Low SWaP Semiconductor Laser Transmitter Modules For ASCENDS Mission Applications

The National Research Council's (NRC) Decadal Survey (DS) of Earth Science and Applications from Space has identified the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) as an important atmospheric science mission. NASA Langley Research Center, working with its partners, is developing fiber laser architecture based intensity modulated CW laser absorption spectrometer for measuring XCO2 in the 1571 nm spectral band. In support of this measurement, remote sensing of O2 in the 1260 nm spectral band for surface pressure measurements is also being developed. In this paper, we will present recent progress made in the development of advanced transmitter modules for CO2 and O2 sensing. Advanced DFB seed laser modules incorporating low-noise variable laser bias current supply and low-noise variable temperature control circuit have been developed. The 1571 nm modules operate at >80 mW and could be tuned continuously over the wavelength range of 1569-1574nm at a rate of 2 pm/mV. Fine tuning was demonstrated by adjusting the laser drive at a rate of 0.7 pm/mV. Heterodyne linewidth measurements have been performed showing linewidth ~200 kHz and frequency jitter ~75 MHz. In the case of 1260 nm DFB laser modules, we have shown continuous tuning over a range of 1261.4 - 1262.6 nm by changing chip operating temperature and 1261.0 - 1262.0 nm by changing the laser diode drive level. In addition, we have created a new laser package configuration which has been shown to improve the TEC coefficient of performance by a factor of 5 and improved the overall efficiency of the laser module by a factor of 2

Development of Advanced Seed Laser Modules for Lidar and Spectroscopy Applications

We report on recent progress made in the development of highly compact, single mode, distributed feedback laser (DFB) seed laser modules for lidar and spectroscopy applications from space based platforms. One of the intended application of this technology is in the NASA's Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission. The DFB laser modules operating at 1571 nm and 1262 nm have advanced current and temperature drivers built into them. A combination of temperature and current tuning allows coarse and fine adjustment of the diode wavelengths

The TreaT-Assay: A Novel Urine-Derived Donor Kidney Cell-Based Assay for Prediction of Kidney Transplantation Outcome

Donor-reactive immunity plays a major role in rejection after kidney transplantation, but analysis of donor-reactive T-cells is not applied routinely. However, it has been shown that this could help to identify patients at risk of acute rejection. A major obstacle is the limited quantity or quality of the required allogenic stimulator cells, including a limited availability of donor-splenocytes or an insufficient HLA-matching with HLA-bank cells. To overcome these limitations, we developed a novel assay, termed the TreaT (Transplant reactive T-cells)-assay. We cultivated renal tubular epithelial cells from the urine of kidney transplant patients and used them as stimulators for donor-reactive T-cells, which we analyzed by flow cytometry. We could demonstrate that using the TreaT-assay the quantification and characterization of alloreactive T-cells is superior to other stimulators. In a pilot study, the number of pre-transplant alloreactive T-cells negatively correlated with the post-transplant eGFR. Frequencies of pre-transplant CD161+ alloreactive CD4+ T-cells and granzyme B producing alloreactive CD8+ T-cells were substantially higher in patients with early acute rejection compared to patients without complications. In conclusion, we established a novel assay for the assessment of donor-reactive memory T-cells based on kidney cells with the potential to predict early acute rejection and post-transplant eGFR

iPSC-derived reactive astrocytes from patients with multiple-sclerosis protect cocultured neurons in inflammatory conditions

Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system (CNS). The individual course is highly variable with complete remission in some patients and relentless courses in others. We generated induced pluripotent stem cells (iPSCs) to investigate possible mechanisms in benign MS (BMS), compared to progressive MS (PMS). We differentiated neurons and astrocytes that were then stressed with inflammatory cytokines typically associated with MS. TNFα/IL-17A treatment increased neurite damage in MS neurons irrespective of clinical phenotypes. In contrast, TNFα/IL-17A-reactive BMS astrocytes cultured with healthy control (HC) neurons exhibited significantly decreased axonal damage, compared to PMS astrocytes. Accordingly, single cell transcriptomic analysis of BMS-astrocyte co-cultured neurons demonstrated upregulated pathways of neuronal resilience, namely these astrocytes revealed differential growth factor expression. Moreover, supernatants from BMS astrocyte-neuron co-cultures rescued TNFα/IL-17-induced neurite damage. This process was associated with the unique expression of the growth factors, LIF and TGF-β1, as induced by TNFα/IL-17 and JAK-STAT activation. Our findings highlight a potential therapeutic role of modulating astrocyte phenotypes that generate a neuroprotective milieu preventing permanent neuronal damage

HIF prolyl hydroxylase 2/3 deletion disrupts astrocytic integrity and exacerbates neuroinflammation

Astrocytes constitute the parenchymal border of the blood-brain barrier (BBB), modulate the exchange of soluble and cellular elements, and are essential for neuronal metabolic support. Thus, astrocytes critically influence neuronal network integrity. In hypoxia, astrocytes upregulate a transcriptional program that has been shown to boost neuroprotection in several models of neurological diseases. We investigated transgenic mice with astrocyte-specific activation of the hypoxia-response program by deleting the oxygen sensors, HIF prolyl-hydroxylase domains 2 and 3 (Phd2/3). We induced astrocytic Phd2/3 deletion after onset of clinical signs in experimental autoimmune encephalomyelitis (EAE) that led to an exacerbation of the disease mediated by massive immune cell infiltration. We found that Phd2/3-ko astrocytes, though expressing a neuroprotective signature, exhibited a gradual loss of gap-junctional Connexin-43 (Cx43), which was induced by vascular endothelial growth factor-alpha (Vegf-a) expression. These results provide mechanistic insights into astrocyte biology, their critical role in hypoxic states, and in chronic inflammatory CNS diseases

High incidence and viral load of HHV-6A in a multi-centre kidney transplant cohort

Human herpesvirus 6 (HHV-6) is a common opportunistic pathogen in kidney transplant recipients. Two distinct species of HHV-6, HHV-6A and HHV-6B, have been identified, of which the latter seems to be dominant. However, it is unclear whether they increase the likelihood of other viral reactivations. We characterized a multi-centre cohort of 93 patients along nine study visits for viral load. We tested for the following viruses: HHV-6A and HHV-6B, the herpesviruses cytomegalovirus (CMV) and Epstein-Barr virus (EBV) and the polyomavirus BK (BKV). We detected HHV-6A viral load in 48 (51.6%) patients, while the incidence of HHV-6B was much lower, being detected in 6 (6.5%) patients. The incidence of HHV-6A was higher than of BKV, CMV and EBV. HHV-6A also demonstrated higher viral loads than the rest of viruses. There was a non-significant trend of association between HHV-6A and HHV-6B as co-infection, whereas no increased incidence of other viruses among patients with HHV-6A reactivation was observed. There was no negative effect of high HHV-6A (>10,000 copies/ml) load on markers of renal graft and hepatic function or blood count twelve months post-transplant. In contrast to previously published data, our results show a clear dominance of HHV-6A in peripheral blood when compared to HHV-6B, with higher incidence and viral load levels. Despite the high HHV-6A loads observed, we did not identify any negative effects on posttransplant outcome

Studies of the electron density of states in amorphous semiconductors by electron tunnelling

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