologically relevant shear stress regulates osteogenic differentiation through Notch signaling. Inhibition of Notch signaling mediates the effects of shear stress on osteogenic differentiation, with reduced ALP enzyme activity and decreased Dll4 mRNA expression. In conclusion, our results will add new information concerning osteogenic differentiation of hMSCs under shear stress and the regulatory role of Notch signaling. Further studies may elucidate the mechanisms underlying the mechanosensitive role of Notch signaling in stem cell differentiation. 

Human mesenchymal stem cells (hMSCs) have great potential in cell-based therapies for tissue engineering and regenerative medicine due to their self-renewal and multipotent properties. Recent studies indicate that Notch1-Dll4 signaling is an important pathway in regulating osteogenic differentiation of hMSCs. However, the fundamental mechanisms that govern osteogenic differentiation are poorly understood due to a lack of effective tools to detect gene expression at single cell level. Here, we established a double-stranded locked nucleic acid (LNA)/DNA (LNA/DNA) nanobiosensor for gene expression analysis in single hMSC in both 2D and 3D microenvironments. We first characterized this LNA/DNA nanobiosensor and demonstrated the Dll4 mRNA expression dynamics in hMSCs during osteogenic differentiation. By incorporating this nanobiosensor with live hMSCs imaging during osteogenic induction, we performed dynamic tracking of hMSCs differentiation and Dll4 mRNA gene expression profiles of individual hMSC during osteogenic induction. Our results showed the dynamic expression profile of Dll4 during osteogenesis, indicating the heterogeneity of hMSCs during this dynamic process. We further investigated the role of Notch1-Dll4 signaling in regulating hMSCs during osteogenic differentiation. Pharmacological perturbation is applied to disrupt Notch1-Dll4 signaling to investigate the molecular mechanisms that govern osteogenic differentiation. In addition, the effects of Notch1-Dll4 signaling on hMSCs spheroids differentiation were also investigated. Our results provide convincing evidence supporting that Notch1-Dll4 signaling is involved in regulating hMSCs osteogenic differentiation. Specifically, Notch1-Dll4 signaling is active during osteogenic differentiation. Our results also showed that Dll4 is a molecular signature of differentiated hMSCs during osteogenic induction. Notch inhibition mediated osteogenic differentiation with reduced Alkaline Phosphatase (ALP) activity. Lastly, we elucidated the role of Notch1-Dll4 signaling during osteogenic differentiation in a 3D spheroid model. Our results showed that Notch1-Dll4 signaling is required and activated during osteogenic differentiation in hMSCs spheroids. Inhibition of Notch1-Dll4 signaling mediated osteogenic differentiation and enhanced hMSCs proliferation, with increased spheroid sizes. Taken together, the capability of LNA/DNA nanobiosensor to probe gene expression dynamics during osteogenesis, combined with the engineered 2D/3D microenvironment, enables us to study in detail the role of Notch1-Dll4 signaling in regulating osteogenesis in 2D and 3D microenvironment. These findings will provide new insights to improve cell-based therapies and organ repair techniques.