Rapid Induction of the Unfolded Protein Response and Apoptosis by Estrogen Mimic TTC-352 for the Tre
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Changes in gene expression represent an important source of phenotypic innovation. Yet how such changes emerge and impact the evolution of traits remains elusive. Here, we explore the molecular mechanisms associated with the development of masculinizing ovotestes in female moles. By performing integrative analyses of epigenetic and transcriptional data in mole and mouse, we identified the co-option of SALL1 expression in mole ovotestes formation. Chromosome conformation capture analyses highlight a striking conservation of the 3D organization at the SALL1 locus, but an evolutionary divergence of enhancer activity. Interspecies reporter assays support the capability of mole-specific enhancers to activate transcription in urogenital tissues. Through overexpression experiments in transgenic mice, we further demonstrate the capability of SALL1 to induce kidney-related gene programs, which are a signature of mole ovotestes. Our results highlight the co-option of gene expression, through changes in enhancer activity, as a plausible mechanism for the evolution of traits.
Improvements in survival rates with gonad-sparing protocols for childhood and adolescence cancer have increased the optimism of survivors to become parents after treatment. Findings in rodents indicate that chromosomal aberrations can be induced in male germ cells by genotoxic exposures and transmitted to offspring and future generations with effects on development, fertility and health. Thus, there is a need for effective technologies to identify human sperm carrying chromosomal aberrations to assess the germ-line risks, especially for cancer survivors who have received genotoxic therapies. The time-dependent changes in the burden of sperm carrying structural chromosomal aberrations were assessed for the first time in a cancer setting, using the AM8 sperm FISH protocol which simultaneously detects abnormalities in chromosomal structure and number in sperm. Nine Hodgkin lymphoma (HL) patients provided 20 semen samples before, during, and after NOVP therapy (Novantrone, Oncovin, Velban and Prednisone) and radiation therapy that produced scattered gonadal doses from <0.05 to 0.6 Gy. Late meiosis was found to be the most sensitive to NOVP treatment for the production of sperm with chromosomal abnormalities, both in structure and number. Earlier stages of spermatogenesis were less sensitive and there was no evidence that therapy-exposed stem cells resulted in increased frequencies of sperm with abnormalities in chromosomal structure or number. This indicates that NOVP therapy may increase the risks for paternal transmission of chromosomal structural aberrations for sperm produced 32 to 45 days after a treatment with these drugs and implies that there are no excess risks for pregnancies conceived more than 6 months after this therapy. This clinical evaluation of the AM8 sperm FISH protocol indicates that it is a promising tool for assessing an individual’s burden of sperm carrying chromosomal structural aberrations as well as aneuploidies after cancer therapy, with broad applications in other clinical and environmental situations that may pose aneugenic or clastogenic risks to human spermatogenesis.
It has been proposed to use solid-state pulsed-power modules to power the new Scorpius accelerator. Since this highcurrent accelerator would have 360 gaps (more than five times the number of cells as present radiography LIAs), it is natural to be concerned about the beam-breakup (BBU) instability. Earlier calculations of this effect used a half-scale model of the accelerator to avoid the limitation to 200 gaps in the code. We have now updated the code to accommodate the extraordinary number of gaps in this proposed LIA. The results of these early simulations are presented here. They indicate that BBU can only be suppressed to the same level as in designs powered by conventional pulsed power, if the calculated cell impedance can truly be achieved in practice. The magnetic focusing field required for this is of the same order as the field required for a conventionally powered LIA only if the transverse impedance can indeed be constrained to the values obtained in some simulations of the cell.
This is for the IEEE ICOPS 2021 Virtual Conference, scheduled for September 12-16, 2021. Michael Weller will be giving a virtual talk. Website found here: http://ece-events.unm.edu/icops2021/index.html
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General Motors Research & Development (GM R&D) and Pacific Northwest National Laboratory (PNNL) will develop an electric rotor manufacturing technology with the potential of making electric motors lighters and more efficient. This will be achieved by developing a solid phase joining method to effectively join the Copper shorting bars to Aluminum end cap.
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As previously described, we have built a non-interceptive beam radius monitor that employs a diamagnetic loop. This device has been installed and tested with beam on the DARHT-I downstream transport. Installation details and sample test results are given in this report.
Conference: 14th International Particle Accelerator Conference Date: May 7th-12th, 2023 Location: Lido di Venezia, Italy Presenter: Evan R Scott
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