The best measurements of space and time currently possible (e.g., gravitational-wave detectors and optical reference cavities) rely on optical resonators, and are ultimately limited by thermally ...induced fluctuations in the reflective coatings which form the resonator. We present measurements of coating thermal noise in the audio band and show that for a standard ion-beam sputtered coating, the power spectrum of the noise does not have the expected power-law behavior.
Malignant melanoma is an aggressive cancer known for its notorious resistance to most current therapies. The basic helix-loop-helix microphthalmia transcription factor (MITF) is the master regulator ...determining the identity and properties of the melanocyte lineage, and is regarded as a lineage-specific 'oncogene' that has a critical role in the pathogenesis of melanoma. MITF promotes melanoma cell proliferation, whereas sustained supression of MITF expression leads to senescence. By combining chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq) and RNA sequencing analyses, we show that MITF directly regulates a set of genes required for DNA replication, repair and mitosis. Our results reveal how loss of MITF regulates mitotic fidelity, and through defective replication and repair induces DNA damage, ultimately ending in cellular senescence. These findings reveal a lineage-specific control of DNA replication and mitosis by MITF, providing new avenues for therapeutic intervention in melanoma. The identification of MITF-binding sites and gene-regulatory networks establish a framework for understanding oncogenic basic helix-loop-helix factors such as N-myc or TFE3 in other cancers.
Interferometric gravitational-wave detectors like LIGO need to be able to measure changes in their arm lengths of order 10−18 m or smaller. This requires very high laser power in order to raise the ...signal above shot noise. One significant limitation to increased laser power is an optomechanical interaction between the laser field and the detector's test masses that can form an unstable feedback loop. Such parametric instabilities have long been studied as a limiting effect at high power, and were first observed to occur in LIGO in 2014. Since then, passive and active means have been used to avoid these instabilities, though at power levels well below the final design value. Here we report on the successful implementation of tuned, passive dampers to tame parametric instabilities in LIGO. These dampers are applied directly to all interferometer test masses to reduce the quality factors of their internal vibrational modes, while adding a negligible amount of noise to the gravitational-wave output. In accordance with our model, the measured mode quality factors have been reduced by at least a factor of 10 with no visible increase in the interferometer's thermal noise level. We project that these dampers should remove most of the parametric instabilities in LIGO when operating at full power, while limiting the concomitant increase in thermal noise to approximately 1%.
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•A qualitative toolbox for food extrusion is presented.•Formulation based engineering can be used to optimize 3D-printing processes of food.•Extrudability and buildability are a ...function of material properties.•Theoretical framework provides guidance for practical application.
The efficient development of extrusion-based 3D-printing requires flexibility in both formulation- and process design. This task requires a fundamental understanding of the influence of material rheological properties on the extrusion process. Within this review, a qualitative toolbox for food extrusion is presented which provides guidelines for the formulation and engineering of extrusion processes in general and 3D-printing in particular. The toolbox is based on current knowledge of highly viscous food systems and the influence of individual components on the overall rheology. It includes the efficiency of particle packing, microstructure and the influence of shear rate, as well as the formation of self-supporting structures by gelation of the liquid phase and crowding of particles. Physical laws and semi-empirical equations are discussed to describe the rheology and relate relevant theory to the extrusion process. Practical information is presented, including examples of extrusion and 3D-printing of food and non-food systems. The qualitative extrusion toolbox provides a general framework for the emerging field of extrusion-based 3D-printing of food products. It can be used to identify which specific material and process parameters can be changed and how they may be altered to optimize the 3D-printing process. The general framework will assist researchers, as well as industry.
N-Acetyllactosamine (LacNAc) or more specifically β-d-galactopyranosyl-1,4-N-acetyl-d-glucosamine is a unique acyl-amino sugar and a key structural unit in human milk oligosaccharides, an antigen ...component of many glycoproteins, and an antiviral active component for the development of effective drugs against viruses. LacNAc is useful itself and as a basic building block for producing various bioactive oligosaccharides, notably because this synthesis may be used to add value to dairy lactose. Despite a significant amount of information in the literature on the benefits, structures, and types of different LacNAc-derived oligosaccharides, knowledge about their effective synthesis for large-scale production is still in its infancy. This work provides a comprehensive analysis of existing production strategies for LacNAc and important LacNAc-based structures, including sialylated LacNAc as well as poly- and oligo-LacNAc. We conclude that direct extraction from milk is too complex, while chemical synthesis is also impractical at an industrial scale. Microbial routes have application when multiple step reactions are needed, but the major route to large-scale biochemical production will likely lie with enzymatic routes, particularly those using β-galactosidases (for LacNAc synthesis), sialidases (for sialylated LacNAc synthesis), and β-N-acetylhexosaminidases (for oligo-LacNAc synthesis). Glycosyltransferases, especially for the biosynthesis of extended complex LacNAc structures, could also play a major role in the future. In these cases, immobilization of the enzyme can increase stability and reduce cost. Processing parameters, such as substrate concentration and purity, acceptor/donor ratio, water activity, and temperature, can affect product selectivity and yield. More work is needed to optimize these reaction parameters and in the development of robust, thermally stable enzymes to facilitate commercial production of these important bioactive substances.
In modern high precision optical instruments, such as in gravitational wave detectors or frequency references, thermally induced fluctuations in the reflective coatings can be a limiting noise ...source. This noise, known as coating thermal noise, can be reduced by choosing materials with low mechanical loss. Examination of new materials becomes a necessity in order to further minimize the coating thermal noise and thus improve sensitivity of next generation instruments. We present a novel approach to directly measure coating thermal noise using a high finesse folded cavity in which multiple Hermite-Gaussian modes coresonate. This method is used to probe surface fluctuations on the order 10−17 m/Hz in the frequency range 30–400 Hz. We applied this technique to measure thermal noise and loss angle of the coating used in Advanced LIGO.
Saline wastewater is a by-product of cheese manufacturing and whey processing that can have serious environmental and economic consequences. Salty streams originating from dairy processing operations ...include chromatography wastes, clean-in-place wastewater, acid whey, salty whey and waste generated from whey demineralization processes such as nanofiltration, electrodialysis and ion exchange. With the participation of the major dairy companies in Australia, an industry wide survey was conducted to acquire a comprehensive understanding of the management strategies for these salty waste streams. High salinity waste streams are commonly directed to evaporation ponds. However, environmental impacts from land degradation, odour and dust have prevented the construction of further evaporation ponds in some areas of Australia. The survey results also show that disposal to municipal trade waste is not always effective, as the current levels of some salinity-related parameters are significantly higher than the levels allowed by the local water/environmental authorities. For high salinity streams, salt removal can lead to more substantial savings in trade waste charges compared to wastewater volume reduction. Thus, salt removal and recovery from salty waste streams has become a major focus of the sustainability agenda of the Australian dairy industry.
•Industry wide survey of saline management practices in Australian dairy.•Saline waste is generated from a number of processing operations.•Both brine ponds and trade waste options for brine becoming more difficult.•Salt removal from effluent is effective in reducing trade waste charges.
Confocal laser scanning microscopy (CLSM) was successfully used to observe the effect of milk processing on the size and the morphology of the milk fat globule in raw milk, raw ultrafiltered milk, ...and standardized and pasteurized milk prepared for cheese manufacture (cheese‐milk) and commercial pasteurized and homogenized milk. Fat globule size distributions for the milk preparations were analyzed using both image analysis and light scattering and both measurements produced similar data trends. Changes to the native milk fat globule membrane (MFGM) were tracked using a MFGM specific fluorescent stain that allowed MFGM proteins and adsorbed proteins to be differentiated on the fat globule surface. Sodium dodecyl sulfate polyacrylamide gel electrophoresis confirmed the identity of native MFGM proteins isolated from the surface of fat globules within raw, UF retentate, and cheese‐milk preparations, whereas only casein was detected on the surface of fat globules in homogenized milk. The microstructure, porosity, and gel strength of the rennet induced gel made from raw milk and cheese‐milk was also found to be comparable and significantly different to that made from homogenized milk. Our results highlight the potential use of CLSM as a tool to observe the structural details of the fat globule and associated membrane close to its native environment.
The solubility of calcium phosphate in concentrated dairy brine streams is important in understanding mineral scaling on equipment, such as membrane modules, evaporators, and heat exchangers, and in ...brine pond operation. In this study, the solubility of calcium phosphate has been assessed in the presence of up to 300 g/L sodium chloride as well as lactose, organic acids, and anions at 10, 30, and 50 °C. As a neutral molecule, lactose has a marginal but still detectable effect upon calcium solubility. However, additions of sodium chloride up to 100 g/L result in a much greater increase in calcium solubility. Beyond this point, the concentrations of ions in the solution decrease significantly. These changes in calcium solubility can readily be explained through changes in the activity coefficients. There is little difference in calcium phosphate speciation between 10 and 30 °C. However, at 50 °C, the ratio of calcium to phosphate in the solution is lower than at the other temperatures and varies less with ionic strength. While the addition of sodium lactate has less effect upon calcium solubility than sodium citrate, it still has a greater effect than sodium chloride at an equivalent ionic strength. Conversely, when these organic anions are present in the solution in the acid form, the effect of pH dominates and results in much higher solubility and a calcium/phosphate ratio close to one, indicative of dicalcium phosphate dihydrate as the dominant solid phase.
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