Rolling-Tooth Core Breakoff and Retention Mechanism

Sampling cores requires the controlled breakoff of the core at a known location with respect to the drill end. An additional problem is designing a mechanism that can be implemented at a small scale that is robust and versatile enough to be used for a variety of core samples. This design consists of a set of tubes (a drill tube and an inner tube) and a rolling element (rolling tooth). An additional tube can be used as a sample tube. The drill tube and the inner tube have longitudinal holes with the axes offset from the axis of each tube. The two eccentricities are equal. The inner tube fits inside the drill tube, and the sample tube fits inside the inner tube. While drilling, the two tubes are positioned relative to each other such that the sample tube is aligned with the drill tube axis and core. The drill tube includes teeth and flutes for cuttings removal. The inner tube includes, at the base, the rolling element implemented as a wheel on a shaft in an eccentric slot. An additional slot in the inner tube and a pin in the drill tube limit the relative motion of the two tubes. While drilling, the drill assembly rotates relative to the core and forces the rolling tooth to stay hidden in the slot along the inner tube wall. When the drilling depth has been reached, the drill bit assembly is rotated in the opposite direction, and the rolling tooth is engaged and penetrates into the core. Depending on the strength of the created core, the rolling tooth can score, lock the inner tube relative to the core, start the eccentric motion of the inner tube, and break the core. The tooth and the relative position of the two tubes can act as a core catcher or core-retention mechanism as well. The design was made to fit the core and hole parameters produced by an existing bit; the parts were fabricated and a series of demonstration tests were performed. This invention is potentially applicable to sample return and in situ missions to planets such as Mars and Venus, to moons such as Titan and Europa, and to comets. It is also applicable to terrestrial applications like forensic sampling and geological sampling in the field

Reduced crying in term infants fed high beta-palmitate formula: a double-blind randomized clinical trial

BACKGROUND: Beta-palmitate (sn-2 palmitate) mimics human milk fat, enabling easier digestion. Therefore, we hypothesized that infants consuming high beta-palmitate formula would have more frequent, softer stools and reduced crying compared to infants consuming low beta-palmitate formula. METHODS: Formula-fed infants were randomly assigned to receive either (1) formula with high beta-palmitate (HBP, n = 21) or (2) regular formula with a standard vegetable oil mix (LBP, n = 21). A matched group of breastfed infants served as a reference (BF, n = 21). Crying and stool characteristics data were recorded by the parents for 3 days before the 6- and 12-week visits. RESULTS: We found no significant differences in the stool frequency or consistency between the two formula groups. The percentage of crying infants in the LBP group was significantly higher than that in the HBP and BF groups during the evening at 6 weeks (88.2% vs. 56.3% and 55.6%, p < 0.05) and during the afternoon at 12 weeks (91.7% vs. 50.0% and 40%, p < 0.05). The infants fed HBP had significantly shorter crying durations when compared with infants fed LBP formula (14.90 ± 3.85 vs.63.96 ± 21.76 min/day, respectively; p = 0.047). CONCLUSIONS: Our study indicates that consumption of a high beta-palmitate formula affects infant crying patterns during the first weeks of life. Comparable to breastfeeding, it reduced crying duration and frequency, primarily during the afternoon and evening hours, thereby improving the well-being of formula-fed infants and their parents. TRIAL REGISTRATION: NCT00874068. Registration date March 31, 200

Oroxylin A promotes PTEN-mediated negative regulation of MDM2 transcription via SIRT3-mediated deacetylation to stabilize p53 and inhibit glycolysis in wt-p53 cancer cells

Introduction p53 plays important roles in regulating the metabolic reprogramming of cancer, such as aerobic glycolysis. Oroxylin A is a natural active flavonoid with strong anticancer effects both in vitro and in vivo. Methods wt-p53 (MCF-7 and HCT116 cells) cancer cells and p53-null H1299 cancer cells were used. The glucose uptake and lactate production were analyzed using Lactic Acid production Detection kit and the Amplex Red Glucose Assay Kit. Then, the protein levels and RNA levels of p53, mouse double minute 2 (MDM2), and p53-targeted glycolytic enzymes were quantified using Western blotting and quantitative polymerase chain reaction (PCR), respectively. Immunoprecipitation were performed to assess the binding between p53, MDM2, and sirtuin-3 (SIRT3), and the deacetylation of phosphatase and tensin homolog (PTEN). Reporter assays were performed to assess the transcriptional activity of PTEN. In vivo, effects of oroxylin A was investigated in nude mice xenograft tumor-inoculated MCF-7 or HCT116 cells. Results Here, we analyzed the underlying mechanisms that oroxylin A regulated p53 level and glycolytic metabolism in wt-p53 cancer cells, and found that oroxylin A inhibited glycolysis through upregulating p53 level. Oroxylin A did not directly affect the transcription of wt-p53, but suppressed the MDM2-mediated degradation of p53 via downregulating MDM2 transcription in wt-p53 cancer cells. In further studies, we found that oroxylin A induced a reduction in MDM2 transcription by promoting the lipid phosphatase activity of phosphatase and tensin homolog, which was upregulated via sirtuin3-mediated deacetylation. In vivo, oroxylin A inhibited the tumor growth of nude mice-inoculated MCF-7 or HCT116 cells. The expression of MDM2 protein in tumor tissue was downregulated by oroxylin A as well. Conclusions These results provide a p53-independent mechanism of MDM2 transcription and reveal the potential of oroxylin A on glycolytic regulation in both wt-p53 and mut-p53 cancer cells. The studies have important implications for the investigation on anticancer effects of oroxylin A, and provide the academic basis for the clinical trial of oroxylin A in cancer patients

Metabolic regulation by p53

We are increasingly aware that cellular metabolism plays a vital role in diseases such as cancer, and that p53 is an important regulator of metabolic pathways. By transcriptional activation and other means, p53 is able to contribute to the regulation of glycolysis, oxidative phosphorylation, glutaminolysis, insulin sensitivity, nucleotide biosynthesis, mitochondrial integrity, fatty acid oxidation, antioxidant response, autophagy and mTOR signalling. The ability to positively and negatively regulate many of these pathways, combined with feedback signalling from these pathways to p53, demonstrates the reciprocal and flexible nature of the regulation, facilitating a diverse range of responses to metabolic stress. Intriguingly, metabolic stress triggers primarily an adaptive (rather than pro-apoptotic) p53 response, and p53 is emerging as an important regulator of metabolic homeostasis. A better understanding of how p53 coordinates metabolic adaptation will facilitate the identification of novel therapeutic targets and will also illuminate the wider role of p53 in human biology

Reciprocal influence of the p53 and the hypoxic pathways

When cells sense a decrease in oxygen availability (hypoxia), they develop adaptive responses in order to sustain this condition and survive. If hypoxia lasts too long or is too severe, the cells eventually die. Hypoxia is also known to modulate the p53 pathway, in a manner dependent or not of HIF-1 (hypoxia-inducible factor-1), the main transcription factor activated by hypoxia. The p53 protein is a transcription factor, which is rapidly stabilised by cellular stresses and which has a major role in the cell responses to these stresses. The aim of this review is to compile what has been reported until now about the interconnection between these two important pathways. Indeed, according to the cell line, the severity and the duration of hypoxia, oxygen deficiency influences very differently p53 protein level and activity. Conversely, p53 is also described to affect HIF-1α stability, one of the two subunits of HIF-1, and HIF-1 activity. The direct and indirect interactions between HIF-1α and p53 are described as well as the involvement in this complex network of their respective ubiquitin ligases von Hippel Lindau protein and murine double minute 2. Finally, the synergistic or antagonistic effects of p53 and HIF-1 on some important cellular pathways are discussed