Orientation Control Method and System for Object in Motion

An object in motion has a force applied thereto at a point of application. By moving the point of application such that the distance between the object's center-of-mass and the point of application is changed, the object's orientation can be changed/adjusted

Regulation of G protein-coupled receptors by palmitoylation and cholesterol

Due to their membrane location, G protein-coupled receptors (GPCRs) are subject to regulation by soluble and integral membrane proteins as well as membrane components, including lipids and sterols. GPCRs also undergo a variety of post-translational modifications, including palmitoylation. A recent article by Zheng et al. in BMC Cell Biology demonstrates cooperative roles for receptor palmitoylation and cholesterol binding in GPCR dimerization and G protein coupling, underlining the complex regulation of these receptors

Approaches to Characterize and Quantify Oligomerization of GPCRs

Fluorescence resonance energy transfer (FRET) is an approach widely used to detect protein–protein interactions in live cells. This approach is based on the sensitization of an “acceptor” molecule by the energy transfer from a “donor” when there is an overlap between the emission spectrum of the “donor” and the excitation spectrum of the “acceptor” and close proximity between the two fluorophore species (in the region of 8 nm). Various methods exist to quantify FRET signals: here, we describe the application of homogeneous time-resolved FRET (htrFRET) combined with Tag-lite™ technology and its application to determine not only protein–protein interactions but also the capability of GPCR mutant variants to form homomers compared to the wild type GPCR within the plasma membrane of transfected cells

Quaternary structure of a G-protein coupled receptor heterotetramer in complex with Gi and Gs

Background: G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. Results: We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. Conclusions: The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function

Internalization Dissociates β2-Adrenergic Receptors

G protein-coupled receptors (GPCRs) self-associate as dimers or higher-order oligomers in living cells. The stability of associated GPCRs has not been extensively studied, but it is generally thought that these receptors move between the plasma membrane and intracellular compartments as intact dimers or oligomers. Here we show that β2-adrenergic receptors (β2ARs) that self-associate at the plasma membrane can dissociate during agonist-induced internalization. We use bioluminescence-resonance energy transfer (BRET) to monitor movement of β2ARs between subcellular compartments. BRET between β2ARs and plasma membrane markers decreases in response to agonist activation, while at the same time BRET between β2ARs and endosome markers increases. Energy transfer between β2ARs is decreased in a similar manner if either the donor- or acceptor-labeled receptor is mutated to impair agonist binding and internalization. These changes take place over the course of 30 minutes, persist after agonist is removed, and are sensitive to several inhibitors of arrestin- and clathrin-mediated endocytosis. The magnitude of the decrease in BRET between donor- and acceptor-labeled β2ARs suggests that at least half of the receptors that contribute to the BRET signal are physically segregated by internalization. These results are consistent with the possibility that β2ARs associate transiently with each other in the plasma membrane, or that β2AR dimers or oligomers are actively disrupted during internalization

MODEL CORRELATION STUDY OF A RETRACTABLE BOOM FOR A SOLAR SAIL SPACECRAFT

To realize design concepts, predict dynamic behavior and develop appropriate control strategies for high performance operation of a solar-sail spacecraft, we developed a simple analytical model that represents dynamic behavior of spacecraft with various sizes. Since motion of the vehicle is dominated by retractable booms that support the structure, our study concentrates on developing and validating a dynamic model of a long retractable boom. Extensive tests with various configurations were conducted for the 30 Meter, light-weight, retractable, lattice boom at NASA MSFC that is structurally and dynamically similar to those of a solar-sail spacecraft currently under construction. Experimental data were then compared with the corresponding response of the analytical model. Though mixed results were obtained, the analytical model emulates several key characteristics of the boom. The paper concludes with a detailed discussion of issues observed during the study

Environment, human reproduction, menopause, and andropause.

As the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator is an integrator of hormonal, metabolic, and neural signals, it is not surprising that the function of the hypothalamogonadal axis is subject to the influence of a large array of environmental factors. Before puberty, the central nervous system (CNS) restrains the GnRH pulse generator. Undernutrition, low socioeconomic status, stress, and emotional deprivation, all delay puberty. During reproductive life, among peripheral factors that effect the reproductive system, stress plays an important role. Stress, via the release of corticotropin-releasing factor (CRF), eventually triggered by interleukin 1, inhibits GnRH release, resulting in hypogonadism. Effects of CRF are probably mediated by the opioid system. Food restriction and underweight (anorexia nervosa), obesity, smoking, and alcohol all have negative effects on the GnRH pulse generator and gonadal function. Age and diet are important determinants of fertility in both men and women. The age-associated decrease in fertility in women has as a major determinant chromosomal abnormalities of the oocyte, with uterine factors playing a subsidiary role. Age at menopause, determined by ovarian oocyte depletion, is influenced by occupation, age at menarche, parity, age at last pregnancy, altitude, smoking, and use of oral contraceptives. Smoking, however, appears to be the major determinant. Premature menopause is most frequently attributable to mosaicism for Turner Syndrome, mumps ovaritis, and, above all, total hysterectomy, which has a prevalence of about 12-15% in women 50 years old. Premature ovarian failure with presence of immature follicles is most frequently caused by autoimmune diseases or is the consequence of irradiation or chemotherapy with alkylating cytostatics. Plasma estrogens have a physiological role in the prevention of osteoporosis. Obese women have osteoporosis less frequently than women who are not overweight. Early menopause, suppression of adrenal function (corticoids), and thyroid hormone treatment all increase the frequency of osteoporosis. Aging in men is accompanied by decreased Leydig cell and Sertoli cell function, which has a predominantly primary testicular origin, although changes also occur at the hypothalamopituitary level. Plasma testosterone levels, sperm production, and sperm quality decrease, but fertility, although declining, is preserved until senescence. Stress and disease states accelerate the decline on Leydig cell function. Many occupational noxious agents have a negative effect on fertility.(ABSTRACT TRUNCATED AT 400 WORDS

Identifying hazardousness of sewer pipeline gas mixture using classification methods: a comparative study

In this work, we formulated a real-world problem related to sewer pipeline gas detection using the classification-based approaches. The primary goal of this work was to identify the hazardousness of sewer pipeline to offer safe and non-hazardous access to sewer pipeline workers so that the human fatalities, which occurs due to the toxic exposure of sewer gas components, can be avoided. The dataset acquired through laboratory tests, experiments, and various literature sources was organized to design a predictive model that was able to identify/classify hazardous and non-hazardous situation of sewer pipeline. To design such prediction model, several classification algorithms were used and their performances were evaluated and compared, both empirically and statistically, over the collected dataset. In addition, the performances of several ensemble methods were analyzed to understand the extent of improvement offered by these methods. The result of this comprehensive study showed that the instance-based learning algorithm performed better than many other algorithms such as multilayer perceptron, radial basis function network, support vector machine, reduced pruning tree. Similarly, it was observed that multi-scheme ensemble approach enhanced the performance of base predictors