Plug-In Electric Vehicles

Did you know?Using electricity to power an automotive vehicle would cost the equivalent of paying less than $2.00 per gallon of gasoline at current electric prices. In some states, the cost would be under$1.00 per gallon.A typical mid-size sedan, when running on electricity from the current U.S. grid, would have the same carbon footprint as a car that gets 50 miles per gallon (mpg) of gasoline. As more electricity comes from renewable sources, net carbon emissions would be reduced further. Plug-in electric vehicles could be on the market very soon

The impact of ozone field horizontal inhomogeneities on nadir-viewing orbital backscatter UV measurements

Radiative transfer calculations for nadir-viewing satellites normally assume the atmosphere to be horizontally homogeneous. Yet it has been shown recently that horizontal gradients can lead to significant errors in satellite infrared and microwave soundings. We extend the methodology to backscatter ultra-violet observations of ozone, and present a first estimate of the effect s magnitude. The Solar Backscatter Ultra-Violet/2 (SBUV/2) instrument, a pure nadir sounder, serves as our test bed. Our results indicate that in a vast majority of cases the abovementioned errors can be neglected. However, occurrence of higher errors, particularly at wavelengths longer than 300 nm, coincides with some of the most interesting atmospheric phenomena like tropopause folds and the South polar ozone hole. This leads to a seasonal variation of the magnitude of the effect. Due to the mostly zonal geometry of the ozone distribution, there is also the possibility that biases may be introduced, which is particularly critical if the data are to be assimilated or used to determine trends. The results presented are tested for robustness using different model atmospheres. The influence of horizontal inhomogeneities will be even more pronounced for cross-track sounders and limb viewers, and easier to detect once higher resolution atmospheric models are available. This will be investigated in future studies

Simultaneous isolation of pure and intact chloroplasts and mitochondria from moss as the basis for sub-cellular proteomics

The moss Physcomitrella patens is increasingly being used as a model for plant systems biology studies. While genomic and transcriptomic resources are in place, tools and experimental conditions for proteomic studies need to be developed. In the present study we describe a rapid and efficient protocol for the simultaneous isolation of chloroplasts and mitochondria from moss protonema. Routinely, 60–100 μg mitochondrial and 3–5 mg chloroplast proteins, respectively, were obtained from 20 g fresh weight of green moss tissue. Using 14 plant compartment marker antibodies derived from seed plant and algal protein sequences, respectively, the evolutionary conservation of the compartment marker proteins in the moss was demonstrated and purity and intactness of the extracted organelles confirmed. This isolation protocol and these validated compartment markers may serve as basis for sub-cellular proteomics in P. patens and other mosses

Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with Endometriosis.

Identifying tissue-specific molecular signatures of active regulatory elements is critical to understanding gene regulatory mechanisms. In this study, transcription start sites (TSS) and enhancers were identified using Cap analysis of gene expression (CAGE) across endometrial stromal cell (ESC) samples obtained from women with (n = 4) and without endometriosis (n = 4). ESC TSSs and enhancers were compared to those reported in other tissue and cell types in FANTOM5 and were integrated with RNA-seq and ATAC-seq data from the same samples for regulatory activity and network analyses. CAGE tag count differences between women with and without endometriosis were statistically tested and tags within close proximity to genetic variants associated with endometriosis risk were identified. Over 90% of tag clusters mapping to promoters were observed in cells and tissues in FANTOM5. However, some potential cell-type-specific promoters and enhancers were also observed. Regions of open chromatin identified using ATAC-seq provided further evidence of the active transcriptional regions identified by CAGE. Despite the small sample number, there was evidence of differences associated with endometriosis at 210 consensus clusters, including IGFBP5, CALD1 and OXTR. ESC TSSs were also located within loci associated with endometriosis risk from genome-wide association studies. This study provides novel evidence of transcriptional differences in endometrial stromal cells associated with endometriosis and provides a valuable cell-type specific resource of active TSSs and enhancers in endometrial stromal cells

Targeted gene delivery to the enteric nervous system using AAV: a comparison across serotypes and capsid mutants

Recombinant adeno-associated virus (AAV) vectors are one of the most widely used gene transfer systems in research and clinical trials. AAV can transduce a wide range of biological tissues, however to date, there has been no investigation on targeted AAV transduction of the enteric nervous system (ENS). Here, we examined the efficiency, tropism, spread, and immunogenicity of AAV transduction in the ENS. Rats received direct injections of various AAV serotypes expressing green fluorescent protein (GFP) into the descending colon. AAV serotypes tested included; AAV 1, 2, 5, 6, 8, or 9 and the AAV2 and AAV8 capsid mutants, AAV2-Y444F, AAV2-tripleY-F, AAV2-tripleY-F+T-V, AAV8-Y733F, and AAV8-doubeY-F+T-V. Transduction, as determined by GFP-positive cells, occurred in neurons and enteric glia within the myenteric and submucosal plexuses of the ENS. AAV6 and AAV9 showed the highest levels of transduction within the ENS. Transduction efficiency scaled with titer and time, was translated to the murine ENS, and produced no vector-related immune response. A single injection of AAV into the colon covered an area of ~47 mm(2). AAV9 primarily transduced neurons, while AAV6 transduced enteric glia and neurons. This is the first report on targeted AAV transduction of neurons and glia in the ENS

Metastable Pores at the Onset of Constant-Current Electroporation

Single metastable nanopores, appearing before the actual electroporation under constant-current conditions, are used to characterize the onset of electroporation. Unlike the long-lived electropores typical of the current controlled methods, these pores survive for milliseconds and observing them is possible due to slow development of electroporation, provided by the gradual accumulation of charges on a planar membrane. Analysis of the metastable pore appearance frequency and lifetime shows the first introductory stage of electroporation. During this stage two species of metastable pores open, the majority of very low conductance that seem not fully developed as hydrophilic electropores. The experiments reveal that voltage value defines the electroporation onset while the current value affects the rate of electroporation. Membrane capacitance has a great impact on the membrane susceptibility to the pore appearance, related to its thickness and integrity. Pores of nonperfect membranes appear more easily, but they do not live any longer than others

Optical Properties of (162173) 1999 JU3: In Preparation for the JAXA Hayabusa 2 Sample Return Mission

We investigated the magnitude-phase relation of (162173) 1999 JU3, a target asteroid for the JAXA Hayabusa 2 sample return mission. We initially employed the international Astronomical Union's H-G formalism but found that it fits less well using a single set of parameters. To improve the inadequate fit, we employed two photometric functions, the Shevchenko and Hapke functions. With the Shevchenko function, we found that the magnitude-phase relation exhibits linear behavior in a wide phase angle range (alpha = 5-75 deg) and shows weak nonlinear opposition brightening at alpha< 5 deg, providing a more reliable absolute magnitude of Hv = 19.25 +- 0.03. The phase slope (0.039 +- 0.001 mag/deg) and opposition effect amplitude (parameterized by the ratio of intensity at alpha=0.3 deg to that at alpha=5 deg, I(0.3)/I(5)=1.31+-0.05) are consistent with those of typical C-type asteroids. We also attempted to determine the parameters for the Hapke model, which are applicable for constructing the surface reflectance map with the Hayabusa 2 onboard cameras. Although we could not constrain the full set of Hapke parameters, we obtained possible values, w=0.041, g=-0.38, B0=1.43, and h=0.050, assuming a surface roughness parameter theta=20 deg. By combining our photometric study with a thermal model of the asteroid (Mueller et al. in preparation), we obtained a geometric albedo of pv = 0.047 +- 0.003, phase integral q = 0.32 +- 0.03, and Bond albedo AB = 0.014 +- 0.002, which are commensurate with the values for common C-type asteroids.Comment: 27 pages, 4 figure, accepted for publication in the Astrophysical Journa

Altered differentiation of endometrial mesenchymal stromal fibroblasts is associated with endometriosis susceptibility.

Cellular development is tightly regulated as mature cells with aberrant functions may initiate pathogenic processes. The endometrium is a highly regenerative tissue, shedding and regenerating each month. Endometrial stromal fibroblasts are regenerated each cycle from mesenchymal stem cells and play a pivotal role in endometriosis, a disease characterised by endometrial cells that grow outside the uterus. Why the cells of some women are more capable of developing into endometriosis lesions is not clear. Using isolated, purified and cultured endometrial cells of mesenchymal origin from 19 women with (n = 10) and without (n = 9) endometriosis we analysed the transcriptome of 33,758 individual cells and compared these to clinical characteristics and in vitro growth profiles. We show purified mesenchymal cell cultures include a mix of mesenchymal stem cells and two endometrial stromal fibroblast subtypes with distinct transcriptomic signatures indicative of varied progression through the differentiation processes. The fibroblast subgroup characterised by incomplete differentiation was predominantly (81%) derived from women with endometriosis and exhibited an altered in vitro growth profile. These results uncover an inherent difference in endometrial cells of women with endometriosis and highlight the relevance of cellular differentiation and its potential to contribute to disease susceptibility

Shooting at Moving and Hidden Targets-Tumour Cell Plasticity and the Notch Signalling Pathway in Head and Neck Squamous Cell Carcinomas

Simple Summary Cancers in the head and neck region are often aggressive and poorly respond to both irradiation or chemotherapy. Chemotherapy is currently limited by a small number of approved drugs. Newer "targeted" drugs, aiming for specific molecules expressed by tumour cells, have not been as beneficial as expected. Research is now investigating new drug targets, involved in the way how tumour cells interact with non-cancer cells from the stroma, the vasculature, and the immune system within the tumour tissues. These highly dynamic processes assist tumour cells to rapidly adapt to any challenges they may encounter during cancer progression or therapy. One such central molecular mechanism, regulating increased tumour cell plasticity, is the Notch signalling pathway. We currently are only beginning to understand the complex interactions of Notch receptors with their ligands, in a broad spectrum of tumour and tumour-associated cells, and how such interactions could represent targets for cancer chemotherapy and personalized medicine. Head and Neck Squamous Cell Carcinoma (HNSCC) is often aggressive, with poor response to current therapies in approximately 40-50% of the patients. Current therapies are restricted to operation and irradiation, often combined with a small number of standard-of-care chemotherapeutic drugs, preferentially for advanced tumour patients. Only very recently, newer targeted therapies have entered the clinics, including Cetuximab, which targets the EGF receptor (EGFR), and several immune checkpoint inhibitors targeting the immune receptor PD-1 and its ligand PD-L1. HNSCC tumour tissues are characterized by a high degree of intra-tumour heterogeneity (ITH), and non-genetic alterations that may affect both non-transformed cells, such as cancer-associated fibroblasts (CAFs), and transformed carcinoma cells. This very high degree of heterogeneity likely contributes to acquired drug resistance, tumour dormancy, relapse, and distant or lymph node metastasis. ITH, in turn, is likely promoted by pronounced tumour cell plasticity, which manifests in highly dynamic and reversible phenomena such as of partial or hybrid forms of epithelial-to-mesenchymal transition (EMT), and enhanced tumour stemness. Stemness and tumour cell plasticity are strongly promoted by Notch signalling, which remains poorly understood especially in HNSCC. Here, we aim to elucidate how Notch signal may act both as a tumour suppressor and proto-oncogenic, probably during different stages of tumour cell initiation and progression. Notch signalling also interacts with numerous other signalling pathways, that may also have a decisive impact on tumour cell plasticity, acquired radio/chemoresistance, and metastatic progression of HNSCC. We outline the current stage of research related to Notch signalling, and how this pathway may be intricately interconnected with other, druggable targets and signalling mechanisms in HNSCC