General analysis on the use of tesla's resonators in domino forms for wireless power transfer

In this paper, we present a brief overview of historical developments of wireless power and an analysis on the use of Tesla's resonators in domino forms for wireless power transfer. Relay resonators are spaced between the transmitter and receiver coils with the objectives of maximizing energy efficiency and increasing the overall transmission distance between the power source and the load. Analytical expressions for the optimal load and maximum efficiency at resonance frequency are derived. These equations are verified with practical measurements obtained from both coaxial and noncoaxial domino resonator systems. To avoid the use of high operating frequency for wireless power transfer in previous related research, the technique presented here can be used at submegahertz operation so as to minimize the power loss in both the power supply and the output stage. We demonstrated both theoretically and practically that unequal spacing for the coaxial straight domino systems has better efficiency performance than the equal-spacing method. Also, the flexibility of using resonators in various domino forms is demonstrated. © 2012 IEEE.published_or_final_versio

A single-phase three-level flying-capacitor PFC rectifier without electrolytic capacitors

A component-minimized and low-voltage-stress single-phase power factor correction rectifier without electrolytic capacitor is proposed in this paper. Component minimization is achieved by embedding an active pulsating-power-buffering (PPB) function within each switching period, such that typical add-on power electronic circuits for PPB are no longer needed. Additionally, with a three-level flying-capacitor configuration, the voltage stresses of switching devices can be reduced more than 50% as compared to existing solutions that are based on embedded PPB. The relationship between the inductance requirement and the patterns of the modulation carriers, and how it can be utilized to minimize the magnetics of the rectifier, is also discussed. A 110 W hardware prototype is designed and tested to demonstrate the feasibilities of the proposed rectifier. An input power factor of more than 0.97, peak efficiency of 95.1%, and an output voltage ripple of less than 4.3% across a wide load range have been experimentally obtained.</p

Design Considerations for Voltage Sensorless Control of a PFC Single-Phase Rectifier Without Electrolytic Capacitors

In this paper, a voltage sensorless controller is developed for a two-switch single-phase rectifier that involves power factor correction and active pulsating power buffering without electrolytic capacitors. While a two-switch rectifier normally requires four sensed signals for control, only one current sensor is required in this proposal, thereby offering advantages such as low cost, high compactness, isolation between control and power circuits, and improved reliability. While the basic operating principle follows that of a conventional voltage sensorless controller for single-switch converters, several critical design considerations are the key to the success of the implementation which is explained in detail. The feasibilities of the controller are experimentally testified with a 100-W rectifier prototype regarding both steady state and dynamic performance.</p

The Particle Spectrum of Heterotic Compactifications

Techniques are presented for computing the cohomology of stable, holomorphic vector bundles over elliptically fibered Calabi-Yau threefolds. These cohomology groups explicitly determine the spectrum of the low energy, four-dimensional theory. Generic points in vector bundle moduli space manifest an identical spectrum. However, it is shown that on subsets of moduli space of co-dimension one or higher, the spectrum can abruptly jump to many different values. Both analytic and numerical data illustrating this phenomenon are presented. This result opens the possibility of tunneling or phase transitions between different particle spectra in the same heterotic compactification. In the course of this discussion, a classification of SU(5) GUT theories within a specific context is presented.Comment: 77 pages, 3 figure

A Phos-Tag-Based Approach Reveals the Extent of Physiological Endoplasmic Reticulum Stress

Cellular response to endoplasmic reticulum (ER) stress or unfolded protein response (UPR) is a key defense mechanism associated with many human diseases. Despite its basic and clinical importance, the extent of ER stress inflicted by physiological and pathophysiological conditions remains difficult to quantitate, posing a huge obstacle that has hindered our further understanding of physiological UPR and its future therapeutic potential. Here we have optimized a Phos-tag-based system to detect the activation status of two proximal UPR sensors at the ER membrane. This method allowed for a quantitative assessment of the level of stress in the ER. Our data revealed quantitatively the extent of tissue-specific basal ER stress as well as ER stress caused by the accumulation of misfolded proteins and the fasting-refeeding cycle. Our study may pave the foundation for future studies on physiological UPR, aid in the diagnosis of ER-associated diseases and improve and facilitate therapeutic strategies targeting UPR in vivo

Regulation of PERK Signaling and Leukemic Cell Survival by a Novel Cytosolic Isoform of the UPR Regulator GRP78/BiP

The unfolded protein response (UPR) is an evolutionarily conserved mechanism to allow cells to adapt to stress targeting the endoplasmic reticulum (ER). Induction of ER chaperone GRP78/BiP increases protein folding capacity; as such it represents a major survival arm of UPR. Considering the central importance of the UPR in regulating cell survival and death, evidence is emerging that cells evolve feedback regulatory pathways to modulate the key UPR executors, however, the precise mechanisms remain to be elucidated. Here, we report the fortuitous discovery of GRP78va, a novel isoform of GRP78 generated by alternative splicing (retention of intron 1) and alternative translation initiation. Bioinformatic and biochemical analyses revealed that expression of GRP78va is enhanced by ER stress and is notably elevated in human leukemic cells and leukemia patients. In contrast to the canonical GRP78 which is primarily an ER lumenal protein, GRP78va is devoid of the ER signaling peptide and is cytosolic. Through specific knockdown of endogenous GRP78va by siRNA without affecting canonical GRP78, we showed that GRP78va promotes cell survival under ER stress. We further demonstrated that GRP78va has the ability to regulate PERK signaling and that GRP78va is able to interact with and antagonize PERK inhibitor P58IPK. Our study describes the discovery of GRP78va, a novel cytosolic isoform of GRP78/BiP, and the first characterization of the modulation of UPR signaling via alternative splicing of nuclear pre-mRNA. Our study further reveals a novel survival mechanism in leukemic cells and other cell types where GRP78va is expressed

Identification and single-base gene-editing functional validation of a cis-EPO variant as a genetic predictor for EPO-increasing therapies

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are currently under clinical development for treating anemia in chronic kidney disease (CKD), but it is important to monitor their cardiovascular safety. Genetic variants can be used as predictors to help inform the potential risk of adverse effects associated with drug treatments. We therefore aimed to use human genetics to help assess the risk of adverse cardiovascular events associated with therapeutically altered EPO levels to help inform clinical trials studying the safety of HIF-PHIs. By performing a genome-wide association meta-analysis of EPO (n = 6,127), we identified a cis-EPO variant (rs1617640) lying in the EPO promoter region. We validated this variant as most likely causal in controlling EPO levels by using genetic and functional approaches, including single-base gene editing. Using this variant as a partial predictor for therapeutic modulation of EPO and large genome-wide association data in Mendelian randomization tests, we found no evidence (at p < 0.05) that genetically predicted long-term rises in endogenous EPO, equivalent to a 2.2-unit increase, increased risk of coronary artery disease (CAD, OR [95% CI] = 1.01 [0.93, 1.07]), myocardial infarction (MI, OR [95% CI] = 0.99 [0.87, 1.15]), or stroke (OR [95% CI] = 0.97 [0.87, 1.07]). We could exclude increased odds of 1.15 for cardiovascular disease for a 2.2-unit EPO increase. A combination of genetic and functional studies provides a powerful approach to investigate the potential therapeutic profile of EPO-increasing therapies for treating anemia in CKD

GLP-1 Analogs Reduce Hepatocyte Steatosis and Improve Survival by Enhancing the Unfolded Protein Response and Promoting Macroautophagy

Nonalcoholic fatty liver disease (NAFLD) is a known outcome of hepatosteatosis. Free fatty acids (FFA) induce the unfolded protein response (UPR) or endoplasmic reticulum (ER) stress that may induce apoptosis. Recent data indicate ER stress to be a major player in the progression of fatty liver to more aggressive lesions. Autophagy on the other hand has been demonstrated to be protective against ER stress-induced cell death. We hypothesized that exendin-4 (GLP-1 analog) treatment of fat loaded hepatocytes can reduce steatosis by autophagy which leads to reduced ER stress-related hepatocyte apoptosis.Primary human hepatocytes were loaded with saturated, cis- and trans-unsaturated fatty acids (palmitic, oleic and elaidic acid respectively). Steatosis, induced with all three fatty acids, was significantly resolved after exendin-4 treatment. Exendin-4 sustained levels of GRP78 expression in fat-loaded cells when compared to untreated fat-loaded cells alone. In contrast, CHOP (C/EBP homologous protein); the penultimate protein that leads to ER stress-related cell death was significantly decreased by exendin-4 in hepatocytes loaded with fatty acids. Finally, exendin-4 in fat loaded hepatocytes clearly promoted gene products associated with macroautophagy as measured by enhanced production of both Beclin-1 and LC3B-II, markers for autophagy; and visualized by transmission electron microscopy (TEM). Similar observations were made in mouse liver lysates after mice were fed with high fat high fructose diet and treated with a long acting GLP-1 receptor agonist, liraglutide.GLP-1 proteins appear to protect hepatocytes from fatty acid-related death by prohibition of a dysfunctional ER stress response; and reduce fatty acid accumulation, by activation of both macro-and chaperone-mediated autophagy. These findings provide a novel role for GLP-1 proteins in halting the progression of more aggressive lesions from underlying steatosis in humans afflicted with NAFLD