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The run-on flat tire is an important technology in the area of vehicle safety technology. Nowadays, traveling by a personal vehicle from one place to another has increased due to the increase in the global economy. The main problem that is faced while traveling is tire puncture. The tire may get punctured by any sharp objects on the road such as screws and iron pins that traps the tire surface. A situation like this may be overcome by the usage of the drive on a puncher tire device which will be used to reach the destination without any need for a puncher shop. Using this device will reduce the damage of the tire and tube. This device is portable and can be placed in a vehicle itself. For this reason, a design has been developed by the CATIA 3D experience. The drive on a puncher tire device was designed using the software developed by the Dassault systems named CATIA 3D experience. Aluminum alloy was chosen as the base material to design and simulate this product. Also, the network distribution simulations were used to develop the mathematical equations to check the adequacy of the model. This device is very useful while traveling long distances if any puncher will occur. The sensors were attached to the product to receive the signal from the vehicle, so that the vehicle will run smoothly for a short distance. Drive on a puncher tire will be suitable for both two- and four-wheeler vehicles and also useful for all the areas like villages, towns, panchayats, and cities. If the tire is puncher, we cannot drive the vehicle; hence, a skating device is fixed at a tired bottom, which is used to move the vehicle. The proposal will be beneficial for a huge number of people who own two and four wheelers. This design and simulation will address the problem of the two- and four-wheeler owners traveling long distances., Author(s): V Sivamaran [1]; Hariprasath Manoharan [2]; Yuvaraja Teekaraman (corresponding author) [3]; Ramya Kuppusamy [4]; Arun Radhakrishnan (corresponding author) [5] 1. Introduction The safety of the automobile vehicles was highly [...]

Byline: Ruckmani. Arunachalam, Venu. Rao Konda, Madhavi. Eerike, Arun. Radhakrishnan, Sobita. Devi OBJECTIVES: To evaluate the effects of ethanolic root Ethanolic extract of Azima tetracantha. Lam roots (EEATR) in adenine-induced [...]

A handoff model has been proposed to explain the egress from lysosomes of cholesterol derived from receptor-mediated endocytosis of LDL. Cholesterol is first bound by soluble Niemann-Pick C2 (NPC2) protein, which hands off the cholesterol to the N-terminal domain of membrane-bound NPC1. Cells lacking NPC1 or NPC2 accumulate LDL-derived cholesterol in lysosomes and fail to deliver LDL cholesterol to the endoplasmic reticulum (ER) for esterification by acyl-CoA acyltransferase (ACAT) and for inhibition of sterol regulatory element-binding protein cleavage. Here, we support this model by showing that the cholesterol transport defect in NPC1 mutant cells is restricted to lysosomal export. Other cholesterol transport pathways appear normal, including the movement of cholesterol from the plasma membrane to the ER after treatment of cells with 25-hydroxycholesterol or sphingomyelinase. The NPC1 or NPC2 block in cholesterol delivery to the ER can be overcome by 2-hydroxypropyl[beta]-cyclodextrin, which leads to a marked increase in ACAT-mediated cholesterol esterification. The buildup of cholesteryl esters in the cytosol is expected to be much less toxic than the buildup of free cholesterol in the lysosomes of patients with mutations in NPC1 or NPC2. cholesterol esterification | NPC1 and NPC2 proteins | sphingomyelinase www.pnas.org/cgi/doi/10.1073/pnas.0910916106

Egress of lipoprotein-derived cholesterol from lysosomes requires two lysosomal proteins, polytopic membrane-bound Niemann-Pick C1 (NPC1) and soluble Niemann-Pick C2 (NPC2). The reason for this dual requirement is unknown. Previously, we showed that the soluble luminal N-terminal domain (NTD) of NPC1 (amino acids 25-264) binds cholesterol. This NTD is designated NPCI(NTD). We and others showed that soluble NPC2 also binds cholesterol. Here, we establish an in vitro assay to measure transfer of [[sup.3]H]cholesterol between these two proteins and phosphatidylcholine liposomes. Whereas NPC2 rapidly donates or accepts cholesterol from liposomes, NPCI(NTD) acts much more slowly. Bidirectional transfer of cholesterol between NPCI(NTD) and liposomes is accelerated >100-fold by NPC2. A naturally occurring human mutant of NPC2 (Pro120Ser) fails to bind cholesterol and fails to stimulate cholesterol transfer from NPCI(NTD) to liposomes. NPC2 may be essential to deliver or remove cholesterol from NPC1, an interaction that links both proteins to the cholesterol egress process from lysosomes. These findings may explain how mutations in either protein can produce a similar clinical phenotype. cholesterol trafficking | kinetics of cholesterol binding | Nierman-Pick C disease

Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs. Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap. These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells. cholesterol homeostasis | Scap | sterol regulatory element-binding protein pathway | COPII vesicles

A general theoretical model is described for the NMR spectra of mixtures of sterols and deuterium-labeled phospholipids. In the case of homogeneous membranes, the average quadrupole splittings are determined by equilibria between lipids in cholesterol-phospholipid complexes and lipids not in complexes. Chemical exchange of lipids between those in the free state and those in the complex state affects the deuterium resonance line shapes. The lifetime of a phospholipid molecule in an ergosterol-dipalmitoylphosphatidylcholine complex is estimated to be of the order of 10-s s on the basis of the observed line broadenings. In the vicinity of a critical point of a cholesterol-phospholipid mixture, fluctuations in the concentration of complexes also can contribute to the deuterium nuclear resonance line broadening. At the critical point, the temperature derivative of the concentration of complexes is discontinuous. There is a corresponding jump in the calculated heat capacity as well as in the temperature derivative of the deuterium NMR first moment. condensed complexes | critical point fluctuations | order parameters | phase diagrams | reaction kinetics

Animal cell membranes pose conceptual problems related to the physical chemistry of liquids. An avenue to the solution of some of these problems has been opened by the discovery of liquid--liquid immiscibility in synthetic membranes composed of cholesterol and phospholipids. This discovery has led to the development of a thermodynamic model involving condensed complexes. In this model, the phospholipids with longer fatty-acid chains react reversibly with cholesterol to form complexes. The complexes themselves can have a repulsive interaction with other phospholipids, leading to immiscibility. A striking example of this effect is revealed in the phase diagrams of ternary mixtures of cholesterol, a saturated phosphatidylcholine (or sphingomyelin), and an unsaturated phosphatidylcholine. As found by a number of investigators, all binary pairs are miscible in bilayers, whereas the ternary mixture can form two liquid phases. The model of condensed complexes accounts for this effect. Condensed complexes also have a major effect on the chemical activity of cholesterol and on the ordering of phospholipid acyl chains both in the presence and absence of phase separations. Model calculations of phospholipid order parameters account for several features of the deuterium NMR spectra of labeled phospholipid molecules in bilayer mixtures with cholesterol. chemical activity | deuterium NMR | membrane | phase diagrams

The polytopic membrane protein SCAP transports sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi, thereby activating cholesterol synthesis. Cholesterol accumulation in the ER membranes changes SCAP to an alternate conformation in which it binds ER retention proteins called Insigs, thereby terminating cholesterol synthesis. Here, we show that the conserved Asp-428 in the sixth transmembrane helix of SCAP is essential for SCAP's dissociation from Insigs. In transfected hamster cells, mutant SCAP in which Asp-428 is replaced by alanine (D428A) remained in an Insig-binding conformation when cells were depleted of sterols. As a result, mutant SCAP failed to dissociate from Insigs, and it failed to carry SREBPs to the Golgi. These data identify an important functional residue in SCAP, and they provide genetic evidence that the conformation of SCAP dictates the rate of cholesterol synthesis in animal cells. Insig | membrane proteins | sterol regulatory element-binding protein

Epifluorescence microscopy is used to determine phase diagrams for lipid monolayers containing binary mixtures of cholesterol or dihydrocholesterol and dimyristoylphosphatidylserine, as well as ternary mixtures that also contain ganglioside [G.sub.M1]. The phase diagrams are unusual in that they show multiple critical points: two upper miscibility critical points and one lower miscibility critical point. These critical points all are associated with the formation of condensed complexes between these lipids and cholesterol (or dihydrocholesterol). The miscibility critical pressures depend on subphase pH and ionic strength. Changes in critical pressures due to changes in subphase composition are closely related to changes in membrane electrostatic pressure and surface ionization. phospholipids | sphingomyelin | phase diagrams | condensed complexes | liquid immiscibility

Research has been conducted on the cholesterol release to beta-cyclodextrin from mixtures with phospholipids. The measurements for the release rate constants are presented.

Epifluorescence microscopy studies of mixtures of phospholipids and cholesterol at the air-water interface often exhibit coexisting liquid phases. The properties of these liquids point to the formation of 'condensed complexes' between cholesterol and certain phospholipids, such as sphingomyelin. It is found that monolayers that form complexes can incorporate a low concentration of a ganglioside [G.sub.M1]. This glycolipid is visualized by using a fluorescently labeled B subunit of cholera toxin. Three coexisting liquid phases are found by using this probe together with a fluorescent phospholipid probe. The three liquid phases are identified as a phospholipid-rich phase, a cholesterol-rich phase, and a condensed complex-rich phase. The cholera toxin B labeled ganglioside [G.sub.M1] is found exclusively in the condensed complex-rich phase. Condensed complexes are likely present in animal cell membranes, where they should facilitate the formation of specialized domains such as rafts. Condensed complexes also have a major effect in determining the chemical activity of cholesterol. It is suggested that this chemical activity plays an essential role in the regulation of cholesterol biosynthesis. Gradients in the chemical activity of cholesterol should likewise govern the rates and direction of intracellular intermembrane cholesterol transport. monolayers | liquid phase separations | phospholipids | sphingomyelin

An empirical connection between high melting temperatures of saturated phospholipid bilayers and the appearance of two upper miscibility critical points in cholesterol-phospholipid monolayers is described. A rough correlation is found between melting temperature and the composition of the complex. It is proposed that melting temperature is a convenient measure of the tendency of the phospolipid acyl chains to order.

Monolayer mixtures of dihydrocholesterol and phospholipids at the air-water interface are used to model membranes containing cholesterol and phospholipids. Specific, stoichiometric interactions between cholesterol and some but not all phospholipids have been proposed to lead to the formation of condensed complexes. It is reported here that an externally applied electric field of the appropriate sign can destabilize these complexes, resulting in their dissociation. This is demonstrated through the application of an electric field gradient that leads to phase separations in otherwise homogeneous monolayers. This is observed only when the monolayer composition is close to the stoichiometry of the complex. The electric field effect is analyzed with the same mean field thermodynamic model as that used previously to account for pairs of upper miscibility critical points in these mixtures. The concentrations of dihydrocholesterol, phospholipid, and complex vary strongly and sometimes discontinuously in the monolayer membrane in the field gradient. The model is an approximation to a two-dimensional liquid in which molecules freely exchange between free and complexed form so that the chemical potentials are constant throughout the membrane. The calculations are illustrated for a complex of about 15 molecules, composed of 5 cholesterol molecules and 10 phospholipid molecules.

Evidence for complex formation in lipid monolayers in biological membranes at the air-water interface composed of dihydrocholesterol (C) and phospholipids (P) were described. The binary mixtures of C and P underwent a contraction in area when mixed at constant pressure. A thermodynamic model showed how this contraction results in a decrease in critical temperature with increasing pressure. The monolayer pressure was changed until the critical temperature was equal to room temperature.