Therapeutic Implications of Targeting AKT Signaling in Melanoma

Identification of key enzymes regulating melanoma progression and drug resistance has the potential to lead to the development of novel, more effective targeted agents for inhibiting this deadly form of skin cancer. The Akt3, also known as protein kinase B gamma, pathway enzymes regulate diverse cellular processes including proliferation, survival, and invasion thereby promoting the development of melanoma. Accumulating preclinical evidence demonstrates that therapeutic agents targeting these kinases alone or in combination with other pathway members could be effective for the long-term treatment of advanced-stage disease. However, currently, no selective and effective therapeutic agent targeting these kinases has been identified for clinical use. This paper provides an overview of the key enzymes of the PI3K pathway with emphasis placed on Akt3 and the negative regulator of this kinase called PTEN (phosphatase and tensin homolog deleted on chromosome 10). Mechanisms regulating these enzymes, their substrates and therapeutic implications of targeting these proteins to treat melanoma are also discussed. Finally, key issues that remain to be answered and future directions for interested researchers pertaining to this signaling cascade are highlighted

Pressure induced electronic topological transition in Sb2S3

Pressure induced electronic topological transitions in the wide band gap semiconductor Sb2S3 (Eg = 1.7-1.8 eV) with similar crystal symmetry (SG: Pnma) to its illustrious analog, Sb2Se3, has been studied using Raman spectroscopy, resistivity and the available literature on the x-ray diffraction studies. In this report, the vibrational and the transport properties of Sb2S3 have been studied up to 22 GPa and 11 GPa, respectively. We observed the softening of phonon modes Ag(2), Ag(3) and B2g and a sharp anomaly in their line widths at 4 GPa. The resistivity studies also shows an anomaly around this pressure. The changes in resistivity as well as Raman line widths can be ascribed to the changes in the topology of the Fermi surface which induces the electron-phonon and the strong phonon-phonon coupling, indicating a clear evidence of the electronic topological transition (ETT) in Sb2S3. The pressure dependence of a/c ratio plot obtained from the literature showed a minimum at ~ 5 GPa, which is consistent with our high pressure Raman and resistivity results. Finally, we give the plausible reasons for the non-existence of a non-trivial topological state in Sb2S3 at high pressures.Comment: 24 pages, 6 Figures, 2 tables submitted for publicatio

Sorgoleone release from sorghum roots shapes the composition of nitrifying populations, total bacteria, and archaea and determines the level of nitrification

Sorgoleone is a secondary sorghum metabolite released from roots. It has allelopathic properties and is considered to inhibit ammonia-oxidizing archaea (AOA) and bacteria (AOB) responsible for the rate-limiting step (ammonia oxidation) in nitrification. Low activity of these microorganisms in soil may contribute to slow down nitrification and reduce nitrogen loss via denitrification and NO3 − leaching. The potential nitrification rate (PNR) and the composition of microbial communities were monitored in rhizosphere soil to investigate the growth effect sorghum on biological nitrification inhibition (BNI). A greenhouse pipe experiment was conducted using sorghum lines IS20205 (highsorgoleone release ability), IS32234 (medium-sorgoleone release ability), 296B (low-sorgoleone release ability), and a control (no plants) combined with fertilization application of 0 or 120 kg N ha−1. We applied nitrogen as ammonium sulfate at 16 days (20 N), 37 days (40 N), and 54 days (60 N). We collected soil solutions at 7.5 cm depths every 3 days and measured the pH and nitrate levels. At 1 and 2.3 months, we sampled the bulk and rhizosphere soils and roots in the 0–10 cm, 10–30 cm, and 30–80 cm depths to determine NO2, mineral N, total N, total C, sorgoleone, the composition of AOA, AOB, and total bacteria and archaea. Sorgoleone was continuously released throughout the 2.3 months’ growth and was significantly higher in IS20205, followed by IS32234 then 296B, which showed shallow levels. The IS2020 5rhizosphere showed lower NO2 and nitrate levels and significant inhibition of AOA populations. However, we did not find significant differences in the abundance of AOB between plant treatments. Multivariate analysis and Spearman’s correlations revealed that sorgoleone as well as environmental factors such as soil pH, soil moisture, NO3 −-N, and NH4 +- N shape the composition of microbial communities. This study demonstrated that the release of higher amounts of sorgoleone has great potential to inhibit the abundance of AOA and soil nitrification. The breeding of sorghum lines with the ability to release higher amounts of sorgoleone could be a strategic way to improve the biological nitrification inhibition during cultivation

Additional Ultracool White Dwarfs Found in the Sloan Digital Sky Survey

We identify seven new ultracool white dwarfs discovered in the Sloan Digital Sky Survey (SDSS). The SDSS photometry, spectra, and proper motions are presented, and additional BVRI data are given for these and other previously discovered ultracool white dwarfs. The observed colors span a remarkably wide range, qualitatively similar to colors predicted by models for very cool white dwarfs. One of the new stars (SDSS J1251+44) exhibits strong collision-induced absorption (CIA) in its spectra, while the spectra and colors of the other six are consistent with mild CIA. Another of the new discoveries (SDSS J2239+00A) is part of a binary system -- its companion is also a cool white dwarf, and other data indicate that the companion exhibits an infrared flux deficiency, making this the first binary system composed of two CIA white dwarfs. A third discovery (SDSS J0310-00) has weak Balmer emission lines. The proper motions of all seven stars are consistent with membership in the disk or thick disk.Comment: Accepted for Astrophysical Journal. 16 pages (includes 3 figures

Requirements for Defining Utility Drive Cycles: An Exploratory Analysis of Grid Frequency Regulation Data for Establishing Battery Performance Testing Standards

Battery testing procedures are important for understanding battery performance, including degradation over the life of the battery. Standards are important to provide clear rules and uniformity to an industry. The work described in this report addresses the need for standard battery testing procedures that reflect real-world applications of energy storage systems to provide regulation services to grid operators. This work was motivated by the need to develop Vehicle-to-Grid (V2G) testing procedures, or V2G drive cycles. Likewise, the stationary energy storage community is equally interested in standardized testing protocols that reflect real-world grid applications for providing regulation services. As the first of several steps toward standardizing battery testing cycles, this work focused on a statistical analysis of frequency regulation signals from the Pennsylvania-New Jersey-Maryland Interconnect with the goal to identify patterns in the regulation signal that would be representative of the entire signal as a typical regulation data set. Results from an extensive time-series analysis are discussed, and the results are explained from both the statistical and the battery-testing perspectives. The results then are interpreted in the context of defining a small set of V2G drive cycles for standardization, offering some recommendations for the next steps toward standardizing testing protocols

Fuzzy Controlled 1-Φ Integrated AC/DC PFC Converter

Design and performance analysis of 1-Φ, single switch, isolate integrated AC/DC converter is presented in this work. In this proposed topology voltage across the bulk capacitor is low and having single switch, hence reduce in controller complexity and cost. Because of the robust and effective than conventional controllers, in this paper the fuzzy controller (FLC) is proposed to generate control signal to switch. The proposed converter has been implemented and evaluated using a Texas Instruments (TI) TMS320F2812. The proposed system is designed for input of (90–230 V, AC), 50 Hz, output of 48 V (DC) and operating at 100 kHz and verified experimentally & simulation at various load conditions. The designs and realizes digital (TMS320F2812) fuzzy controlled 1-Φ, single switch, integrated AC/DC converter meet the international regularity standards for class-C & D appliances

Fuzzy Controlled 1-Φ Integrated AC/DC PFC Converter

837-842Design and performance analysis of 1-Φ, single switch, isolate integrated AC/DC converter is presented in this work. In this proposed topology voltage across the bulk capacitor is low and having single switch, hence reduce in controller complexity and cost. Because of the robust and effective than conventional controllers, in this paper the fuzzy controller (FLC) is proposed to generate control signal to switch. The proposed converter has been implemented and evaluated using a Texas Instruments (TI) TMS320F2812. The proposed system is designed for input of (90–230 V, AC), 50 Hz, output of 48 V (DC) and operating at 100 kHz and verified experimentally & simulation at various load conditions. The designs and realizes digital (TMS320F2812) fuzzy controlled 1-Φ, single switch, integrated AC/DC converter meet the international regularity standards for class-C & D appliances