Alignment and Composition of Laminin-Polycaprolactone Nanofiber Blends Enhance Peripheral Nerve Regeneration

Peripheral nerve transection occurs commonly in traumatic injury, causing deficits distal to the injury site. Conduits for repair currently on the market are hollow tubes; however, they often fail due to slow regeneration over long gaps. To facilitate increased regeneration speed and functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in regeneration. To that end, laminin and lamininpolycaprolactone (PCL) blend nanofibers were fabricated to mimic peripheral nerve basement membrane. In vitro assays established 10% (wt) laminin content is sufficient to retain neurite-promoting effects of laminin. In addition, modified collector plate design to introduce an insulating gap enabled the fabrication of aligned nanofibers. The effects of laminin content and fiber orientation were evaluated in rat tibial nerve defect model. The lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment to assess changes in motor and sensory recovery. Retrograde nerve conduction speed at 6 weeks was significantly faster in animals receiving aligned nanofiber conduits than in those receiving random nanofiber conduits. Animals receiving nanofiber-filled conduits showed some conduction in both anterograde and retrograde directions, whereas in animals receiving hollow conduits, no impulse conduction was detected. Aligned PCL nanofibers significantly improved motor function; aligned laminin blend nanofibers yielded the best sensory function recovery. In both cases, nanofiber-filled conduits resulted in better functional recovery than hollow conduits. These studies provide a firm foundation for the use of naturalsynthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits

Patterns of Natural and Human-Caused Mortality Factors of a Rare Forest Carnivore, the Fisher (Pekania pennanti) in California.

Wildlife populations of conservation concern are limited in distribution, population size and persistence by various factors, including mortality. The fisher (Pekania pennanti), a North American mid-sized carnivore whose range in the western Pacific United States has retracted considerably in the past century, was proposed for threatened status protection in late 2014 under the United States Endangered Species Act by the United States Fish and Wildlife Service in its West Coast Distinct Population Segment. We investigated mortality in 167 fishers from two genetically and geographically distinct sub-populations in California within this West Coast Distinct Population Segment using a combination of gross necropsy, histology, toxicology and molecular methods. Overall, predation (70%), natural disease (16%), toxicant poisoning (10%) and, less commonly, vehicular strike (2%) and other anthropogenic causes (2%) were causes of mortality observed. We documented both an increase in mortality to (57% increase) and exposure (6%) from pesticides in fishers in just the past three years, highlighting further that toxicants from marijuana cultivation still pose a threat. Additionally, exposure to multiple rodenticides significantly increased the likelihood of mortality from rodenticide poisoning. Poisoning was significantly more common in male than female fishers and was 7 times more likely than disease to kill males. Based on necropsy findings, suspected causes of mortality based on field evidence alone tended to underestimate the frequency of disease-related mortalities. This study is the first comprehensive investigation of mortality causes of fishers and provides essential information to assist in the conservation of this species

The SXS Collaboration catalog of binary black hole simulations

Accurate models of gravitational waves from merging black holes are necessary for detectors to observe as many events as possible while extracting the maximum science. Near the time of merger, the gravitational waves from merging black holes can be computed only using numerical relativity. In this paper, we present a major update of the Simulating eXtreme Spacetimes (SXS) Collaboration catalog of numerical simulations for merging black holes. The catalog contains 2018 distinct configurations (a factor of 11 increase compared to the 2013 SXS catalog), including 1426 spin-precessing configurations, with mass ratios between 1 and 10, and spin magnitudes up to 0.998. The median length of a waveform in the catalog is 39 cycles of the dominant $\ell=m=2$ gravitational-wave mode, with the shortest waveform containing 7.0 cycles and the longest 351.3 cycles. We discuss improvements such as correcting for moving centers of mass and extended coverage of the parameter space. We also present a thorough analysis of numerical errors, finding typical truncation errors corresponding to a waveform mismatch of $\sim 10^{-4}$. The simulations provide remnant masses and spins with uncertainties of 0.03% and 0.1% ($90^{\text{th}}$ percentile), about an order of magnitude better than analytical models for remnant properties. The full catalog is publicly available at https://www.black-holes.org/waveforms .Comment: 33+18 pages, 13 figures, 4 tables, 2,018 binaries. Catalog metadata in ancillary JSON file. v2: Matches version accepted by CQG. Catalog available at https://www.black-holes.org/waveform

On the evolutionary history of a simulated disc galaxy as seen by phylogenetic trees

© The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Phylogenetic methods have long been used in biology, and more recently have been extended to other fields - for example, linguistics and technology - to study evolutionary histories. Galaxies also have an evolutionary history, and fall within this broad phylogenetic framework. Under the hypothesis that chemical abundances can be used as a proxy for interstellar medium's DNA, phylogenetic methods allow us to reconstruct hierarchical similarities and differences among stars - essentially a tree of evolutionary relationships and thus history. In this work, we apply phylogenetic methods to a simulated disc galaxy obtained with a chemo-dynamical code to test the approach. We found that at least 100 stellar particles are required to reliably portray the evolutionary history of a selected stellar population in this simulation, and that the overall evolutionary history is reliably preserved when the typical uncertainties in the chemical abundances are smaller than 0.08 dex. The results show that the shape of the trees are strongly affected by the age-metallicity relation, as well as the star formation history of the galaxy. We found that regions with low star formation rates produce shorter trees than regions with high star formation rates. Our analysis demonstrates that phylogenetic methods can shed light on the process of galaxy evolution.Peer reviewe

On the evolutionary history of a simulated disc galaxy as seen by phylogenetic trees

Phylogenetic methods have long been used in biology, and more recently have been extended to other fields - for example, linguistics and technology - to study evolutionary histories. Galaxies also have an evolutionary history, and fall within this broad phylogenetic framework. Under the hypothesis that chemical abundances can be used as a proxy for interstellar medium's DNA, phylogenetic methods allow us to reconstruct hierarchical similarities and differences among stars - essentially a tree of evolutionary relationships and thus history. In this work, we apply phylogenetic methods to a simulated disc galaxy obtained with a chemo-dynamical code to test the approach. We found that at least 100 stellar particles are required to reliably portray the evolutionary history of a selected stellar population in this simulation, and that the overall evolutionary history is reliably preserved when the typical uncertainties in the chemical abundances are smaller than 0.08 dex. The results show that the shape of the trees are strongly affected by the age-metallicity relation, as well as the star formation history of the galaxy. We found that regions with low star formation rates produce shorter trees than regions with high star formation rates. Our analysis demonstrates that phylogenetic methods can shed light on the process of galaxy evolution.Comment: Accepted for publication in ApJ, October 12th 202

On the Evolutionary History of a Simulated Disk Galaxy as Seen by Phylogenetic Trees

© 2024 The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Phylogenetic methods have long been used in biology and more recently have been extended to other fields—for example, linguistics and technology—to study evolutionary histories. Galaxies also have an evolutionary history and fall within this broad phylogenetic framework. Under the hypothesis that chemical abundances can be used as a proxy for the interstellar medium’s DNA, phylogenetic methods allow us to reconstruct hierarchical similarities and differences among stars—essentially, a tree of evolutionary relationships and thus history. In this work, we apply phylogenetic methods to a simulated disk galaxy obtained with a chemodynamical code to test the approach. We found that at least 100 stellar particles are required to reliably portray the evolutionary history of a selected stellar population in this simulation, and that the overall evolutionary history is reliably preserved when the typical uncertainties in the chemical abundances are smaller than 0.08 dex. The results show that the shapes of the trees are strongly affected by the age–metallicity relation, as well as the star formation history of the galaxy. We found that regions with low star formation rates produce shorter trees than regions with high star formation rates. Our analysis demonstrates that phylogenetic methods can shed light on the process of galaxy evolution.Peer reviewe

Fully covered self-expanding metal stents placed temporarily in the bile duct: safety profile and histologic classification in a porcine model

<p>Abstract</p> <p>Background</p> <p>Fully covered Self-Expanding metal stents (FCSEMS) have been shown efficacious in palliating malignant biliary obstructions. There is little data analyzing mucosal response to their temporary placement in the bile duct.</p> <p>Methods</p> <p>Ten mini pigs underwent endoscopic placement of a FCSEMS (Wallflex, Boston Scientific). FCSEMS were kept in place for three months. At the end of the 3 months, FCSEMS were removed endoscopically. Five pigs were euthanized and their bile ducts harvested. The other five were kept alive for another month post removal. A single pathologist, created a scoring system (to determine degree of inflammation, fibrosis, and epithelial injury), examined all specimens in a blinded fashion.</p> <p>Results</p> <p>Four FCSEMS spontaneously migrated in the duodenum. On post mortem examination, mild mucosal thickness was noted in three bile duct specimens while superficial inflammation of the bile duct was noted in five animals. Histologic examination of the bile duct revealed focal acute inflammation in both groups. For the 5 animals euthanized immediately after stent removal, there was a tendency to have superficial mucosal erosion and fibrosis. In contrast, increased chronic inflammation was more commonly seen in the animals 1 month post stent removal, with all animals in this group showing moderate degrees of mononuclear inflammatory cell mucosal infiltrates. No severe inflammatory or fibrotic duct injury was observed in any of the study animals, with degree of injury graded as mild to moderate.</p> <p>Conclusion</p> <p>FCSEMS appear to induce minimal tissue overgrowth or fibrosis post placement. Ease of removability and no significant histologic injury are advantages noted with FCSEMS., however, further studies are needed to evaluate treating benign biliary strictures with FCSEMS in humans.</p

Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34+ Cells for Correction of Fabry Disease

Fabry disease is a rare lysosomal storage disorder (LSD). We designed multiple recombinant lentivirus vectors (LVs) and tested their ability to engineer expression of human α-galactosidase A (α-gal A) in transduced Fabry patient CD34+ hematopoietic cells. We further investigated the safety and efficacy of a clinically directed vector, LV/AGA, in both ex vivo cell culture studies and animal models. Fabry mice transplanted with LV/AGA-transduced hematopoietic cells demonstrated α-gal A activity increases and lipid reductions in multiple tissues at 6 months after transplantation. Next we found that LV/AGA-transduced Fabry patient CD34+ hematopoietic cells produced even higher levels of α-gal A activity than normal CD34+ hematopoietic cells. We successfully transduced Fabry patient CD34+ hematopoietic cells with “near-clinical grade” LV/AGA in small-scale cultures and then validated a clinically directed scale-up transduction process in a GMP-compliant cell processing facility. LV-transduced Fabry patient CD34+ hematopoietic cells were subsequently infused into NOD/SCID/Fabry (NSF) mice; α-gal A activity corrections and lipid reductions were observed in several tissues 12 weeks after the xenotransplantation. Additional toxicology studies employing NSF mice xenotransplanted with the therapeutic cell product demonstrated minimal untoward effects. These data supported our successful clinical trial application (CTA) to Health Canada and opening of a “first-in-the-world” gene therapy trial for Fabry disease