Shocks and a Giant Planet in the Disk Orbiting BP Piscium?

Spitzer IRS spectroscopy supports the interpretation that BP Piscium, a gas and dust enshrouded star residing at high Galactic latitude, is a first-ascent giant rather than a classical T Tauri star. Our analysis suggests that BP Piscium's spectral energy distribution can be modeled as a disk with a gap that is opened by a giant planet. Modeling the rich mid-infrared emission line spectrum indicates that the solid-state emitting grains orbiting BP Piscium are primarily composed of ~75 K crystalline, magnesium-rich olivine; ~75 K crystalline, magnesium-rich pyroxene; ~200 K amorphous, magnesium-rich pyroxene; and ~200 K annealed silica ('cristobalite'). These dust grains are all sub-micron sized. The giant planet and gap model also naturally explains the location and mineralogy of the small dust grains in the disk. Disk shocks that result from disk-planet interaction generate the highly crystalline dust which is subsequently blown out of the disk mid-plane and into the disk atmosphere.Comment: 25 pages, 4 figures, 1 table. Accepted to Ap

Combined SIRT3 and SIRT5 deletion is associated with inner retinal dysfunction in a mouse model of type 1 diabetes

Abstract Diabetic retinopathy (DR) is a major cause of blindness in working adults in the industrialized world. In addition to vision loss caused by macular edema and pathological angiogenesis, DR patients often exhibit neuronal dysfunction on electrophysiological testing, suggesting that there may be an independent neuronal phase of disease that precedes vascular disease. Given the tremendous metabolic requirements of the retina and photoreceptors in particular, we hypothesized that derangements in metabolic regulation may accelerate retinal dysfunction in diabetes. As such, we induced hyperglycemia with streptozotocin in mice with monoallelic Nampt deletion from rod photoreceptors, mice lacking SIRT3, and mice lacking SIRT5 and tested multiple components of retinal function with electroretinography. None of these mice exhibited accelerated retinal dysfunction after induction of hyperglycemia, consistent with normal-appearing retinal morphology in hyperglycemic Sirt3 −/− or Sirt5 −/− mice. However, mice lacking both SIRT3 and SIRT5 (Sirt3 −/− Sirt5 −/− mice) exhibited significant evidence of inner retinal dysfunction after induction of hyperglycemia compared to hyperglycemic littermate controls, although this dysfunction was not accompanied by gross morphological changes in the retina. These results suggest that SIRT3 and SIRT5 may be involved in regulating neuronal dysfunction in DR and provide a foundation for future studies investigating sirtuin-based therapies

Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test

Journal ArticleObject. Transsphenoidal adenomectomy with resection of a defined pituitary adenoma has been the treatment of choice for CD for the last 30 years. Surgical resection, however, may not always result in long-term remission of CD. This is particularly important in light of the high risk of morbidity and mortality in patients in the unsuccessfully treated cushingoid state. As such, it is interesting to identify prognostic factors that may predict the likelihood of long-term remission. Methods. The authors review their series of 174 patients who have undergone transsphenoidal procedures for CD over a period of 20 years with minimum follow-up periods of 5 years. Selection of these patients was based on clinical, imaging, and laboratory criteria that included serum cortisol levels, loss of diurnal variation in serum cortisol levels, urinary free cortisol concentration, and results of a dexamethasone suppression test, petrosal sinus sampling, and corticotroph-releasing hormone stimulation tests as indicated. All patients who met the biochemical criteria underwent transsphenoidal microsurgery. The authors found an overall rate of remission of 74% at 5 years postoperatively. Patients in whom morning serum cortisol concentrations were lower than 3 μg/dl (83 nmol/L) on postoperative day 3, following an overnight dexamethasone suppression test, had a 93% chance of remission at the 5-year follow-up examination. Patients with cortisol concentrations higher than this level uniformly failed to achieve long-term remission. Conclusions. Transsphenoidal microsurgery is an effective means of control for patients with adrenocorticotrophic hormone-producing microadenomas. Clinical outcome correlated well with the size of the tumor, as measured on preoperative imaging studies, and with postoperative morning cortisol levels following an overnight dexamethasone suppression test. Postoperative cortisol levels can be used as a useful prognostic indicator of the likelihood of future recurrence following transsphenoidal adenomectomy in CD

Progestins Related to Progesterone and Testosterone Elicit Divergent Human Endometrial Transcriptomes and Biofunctions.

Progestins are widely used for the treatment of gynecologic disorders and alone, or combined with an estrogen, are used as contraceptives. While their potencies, efficacies and side effects vary due to differences in structures, doses and routes of administration, little is known about their effects on the endometrial transcriptome in the presence or absence of estrogen. Herein, we assessed the transcriptome and pathways induced by progesterone (P4) and the three most commonly used synthetic progestins, medroxyprogesterone acetate (MPA), levonorgestrel (LNG), and norethindrone acetate (NETA), on human endometrial stromal fibroblasts (eSF), key players in endometrial physiology and reproductive success. While there were similar transcriptional responses, each progestin induced unique genes and biofunctions, consistent with their structural similarities to progesterone (P4 and MPA) or testosterone (LNG and NETA), involving cellular proliferation, migration and invasion. Addition of estradiol (E2) to each progestin influenced the number of differentially expressed genes and biofunctions in P4 and MPA, while LNG and NETA signatures were more independent of E2. Together, these data suggest different mechanisms of action for different progestins, with progestin-specific altered signatures when combined with E2. Further investigation is warranted for a personalized approach in different gynecologic disorders, for contraception, and minimizing side effects associated with their use

Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.

Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations that drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma. Treatment options for all malignant mesotheliomas are currently limited, with no known targeted therapies available. To better understand the molecular pathogenesis of malignant peritoneal mesothelioma, we sequenced 510 cancer-related genes in 13 patients with malignant mesothelioma arising in the peritoneal cavity. The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional two cases demonstrating monoallelic loss of BAP1. All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas two tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum (8 multilocular peritoneal inclusion cyst, 6 well-differentiated papillary mesothelioma of the peritoneum, 16 adenomatoid tumor, and 12 low-grade serous carcinoma of the ovary) demonstrated intact BAP1 nuclear staining. Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13). While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20-30% of pleural tumors. Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies

Waste CO₂ to CO for Energy Storage

In this report, we present a process design for the storage of electricity using solid oxide fuel cell (SOFC) technology to convert electrical energy to chemical fuel via the reduction of carbon dioxide. The goal of this project was to design a system that could alleviate the issues around the intermittent nature of renewable energy production, which must phase out the use of fossil fuels in the future. The overall process was developed for two storage strategies, and the economics feasibility of the design is considered and reported. The key aspect of this process is its reversible nature. Both the production and consumption of the chemical fuel are achieved in the same plant, both with the SOFC technology. Two cases are presented. In both, carbon monoxide is produced via electrolysis during high-production hours for solar and wind power. Carbon dioxide is renewably sourced from fermentation plants. In the first case, the carbon monoxide is pressurized for storage at 2,000 psig. In the second case, the carbon monoxide is minimally compressed to 5 psig and stored at near atmospheric conditions. It was found that for the high-pressure storage case, the efficiency of the process was 53.5%, and in the low-pressure storage case, the efficiency was 54.6%. Two pricing strategies were considered. The first assigned an opportunity cost of electricity storage to the off-peak electricity price. In this scenario, the high- and low-pressure cases had negative ROI’s of -32.5% and -29.4%, respectively. In the second pricing strategy, we consider the eventuality of overproduction of solar and wind energy, when renewable energy sources comprise a majority of the supply. In this scenario, the opportunity cost of the excess electricity production would be zero, and the ROI of the high- and low-pressure cases are then positive at 29.9% and 31.8%, respectively. Though the latter is not reflective of the current economic reality, in the future it may become more relevant, and a design such as the one presented here should be considered as a potentially profitable solution