Understanding organelle biogenesis is a central focus of cell biology. Whereas some are generated from existing organelles, others can be generated de novo. Most de novo organelle biogenesis occurs ...in the endoplasmic reticulum (ER). Here, we review the role of the ER in the generation of peroxisomes, lipid droplets, and omegasomes, which are platforms for autophagosome production, and discuss how ER subdomains with specific protein and lipid composition form and promote organelle biogenesis.
We present an enhanced continuum model for the size-dependent strengthening and failure of particle-reinforced composites. The model accounts explicitly for the enhanced strength in a discretely ...defined “punched zone” around the particle in a metal matrix composite as a result of geometrically necessary dislocations developed through a mismatch in the coefficients of thermal expansion. We incorporate the punched zone explicitly through a unit-cell model within this work, but the approach can be used more generally to account for discrete particle distributions and particle shapes. Smaller particles lead to greater strengthening, and this size effect is larger for larger volume fractions. An equation for the coupling of the size-dependent increase of yield strength of metal matrix composites with the particle volume fraction is obtained. The results indicate that the punched zone effect may amplify the occurrence of a variety of failure modes such as matrix localization, particle fracture and/or particle–matrix interface failure; smaller particles perceive higher stresses. We account for interface failure through a cohesive approach, and show that the interface damage mechanism is also particle-size-dependent. Some implications are presented for microstructural design of metal matrix composites.
Cysteamine, an anti-oxidant aminothiol, is the treatment of choice for nephropathic cystinosis, a rare lysosomal storage disease. Cysteamine is a chemo-sensitization and radioprotection agent and its ...antitumor effects have been investigated in various tumor cell lines and chemical induced carcinogenesis. Here, we investigated whether cysteamine has anti-tumor and anti-metastatic effects in transplantable human pancreatic cancer, an aggressive metastatic disease.
Cysteamine's anti-invasion effects were studied by matrigel invasion and cell migration assays in 10 pancreatic cancer cell lines. To study mechanism of action, we examined cell viability and matrix metalloproteinases (MMPs) activity in the cysteamine-treated cells. We also examined cysteamine's anti-metastasis effect in two orthotopic murine models of human pancreatic cancer by measuring peritoneal metastasis and survival of animals. Cysteamine inhibited both migration and invasion of all ten pancreatic cancer cell lines at concentrations (<25 mM) that caused no toxicity to cells. It significantly decreased MMPs activity (IC(50) 38-460 µM) and zymographic gelatinase activity in a dose dependent manner in vitro and in vivo; while mRNA and protein levels of MMP-9, MMP-12 and MMP-14 were slightly increased using the highest cysteamine concentration. In vivo, cysteamine significantly decreased metastasis in two established pancreatic tumor models, although it did not affect the size of primary tumors. Additionally, cysteamine prolonged survival of mice in a dose-dependent manner without causing any toxicity. Similar to the in vitro results, MMP activity was significantly decreased in animal tumors treated with cysteamine. Cysteamine had no clinical or preclinical adverse effects in the host even at the highest dose.
Our results suggest that cysteamine, an agent with a proven safety profile, may be useful for inhibition of metastasis and prolonging the survival of a host with pancreatic cancer.
•Yolk-shelled ZnCo2O4 structures have been synthesized by a one-step co-precipitation method.•FESEM images revealed that the morphology is based on a yolk-shelled shape.•The yolk-shelled ZnCo2O4 ...exhibits a good sensitivity towards sub-ppb (80-890 ppb) level of ozone.•The sensor worked within a wide range of ozone concentrations,being also selective to ozone compared to CO, NH3 and NO2.
The need to improve the sensitivity, selectivity and stability of ozone gas sensors capable of monitoring the environment to prevent hazard to humans has sparked research on binary metal oxides. Here we report on a novel ozone gas sensor made with ca. 0.5μm yolk-shelled ZnCo2O4 microstructures synthesized via an eco-friendly, co-precipitation method and subsequent annealing. With these ZnCo2O4 microspheres, ozone concentrations down to 80 parts per billion (ppb) could be detected with a.c. and d.c. electrical measurements. The sensor worked within a wide range of ozone concentrations, from 80 to 890ppb, being also selective to ozone compared to CO, NH3 and NO2. The high performance could be attributed to the large surface area to volume ratio inherent in yolk-shell structures. Indeed, ozone molecules adsorbed on the ZnCo2O4 surface create a layer of holes that affect the conductivity, as in a p-type semiconductor. Since this mechanism of detection is generic, ZnCo2O4 microspheres can be further used in other environment monitoring devices.
The mechanism of serrated chip formation during high-speed turning of Inconel 718 using PCBN cutting tools has been investigated with the aid of scanning electron microscopy and optical microscopy. A ...conceptual model of chip formation has been developed knowing the chip morphology. It is followed by the analysis of chip segmentation frequency and the chip forms. Further, the chip segment forms and geometry were quantitatively characterized as a function of machining parameters and the cutting edge geometry using statistical methods. The chip morphology has been correlated with the cutting forces, specific shearing energy and the resultant roughness of the machined surfaces.
Over the course of 3 hr on 2008 December 27, we obtained optical (R band) observations of the blazar S5 0716+714 at a very fast cadence of 10 s. Using several different techniques, we find ...fluctuations with an approximately 15 minute quasi-period to be present in the first portion of these data at a >3{sigma} confidence level. This is the fastest quasi-periodic oscillation that has been claimed to be observed in any blazar at any wavelength. While these data are insufficient to strongly constrain models for such fluctuations, the presence of such a short timescale when the source is not in a very low state seems to favor the action of turbulence behind a shock in the blazar's relativistic jet.
•Hexyl acetate, safety assessment based on RIFM's criteria.•Safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, read-across, and/or ...TTC.
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