It is widely assumed that mineral inclusions and their host diamonds are 'syngenetic' in origin, which means that they formed simultaneously and from the same chemical processes. Mineral inclusions ...that, instead, were formed earlier with respect to diamonds are termed protogenetic. However, minerals can have the same age as the diamonds in that they become enclosed in and isolated from any further isotopic exchange. But this is termed 'synchronous' not 'syngenetic'. Here we demonstrate conclusively the protogenesis of inclusions in diamonds, based upon data from an exceptional fragment of a diamond-bearing peridotite, its clinopyroxene and a gem-quality diamond. Clinopyroxenes in the xenolith had the same chemistry and crystallographic orientation as those for inclusions in the diamond. With our results with garnets, olivines and sulfides, we can state that a major portion of the mineral inclusions in non-coated, monocrystalline-lithospheric diamonds are protogenetic. Our discovery here presented has implications for all genetic aspects of diamond growth, including their ages.
This paper describes the development and characterization of a microphysiology platform for drug safety and efficacy in liver models of disease that includes a human, 3D, microfluidic, four-cell, ...sequentially layered, self-assembly liver model (SQL-SAL); fluorescent protein biosensors for mechanistic readouts; as well as a microphysiology system database (MPS-Db) to manage, analyze, and model data. The goal of our approach is to create the simplest design in terms of cells, matrix materials, and microfluidic device parameters that will support a physiologically relevant liver model that is robust and reproducible for at least 28 days for stand-alone liver studies and microfluidic integration with other organs-on-chips. The current SQL-SAL uses primary human hepatocytes along with human endothelial (EA.hy926), immune (U937) and stellate (LX-2) cells in physiological ratios and is viable for at least 28 days under continuous flow. Approximately, 20% of primary hepatocytes and/or stellate cells contain fluorescent protein biosensors (called sentinel cells) to measure apoptosis, reactive oxygen species (ROS) and/or cell location by high content analysis (HCA). In addition, drugs, drug metabolites, albumin, urea and lactate dehydrogenase (LDH) are monitored in the efflux media. Exposure to 180 μM troglitazone or 210 μM nimesulide produced acute toxicity within 2–4 days, whereas 28 μM troglitazone produced a gradual and much delayed toxic response over 21 days, concordant with known mechanisms of toxicity, while 600 µM caffeine had no effect. Immune-mediated toxicity was demonstrated with trovafloxacin with lipopolysaccharide (LPS), but not levofloxacin with LPS. The SQL-SAL exhibited early fibrotic activation in response to 30 nM methotrexate, indicated by increased stellate cell migration, expression of alpha-smooth muscle actin and collagen, type 1, alpha 2. Data collected from the in vitro model can be integrated into a database with access to related chemical, bioactivity, preclinical and clinical information uploaded from external databases for constructing predictive models.
Evaluations of lunar regolith simulants Taylor, Lawrence A.; Pieters, Carle M.; Britt, Daniel
Planetary and space science,
July 2016, 2016-07-00, 20160701, Volume:
126
Journal Article
Peer reviewed
Apollo lunar regolith samples are not available in quantity for engineering studies with In-Situ Resource Utilization (ISRU). Therefore, with expectation of a return to the Moon, dozens of regolith ...(soil) simulants have been developed, to some extent a result of inefficient distribution of NASA-sanctioned simulants. In this paper, we review many of these simulants, with evaluations of their short-comings. In 2010, the NAC–PSS committee instructed the Lunar Exploration Advisory Group (LEAG) and CAPTEM (the NASA committee recommending on the appropriations of Apollo samples) to report on the status of lunar regolith simulants. This report is reviewed here-in, along with a list of the plethora of lunar regolith simulants and references. In addition, and importantly, a special, unique Apollo 17 soil sample (70050) discussed, which has many of the properties sought for ISRU studies, should be available in reasonable amounts for ISRU studies.
•Importance of choosing appropriate simulant for their specific end uses. One type of lunar soil simulant does not fit all possible uses.•Each simulant has its limitations (i.e., made for a particular purpose).•The lack of appreciation of these principles has led to many miss-uses.•Comparison of available lunar simulants and their properties.•Apollo 17 soil 70050 would appear good for many engineering studies.
Full text
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
6.
The Procedural Yips Haber, Lawrence A.; Taylor, Evan M.
Journal of general internal medicine : JGIM,
07/2024, Volume:
39, Issue:
9
Journal Article
Peer reviewed
Full text
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Compare effectiveness of maternal vitamin D3 supplementation with 6400 IU per day alone to maternal and infant supplementation with 400 IU per day.
Exclusively lactating women living in Charleston, ...SC, or Rochester, NY, at 4 to 6 weeks postpartum were randomized to either 400, 2400, or 6400 IU vitamin D3/day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitamin D3/day; infants in 2400 and 6400 IU groups received 0 IU/day (placebo). Vitamin D deficiency was defined as 25-hydroxy-vitamin D (25(OH)D) <50 nmol/L. 2400 IU group ended in 2009 as greater infant deficiency occurred. Maternal serum vitamin D, 25(OH)D, calcium, and phosphorus concentrations and urinary calcium/creatinine ratios were measured at baseline then monthly, and infant blood parameters were measured at baseline and months 4 and 7.
Of the 334 mother-infant pairs in 400 IU and 6400 IU groups at enrollment, 216 (64.7%) were still breastfeeding at visit 1; 148 (44.3%) continued full breastfeeding to 4 months and 95 (28.4%) to 7 months. Vitamin D deficiency in breastfeeding infants was greatly affected by race. Compared with 400 IU vitamin D3 per day, 6400 IU/day safely and significantly increased maternal vitamin D and 25(OH)D from baseline (P < .0001). Compared with breastfeeding infant 25(OH)D in the 400 IU group receiving supplement, infants in the 6400 IU group whose mothers only received supplement did not differ.
Maternal vitamin D supplementation with 6400 IU/day safely supplies breast milk with adequate vitamin D to satisfy her nursing infant's requirement and offers an alternate strategy to direct infant supplementation.
Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is ...hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH.
In this article, we review the past applications of in vitro models in identifying human hepatotoxins and then focus on the use of multiscale experimental models in drug development, including the ...use of zebrafish and human cell-based, 3-dimensional, microfluidic systems of liver functions as key components in applying Quantitative Systems Pharmacology (QSP). We have implemented QSP as a platform to improve the rate of success in the process of drug discovery and development of therapeutics.
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