School of Natural Sciences and Mathematics

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(111) Surface States of SnTe
(2014-12--08) Shi, Yin; Wu, Meng; Zhang, Fan; Feng, Ji; Zhang, Fan
The characterization and applications of topological insulators depend critically on their protected surface states, which, however, can be obscured by the presence of trivial dangling bond states. Our first-principle calculations show that this is the case for the pristine (111) surface of SnTe. Yet, the predicted surface states unfold when the dangling bond states are passivated in proper chemisorption. We further extract the anisotropic Fermi velocities, penetration lengths, and anisotropic spin textures of the unfolded (Gamma) over bar -and (M) over bar -surface states, which are consistent with the theory in Zhang et al. [Phys. Rev. B 86, 081303 (2012)]. More importantly, this chemisorption scheme provides an external control of the relative energies of different Dirac nodes, which is particularly desirable in multivalley transport.
2d Frequency-Domain Elastic Full-Waveform Inversion Using Time-Domain Modeling and a Multistep-Length Gradient Approach
(Soc Exploration Geophysicists, 2014-02-17) Xu, Kun; McMechan, George A.; McMechan, George A.
To decouple the parameters in elastic full-waveform inversion (FWI), we evaluated a new multistep-length gradient approach to assign individual weights separately for each parameter gradient and search for an optimal step length along the composite gradient direction. To perform wavefield extrapolations for the inversion, we used parallelized high-precision finite-element (FE) modeling in the time domain. The inversion was implemented in the frequency domain; the data were obtained at every subsurface grid point using the discrete Fourier transform at each time-domain extrapolation step. We also used frequency selection to reduce cycle skipping, time windowing to remove the artifacts associated with different source spatial patterns between the test and predicted data, and source wavelet estimation at the receivers over the full frequency spectrum by using a fast Fourier transform. In the inversion, the velocity and density re-constructions behaved differently; as a low-wavenumber tomography (for velocities) and as a high-wavenumber migration (for density). Because velocities and density were coupled to some extent, variations were usually underestimated (smoothed) for V_P and V_S and correspondingly overestimated (sharpened) for ρ. The impedances I_P and I_S from the products of the velocity and density results compensated for the under-or overestimations of their variations, so the recovered impedances were closer to the correct ones than V_P, V_S, and ρ were separately. Simultaneous reconstruction of V_P, V_S, and ρ was robust on the FE and finite-difference synthetic data (without surface waves) from the elastic Marmousi-2 model; satisfactory results are obtained for V_P, V_S, ρ, and the recovered I_P and I_S from their products. Convergence is fast, needing only a few tens of iterations, rather than a few hundreds of iterations that are typical in most other elastic FWI algorithms.
3CPET: Finding Co-Factor Complexes from ChIA-Pet Data Using a Hierarchical Dirichlet Process
(BioMed Central Ltd, 2015-12-22) Djekidel, Mohamed Nadhir; Liang, Zhengyu; Wang, Qi; Hu, Zhirui; Li, Guipeng; Chen, Yang; Zhang, Michael Q.; 0000 0001 1707 1372 (Zhang, MQ); Zhang, Michael Q.
Various efforts have been made to elucidate the cooperating proteins involved in maintaining chromatin interactions; however, many are still unknown. Here, we present 3CPET, a tool based on a non-parametric Bayesian approach, to infer the set of the most probable protein complexes involved in maintaining chromatin interactions and the regions that they may control, making it a valuable downstream analysis tool in chromatin conformation studies. 3CPET does so by combining data from ChIA-PET, transcription factor binding sites, and protein interactions. 3CPET results show biologically significant and accurate predictions when validated against experimental and simulation data.
3D, 9C Seismic Modeling and Inversion of Weyburn Field Data
(2012-06-18) Rusmanugroho, H.; McMechan, George A.; McMechan, George A.
Inversion of 3D, 9C wide azimuth vertical seismic profiling (VSP) data from the Weyburn Field for 21 independent elastic tensor elements was performed based on the Christoffel equation, using slowness and polarization vectors measured from field data. To check the ability of the resulting elastic tensor to account for the observed data, simulation of the 3C particle velocity seismograms was done using eighth-order, staggered-grid, finite-differencing with the elastic tensor as input. The inversion and forward modeling results were consistent with the anisotropic symmetry of the Weyburn Field being orthorhombic. It was dominated by a very strong, tranverse isotropy with a vertical symmetry axis, superimposed with minor near-vertical fractures with azimuth ∼55° from the inline direction. The predicted synthetic seismograms were very similar to the field VSP data. The examples defined and provided a validation of a complete workflow to recover an elastic tensor from 9C data. The number and values of the nonzero tensor elements identified the anisotropic symmetry present in the neighborhood of a 3C borehole geophone. Computation of parameter correlation matrices allowed evaluation of solution quality through relative parameter independence. © 2012 Society of Exploration Geophysicists.
The 4-D Microgravity Method for Waterflood Surveillance: A Model Study for the Prudhoe Bay Reservoir, Alaska
(Society of Exploration Geophysicists, 1999-01) Hare, J. L.; Ferguson, John F.; Aiken, Carlos L. V.; Brady, J. L.; 67724342 (Aiken, CLV); Ferguson, J. F.; Aiken, Carlos L. V.
Forward and inverse gravity modeling is carried out on a suite of reservoir simulations of a proposed water injection on the Prudhoe Bay reservoir, Alaska. A novel surveillance technique is developed in which surface gravity observations are used to monitor the progress of a gas cap waterflood in the reservoir at 8200-ft depth. The results of the modeling showed that the inversion of time-lapse gravity data is a viable technique for monitoring reservoir gas cap waterfloods. Forward and inverse gravity modeling is carried out on a suite of reservoir simulations of a proposed water injection in the Prudhoe Bay reservoir, Alaska. A novel surveillance technique is developed in which surface gravity observations are used to monitor the progress of a gas cap waterflood in the reservoir at 8200-ft (2500-m) depth. This cost-effective method requires that high-precision gravity surveys be repeated over periods of years. Differences in the gravity field with time reflect changes in the reservoir fluid densities. Preliminary field tests at Prudhoe Bay indicates survey accuracy of 5-10 μGal can be achieved for gravity data using a modified Lacoste and Romberg 'G' type meter or Scintrex CG-3M combined with the NAVSTAR Global Positioning System (GPS). Forward gravity modeling predicts variations in surface measurements of 100 μGal after 5 years of water injection, and 180-250 μGal after 15 years. We use a constrained least-squares method to invert synthetic gravity data for subsurface density distributions. The modeling procedure has been formulated and coded to allow testing of the models for sensitivity to gravity sampling patterns, noise types, and various constraints on model parameters such as density, total mass, and moment of inertia. Horizontal-feature resolution of the waterflood is about 5000 ft (1520 m) for constrained inverse models from synthetic gravity with 5 μGal standard deviation (SD) noise. The inversion method can account for total mass of injected water to within a few percent. Worst-case scenarios result from inversion of gravity data which are contaminated by high levels (greater than 10-15 μGal SD) of spatially correlated noise, in which case the total mass estimate from inverse models may over or underestimate the mass by 10-20%. The results of the modeling indicate that inversion of time-lapse gravity data is a viable technique for the monitoring of reservoir gas cap waterfloods.
5-Methoxy-α-Methyltryptamine (5-MeO-AMT), A Tryptamine Derivative, Induces Head-Twitch Responses in Mice through the Activation of Serotonin Receptor 2a in the Prefrontal Cortex
(Elsevier Science Bv, 2018-07-24) Abiero, Arvie; Botanas, Chrislean Jun; Sayson, Leandro Val; Custodio, Raly James; de la Peña, June Bryan; Kim, Mikyung; Lee, Hyun Jun; Seo, Joung-Wook; Ryu, In Soo; Chang, Cho Min; Yang, Ji Seul; Lee, Yong Sup; Jang, Choon-Gon; Kim, Hee Jin; Cheong, Jae Hoon; de la Peña, June Bryan
5-Methoxy-α-methyltryptamine (5-MeO-AMT) is a tryptamine derivative that is used recreationally because of its reported hallucinogenic and mood elevating effects. Studies suggest that the psychopharmacological effects of tryptamines involve serotonin receptor 2a (5-HTR2a) activation in the brain. The head-twitch response (HTR) is widely used as a behavioral correlate for assessing 5-HTR2a agonist activity of a drug. Thus, we investigated whether 5-MeO-AMT induces HTR in mice and explored its mechanism of action. 5-MeO-AMT (0.3, 1, 3, 10 mg/kg) was administered once a day for 7 days, and the HTR was measured after 1 day (acute) and 7 days (repeated) of administration. Another cohort of mice was treated with 5-HTR2a antagonist ketanserin (KS) before 5-MeO-AMT administration. We measured 5-HTR2a and 5-HTR2c mRNA levels in the prefrontal cortex of the mice treated acutely or repeatedly with 5-MeO-AMT. We performed western blotting to determine the effects of the drug on the expression of G protein (G_{q/11}), protein kinase C gamma (PKC-γ), and extracellular signal-regulated kinases 1/2 (ERK1/2), in addition to PKC-γ and ERK1/2 phosphorylation. Additionally, we evaluated potential rewarding and reinforcing effects of 5-MeO-AMT using locomotor sensitization, conditioned place preference (CPP), and self-administration (SA) paradigms. Acute 5-MeO-AMT administration elicited the HTR, while repeated administration resulted in tolerance. KS blocked the 5-MeO-AMT-induced HTR. 5-MeO-AMT increased 5-HTR2a mRNA levels and induced PKC-γ phosphorylation in the prefrontal cortex. 5-MeO-AMT did not induce locomotor sensitization, CPP, or SA. This study shows that 5-MeO-AMT induces HTR through 5-HTR2a activation in the prefrontal cortex, and may have low potential for abuse.
A Bayesian Latent Variable Approach to Aggregation of Partial and Top-Ranked Lists in Genomic Studies
(Wiley) Li, X.; Choudhary, Pankaj K.; Biswas, Swati; Wang, X.; 0000 0001 2704 188X (Biswas, S); 0000-0002-0398-7459 (Choudary, PK); Choudhary, Pankaj K.; Biswas, Swati
In genomic research, it is becoming increasingly popular to perform meta-analysis, the practice of combining results from multiple studies that target a common essential biological problem. Rank aggregation, a robust meta-analytic approach, consolidates such studies at the rank level. There exists extensive research on this topic, and various methods have been developed in the past. However, these methods have two major limitations when they are applied in the genomic context. First, they are mainly designed to work with full lists, whereas partial and/or top-ranked lists prevail in genomic studies. Second, the component studies are often clustered, and the existing methods fail to utilize such information. To address the above concerns, a Bayesian latent variable approach, called BiG, is proposed to formally deal with partial and top-ranked lists and incorporate the effect of clustering. Various reasonable prior specifications for variance parameters in hierarchical models are carefully studied and compared. Simulation results demonstrate the superior performance of BiG compared with other popular rank aggregation methods under various practical settings. A non–small-cell lung cancer data example is analyzed for illustration.
A Few-Minute Synthesis of CsPbBr₃ Nanolasers with a High Quality Factor by Spraying at Ambient Conditions
(Amer Chemical Soc, 2018-12-12) Pushkarev, Anatoly P.; Korolev, Viacheslav, I.; Markina, Daria, I.; Komissarenko, Filipp E.; Naujokaitis, Arnas; Drabavicius, Audrius; Pakstas, Vidas; Franckevicius, Marius; Khubezhov, Soslan A.; Sannikov, Denis A.; Zasedatelev, Anton, V.; Lagoudakis, Pavlos G.; Zakhidov, Anvar A.; Makarov, Sergey, V.; 0000-0003-3983-2229 (Zakhidov, AA); Zakhidov, Anvar A.
Inorganic cesium lead halide perovskite nanowires, generating laser emission in the broad spectral range at room temperature and low threshold, have become powerful tools for the cutting-edge applications in the optoelectronics and nanophotonics. However, to achieve high-quality nanowires with the outstanding optical properties, it was necessary to employ long-lasting and costly methods of their synthesis, as well as postsynthetic separation and transfer procedures that are not convenient for large-scale production. Here we report a novel approach to fabricate high quality CsPbBr₃ nanolasers obtained by rapid precipitation from dimethyl sulfoxide solution sprayed onto hydrophobic substrates at ambient conditions. The synthesis technique allows producing the well-separated nanowires with a broad size distribution of 2-50 μm in 5-7 min, being the fastest method to the best of our knowledge. The formation of nanowires occurs via ligand-assisted reprecipitation triggered by intermolecular proton transfer from (CH₃)₂CHOH to H₂O in the presence of a minor amount of water. The XRD patterns confirm an orthorhombic crystal structure of the as-grown CsPbBr₃ single nanowires. Scanning electron microscopy images reveal their regular shape and truncated pyramidal end facets, while high-resolution transmission electron microscopy ones demonstrate their single-crystal structure. The lifetime of excitonic emission of the nanowires is found to be 7 ns, when the samples are excited with energy below the lasing threshold, manifesting the low concentration of defect states. The measured nanolasers of different lengths exhibit pronounced stimulated emission above 13 μJ cm⁻² excitation threshold with quality factor Q = 1017-6166. Their high performance is assumed to be related to their monocrystalline structure, low concentration of defect states, and improved end facet reflectivity.
A Holistic View of Cancer Bioenergetics: Mitochondrial Function and Respiration Play Fundamental Roles in the Development and Progression of Diverse Tumors
(Springer) Alam, Md Maksudul; Lal, Sneha; FitzGerald, Keely E.; Zhang, Li; Alam, Md Maksudul; Lal, Sneha; FitzGerald, Keely E.; Zhang, Li
Since Otto Warburg made the first observation that tumor cells exhibit altered metabolism and bioenergetics in the 1920s, many scientists have tried to further the understanding of tumor bioenergetics. Particularly, in the past decade, the application of the state-of the-art metabolomics and genomics technologies has revealed the remarkable plasticity of tumor metabolism and bioenergetics. Firstly, a wide array of tumor cells have been shown to be able to use not only glucose, but also glutamine for generating cellular energy, reducing power, and metabolic building blocks for biosynthesis. Secondly, many types of cancer cells generate most of their cellular energy via mitochondrial respiration and oxidative phosphorylation. Glutamine is the preferred substrate for oxidative phosphorylation in tumor cells. Thirdly, tumor cells exhibit remarkable versatility in using bioenergetics substrates. Notably, tumor cells can use metabolic substrates donated by stromal cells for cellular energy generation via oxidative phosphorylation. Further, it has been shown that mitochondrial transfer is a critical mechanism for tumor cells with defective mitochondria to restore oxidative phosphorylation. The restoration is necessary for tumor cells to gain tumorigenic and metastatic potential. It is also worth noting that heme is essential for the biogenesis and proper functioning of mitochondrial respiratory chain complexes. Hence, it is not surprising that recent experimental data showed that heme flux and function are elevated in non-small cell lung cancer (NSCLC) cells and that elevated heme function promotes intensified oxygen consumption, thereby fueling tumor cell proliferation and function. Finally, emerging evidence increasingly suggests that clonal evolution and tumor genetic heterogeneity contribute to bioenergetic versatility of tumor cells, as well as tumor recurrence and drug resistance. Although mutations are found only in several metabolic enzymes in tumors, diverse mutations in signaling pathways and networks can cause changes in the expression and activity of metabolic enzymes, which likely enable tumor cells to gain their bioenergetic versatility. A better understanding of tumor bioenergetics should provide a more holistic approach to investigate cancer biology and therapeutics. This review therefore attempts to comprehensively consider and summarize the experimental data supporting our latest view of cancer bioenergetics.
A Multiscale Direct Solver for the Approximation of Flows in High Contrast Porous Media
(Elsevier B.V.) Akbari, H.; Engsig-Karup, A. P.; Ginting, V.; Pereira, L. Felipe; Pereira, L. Felipe
We consider a non-overlapping domain decomposition approach to approximate the solution of elliptic boundary value problems with high contrast in their coefficients. We propose a method such that initially local solutions subject to Robin boundary conditions in each primal subdomain are constructed with (locally conservative) finite element or finite volume methods. Then, a novel approach is introduced to obtain a (discontinuous) global solution in terms of linear combination of the local subdomain solutions. In the proposed algorithm the computation of local solutions for unions of subdomains are localized at nearest-neighbor subdomain boundaries, thus avoiding the solution of global interface problems. We remove discontinuities in a smoothing step that is defined on a staggered grid or dual subdomains. The resulting algorithm is naturally parallelizable and can be employed as a parallel direct solver, offering great potential for the numerical solution of large problems. In fact, subdomains can be considered small enough to fit well in GPUs and the proposed procedure can handle adaptive (in space) simulations effectively. Numerical simulations are presented and discussed. We demonstrate the effectiveness of the proposed approach with two and three dimensional high contrast and channelized coefficients, that lead to challenging approximation problems. The new procedure, although designed for parallel processing, is also of value for serial calculations. ©2019 Elsevier B.V.
A Multiscale Model to Study the Enhancement in the Compressive Strength of Multi-Walled CNT Sheet Overwrapped Carbon Fiber Composites
(Elsevier Ltd) Ravindranath, P. K.; Roy, S.; Unnikrishnan, V.; Wang, X.; Xu, Tingge; Baughman, Ray H.; Lu, Hongbing; 0000-0001-5845-5137 (Baughman, RH); Xu, Tingge; Baughman, Ray H.; Lu, Hongbing
The high tensile strength of polymer matrix composites is derived primarily from the high strength of the carbon fibers embedded in the polymer matrix. However, their compressive strength is generally much lower due to the fact that under compression, the fibers tend to fail through micro-buckling well before compressive fracture occurs. In this work, we consider multi-walled carbon nanotube (MWNT) sheets wrapped around carbon fiber at room temperature to improve fiber/matrix interfacial properties which, in turn, influences compressive strength of the composite. To investigate the effect of the wrapping of MWNT sheet on composite strength, Molecular Dynamics simulations were performed on an atomistic model of the interface region between the epoxy, carbon fiber and the scrolled MWNT sheets. The compressive strength of the unidirectional composite was computed using a novel hierarchical multi-scale model comprising of the rule of mixtures at the microscale, and the modified Argon's formula for composites at the macroscale. Model predictions were benchmarked through comparison with experimental data for different volume fractions of MWNT sheet. ©2019 Elsevier Ltd
A Novel Inhibitor of Pyruvate Dehydrogenase Kinase Stimulates Myocardial Carbohydrate Oxidation in Diet-Induced Obesity
(American Society for Biochemistry and Molecular Biology Inc.) Wu, C. -Y; Satapati, S.; Gui, W.; Max Wynn, R.; Sharma, G.; Lou, M.; Qi, X.; Burgess, S. C.; Malloy, C.; Khemtong, C.; Sherry, A. Dean; Chuang, D. T.; Merritt, M. E.; Sherry, A. Dean
The pyruvate dehydrogenase complex (PDC) is a key control point of energy metabolism and is subject to regulation by multiple mechanisms, including posttranslational phosphorylation by pyruvate dehydrogenase kinase (PDK). Pharmacological modulation of PDC activity could provide a new treatment for diabetic cardiomyopathy, as dysregulated substrate selection is concomitant with decreased heart function. Dichloroacetate (DCA), a classic PDK inhibitor, has been used to treat diabetic cardiomyopathy, but the lack of specificity and side effects of DCA indicate a more specific inhibitor of PDK is needed. This study was designed to determine the effects of a novel and highly selective PDK inhibitor, 2((2,4-dihydroxyphenyl)sulfonyl) isoindoline-4,6-diol (designated PS10), on pyruvate oxidation in diet-induced obese (DIO) mouse hearts compared with DCA-treated hearts. Four groups of mice were studied: lean control, DIO, DIO + DCA, and DIO + PS10. Both DCA and PS10 improved glucose tolerance in the intact animal. Pyruvate metabolism was studied in perfused hearts supplied with physiological mixtures of long chain fatty acids, lactate, and pyruvate. Analysis was performed using conventional ¹H and ¹³C isotopomer methods in combination with hyperpolarized [1-¹³C]pyruvate in the same hearts. PS10 and DCA both stimulated flux through PDC as measured by the appearance of hyperpolarized [¹³C]bicarbonate. DCA but not PS10 increased hyperpolarized [1-¹³C]lactate production. Total carbohydrate oxidation was reduced in DIO mouse hearts but increased by DCA and PS10, the latter doing so without increasing lactate production. The present results suggest that PS10 is a more suitable PDK inhibitor for treatment of diabetic cardiomyopathy.
A Phenotypic Cell-Binding Screen Identifies a Novel Compound Targeting Triple-Negative Breast Cancer
Chen, Luxi; Long, Chao; Youn, Jonghae; Lee, Jiyong; 0000-0002-4455-3358 (Lee, J); Chen, Luxi; Long, Chao; Youn, Jonghae; Lee, Jiyong
We describe a "phenotypic cell-binding screen" by which therapeutic candidate targeting cancer cells of a particular phenotype can be isolated without knowledge of drug targets. Chemical library beads are incubated with cancer cells of the phenotype of interest in the presence of cancer cells lacking the phenotype of interest, and then the beads bound to only cancer cells of the phenotype of interest are selected as hits. We have applied this screening strategy in discovering a novel compound (LC129-8) targeting triple-negative breast cancer (TNBC). LC129-8 displayed highly specific binding to TNBC in cancer cell lines and patient-derived tumor tissues. LC129-8 exerted anti-TNBC activity by inducing apoptosis, inhibiting proliferation, reversing epithelial-mesenchymal transition, downregulating cancer stem cell activity and blocking in vivo tumor growth.
A Type I Restriction-Modification System Associated with Enterococcus Faecium Subspecies Separation
(Amer Soc Microbiology, 2019-01-09) Huo, Wenwen; Adams, Hannah M.; Trejo, Cristian; Badia, Rohit; Palmer, Kelli L.; 0000-0002-7343-9271 (Palmer, KL); Huo, Wenwen; Adams, Hannah M.; Trejo, Cristian; Badia, Rohit; Palmer, Kelli L.
The gastrointestinal colonizer Enterococcus faecium is a leading cause of hospital-acquired infections. Multidrug-resistant (MDR) E. faecium isolates are particularly concerning for infection treatment. Previous comparative genomic studies revealed that subspecies referred to as clade A and clade B exist within E. faecium. MDR E. faecium isolates belong to clade A, while clade B consists of drug-susceptible fecal commensal E. faecium isolates. Isolates from clade A are further grouped into two subclades, clades A1 and A2. In general, clade A1 isolates are hospital-epidemic isolates, whereas clade A2 isolates are isolates from animals and sporadic human infections. Such phylogenetic separation indicates that reduced gene exchange occurs between the clades. We hypothesize that endogenous barriers to gene exchange exist between E. faecium clades. Restriction-modification (R-M) systems are such barriers in other microbes. We utilized a bioinformatics analysis coupled with second-generation and third-generation deep-sequencing platforms to characterize the methylomes of two representative E. faecium strains, one from clade A1 and one from clade B. We identified a type I R-M system that is clade A1 specific, is active for DNA methylation, and significantly reduces the transformability of clade A1 E. faecium. Based on our results, we conclude that R-M systems act as barriers to horizontal gene exchange in E. faecium and propose that R-M systems contribute to E. faecium subspecies separation. IMPORTANCE Enterococcus faecium is a leading cause of hospital-acquired infections around the world. Rising antibiotic resistance in certain E. faecium lineages leaves fewer treatment options. The overarching aim of this work was to determine whether restriction-modification (R-M) systems contribute to the structure of the E. faecium species, wherein hospital-epidemic and non-hospital-epidemic isolates have distinct evolutionary histories and highly resolved clade structures. R-M provides bacteria with a type of innate immunity to horizontal gene transfer (HGT). We identified a type I R-M system that is enriched in the hospital-epidemic clade and determined that it is active for DNA modification activity and significantly impacts HGT. Overall, this work is important because it provides a mechanism for the observed clade structure of E. faecium as well as a mechanism for facilitated gene exchange among hospital-epidemic E. faecium isolates.
Absence of Thermalization in Finite Isolated Interacting Floquet Systems
(Amer Physical Soc, 2018-10-22) Seetharam, Karthik; Titum, Paraj; Kolodrubetz, Michael; Refael, Gil; Kolodrubetz, Michael
Conventional wisdom suggests that the long-time behavior of isolated interacting periodically driven (Floquet) systems is a featureless maximal-entropy state characterized by an infinite temperature. Efforts to thwart this uninteresting fixed point include adding sufficient disorder to realize a Floquet many-body localized phase or working in a narrow region of drive frequencies to achieve glassy nonthermal behavior at long time. Here we show that in clean systems the Floquet eigenstates can exhibit nonthermal behavior due to finite system size. We consider a one-dimensional system of spinless fermions with nearest-neighbor interactions where the interaction term is driven. Interestingly, even with no static component of the interaction, the quasienergy spectrum contains gaps and a significant fraction of the Floquet eigenstates, at all quasienergies, have nonthermal average doublon densities. We show that this nonthermal behavior arises due to emergent integrability at large interaction strength and discuss how the integrability breaks down with power-law dependence on system size.
Accumulation Capacitance Frequency Dispersion of Ⅲ-Ⅴ Metal-Insulator-Semiconductor Devices due to Disorder Induced Gap States
(American Institute of Physics Inc., 2014-07-07) Galatage, R. V.; Zhernokletov, Dmitry M.; Dong, Hong; Brennan, Barry; Hinkle, Christopher L.; Wallace, Robert M.; Vogel, E. M.
The origin of the anomalous frequency dispersion in accumulation capacitance of metal-insulator-semiconductor devices on InGaAs and InP substrates is investigated using modeling, electrical characterization, and chemical characterization. A comparison of the border trap model and the disorder induced gap state model for frequency dispersion is performed. The fitting of both models to experimental data indicate that the defects responsible for the measured dispersion are within approximately 0.8nm of the surface of the crystalline semiconductor. The correlation between the spectroscopically detected bonding states at the dielectric/III-V interface, the interfacial defect density determined using capacitance-voltage, and modeled capacitance-voltage response strongly suggests that these defects are associated with the disruption of the III-V atomic bonding and not border traps associated with bonding defects within the high-k dielectric.
Activation of the Integrated Stress Response in Nociceptors Drives Methylglyoxal-Induced Pain
(Lippincott Williams & Wilkins, 2019-01) Barragan-Iglesias, Paulino; Kuhn, Jasper; Vidal-Cantu, Guadalupe C.; Belen Salinas-Abarca, Ana; Granados-Soto, Vinicio; Dussor, Gregory; Campbell, Zachary T.; Price, Theodore J.; 0000-0002-3768-6996 (Campbell, ZT); 0000-0002-6971-6221 (Price, TJ); Dussor, Gregory; Campbell, Zachary T.; Price, Theodore J.
Methylglyoxal (MGO) is a reactive glycolytic metabolite associated with painful diabetic neuropathy at plasma concentrations between 500 nM and 5 μM. The mechanisms through which MGO causes neuropathic pain at these pathological concentrations are not known. Because MGO has been linked to diabetic neuropathic pain, which is prevalent and poorly treated, insight into this unsolved biomedical problem could lead to much needed therapeutics. Our experiments provide compelling evidence that ~ 1-μM concentrations of MGO activate the integrated stress response (ISR) in IB4-positive nociceptors in the dorsal root ganglion (DRG) of mice in vivo and in vitro. Blocking the integrated stress response with a specific inhibitor (ISRIB) strongly attenuates and reverses MGO-evoked pain. Moreover, ISRIB reduces neuropathic pain induced by diabetes in both mice and rats. Our work elucidates the mechanism of action of MGO in the production of pain at pathophysiologically relevant concentrations and suggests a new pharmacological avenue for the treatment of diabetic and other types of MGO-driven neuropathic pain.
Activity and Pharmacology of Homemade Silver Nanoparticles in Refractory Metastatic Head and Neck Squamous Cell Cancer
(Wiley, 2018-12-11) Singh, Jasmine; Moore, William; Fattah, Farjana; Jiang, Xingya; Zheng, Jie; Kurian, Pamela; Beg, Muhammad S.; Khan, Saad A.; 0000-0001-8546-1882 (Zheng, J); 22147423113244881679 (Zheng, J); Jiang, Xingya; Zheng, Jie
Background Silver nanoparticles (AgNP) show efficacy in cancer cell lines. We present the first in-human outcome of AgNP in a cancer patient. Methods Homemade AgNP solution is manufactured using online instructions by a 78-year old male. He started consuming AgNP while on hospice after he developed nasal cavity squamous cell cancer metastatic to liver and lung. Results Electron microscopy of AgNP solution revealed bimodal nanoparticle size distribution: 3 and 12 nm. Inductively coupled plasma mass spectrometry showed basal silver ion concentrations of 32 ng/g, rising to 46 ng/g 1 hour after ingesting 60 mL of AgNP solution. Urine showed no AgNP. No toxicities were observed and he had complete radiographic resolution of his cancer. He remains without evidence of cancer 18 months later. Conclusions AgNP ingestion was associated with sustained radiographic resolution of cancer. Further testing of AgNP should be done to confirm its efficacy in head and neck cancer.
Activity-Dependent FUS Dysregulation Disrupts Synaptic Homeostasis
(Natl Acad Sciences, 2014-10-16) Sephton, Chantelle F.; Tang, Amy A.; Kulkarni, Ashwinikumar; West, James; Brooks, Mieu; Stubblefield, Jeremy J.; Liu, Yun; Zhang, Michael Q.; Green, Carla B.; Huber, Kimberly M.; Huang, Eric J.; Herz, Joachim; Yu, Gang; 0000 0001 1707 1372 (Zhang, MQ); 99086074‏ (Zhang, MQ); Zhang, Michael Q.
The RNA-binding protein fused-in-sarcoma (FUS) has been associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), two neurodegenerative disorders that share similar clinical and pathological features. Both missense mutations and overexpression of wild-type FUS protein can be pathogenic in human patients. To study the molecular and cellular basis by which FUS mutations and overexpression cause disease, we generated novel transgenic mice globally expressing low levels of human wild-type protein (FUSWT) and a pathological mutation (FUSR521G). FUSWT and FUSR521G mice that develop severe motor deficits also show neuroinflammation, denervated neuromuscular junctions, and premature death, phenocopying the human diseases. A portion of FUSR521G mice escape early lethality; these escapers have modest motor impairments and altered sociability, which correspond with a reduction of dendritic arbors and mature spines. Remarkably, only FUSR521G mice show dendritic defects; FUSWT mice do not. Activation of metabotropic glutamate receptors 1/5 in neocortical slices and isolated synaptoneurosomes increases endogenous mouse FUS and FUSWT protein levels but decreases the FUSR521G protein, providing a potential biochemical basis for the dendritic spine differences between FUSWT and FUSR521G mice.
Acute and Chronic Toxicity of Metal Oxide Nanoparticles in Chemical Mechanical Planarization Slurries with Daphnia Magna
(Royal Society of Chemistry) Karimi, Sarah; Troeung, Meiline; Wang, Ruhung; Draper, Rockford K.; Pantano, Paul; 0000-0001-5535-8358 (Pantano, P); Karimi, Sarah; Troeung, Meiline; Wang, Ruhung; Draper, Rockford K.; Pantano, Paul
The semiconductor manufacturing industry uses metal oxide nanoparticles (NPs), including colloidal silica (c-SiO₂), fumed silica (f-SiO₂), ceria (CeO₂), and alumina (Al₂O₃), as abrasives in chemical mechanical planarization (CMP) processes. Assessing the toxicity of NPs used in commercial CMP slurries is difficult because these mixtures may contain undefined toxic constituents. Herein, the fresh water flea Daphnia magna (D. magna) was used to assess the effects of four model CMP slurries that did not contain known toxic additives. In the acute toxicity assessments, the key findings were that c-SiO₂ slurry caused a modest increase in body size indicative of a hormetic stress response, that the Al₂O₃ slurry was toxic to D. magna with a calculated 96 h LC-50 of 1.1 mg mL-1, that the CeO₂ and Al₂O₃ slurries caused significant dose-dependent decreases in body size, and that NP dissolution was not responsible for these responses. In the chronic toxicity assessments, the key findings were that the c-SiO₂ slurry caused a modest increase in reproduction indicative of a hormetic stress response, that the Al₂O₃ slurry lead to a modest increase in morbidity and a significant decrease in body size, and that the CeO₂ and Al₂O₃ slurries caused dose-dependent decreases in reproductive output. The acute and chronic toxicity results demonstrate that different model CMP slurries exert distinct and unpredictable effects on D. magna morbidity, growth, and reproductive output. Especially important is that the CeO₂ and Al₂O₃ slurries reduced D. magna reproduction upon chronic exposure at low applied doses, which could have adverse consequences to aquatic ecosystems.

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