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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,081 records · Page 60
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Imaginary resistor based Parity-Time symmetry electronics dimers

An approach of fabricating Parity-Time symmetry electronic dimers circuits is demonstrated using an imaginary resistor Z whose impedance is frequency independent. Remarkably, the dynamic rate equations of the coupled oscillators so-called ZRC dimers, uniquely consist of first order partial differential equations which result in a 2 ×2 effective Hamiltonians commuting with the joint Parity-Time (PT) operator. The method helps in describing two groups of PT symmetry electronics. The first group has an eigenspectrum that displays a single spontaneous PT transition or a thresholdless (THL) PT transition. The second group is a PT transitionless normal mode spectrum with essentially negative values of capacitors. The dynamics indicate that the system exhibits high frequencies propagation when operation is done before the thresholdless point is reached. The transitionless regime indicates an equilibrium point in the coupling for which the system turns to be conservative regardless the gain/loss values, and beyond which the gain/loss remarkably decays/amplifies wave. In addition, we observe a value of gain/loss above which there is a limitation of signal amplification.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2024

Enhancing scalability and accuracy of quantum poisson solver

The Poisson equation has many applications across the broad areas of science and engineering. Most quantum algorithms for the Poisson solver presented so far either suffer from lack of accuracy and/or are limited to very small sizes of the problem and thus have no practical usage. In this regard, our previous work showed a proof-of-concept demonstration in advancing quantum Poisson solver algorithm and validated preliminary results for a simple case of 3 x 3 problem. In this work, we delve into comprehensive research details, presenting the results on up to 15 x 15 problems that include step-by-step improvements in Poisson equation solutions, scaling performance, and experimental exploration. In particular, we demonstrate the implementation of eigenvalue amplification by a factor of up to 2 8 , achieving a significant improvement in the accuracy of our quantum Poisson solver and comparing that to the exact solution. Additionally, we present success probability results, highlighting the reliability of our quantum Poisson solver. Moreover, we explore the scaling performance of our algorithm against the circuit depth and width, demonstrating how our approach scales with larger problem sizes and thus further solidifies the practicality of easy adaptation of this algorithm in real-world applications. We also discuss a multilevel strategy for how this algorithm might be further improved to explore much larger problems with greater performance. Finally, through our experiments on the IBM quantum hardware, we conclude that though overall results on the existing NISQ hardware are dominated by the error in the CNOT gates, this work opens a path to realizing a multidimensional Poisson solver on near-term quantum hardware.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2018

Generation of X-Ray Radiation in Free-Electron Lasers with Two-Frequency Undulators

The possibility of creating an x-ray laser with a two-frequency undulator with the help of the phenomenological model of a single-pass free-electron laser (FEL) that takes into account the beam characteristics and the undulator field is studied. The model is used to analyze the FEL dynamics, and the simulation results are compared with the experimental data. The advantages of using a two-frequency undulator in the single-pass FEL and the possibility of generating powerful x-ray radiation in it are demonstrated. The evolution of power of higher-harmonic generation in the FEL and the bunching coefficient at wavelengths of these harmonics are studied. The possibility of their further amplification until saturation in a cascade FEL matched to higher harmonics of the two-frequency undulator is demonstrated.

43 PARTICLE ACCELERATORS↗
DOE OSTI2018

Multicascade X-Ray Free-Electron Laser with Harmonic Multiplier and Two-Frequency Undulator

The feasibility of generation of powerful x-ray radiation by a cascade free-electron laser (FEL) with amplification of higher harmonics using a two-frequency undulator is studied. To analyze the FEL operation, a complex phenomenological single-pass FEL model is developed and used. It describes linear and nonlinear generation of harmonics in the FEL with seed laser that takes into account initial electron beam noise and describes all main losses of each harmonic in each FEL cascade. The model is also calibrated against and approved by the experimental FEL data and available results of three-dimensional numerical simulation. The electron beam in the undulator is assumed to be matched and focused, and the dynamics of power in the singlepass FEL with cascade harmonic multipliers is investigated to obtain x-ray laser radiation in the FEL having the shortest length, beam energy, and frequency of the seed laser as low as possible. In this context, the advantages of the two-frequency undulator used for generation of harmonics are demonstrated. The evolution of harmonics in a multicascade FEL with multiplication of harmonics is investigated. The operation of the cascade FEL at the wavelength λ = 1.14 nm, generating ~30 MW already on 38 m with the seed laser operating at a wavelength of 11.43 nm corresponding to the maximal reflectivity of the multilayered mirror MoRu/Be coating is investigated. In addition, the operation of the multicascade FEL with accessible seed UVlaser operating at a wavelength of 157 nm (F2 excimer UV-laser) and electron beam with energy of ~0.5 GeV is investigated. X-ray radiation simulated in it at the wavelength λ ~ 3.9 nm reaches power of ~50 MW already at ~27 m, which is by two orders of magnitude shorter than 3.4 km of the x-ray FEL recently put into operation in Europe.

43 PARTICLE ACCELERATORS↗
DOE OSTI2019

Effectiveness of a genetic test panel designed for gynecological cancer: an exploratory study

To increase diagnostic efficiency and cost-effectiveness, we performed an exploratory genetic test using a newly designed panel containing 28 actionable and druggable genes, alterations in which are frequently reported in gynecological cancers (TANRE-G, Targeted variants ANalysis RElated to Gynecological cancers). Samples consisted of the formalin-fixed, paraffin-embedded tissue of endometrial (4 cases), cervical (3 cases), and ovarian (4 cases) carcinomas. The sequencing procedure was performed using Ion PGM in our institute with related sequencing kits, and data were analyzed using ClinVar. The present system achieved more than 2500 reads in all tumor samples, and enabled a copy number variation analysis. Results showed that actionable and druggable mutations were detected in 82% (9/11) and 64% (7/11) of cases, respectively, which was similar to other commercially available genetic tests. The amplification of MYC and KRAS was also detected. The analysis cost for each sample was JPY 94,000 (USD 850). These results demonstrate the potential of the TANRE-G panel as an effective tool for examining genetic alterations in gynecological cancers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

SOX4 is activated by C-MYC in prostate cancer

Although MYC proto-oncogene (C-MYC) amplification has been consistently reported to be a potential marker for prostate cancer (PCa) progression and prognosis, the clinicopathological and prognostic significance of C-MYC protein expression remains controversial. Overexpression of SOX4 has been shown to play important roles in multiple cancers including PCa. However, the link between these two critical genetic aberrations is unclear. In the current study, we showed that C-MYC was overexpressed in 16.2% (17/105) of Chinese patients with localized PCa. Overexpression of C-MYC was significantly associated with high Gleason scores (P = 0.012) and high Ki67 labeling index (P = 0.005). C-MYC overexpression was correlated with cancer-related mortality and suggested to be an unfavorable prognostic factor in Chinese PCa patients (P = 0.018). Overexpression of C-MYC is associated with SOX4 overexpression in PCa tissues. Notably, SOX4 is a direct target gene of C-MYC; C-MYC activates SOX4 expression via binding to its promoter. In addition, Co-IP analysis demonstrated a physical interaction between C-MYC and SOX4 protein in PCa cells. Clinically, C-MYC+/SOX4+ characterized poor prognosis in a subset of PCa patients. In total, C-MYC overexpression may contribute to PCa progression by activating SOX4. Our findings highlight an important role of C-MYC/SOX4 in PCa progression in a subset of PCa patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Reassessing the Climate Change Narrative

Abstract We note that the atmosphere has distinct tropical and extratropical regimes. The tropical regime is significantly dependent on the greenhouse effect and is characterized by temperatures that are largely horizontally homogenized. The extratropical regime is dominated by large scale unstable convective eddies that transport heat between the tropics and the poles (leaving the poles warmer than they otherwise would be) and serve to determine the temperature difference between the tropics and the poles. Changes in tropical temperature and in the tropics-to-pole temperature difference both contribute to changes in global mean temperature. It turns out that changes in global mean temperature associated with major climate change (i.e., the last glacial maximum and the warm period of the Eocene about 50 million years ago) were associated primarily with changes in the tropics-to-pole temperature differences. By contrast, changes in global mean temperature over the past 150 years or so are almost entirely associated with changes in tropical temperature. Thus, there is no intrinsic amplification associated with a change in the tropics-to-pole temperature difference. However, model simulations of climate behave differently from both observations and from each other. In particular, they all show more significant contributions for the tropics-to-pole temperature difference – sometimes much more significant. They also show excessive tropical warming.

Meteorology & Atmospheric Sciences↗
DOE OSTI2013

Apoferritin Protein Nanoparticles Dually labeled with Aptamer and Horseradish Peroxidase as a Sensing Probe for Thrombin Detection

A sandwich-type electrochemical aptasensor has been developed for the detection of thrombin, based on dual signal-amplification using HRP and apoferritin. Aptamer1 (Apt1) loaded on core/shell Fe3O4/Au magnetic nanoparticle (AuMNP) was used as recognition elements, and apoferritin dually labeled with Aptamer2 (Apt2) and HRP was used as a detection probe. Sandwich-type complex, Apt1/thrombin/Apt2–apoferritin NPs–HRP was formed by the affinity reactions between AuMNPs–Apt1, thrombin, and Apt2–apoferritin–HRP. The complex was anchored on a screen-printed carbon electrode (SPCE). Differential pulse voltammetry (DPV) was used to monitor the electrode response. The proposed aptasensor yielded a linear current response to thrombin concentrations over a broad range of 0.5 pM to 100 pM with a detection limit of 0.07 pM (S/N = 3). The detection signal was amplified by using apoferritin and HRP. This nanoparticle-based aptasensor offers a new method for rapid, sensitive, selective, and inexpensive quantification of thrombin, and offers a promising potential in biomarker detection and disease diagnosis. --------------------------------------------------------------------------------

aptmer↗
DOE OSTI2013

Propagation of sound waves through a spatially homogeneous but smoothly time-dependent medium

The propagation of sound through a spatially homogeneous but non-stationary medium is investigated within the framework of fluid dynamics. For a non-vortical fluid, especially, a generalized wave equation is derived for the (scalar) potential of the fluid velocity distribution in dependence of the equilibrium mass density of the fluid and the sound wave velocity. A solution of this equation for a finite transition period τ is determined in terms of the hypergeometric function for a phenomenologically realistic, sigmoidal change of the mass density and sound wave velocity. Using this solution, it is shown that the energy flux of the sound wave is not conserved but increases always for the propagation through a non-stationary medium, independent of whether the equilibrium mass density is increased or decreased. It is found, moreover, that this amplification of the transmitted wave arises from an energy exchange with the medium and that its flux is equal to the (total) flux of the incident and the reflected wave. An interpretation of the reflected wave as a propagation of sound backward in time is given in close analogy to Feynman and Stueckelberg for the propagation of anti-particles. The reflection and transmission coefficients of sound propagating through a non-stationary medium is analyzed in more detail for hypersonic waves with transition periods τ between 15 and 200 ps as well as the transformation of infrasound waves in non-stationary oceans. -- Highlights: •Analytically exact study of sound propagation through a non-stationary medium. •Energy exchange between the non-stationary medium and the sound wave. •Transformation of hypersonic and ultrasound frequencies in non-stationary media. •Propagation of sound backward in time in close analogy to anti-particles. •Prediction of tsunamis both in spatially and temporally inhomogeneous oceans.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2016

Decoherence of odd compass states in the phase-sensitive amplifying/dissipating environment

We study the evolution of odd compass states (specific superpositions of four coherent states), governed by the standard master equation with phase-sensitive amplifying/attenuating terms, in the presence of a Hamiltonian describing a parametric degenerate linear amplifier. Explicit expressions for the time-dependent Wigner function are obtained. The time of disappearance of the so called “sub-Planck structures” is calculated using the negative value of the Wigner function at the origin of phase space. It is shown that this value rapidly decreases during a short “conventional interference degradation time” (CIDT), which is inversely proportional to the size of quantum superposition, provided the anti-Hermitian terms in the master equation are of the same order (or stronger) as the Hermitian ones (governing the parametric amplification). The CIDT is compared with the final positivization time (FPT), when the Wigner function becomes positive. It appears that the FPT does not depend on the size of superpositions, moreover, it can be much bigger in the amplifying media than in the attenuating ones. Paradoxically, strengthening the Hamiltonian part results in decreasing the CIDT, so that the CIDT almost does not depend on the size of superpositions in the asymptotical case of very weak reservoir coupling. We also analyze the evolution of the Mandel factor, showing that for some sets of parameters this factor remains significantly negative, even when the Wigner function becomes positive.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2018

Controllable generation of photons and phonons in a coupled Bose–Einstein condensate-optomechanical cavity via the parametric dynamical Casimir effect

We theoretically propose and investigate a feasible experimental scheme for the realization of the dynamical Casimir effect (DCE) in a hybrid optomechanical cavity with a moving end mirror containing an interacting cigar-shaped Bose–Einstein condensate (BEC). We show that in the red-detuned regime of cavity optomechanics together with the weak optomechanical coupling limit by coherent modulation of the s-wave scattering frequency of the BEC and the mechanical spring coefficient of the mechanical oscillator (MO), the mechanical and atomic quantum vacuum fluctuations are parametrically amplified, which consequently lead to the generation of the mechanical/Bogoliubov-type Casimir phonons. Interestingly, in the coherent regime corresponding to the case of largely different optomechanical coupling strengths of the cavity field to the BEC and the MO, or equivalently largely different cooperativities, one can generate a large number of Casimir photons due to the amplification of the intracavity vacuum fluctuations induced by the time modulations of the BEC and the MO. The number of generated Casimir particles are externally controllable by the cooperativities, and the modulation amplitudes of the atomic collisions rate and the mechanical spring coefficient.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2011

Tigutcystatin, a cysteine protease inhibitor from Triatoma infestans midgut expressed in response to Trypanosoma cruzi

Highlights: {yields} Tigutcystatin inhibits Trypanosoma cruzi cysteine proteases with high specificity. {yields} Tigutcystatin expression is up-regulated in response to T. cruzi infection. {yields} It is the first cysteine proteases inhibitor characterized from a triatomine insect. -- Abstract: The insect Triatoma infestans is a vector of Trypanosoma cruzi, the etiological agent of Chagas disease. A cDNA library was constructed from T. infestans anterior midgut, and 244 clones were sequenced. Among the EST sequences, an open reading frame (ORF) with homology to a cystatin type 2 precursor was identified. Then, a 288-bp cDNA fragment encoding mature cystatin (lacking signal peptide) named Tigutcystatin was cloned fused to a N-terminal His tag in pET-14b vector, and the protein expressed in Escherichia coli strain Rosetta gami. Tigutcystatin purified and cleaved by thrombin to remove His tag presented molecular mass of 11 kDa and 10,137 Da by SDS-PAGE and MALDI-TOF mass spectrometry, respectively. Purified Tigutcystatin was shown to be a tight inhibitor towards cruzain, a T. cruzi cathepsin L-like enzyme (K{sub i} = 3.29 nM) and human cathepsin L (K{sub i} = 3.78 nM). Tissue specific expression analysis showed that Tigutcystatin was mostly expressed in anterior midgut, although amplification in small intestine was also detected by semi quantitative RT-PCR. qReal time PCR confirmed that Tigutcystatin mRNA is significantly up-regulated in anterior midgut when T. infestans is infected with T. cruzi. Together, these results indicate that Tigutcystatin may be involved in modulation of T. cruzi in intestinal tract by inhibiting parasite cysteine proteases, which represent the virulence factors of this protozoan.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Rapid imaging of mycoplasma in solution using Atmospheric Scanning Electron Microscopy (ASEM)

Highlights: Black-Right-Pointing-Pointer Mycoplasma mobile was observed in buffer with the Atmospheric Scanning Electron Microscope. Black-Right-Pointing-Pointer Characteristic protein localizations were visualized using immuno-labeling. Black-Right-Pointing-Pointer M. mobile attached to sialic acid on the SiN film surface within minutes. Black-Right-Pointing-Pointer Cells were observed at low concentrations. Black-Right-Pointing-Pointer ASEM should promote study and early-stage diagnosis of mycoplasma. -- Abstract: Mycoplasma is a genus of bacterial pathogen that causes disease in vertebrates. In humans, the species Mycoplasma pneumoniae causes 15% or more of community-acquired pneumonia. Because this bacterium is tiny, corresponding in size to a large virus, diagnosis using optical microscopy is not easy. In current methods, chest X-rays are usually the first action, followed by serology, PCR amplification, and/or culture, but all of these are particularly difficult at an early stage of the disease. Using Mycoplasma mobile as a model species, we directly observed mycoplasma in buffer with the newly developed Atmospheric Scanning Electron Microscope (ASEM). This microscope features an open sample dish with a pressure-resistant thin film window in its base, through which the SEM beam scans samples in solution, from below. Because of its 2-3 {mu}m-deep scanning capability, it can observe the whole internal structure of mycoplasma cells stained with metal solutions. Characteristic protein localizations were visualized using immuno-labeling. Cells were observed at low concentrations, because suspended cells concentrate in the observable zone by attaching to sialic acid on the silicon nitride (SiN) film surface within minutes. These results suggest the applicability of the ASEM for the study of mycoplasmas as well as for early-stage mycoplasma infection diagnosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Quantitative analysis of wet-heat inactivation in bovine spongiform encephalopathy

Highlights: ► We quantitatively analyzed wet-heat inactivation of the BSE agent. ► Infectivity of the BSE macerate did not survive 155 °C wet-heat treatment. ► Once the sample was dehydrated, infectivity was observed even at 170 °C. ► A quantitative PMCA assay was used to evaluate the degree of BSE inactivation. - Abstract: The bovine spongiform encephalopathy (BSE) agent is resistant to conventional microbial inactivation procedures and thus threatens the safety of cattle products and by-products. To obtain information necessary to assess BSE inactivation, we performed quantitative analysis of wet-heat inactivation of infectivity in BSE-infected cattle spinal cords. Using a highly sensitive bioassay, we found that infectivity in BSE cattle macerates fell with increase in temperatures from 133 °C to 150 °C and was not detected in the samples subjected to temperatures above 155 °C. In dry cattle tissues, infectivity was detected even at 170 °C. Thus, BSE infectivity reduces with increase in wet-heat temperatures but is less affected when tissues are dehydrated prior to the wet-heat treatment. The results of the quantitative protein misfolding cyclic amplification assay also demonstrated that the level of the protease-resistant prion protein fell below the bioassay detection limit by wet-heat at 155 °C and higher and could help assess BSE inactivation. Our results show that BSE infectivity is strongly resistant to wet-heat inactivation and that it is necessary to pay attention to BSE decontamination in recycled cattle by-products.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

A novel photoinduced electron transfer (PET) primer technique for rapid real-time PCR detection of Cryptosporidium spp

Highlights: •Uses a single-labeled fluorescent primer for real-time PCR. •The detection sensitivity of PET PCR was comparable to TaqMan PCR. •Melt curve analysis can be performed to confirm target amplicon production. •Conventional PCR primers can be converted to PET PCR primers. -- Abstract: We report the development of a fluorescently labeled oligonucleotide primer that can be used to monitor real-time PCR. The primer has two parts, the 3′-end of the primer is complimentary to the target and a universal 17-mer stem loop at the 5′-end forms a hairpin structure. A fluorescent dye is attached to 5′-end of either the forward or reverse primer. The presence of guanosine residues at the first and second position of the 3′ dangling end effectively quenches the fluorescence due to the photo electron transfer (PET) mechanism. During the synthesis of nucleic acid, the hairpin structure is linearized and the fluorescence of the incorporated primer increases several-fold due to release of the fluorescently labeled tail and the absence of guanosine quenching. As amplicons are synthesized during nucleic acid amplification, the fluorescence increase in the reaction mixture can be measured with commercially available real-time PCR instruments. In addition, a melting procedure can be performed to denature the double-stranded amplicons, thereby generating fluorescence peaks that can differentiate primer dimers and other non-specific amplicons if formed during the reaction. We demonstrated the application of PET-PCR for the rapid detection and quantification of Cryptosporidium parvum DNA. Comparison with a previously published TaqMan® assay demonstrated that the two real-time PCR assays exhibited similar sensitivity for a dynamic range of detection of 6000–0.6 oocysts per reaction. PET PCR primers are simple to design and less-expensive than dual-labeled probe PCR methods, and should be of interest for use by laboratories operating in resource-limited environments.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Characterization of rat serum amyloid A4 (SAA4): A novel member of the SAA superfamily

Highlights: • The full length rat SAA4 (rSAA4) mRNA was characterized by rapid amplification of cDNA ends. • rSAA4 mRNA has 1830 bases including a GA dinucleotide tandem repeat in the 5′UTR. • Three consecutive C/EBP promoter elements are crucial for transcription of rSAA4. • rSAA4 is abundantly expressed in the liver on mRNA and protein level. - Abstract: The serum amyloid A (SAA) family of proteins is encoded by multiple genes, which display allelic variation and a high degree of homology in mammals. The SAA1/2 genes code for non-glycosylated acute-phase SAA1/2 proteins, that may increase up to 1000-fold during inflammation. The SAA4 gene, well characterized in humans (hSAA4) and mice (mSaa4) codes for a SAA4 protein that is glycosylated only in humans. We here report on a previously uncharacterized SAA4 gene (rSAA4) and its product in Rattus norvegicus, the only mammalian species known not to express acute-phase SAA. The exon/intron organization of rSAA4 is similar to that reported for hSAA4 and mSaa4. By performing 5′- and 3′RACE, we identified a 1830-bases containing rSAA4 mRNA (including a GA-dinucleotide tandem repeat). Highest rSAA4 mRNA expression was detected in rat liver. In McA-RH7777 rat hepatoma cells, rSAA4 transcription was significantly upregulated in response to LPS and IL-6 while IL-1α/β and TNFα were without effect. Luciferase assays with promoter-truncation constructs identified three proximal C/EBP-elements that mediate expression of rSAA4 in McA-RH7777 cells. In line with sequence prediction a 14-kDa non-glycosylated SAA4 protein is abundantly expressed in rat liver. Fluorescence microscopy revealed predominant localization of rSAA4-GFP-tagged fusion protein in the ER.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

YY1 positively regulates human UBIAD1 expression

Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K{sub 1}) and a series of bacterial menaquionones (MK-n; vitamin K{sub 2}). Menadione (vitamin K{sub 3}) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1 promoter.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation

The p53 tumor suppressor gene plays a critical role in regulation of proliferation, cell death and differentiation. The MDM2 oncoprotein is a major negative regulator for p53 by binding to and targeting p53 for proteasome-mediated degradation. The small molecule inhibitor, nutlin-3, disrupts MDM2-p53 interaction resulting in stabilization and activation of p53 protein. We have previously shown that nutlin-3 activates p53, leading to MDM2 accumulation as concomitant of reduced retinoblastoma (Rb) protein stability. It is well known that Rb is important in muscle development and myoblast differentiation and that rhabdomyosarcoma (RMS), or cancer of the skeletal muscle, typically harbors MDM2 amplification. In this study, we show that nutlin-3 inhibited myoblast proliferation and effectively prevented myoblast differentiation, as evidenced by lack of expression of muscle differentiation markers including myogenin and myosin heavy chain (MyHC), as well as a failure to form multinucleated myotubes, which were associated with dramatic increases in MDM2 expression and decrease in Rb protein levels. These results indicate that nutlin-3 can effectively inhibit muscle cell differentiation. - Highlights: • Nutlin-3 inhibits myoblast proliferation and prevents differentiation into myotubes. • Nutlin-3 increases MDM2 expression and down-regulates Rb protein levels. • This study has implication in nutlin-3 treatment of rhabdomyosarcomas.

60 APPLIED LIFE SCIENCES↗