Identification of Novel Fibrosis Modifiers by In Vivo siRNA Silencing.

Fibrotic diseases contribute to 45% of deaths in the industrialized world, and therefore a better understanding of the pathophysiological mechanisms underlying tissue fibrosis is sorely needed. We aimed to identify novel modifiers of tissue fibrosis expressed by myofibroblasts and their progenitors in their disease microenvironment through RNA silencing in vivo. We leveraged novel biology, targeting genes upregulated during liver and kidney fibrosis in this cell lineage, and employed small interfering RNA (siRNA)-formulated lipid nanoparticles technology to silence these genes in carbon-tetrachloride-induced liver fibrosis in mice. We identified five genes, Egr2, Atp1a2, Fkbp10, Fstl1, and Has2, which modified fibrogenesis based on their silencing, resulting in reduced Col1a1 mRNA levels and collagen accumulation in the liver. These genes fell into different groups based on the effects of their silencing on a transcriptional mini-array and histological outcomes. Silencing of Egr2 had the broadest effects in vivo and also reduced fibrogenic gene expression in a human fibroblast cell line. Prior to our study, Egr2, Atp1a2, and Fkbp10 had not been functionally validated in fibrosis in vivo. Thus, our results provide a major advance over the existing knowledge of fibrogenic pathways. Our study is the first example of a targeted siRNA assay to identify novel fibrosis modifiers in vivo

Color-Octet-Electroweak-Doublet Scalars and the CDF Dijet Anomaly

We study the phenomenology of color-octet scalars in the (8, 2)1/2 representation in the context of the 3.2\sigma excess, in the dijet invariant mass spectrum of the W+jj final state, recently observed by the CDF collaboration. We consider the region of parameter space with a sizable mass splitting between the charged and neutral color-octet scalars and consistent with electroweak precision data. We implement the principle of Minimal Flavor Violation (MFV) in order to suppress FCNC currents and reduce the number of free parameters. The excess in the W+jj channel corresponds to the charged current decay of the heavier neutral octet scalar into its lighter charged partner which decays into the two jets. In the MFV scenario, the production of the neutral color-octet is dominated by gluon fusion due to the Yukawa suppression of production via initial state quarks. As a result, no visible excess is expected in the \gamma+jj channel due to Yukawa and CKM suppression. Contributions to the Z+jj final state are suppressed for a mass spectrum where the decay of the heavier color-octet to this final state is mediated by an off-shell neutral color-octet partner. MFV allows one to control fraction of bottom quarks in the final state jets by a single ratio of two free parameters.Comment: 14 pages, 6 figures, typos corrected, references added, text and figures modified in some places for better clarity, version to appear in Physics Letters

Pennsylvania Folklife Vol. 41, No. 3

• Love, David • Studebaker and Stutz: The Evolution of Dunkard Entrepreneurs • Latches and Locks • H. L. Mencken and A Girl from Red Lion, PA • Mac E. Barrick (1933-1991): An Appreciation • Aldes un Neies (Old and New)https://digitalcommons.ursinus.edu/pafolklifemag/1134/thumbnail.jp

The psychology of containment: mis/representing emotional and behavioural difficulties in Australian schools

The number of students in special schools has increased at a rapid rate in some Australian states, due in part to increased enrolment under the categories of emotional disturbance (ED) and behaviour disorder (BD). Nonetheless, diagnostic distinctions between ED and BD are unclear. Moreover, despite international findings that students with particular backgrounds are over-represented in special schools, little is known about the backgrounds of students entering such settings in Australia. This study examined the government school enrolment data from New South Wales, the most populous of the Australian states. Linear and quadratic trends were used to describe the numbers and ages of students enrolled in special schools in the ED and BD categories. Changes between 1997 and 2007 were observed. Results showed an over-representation of boys that increased across the decade and a different pattern across age for boys and girls. Consistent with international findings, these results indicate that trends in special school placements are unrelated to disability prevalence in the population. Rather, it is suggested that schools act to preserve time and resources for others by removing their more challenging students: most typically, boys

Staging Loss: Performance as Commemoration

This book locates and critically theorises an emerging field of twenty-first century theatre practice concerned, either thematically, methodologically, or formally, with acts of commemoration and the commemorative. With notions of memorial, celebration, temporality and remembrance at its heart, and as a timely topic for debate, this book asks how theatre and performance intersects with commemorative acts or rituals in contemporary theatre and performance practice. It considers the (re)performance of history, commemoration as a form of, or performance of, ritual, performance as memorial, performance as eulogy and eulogy as performance. It asks where personal acts of remembrance merge with public or political acts of remembrance, where the boundary between the commemorative and the performative might lie, and how it might be blurred, broken or questioned. It explores how we might remake the past in the present, to consider not just how performance commemorates but how commemoration performs

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Detection of a novel, integrative aging process suggests complex physiological integration

Abstract: Many studies of aging examine biomarkers one at a time, but complex systems theory and network theory suggest that interpretations of individual markers may be context-dependent. Here, we attempted to detect underlying processes governing the levels ofmany biomarkers simultaneously by applying principal components analysis to 43 common clinical biomarkers measured longitudinally in 3694 humans from three longitudinal cohort studies on two continents (Women’s Health and Aging I & II, InCHIANTI, and the Baltimore Longitudinal Study on Aging). The first axis was associated with anemia, inflammation, and low levels of calcium and albumin. The axis structure was precisely reproduced in all three populations and in all demographic sub-populations (by sex, race, etc.); we call the process represented by the axis “integrated albunemia.” Integrated albunemia increases and accelerates with age in all populations, and predicts mortality and frailty – but not chronic disease – even after controlling for age. This suggests a role in the aging process, though causality is not yet clear. Integrated albunemia behaves more stably across populations than its component biomarkers, and thus appears to represent a higher-order physiological process emerging from the structure of underlying regulatory networks. If this is correct, detection of this process has substantial implications for physiological organizationmore generally

Contemporary Art Exhibitionists

June 27, 1995. Washington. D. C: The Christian Action Network stages a "degenerate art" exhibition in the Rayburn Building, sponsored by Representative Robert Dornan, to drive the final nail in the coffin of the National Endowment for the Arts. They hand out black-bordered death certificates, which they urge guests to sign and deliver to their congressmen before the 103rd Congress departs for summer recess. The death certificate reads: Decendent's Name: ΝΕΑ. Sex: Anything unnatural. Father's ..

PRO-DAIRY FINANCIAL DATA COLLECTION WORKBOOK

A.E. Ext. 91-27The PRO-DAIRY Financial Data Collection workbook is designed to guide the farm manager through the data collection process necessary for completion of a Cornell dairy farm business summary. It was developed for use specifically with the PRO-DAIRY workshop "Managing With Finance," but can be used outside the course as well