100 research outputs found

    Investigation of High Pressure Fluid Circuit Gas Flow Dynamics in a Hermetic Compressor Using CFD to Improve Qualitative Flow Understanding

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    While many approaches have been investigated to identify areas for hermetic compressor efficiency improvements over the past few decades, there remains no conclusive method to gain a holistic view of the system domain to help identify potential target areas to guide product research direction. Hence, modern tools, methods, and problem perspectives are needed to develop new insight into mature problem-sets on a system level to satisfy increasingly stringent efficiency mandates. Reasonably mature simulation tools currently exist that enable scientists and engineers to gain a new perspective into system domains. One such tool is Computational Fluid Dynamics (CFD). The results of the following investigation will show how CFD, coupled with the knowledge of its inherent strengths and weaknesses, can be leveraged to allow scientists and engineers to view mature problem-sets from a qualitative perspective to yield different results by using the high-pressure fluid circuit of a hermetic compression system as a simulation test-bed

    Walker Percy\u27s Linguistic Alienation

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    The Molecular Mechanism for Receptor-Stimulated Iron Release from the Plasma Iron Transport Protein Transferrin

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    Human transferrin receptor 1 (TfR) binds iron-loaded transferrin (Fe-Tf) and transports it to acidic endosomes where iron is released in a TfR-facilitated process. Consistent with our hypothesis that TfR binding stimulates iron release from Fe-Tf at acidic pH by stabilizing the apo-Tf conformation, a TfR mutant (W641A/F760A-TfR) that binds Fe-Tf, but not apo-Tf, cannot stimulate iron release from Fe-Tf, and less iron is released from Fe-Tf inside cells expressing W641A/F760A-TfR than cells expressing wild-type TfR (wtTfR). Electron paramagnetic resonance spectroscopy shows that binding at acidic pH to wtTfR, but not W641A/F760A-TfR, changes the Tf iron binding site ≥30 Å from the TfR W641/F760 patch. Mutation of Tf histidine residues predicted to interact with the W641/F760 patch eliminates TfR-dependent acceleration of iron release. Identification of TfR and Tf residues critical for TfR-facilitated iron release, yet distant from a Tf iron binding site, demonstrates that TfR transmits long-range conformational changes and stabilizes the conformation of apo-Tf to accelerate iron release from Fe-Tf

    Egg white versus Salmonella Enteritidis! A harsh medium meets a resilient pathogen

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    Salmonella enterica serovar Enteritidis is the prevalent egg-product-related food-borne pathogen. The egg-contamination capacity of S. Enteritidis includes its exceptional survival capability within the harsh conditions provided by egg white. Egg white proteins, such as lysozyme and ovotransferrin, are well known to play important roles in defence against bacterial invaders. Indeed, several additional minor proteins and peptides have recently been found to play known or potential roles in protection against bacterial contamination. However, although such antibacterial proteins are well studied, little is known about their efficacy under the environmental conditions prevalent in egg white. Thus, the influence of factors such as temperature, alkalinity, nutrient restriction, viscosity and cooperative interactions on the activities of antibacterial proteins in egg white remains unclear. This review critically assesses the available evidence on the antimicrobial components of egg white. In addition, mechanisms employed by S. Enteritidis to resist egg white exposure are also considered along with various genetic studies that have shed light upon egg white resistance systems. We also consider how multiple, antibacterial proteins operate in association with specific environmental factors within egg white to generate a lethal protective cocktail that preserves sterility

    Novel roles of the chemorepellent axon guidance molecule RGMa in cell migration and adhesion

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    The repulsive guidance molecule A (RGMa) is a contact-mediated axon guidance molecule that has significant roles in central nervous system (CNS) development. Here we have examined whether RGMa has novel roles in cell migration and cell adhesion outside the nervous system. RGMa was found to stimulate cell migration from Xenopus animal cap explants in a neogenin-dependent and BMP-independent manner. RGMa also stimulated the adhesion of Xenopus animal cap cells, and this adhesion was dependent on neogenin and independent of calcium. To begin to functionally characterize the role of specific domains in RGMa, we assessed the migratory and adhesive activities of deletion mutants. RGMa lacking the partial von Willebrand factor type D (vWF) domain preferentially perturbed cell adhesion, while mutants lacking the RGD motif affected cell migration. We also revealed that manipulating the levels of RGMa in vivo caused major migration defects during Xenopus gastrulation. We have revealed here novel roles of RGMa in cell migration and adhesion and demonstrated that perturbations to the homeostasis of RGMa expression can severely disrupt major morphogenetic events. These results have implications for understanding the role of RGMa in both health and disease

    Economic value of trees in the estate of the Harewood House stately home in the United Kingdom

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    The estates of stately homes or manor houses are an untapped resource for assessing the ecosystem services provided by trees. Many of these estates have large collections of trees with clear value in terms of carbon storage, runoff prevention, and pollution removal along with additional benefits to biodiversity and human health. The estate of Harewood House in North Yorkshire represents an ideal example of such a stately home with a mixture of parkland and more formally planted gardens. The trees in each type of garden were analysed for height, diameter at breast height and light exposure. The data were then processed in iTrees software to generate economic benefits for each tree in both gardens. The analysis found that the larger North Front parkland garden had greater total benefits but the more densely planted formal West Garden had the greater per hectare value. In total, the trees on Harewood House estate are estimated to provide approximately £29 million in ecosystem service benefits. This study is the first to analyse the trees of stately homes for economic benefits and highlights that the trees are a valuable commodity for the estates. This should be considered in future planning and management of such estates

    A structural comparison of human serum transferrin and human lactoferrin

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    The transferrins are a family of proteins that bind free iron in the blood and bodily fluids. Serum transferrins function to deliver iron to cells via a receptor-mediated endocytotic process as well as to remove toxic free iron from the blood and to provide an anti-bacterial, low-iron environment. Lactoferrins (found in bodily secretions such as milk) are only known to have an anti-bacterial function, via their ability to tightly bind free iron even at low pH, and have no known transport function. Though these proteins keep the level of free iron low, pathogenic bacteria are able to thrive by obtaining iron from their host via expression of outer membrane proteins that can bind to and remove iron from host proteins, including both serum transferrin and lactoferrin. Furthermore, even though human serum transferrin and lactoferrin are quite similar in sequence and structure, and coordinate iron in the same manner, they differ in their affinities for iron as well as their receptor binding properties: the human transferrin receptor only binds serum transferrin, and two distinct bacterial transport systems are used to capture iron from serum transferrin and lactoferrin. Comparison of the recently solved crystal structure of iron-free human serum transferrin to that of human lactoferrin provides insight into these differences

    Intracellular Trafficking Considerations in the Development of Natural Ligand-Drug Molecular Conjugates for Cancer

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    Overexpressed receptors, characteristic of many cancers, have been targeted by various researchers to achieve a more specific treatment for cancer. A common approach is to use the natural ligand for the overexpressed receptor as a cancer-targeting agent which can deliver a chemically or genetically conjugated toxic molecule. However, it has been found that the therapeutic efficacy of such ligand-drug molecular conjugates can be limited, since they naturally follow the intracellular trafficking pathways of the endogenous ligands. Therefore, a thorough understanding of the intracellular trafficking properties of these ligands can lead to novel design criteria for engineering ligands to be more effective drug carriers. This review presents a few commonly used ligand/receptor systems where intracellular trafficking considerations can potentially improve the therapeutic efficacy of the ligand-drug molecular conjugates
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