Promoting Clean Reliable Energy Through Smart Technologies and Policies: Lessons from Three Distributed Energy Case Studies

Following the blackout of the electric grid in the 1965 it was hypothesized that large central generation would lead to continued reliability problems. More recently, following Hurricane Sandy, there have been additional criticisms of the risks that large centralized electric systems face in terms of system restoration following catastrophic storms. Together these concerns have led some in the electric industry to conclude that bigger is not always better. In 2007, with the passage of the Energy Independence and Security Act, Congress initiated policy support for a smarter more distributed grid. Since then, utilities have begun to experiment with more distributed, micro-scale projects that allow sections of the grid to “island” and serve customers locally during catastrophic power outages. This paper examines three very different approaches to explore the benefits of distributed energy technologies as well as the public policies necessary to promote their vibrant future

Hydrocephalus Complicating Intrathecal Antisense Oligonucleotide Therapy for Huntington's Disease.

Huntington’s disease (HD) is a genetic disorder caused by an expanded CAG repeat in the huntingtin gene, and although there are currently no disease-modifying treatments, there is much excitement about the prospect of treatments targeting huntingtin expression. In a phase I/2A trial of an antisense oligonucleotide (ASO) treatment (Tominersen), no serious adverse events were recorded, and there was a dose-dependent reduction in cerebrospinal fluid (CSF) huntingtin levels1. In an open-label extension (OLE) study, patients received monthly or bimonthly Tominersen, with preliminary data confirming the reduction in mutant huntingtin levels2. Here we report on a unique major adverse effect occurring during this OLE.Funding sources and conflict of interest – This trial was funded initially by Ionis and subsequently by Roche. The authors received no additional funding for this work and the authors declare that there are no conflicts of interest relevant to this work. Financial disclosures - RAB is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre - 146281 (the views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care) and MRC/WT Stem Cell Institute (203151/Z/16/Z)

Attitudes and Beliefs of African-Americans Toward Genetics, Genetic Testing, and Sickle Cell Disease Education and Awareness

Research among African-Americans indicates this population perceives sickle cell (SCD) to be a serious disease and sickle cell trait (SCT) screening an important intervention. However, studies have consistently demonstrated a lower than desired uptake of SCD education, inadequate knowledge regarding personal and family trait status, and a low perceived susceptibility of giving birth to a child with the disease. We examined general attitudes and beliefs regarding genetics and genetic testing including prenatal testing and newborn screening; we used this information as the foundation to more specifically assess attitudes and beliefs regarding SCD and perceived barriers to SCD education and awareness. Thirty-five African-American adult men and women participated in one of four focus groups. Thematic analysis identified that both prenatal testing and newborn screening are acceptable forms of genetic testing. Based largely on their personal experiences, participants possessed an understanding of the natural progression of SCD but had a limited understanding of the inheritance and probable risk of giving birth to a child with the disease. Barriers to education and greater awareness of SCD were classified as personal, familial, and societal. Community based interventions focused on sharing the stories of individuals with first-hand experiences with SCD should be considered

An Enigmatic Pointlike Feature within the HD 169142 Transitional Disk

We report the detection of a faint pointlike feature possibly related to ongoing planet-formation in the disk of the transition disk star HD 169142. The pointlike feature has a $\Delta$mag(L)$\sim$6.4, at a separation of $\sim$0.11" and PA$\sim$0$^{\circ}$. Given its lack of an H or K$_{S}$ counterpart despite its relative brightness, this candidate cannot be explained by purely photospheric emission and must be a disk feature heated by an as yet unknown source. Its extremely red colors make it highly unlikely to be a background object, but future multi-wavelength followup is necessary for confirmation and characterization of this feature.Comment: Accepted to ApJ Letters, see also Reggiani et al. 201

Discovery and Early Evolution of ASASSN-19bt, the First TDE Detected by TESS

We present the discovery and early evolution of ASASSN-19bt, a tidal disruption event (TDE) discovered by the All-Sky Automated Survey for Supernovae (ASAS-SN) at a distance of $d\simeq115$ Mpc and the first TDE to be detected by TESS. As the TDE is located in the TESS Continuous Viewing Zone, our dataset includes 30-minute cadence observations starting on 2018 July 25, and we precisely measure that the TDE begins to brighten $\sim8.3$ days before its discovery. Our dataset also includes 18 epochs of Swift UVOT and XRT observations, 2 epochs of XMM-Newton observations, 13 spectroscopic observations, and ground data from the Las Cumbres Observatory telescope network, spanning from 32 days before peak through 37 days after peak. ASASSN-19bt thus has the most detailed pre-peak dataset for any TDE. The TESS light curve indicates that the transient began to brighten on 2019 January 21.6 and that for the first 15 days its rise was consistent with a flux $\propto t^2$ power-law model. The optical/UV emission is well-fit by a blackbody SED, and ASASSN-19bt exhibits an early spike in its luminosity and temperature roughly 32 rest-frame days before peak and spanning up to 14 days that has not been seen in other TDEs, possibly because UV observations were not triggered early enough to detect it. It peaked on 2019 March 04.9 at a luminosity of $L\simeq1.3\times10^{44}$ ergs s$^{-1}$ and radiated $E\simeq3.2\times10^{50}$ ergs during the 41-day rise to peak. X-ray observations after peak indicate a softening of the hard X-ray emission prior to peak, reminiscent of the hard/soft states in X-ray binaries.Comment: 23 pages, 14 figures, 5 tables. A machine-readable table containing the host-subtracted photometry presented in this manuscript is included as an ancillary fil

S100A8 and S100A9 in experimental osteoarthritis

INTRODUCTION: The objective was to evaluate the changes in S100A8 S100A9, and their complex (S100A8/S100A9) in cartilage during the onset of osteoarthritis (OA) as opposed to inflammatory arthritis. METHODS: S100A8 and S100A9 protein localization were determined in antigen-induced inflammatory arthritis in mice, mouse femoral head cartilage explants stimulated with interleukin-1 (IL-1), and in surgically-induced OA in mice. Microarray expression profiling of all S100 proteins in cartilage was evaluated at different times after initiation of degradation in femoral head explant cultures stimulated with IL-1 and surgically-induced OA. The effect of S100A8, S100A9 or the complex on the expression of aggrecan (Acan), collagen II (Col2a1), disintegrin and metalloproteases with thrombospondin motifs (Adamts1, Adamts 4 &Adamts 5), matrix metalloproteases (Mmp1, Mmp3, Mmp13 &Mmp14) and tissue inhibitors of metalloproteinases (Timp1, Timp2 &Timp3), by primary adult ovine articular chondrocytes was determined using real time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Stimulation with IL-1 increased chondrocyte S100a8 and S100a9 mRNA and protein levels. There was increased chondrocyte mRNA expression of S100a8 and S100a9 in early but not late mouse OA. However, loss of the S100A8 staining in chondrocytes occurred as mouse OA progressed, in contrast to the positive reactivity for both S100A8 and S100A9 in chondrocytes in inflammatory arthritis in mice. Homodimeric S100A8 and S100A9, but not the heterodimeric complex, significantly upregulated chondrocyte Adamts1, Adamts4 and Adamts 5, Mmp1, Mmp3 and Mmp13 gene expression, while collagen II and aggrecan mRNAs were significantly decreased. CONCLUSIONS: Chondrocyte derived S100A8 and S100A9 may have a sustained role in cartilage degradation in inflammatory arthritis. In contrast, while these proteins may have a role in initiating early cartilage degradation in OA by upregulating MMPs and aggrecanases, their reduced expression in late stages of OA suggests they do not have an ongoing role in cartilage degradation in this non-inflammatory arthropathy

Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify

Plasticity of fimbrial genotype and serotype within populations of <em>Bordetella pertussis</em>:analysis by paired flow cytometry and genome sequencing

The fimbriae of Bordetella pertussis are required for colonization of the human respiratory tract. Two serologically distinct fimbrial subunits, Fim2 and Fim3, considered important vaccine components for many years, are included in the Sanofi Pasteur 5-component acellular pertussis vaccine, and the World Health Organization recommends the inclusion of strains expressing both fimbrial serotypes in whole-cell pertussis vaccines. Each of the fimbrial major subunit genes, fim2, fim3, and fimX, has a promoter poly(C) tract upstream of its −10 box. Such monotonic DNA elements are susceptible to changes in length via slipped-strand mispairing in vitro and in vivo, which potentially causes on/off switching of genes at every cell division. Here, we have described intra-culture variability in poly(C) tract lengths and the resulting fimbrial phenotypes in 22 recent UK B. pertussis isolates. Owing to the highly plastic nature of fimbrial promoters, we used the same cultures for both genome sequencing and flow cytometry. Individual cultures of B. pertussis contained multiple fimbrial serotypes and multiple different fimbrial promoter poly(C) tract lengths, which supports earlier serological evidence that B. pertussis expresses both serotypes during infection.</jats:p