Shaping a Sustainable Old Worthington

Course Code: ENR/AEDE 4567This project is a collaboration between the Old Worthington Partnership, Old Worthington merchants, American Electric Power (AEP), and the Sustainable Worthington Capstone Group from The Ohio State University’s Environment, Economy, Development, and Sustainability (EEDS) major. Old Worthington is located in the historic downtown of Worthington, Ohio. The Old Worthington Partnership is a volunteer group that aims to enhance the Old Worthington experience by pursuing collaboration, engagement, and sustainability. The Old Worthington Partnership reached out to this capstone group for assistance in implementing AEP’s Small Business Express Program among their eligible merchants.Academic Major: Environment, Economy, Development, and Sustainabilit

Quantitative antisense screening and optimization for exon 51 skipping in Duchenne muscular dystrophy

International audienceDuchenne muscular dystrophy (DMD), the most common lethal genetic disorder, is caused by mutations in the dystrophin (DMD) gene. Exon skipping is a therapeutic approach that uses antisense oligonucleotides (AOs) to modulate splicing and restore the reading frame, leading to truncated, yet functional protein expression. In 2016, the US Food and Drug Administration (FDA) conditionally approved the first phosphorodiamidate morpholino oligomer (morpholino)-based AO drug, eteplirsen, developed for DMD exon 51 skipping. Eteplirsen remains controversial with insufficient evidence of its therapeutic effect in patients. We recently developed an in silico tool to design antisense morpholino sequences for exon skipping. Here, we designed morpholino AOs targeting DMD exon 51 using the in silico tool and quantitatively evaluated the effects in immortalized DMD muscle cells in vitro. To our surprise, most of the newly designed morpholinos induced exon 51 skipping more efficiently compared with the eteplirsen sequence. The efficacy of exon 51 skipping and rescue of dystrophin protein expression were increased by up to more than 12-fold and 7-fold, respectively, compared with the eteplirsen sequence. Significant in vivo efficacy of the most effective morpholino, determined in vitro, was confirmed in mice carrying the human DMD gene. These findings underscore the importance of AO sequence optimization for exon skipping

A report on late Quaternary vertebrate fossil assemblages from the eastern San Francisco Bay region, California

Here we report on vertebrate fossil assemblages from two late Quaternary localities in the eastern San Francisco Bay region, Pacheco 1 and Pacheco 2. At least six species of extinct mammalian megaherbivores are known from Pacheco 1. The probable occurrence of Megalonyx jeffersonii suggests a late Pleistocene age for the assemblage. Pacheco 2 has yielded a minimum of 20 species of mammals, and provides the first unambiguous Quaternary fossil record of Urocyon, Procyon, Antrozous, Eptesicus, Lasiurus, Sorex ornatus, Tamias, and Microtus longicaudus from the San Francisco Bay region. While a radiocarbon date of 405 ± 45 RCYBP has been obtained for a single bone sample from Pacheco 2, the possibility that much of the assemblage is considerably older than this date is suggested by (1) the substantial loss of collagen in all other samples for which radiocarbon dating was unsuccessfully attempted and (2) the occurrence of Microtus longicaudus approximately 160 km to the west of, and 600 m lower in elevation than, its present range limit. The taphonomic data and limited stratigraphic information for the two localities suggest deposition of bones within a riparian system. Multiple lines of evidence including the taxonomic composition and the relative abundance of skeletal elements point to the original accumulation of most, if not all, of the small vertebrate remains at Pacheco 2 by owls. Based on taxonomic composition, Pacheco 1 appears to have been located in a mosaic of grassland and woodland habitats, and Pacheco 2 in moist woodland with dense underbrush and a body of freshwater

A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating Properties of Cenderitide in Subjects With Stable Chronic Heart Failure

Cenderitide is a novel designer natriuretic peptide (NP) composed of C-type natriuretic peptide (CNP) fused to the C-terminus of Dendroaspis natriuretic peptide (DNP). Cenderitide was engineered to coactivate the two NP receptors, particulate guanylyl cyclase (pGC)-A and -B. The rationale for its design was to achieve the renal-enhancing and antifibrotic properties of dual receptor activation, but without clinically significant hypotension. Here we report the first clinical trial on the safety, tolerability, and cyclic guanosine monophosphate (cGMP) activating properties of Cenderitide in subjects with stable heart failure (HF). Four-hour infusion of Cenderitide was safe, well-tolerated, and significantly increased plasma cGMP levels and urinary cGMP excretion without adverse effects with no change in blood pressure. Thus, Cenderitide has a favorable safety profile and expected pharmacological effects in stable human HF. Our results support further investigations of Cenderitide in HF as a potential future cGMP-enhancing therapeutic strategy

ILC Reference Design Report Volume 1 - Executive Summary

The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization.The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization