1,887 research outputs found
Initial Comparison of Single Cylinder Stirling Engine Computer Model Predictions with Test Results
A Stirling engine digital computer model developed at NASA Lewis Research Center was configured to predict the performance of the GPU-3 single-cylinder rhombic drive engine. Revisions to the basic equations and assumptions are discussed. Model predictions with the early results of the Lewis Research Center GPU-3 tests are compared
Cybersecurity education in Nigeria: a pre-requisite for the life-long learner in the 21st century.
Teaching and learning in the 21st century have metamorphosed tremendously towards the digitalization of learning as a result of the outbreak of the COVID- 19 pandemic. Instructors and learners deliver and receive instructions respectively using technology. Though technology has been used in the past for teaching and learning, the awareness it has gotten in the recent years after the COVID pandemic- which resulted to a total lockdown of organizations and institutions of learning, is mind blowing. This paper seeks to propose the need for cyber security education to be included in the Nigerian curriculum so as to avail the learners the prerequisite knowledge on how to stay safe while using technology and the internet for learning and other purposes
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Protein Transduction Domain Mimic (PTDM) Self-Assembly?
Intracellular protein delivery is an invaluable tool for biomedical research, as it enables fundamental studies of cellular processes and creates opportunities for novel therapeutic development. Protein delivery reagents such as cell penetration peptides (CPPs) and protein transduction domains (PTDs) are frequently used to facilitate protein delivery. Herein, synthetic polymer mimics of PTDs, called PTDMs, were studied for their ability to self-assemble in aqueous media as it was not known whether self-assembly plays a role in the protein binding and delivery process. The results obtained from interfacial tensiometry (IFT), transmission electron microscopy (TEM), transmittance assays (%T), and dynamic light scattering (DLS) indicated that PTDMs do not readily aggregate or self-assemble at application-relevant time scales and concentrations. However, additional DLS experiments were used to confirm that the presence of protein is required to induce the formation of PTDM-protein complexes and that PTDMs likely bind as single chains
Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating
Sedentary aging results in a diminished rapid cutaneous vasodilator response to local heating. We investigated whether this diminished response was due to altered contributions of noradrenergic sympathetic nerves; assessing 1) the age-related decline and, 2) the effect of aerobic fitness. We measured skin blood flow (SkBF)(laser-Doppler flowmetry) in young (24±1 yr) and older (64±1 yr) endurance-trained and sedentary men (n=7 per group) at baseline and during 35 min of local skin heating to 42 °C at three forearm sites: 1) untreated; 2) bretylium tosylate (BT), preventing neurotransmitter release from noradrenergic sympathetic nerves; and 3) yohimbine and propranolol (YP), antagonising α- and β-adrenergic receptors. SkBF was converted to cutaneous vascular conductance (CVC) (SkBF/mean arterial pressure) and normalized to maximal CVC (%CVCmax) achieved by skin heating to 44 °C. Pharmacological agents were administered using microdialysis. In the young trained, the rapid vasodilator response was reduced at the BT and YP sites (P0.05) but treatment with BT did (P>0.05). Neither BT nor YP treatments affected the rapid vasodilator response in the older sedentary group (P>0.05). These data suggest that the age-related reduction in the rapid vasodilator response is due to an impairment of sympathetic-dependent mechanisms, which can be partly attenuated with habitual aerobic exercise. Rapid vasodilation involves noradrenergic neurotransmitters in young trained men, and non-adrenergic sympathetic cotransmitters (e.g.,
neuropeptide Y) in young sedentary and older trained men, possibly as a compensatory mechanism. Finally, in older sedentary men, the rapid vasodilation appears not to involve the sympathetic system
A stirling engine computer model for performance calculations
To support the development of the Stirling engine as a possible alternative to the automobile spark-ignition engine, the thermodynamic characteristics of the Stirling engine were analyzed and modeled on a computer. The modeling techniques used are presented. The performance of an existing rhombic-drive Stirling engine was simulated by use of this computer program, and some typical results are presented. Engine tests are planned in order to evaluate this model
Anharmonic molecular mechanics: Ab initio based Morse parameterisations for the popular MM3 force field
Methodologies for creating reactive potential energy surfaces from molecular
mechanics force-fields are becoming increasingly popular. To date, molecular
mechanics force-fields use harmonic expressions to treat bonding stretches,
which is a poor approximation in reactive molecular dynamics simulations since
bonds are displaced significantly from their equilibrium positions. For such
applications there is need for a better treatment of anharmonicity. In this
contribution Morse bonding potentials have been extensively parameterised for
the atom types in the MM3 force field of Allinger and co-workers using high
level CCSD(T)(F12*) energies. To our knowledge this is the first instance of a
large-scale paramerization of Morse potentials in a popular force field
S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and Function
S-Glutathionylation of cysteine residues within target proteins is a posttranslational modification that alters structure and function. We have shown that S-glutathionylation of protein disulfide isomerase (PDI) disrupts protein folding and leads to the activation of the unfolded protein response (UPR). PDI is a molecular chaperone for estrogen receptor alpha (ERα). Our present data show in breast cancer cells that S-glutathionylation of PDI interferes with its chaperone activity and abolishes its capacity to form a complex with ERα. Such drug treatment also reverses estradiol-induced upregulation of c-Myc, cyclinD1, and P21Cip, gene products involved in cell proliferation. Expression of an S-glutathionylation refractory PDI mutant diminishes the toxic effects of PABA/NO. Thus, redox regulation of PDI causes its S-glutathionylation, thereby mediating cell death through activation of the UPR and abrogation of ERα stability and signaling
S-glutathionylation of buccal cell proteins as biomarkers of exposure to hydrogen peroxide
AbstractBackgroundExogenous or endogenous hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that can lead to oxidation of cellular nucleophiles, particularly cysteines in proteins. Commercial mouthwashes containing H2O2 provide the opportunity to determine clinically whether changes in S-glutathionylation of susceptible proteins in buccal mucosa cells can be used as biomarkers of ROS exposure.MethodsUsing an exploratory clinical protocol, 18 disease-free volunteers rinsed with a mouthwash containing 1.5% H2O2 (442mM) over four consecutive days. Exfoliated buccal cell samples were collected prior and post-treatment and proteomics were used to identify S-glutathionylated proteins.ResultsFour consecutive daily treatments with the H2O2-containing mouthwash induced significant dose and time-dependent increases in S-glutathionylation of buccal cell proteins, stable for at least 30min following treatments. Elevated levels of S-glutathionylation were maintained with subsequent daily exposure. Increased S-glutathionylation preceded and correlated with transcriptional activation of ROS sensitive genes, such as ATF3, and with the presence of 8-hydroxy deoxyguanosine. Data from a human buccal cell line TR146 were consistent with the trial results. We identified twelve proteins that were S-glutathionylated following H2O2 exposure.ConclusionsBuccal cells can predict exposure to ROS through increased levels of S-glutathionylation of proteins. These post-translationally modified proteins serve as biomarkers for the effects of H2O2 in the oral cavity and in the future, may be adaptable as extrapolated pharmacodynamic biomarkers for assessing the impact of other systemic drugs that cause ROS and/or impact redox homeostasis.General significanceS-glutathionylation of buccal cell proteins can be used as a quantitative measure of exposure to ROS
MGST1, a GSH transferase/peroxidase essential for development and hematopoietic stem cell differentiation.
We show for the first time that, in contrast to other glutathione transferases and peroxidases, deletion of microsomal glutathione transferase 1 (MGST1) in mice is embryonic lethal. To elucidate why, we used zebrafish development as a model system and found that knockdown of MGST1 produced impaired hematopoiesis. We show that MGST1 is expressed early during zebrafish development and plays an important role in hematopoiesis. High expression of MGST1 was detected in regions of active hematopoiesis and co-expressed with markers for hematopoietic stem cells. Further, morpholino-mediated knock-down of MGST1 led to a significant reduction of differentiated hematopoietic cells both from the myeloid and the lymphoid lineages. In fact, hemoglobin was virtually absent in the knock-down fish as revealed by diaminofluorene staining. The impact of MGST1 on hematopoiesis was also shown in hematopoietic stem/progenitor cells (HSPC) isolated from mice, where it was expressed at high levels. Upon promoting HSPC differentiation, lentiviral shRNA MGST1 knockdown significantly reduced differentiated, dedicated cells of the hematopoietic system. Further, MGST1 knockdown resulted in a significant lowering of mitochondrial metabolism and an induction of glycolytic enzymes, energetic states closely coupled to HSPC dynamics. Thus, the non-selenium, glutathione dependent redox regulatory enzyme MGST1 is crucial for embryonic development and for hematopoiesis in vertebrates
Gait parameter estimation from a miniaturized ear-worn sensor using singular spectrum analysis and longest common subsequence
This paper presents a new approach to gait analysis and parameter estimation from a single miniaturised earworn sensor embedded with a triaxial accelerometer. Singular spectrum analysis (SSA) combined with the longest common subsequence (LCSS) algorithm has been used as a basis for gait parameter estimation. It incorporates information from all axes of the accelerometer to estimate parameters including swing, stance and stride times. Rather than only using local features of the raw signals, the periodicity of the signals is also taken into account. The hypotheses tested by this study include: 1) how accurate is the ear-worn sensor in terms of gait parameter extraction compared to the use of an instrumented treadmill; 2) does the ear-worn sensor provide a feasible option for assessment and quantification of gait pattern changes. Key gait events for normal subjects such as heel contact and toe off are validated with a high-speed camera, as well as a force-plate instrumented treadmill. Ten healthy adults walked for 20 minutes on a treadmill with an increasing incline of 2% every 2 minutes. The upper and lower limits of the absolute errors using 95% confidence intervals for swing, stance and stride times were obtained as 35.5±3.99ms, 36.9 ± 3.84ms, and 17.9 ± 2.29ms, respectively
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