Posted by: kelsijo97 | March 20, 2014

March 2014

Miskimins, W. Keith, H. J. Ahn, J. Y. Kim, S. Ryu, Y. S. Jung, & J. Y. Choi. (2014). Synergistic Anti-Cancer Effect of Phenformin and Oxamate. Plos One, 9(1).

Phenformin (phenethylbiguanide; an anti-diabetic agent) plus oxamate [lactate dehydrogenase (LDH) inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS). Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and F-18-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively.

Basic Biomedical Sciences, Vermillion Campus.


Shi, X. P., X. Chen, X. F. Li, …., Xuejun Wang, Q. P. Dou, & J. B. Liu. (2014). Gambogic Acid Induces Apoptosis in Imatinib-Resistant Chronic Myeloid Leukemia Cells via Inducing Proteasome Inhibition and Caspase-Dependent Bcr-Abl Downregulation. Clinical Cancer Research, 20(1), 151-163.

Purpose: Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of Bcr-Abl tyrosine kinase. Bcr-Abl-T315I is the predominant mutation that causes resistance to imatinib, cytotoxic drugs, and the second-generation tyrosine kinase inhibitors. The emergence of imatinib resistance in patients with CML leads to searching for novel approaches to the treatment of CML. Gambogic acid, a small molecule derived from Chinese herb gamboges, has been approved for phase II clinical trial for cancer therapy by the Chinese Food and Drug Administration (FDA). In this study, we investigated the effect of gambogic acid on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl. Experimental Design: CML cell lines (KBM5, KBM5-T315I, and K562), primary cells from patients with CML with clinical resistance to imatinib, and normal monocytes from healthy volunteers were treated with gambogic acid, imatinib, or their combination, followed by measuring the effects on cell growth, apoptosis, and signal pathways. The in vivo antitumor activity of gambogic acid and its combination with imatinib was also assessed with nude xenografts. Results: Gambogic acid induced apoptosis and cell proliferation inhibition in CML cells and inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Our data suggest that GA-induced proteasome inhibition is required for caspase activation in both imatinib-resistant and -sensitive CML cells, and caspase activation is required for gambogic acid-induced Bcr-Abl downregulation and apoptotic cell death. Conclusions: These findings suggest an alternative strategy to overcome imatinib resistance by enhancing Bcr-Abl downregulation with the medicinal compound gambogic acid, which may have great clinical significance in imatinib-resistant cancer therapy. (C) 2013 AACR.

Basic Biomedical Sciences, Vermillion Campus.


Zhang, Y. H., E. I. Dedkov, D. Teplitsky, Nathan Y. Weltman, C. J. Pol, V. Rajagopalan, . . . A. M. Gerdes. (2013). Both Hypothyroidism and Hyperthyroidism Increase Atrial Fibrillation Inducibility in Rats. Circulation-Arrhythmia and Electrophysiology, 6(5), 952-959.

Background Evidence indicates that cardiac hypothyroidism may contribute to heart failure progression. It is also known that heart failure is associated with an increased risk of atrial fibrillation (AF). Although it is established that hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is unclear. This study investigated the effects of different thyroid hormone levels, ranging from hypothyroidism to hyperthyroidism on AF inducibility in thyroidectomized rats. Methods and Results Thyroidectomized rats with serum-confirmed hypothyroidism 1 month after surgery were randomized into hypothyroid (N=9), euthyroid (N=9), and hyperthyroid (N=9) groups. Rats received placebo, 3.3-mg l-thyroxine (T4), or 20-mg T4 pellets (60-day release form) for 2 months, respectively. At the end of treatment, hypothyroid, euthyroid, and hyperthyroid status was confirmed. Hypothyroid animals showed cardiac atrophy and reduced cardiac systolic and diastolic functions, whereas hyperthyroid rats exhibited cardiac hypertrophy and increased cardiac function. Hypothyroidism and hyperthyroidism produced opposite electrophysiological changes in heart rates and atrial effective refractory period, but both significantly increased AF susceptibility. AF incidence was 78% in hypothyroid, 67% in hyperthyroid, and the duration of induced AF was also longer, compared with 11% in the euthyroid group (all P<0.05). Hypothyroidism increased atrial interstitial fibrosis, but connexin 43 was not affected. Conclusions Both hypothyroidism and hyperthyroidism lead to increased AF vulnerability in a rat thyroidectomy model. Our results stress that normal thyroid hormone levels are required to maintain normal cardiac electrophysiology and to prevent cardiac arrhythmias and AF.

Basic Biomedical Sciences, Vermillion Campus.


Kats, L. B., G. Bucciarelli, T. L. Vandergon, …., Jacob L. Kerby, & R. N. Fisher. (2013). Effects of natural flooding and manual trapping on the facilitation of invasive crayfish-native amphibian coexistence in a semi-arid perennial stream. Journal of Arid Environments, 98(x), 109-112.

Aquatic amphibians are known to be vulnerable to a myriad of invasive predators. Invasive crayfish are thought to have eliminated native populations of amphibians in some streams in the semi-arid Santa Monica Mountains of southern California. Despite their toxic skin secretions that defend them from native predators, newts are vulnerable to crayfish attacks, and crayfish have been observed attacking adult newts, and eating newt egg masses and larvae. For 15 years, we have observed invasive crayfish and native California newts coexisting in one stream in the Santa Monica Mountains. During that period, we monitored the densities of both crayfish and newt egg mass densities and compared these to annual rainfall totals. After three seasons of below average rainfall, we reduced crayfish numbers by manual trapping. Our long-term data indicated that crayfish did not fare well in years when rainfall is above the historic average. This invasive predator did not evolve with high velocity streams, and observations indicated that southern California storm events washed crayfish downstream, killing many of them. Newts exhibit increased reproduction in years when crayfish numbers were reduced. A comparison with a nearby stream that does not contain crayfish indicated that newt reproduction positively responded to increased rainfall, but that fluctuations were much greater in the stream that contains crayfish. We suggest that rainfall patterns help explain invasive crayfish/newt coexistence and that management for future coexistence may benefit from manual trapping. (C) 2013 Elsevier Ltd. All rights reserved.

Biology Department.


Liu, Ming, & David L. Swanson. (2014). Physiological Evidence That Anthropogenic Woodlots Can Substitute for Native Riparian Woodlands as Stopover Habitat for Migrant Birds. Physiological and Biochemical Zoology, 87(1), 183-195.

The ability to find sufficient high-quality stopover habitat is a crucial factor for successful migration for woodland migrant birds. Woodland habitats are scarce in the Northern Prairie region of North America, and natural woodlands have been greatly reduced concurrent with the appearance of small anthropogenic woodlands on the landscape. Landbird migrants use both natural and anthropogenic woodlands in this region as stopover habitats, but the relative quality of these two habitats is unknown. We assessed the relative habitat quality of the two habitats by comparing body mass (M-b) and plasma metabolites associated with fattening (triglycerides [TRIG]) or fat catabolism (-hydroxybutyrate [BUTY], glycerol [GLYC]) in individual species, taxa, and foraging guilds of migrating woodland birds during both spring and fall migrations. The only significant difference in M-b between birds in the two habitats occurred for fall yellow-rumped warblers (Setophaga coronata), where M-b was 8% greater in corridors than in woodlots. No significant between-habitat differences occurred for plasma TRIG at either season. Significant between-habitat differences for plasma BUTY occurred only for ruby-crowned kinglets (Regulus calendula; 61% higher in corridors) in fall. Plasma GLYC differed significantly between habitats for a few groups, including vireos (190% higher in woodlots), warbling vireos (Vireo gilvus; 263% higher in woodlots), and Nashville warblers (Oreothlypis ruficapilla; 226% higher in woodlots) in fall. The few significant differences and absence of a consistent direction of variation in M-b and plasma metabolites suggests similar stopover habitat quality in these two habitat types. Thus, during migration through the Northern Prairie region anthropogenic woodlots can, at least partially, substitute as stopover habitat for lost and degraded native riparian habitats for woodland birds.

Biology Department.


Swanson, David L., Marissa O. King, & Erin Harmon. (2014). Seasonal variation in pectoralis muscle and heart myostatin and tolloid-like proteinases in small birds: a regulatory role for seasonal phenotypic flexibility? Journal of Comparative Physiology B-Biochemical Systemic and Environmental Physiology, 184(2), 249-258.

Seasonally variable environments produce seasonal phenotypes in small birds such that winter birds have higher thermogenic capacities and pectoralis and heart masses. One potential regulator of these seasonal phenotypes is myostatin, a muscle growth inhibitor, which may be downregulated under conditions promoting increased energy demand. We examined summer-to-winter variation in skeletal muscle and heart masses and used qPCR and Western blots to measure levels of myostatin and its metalloproteinase activators TLL-1 and TLL-2 for two small temperate-zone resident birds, American goldfinches (Spinus tristis) and black-capped chickadees (Poecile atricapillus). Winter pectoralis and heart masses were significantly greater than in summer for American goldfinches. Neither myostatin expression nor protein levels differed significantly between seasons for goldfinch pectoralis. However, myostatin levels in goldfinch heart were significantly greater in summer than in winter, although heart myostatin expression was seasonally stable. In addition, expression of both metalloproteinase activators was greater in summer than in winter goldfinches for both pectoralis and heart, significantly so except for heart TLL-2 (P = 0.083). Black-capped chickadees showed no significant seasonal variation in muscle or heart masses. Seasonal patterns of pectoralis and heart expression and/or protein levels for myostatin and its metalloproteinase activators in chickadees showed no consistent seasonal trends, which may help explain the absence of significant seasonal variation in muscle or heart masses for chickadees in this study. These data are partially consistent with a regulatory role for myostatin, and especially myostatin processing capacity, in mediating seasonal metabolic phenotypes of small birds.

Biology Department.


Foss, Berit L., T. W. Maxwell, & Ying Deng. (2014). Chondroprotective supplementation promotes the mechanical properties of injectable scaffold for human nucleus pulposus tissue engineering. Journal of the Mechanical Behavior of Biomedical Materials, 29, 56-67.

A result of intervertebral disc (ND) degeneration, the nucleus pulposus (NP) is no longer able to withstand applied load leading to pain and disability. The objective of this study is to fabricate a tissue-engineered injectable scaffold with chondroprotective supplementation in vitro to improve the mechanical properties of a degenerative NP. Tissue-engineered scaffolds were fabricated using different concentrations of alginate and calcium chloride and mechanically evaluated. Fabrication conditions were based on structural and mechanical resemblance to the native NP. Chondroprotective supplementation, glucosamine (GCSN) and chondroitin sulfate (CS), were added to scaffolds at concentrations of 0:0 pg/mL (0:0-S), 125:100 lig/mL (125:100-S), (250:200-S), and 500:400 pg/mL (500:400-5), GCSN and CS, respectively. Scaffolds were used to fabricate tissue-engineered constructs through encapsulation of human nucleus pulposus cells (HNPCs). The tissue-engineered constructs were collected at days 1, 14, and 28 for biochemical and biomechanical evaluations. Confocal microscopy showed HNPC viability and rounded morphology over the 28 day period. MIT analysis resulted in significant increases in cell proliferation for each group. Collagen type II ELISA quantification and compressive aggregate moduli (HA) showed increasing trends for both 250:200-S and the 500:400-S groups on Day 28 with significantly greater HA compared to 0:0-S group. Glycosaminoglycan and water content decreased for all groups. Results indicate the increased mechanical properties of the 250:200-S and the 500:400-S was due to production of a functional matrix. This study demonstrated potential for a chondroprotective supplemented injectable scaffold to restore biomechanical function of a degenerative disc through the production of a mechanically functional matrix. (C) 2013 Elsevier Ltd. All rights reserved.

Biomedical Engineering, Sioux Falls Campus.


Anderson, R. B., S. J. Smith, P. Stanley May, & Mary T. Berry. (2014). Revisiting the NIR-to-Visible Upconversion Mechanism in beta-NaYF4:Yb3+,Er3+. Journal of Physical Chemistry Letters, 5(1), 36-42.

Here, we show that the long-accepted mechanism for the production of red and blue emission through upconversion (UC) of 1 mu m excitation in Yb3+/Er3+-doped materials does not apply in the popular beta-NaYF4 host. We propose a new mechanism involving Yb3+-to-Er3+ energy-transfer UC out of thegreen-emitting H-2(11/2), S-4(3/2) states that quantitatively accounts for all of the observed optical behavior. Rate constants for the relevant radiative and nonradiative processes are reported along with a prediction of the power dependence of the pulsed and continuous-wave UC quantum efficiency.

Chemistry Department.


Chen, Jiangchao, Qingguo Meng, P. Stanley May, Mary T. Berry, & Dimtri S. Kilin. (2014). Time-dependent excited-state molecular dynamics of photodissociation of lanthanide complexes for laser-assisted metal-organic chemical vapour deposition. Molecular Physics, 112(3-4), 508-517.

Ab initio molecular dynamics (AIMD) algorithm was modified for treating time-dependent excited-state molecular dynamics (TDESMD). This algorithm addresses the situations when electron density and nuclear potential are being periodically driven by a strong laser field, which induces periodic population-depopulation Rabi cycles. The electron hopping between different potential energy surfaces, such as ground state and ligand-to-metal charge-transfer (LMCT) state, creates the nuclear trajectories. In the computed trajectories, the inter-atomic distances can demonstrate different regimes, from small oscillations to abrupt elongations, corresponding to fragmentation of the studied compound. This algorithm was used to explore photodissociation mechanisms for laser-assisted metal-organic chemical vapour deposition (LCVD or laser-assisted MOCVD) process using lanthanide cyclopentadienyl-type precursors. The computed fragments are compared with the ones elucidated experimentally using photoionisation time-of-flight mass spectrometry.

Chemistry Department.


Chu, lek-Heng, Dimitri S. Kilin, & Hai-Ping Cheng. (2013). First-Principles Studies of Photoinduced Charge Transfer in Noncovalently Functionalized Carbon Nanotubes. Journal of Physical Chemistry C, 117(35), 17909-17918.

We have studied the energetics, electronic structure, optical excitation, and electron relaxation of dinitromethane molecules (CH2N2O4) adsorbed on semi-conducting carbon nanotubes (CNTs) of chiral index (n,0) (n = 7, 10, 13, 16, 19). Using first-principles density functional theory (DFT) with generalized gradient approximations and van der Waals corrections, we have calculated adsorption energies of dinitropentylpyrene, in which the dinitromethane is linked to the pyrene via an aliphatic chain, on a CNT. A 780 meV (18.0 kcal/mol) binding energy has been found, which explains why such aliphatic chain pyrene units can be and have been used in experiments to bind functional molecules to CNTs. The calculated electronic structures. show that the dinitromethane introduces a localized state inside the band gap of CNT systems of n = 10, 13, 16. and 19; such a state can trap an electron when the CNT is photoexcited. We have therefore investigated the dynamics of intraband relaxations using the reduced density matrix formalism in conjunction with Dn. For pristine CNTs, we have found that the calculated charge relaxation constants agree well with the experimental time scales, Upon adsorption, these constants are modified, but there is not a clear trend for the direction and magnitude of the change. Nevertheless, our calculations predict that electron relaxation in the conduction band is faster than hole relaxation in the valence band for CNTs with and without molecular adsorbates.

Chemistry Department.


Han, Yulun, S. Tretiak, & Dmitri S. Kilin. (2014). Dynamics of charge transfer at Au/Si metal-semiconductor nano-interface. Molecular Physics, 112(3-4), 474-484.

An ab initio analysis of the periodic array of Au/Si nanostructure composed of gold clusters linked to silicon quantum dot (QD) co-doped by aluminium and phosphorus along [111] direction is presented in this paper. The density functional theory (DFT) is used to compute the electronic structure of the simulated system. Non-adiabatic coupling implemented in the form of dissipative equation of motion for reduced density matrix is used to study the phonon-induced relaxation in the simulated system. The density of states clearly shows that the formation of Au-Si bonds contributes states to the band gap of the model. Dynamics of selected photo-excitations shows that hole relaxation in energy and in space is much faster than electron relaxation, which is due to the higher density of states of the valence band.

Chemistry Department.


Huang, Shuping, & Dmitri S. Kilin. (2014). Electronic structure and hot carrier relaxation in (001) anatase TiO2 nanowire. Molecular Physics, 112(3-4), 539-545.

We present an electronic structure and non-adiabatic excited state dynamics study of 001 anatase TiO2 nanowire (NW) by combining density matrix formalism and ab initio electronic structure calculations. Our results show that quantum confinement increases the energy gap as the dimension of TiO2 is reduced from the bulk to a NW with a diameter of several nanometres and that the probability of electronic transitions induced by lattice vibrations for the NW follows band gap law. The electron non-radiative relaxation to the bottom of the conduction band is involving Ti 3d orbitals, while the hole non-radiative relaxation of holes to the top of the valence band occurs by subsequent occupation of O 2p orbitals.

Chemistry Department.


Kryjevski, Andrei, & Dmitri S. Kilin. (2014). Multiple exciton generation in silicon quantum dot arrays: density functional perturbation theory computation. Molecular Physics, 112(3-4), 430-440.

We use the density functional theory (DFT) combined with the many-body perturbation theory to derive expressions for the rates of the optical photonexciton and photonbi-exciton processes in nanoparticles, and for quantum efficiency, all to the leading order in the screened Coulomb interaction between Kohn-Sham quasiparticles. Also, we calculate excitonbi-exciton rates due to the impact ionisation (II) mechanism in Si29H36 quantum dots (QDs) with both crystalline and amorphous core structures, and in quasi-one dimensional (1-D) arrays constructed from these QDs. We observe significant dependence of the carrier multiplication rates on the structure’s morphology and structural disorder. Amorphous silicon QD arrays are predicted to have more efficient bi-exciton generation rates as a function of exciton energy compared to their crystalline counterparts, and the isolated QDs of both kinds.

Chemistry Department.


Mottishaw, Jeffrey D., Dimitri S. Kilin, H. P. Cheng, V. V. Karasiev, Q. H. Fan, & Haoran Sun. (2014). Elucidating the role of non-radiative processes in charge transfer of core-shell Si SiO2 nanoparticles. Molecular Physics, 112(3-4), 422-429.

Crystalline silicon is the most commonly used material in photovoltaics but has limitations due to its high cost and non-tunable band gap. A new approach of using inexpensive, non-toxic materials with layers that have different band gaps which absorb a wide range of the solar spectrum has the potential to dramatically increase the efficiencies and lower the costs. Core-shell Si-SiO2 nanoparticles are ideally suited for the photovoltaic application and have been synthesised by different groups in an array of sizes allowing for absorption in a wide spectral range. A theoretical investigation of fundamental charge transfer processes in these systems can potentially lead to improved devices. Calculations on a model core-shell interface with the formula Si264O160 which features a silicon layer sandwiched between two SiO2 layers were performed using the Vienna ab initio software package. The Perdew-Burke-Ernzerhof functional in the basis of plane waves was used along with pseudopotentials to simulate electronic structure. The nuclear motion was considered using ab initio molecular dynamics. The density of states, absorption spectrum, partial charge densities, and radiative recombination lifetimes have been calculated. This interface shows quantum confinement behaviour similar to a particle in a box. The role of non-radiative recombination was also determined by relaxation dynamics.

Chemistry Department.


Peng, Rui, Cuikun Lin, J. Baltrusaitis, C. M. Wu, N. M. Dimitrijevic, T. Rajh, . . . Ranjit T. Koodali. (2014). Insight into band positions and inter-particle electron transfer dynamics between CdS nanoclusters and spatially isolated TiO2 dispersed in cubic MCM-48 mesoporous materials: a highly efficient system for photocatalytic hydrogen evolution under visible light illumination. Physical Chemistry Chemical Physics, 16(5), 2048-2061.

CdS incorporated Si-MCM-48 and Ti-MCM-48 cubic phased mesoporous photocatalysts were prepared by a two-step modification synthetic approach under relatively mild conditions. A highly efficient (24.8%, apparent quantum yield (AQY)) photocatalyst for visible light (lambda > 400 nm) enabled solar hydrogen evolution can be realized by assembling CdS with Ti-MCM-48 cubic mesoporous materials in the absence of a noble metal co-catalyst. The photocatalytic mechanism was thoroughly investigated and demonstrated by conducting a wealth of characterization techniques such as powder X-ray diffraction (XRD), nitrogen adsorption isotherm, transmission electron microscopy (TEM), UV-visible diffuse reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UVPS), atomic absorption spectroscopy (AAS), photoluminescence (PL) spectroscopy, time-resolved fluorescence emission decay, and electron paramagnetic resonance (EPR) spectroscopy studies. This work is the first to unambiguously identify the band positions of both CdS and TiO2 encapsulated in porous materials. The photocatalytic activity of the CdS incorporated Ti-MCM-48 mesoporous photocatalysts was found to be dependent on the content of both CdS and TiO2. A correlation between the electron injection efficiency and the photocatalytic activity was established as well in the CdS incorporated Ti-MCM-48 mesoporous photocatalysts.

Chemistry Department.


Putta, Anjaneyulu, Jeffrey D. Mottishaw, Zhihua H. Wang, & Haoran R. Sun. (2014). Rational Design of Lamellar pi-pi Stacked Organic Crystalline Materials with Short Interplanar Distance. Crystal Growth & Design, 14(1), 350-356.

Organic crystalline materials having a lamellar pi-pi stacked structural motif with short interplanar distance are significant for many applications. By asymmetrically introducing perfluoroalkyl substituents onto and polarizable sulfur atoms into N-containing heteroaromatics, we successfully synthesized a novel type of aromatic material that preferentially forms lamellar pi-pi stacked crystalline materials with a interplanar pi-pi distance of 3.247 angstrom, more than 0.1 angstrom shorter than that of highly oriented pyrolytic graphite (HOPG) where interplanar distance ranges from 3.35 to 3.39 angstrom.

Chemistry Department.


Yao, Ge, Shuping Huang, Mary T. Berry, P. Stanley May, & Dmitri S. Kilin. (2014). Non-collinear spin DFT for lanthanide ions in doped hexagonal NaYF4. Molecular Physics, 112(3-4), 546-556.

Trivalent lanthanide ions (Ln(3+)) doped in hexagonal ()-NaYF4 nanocrystals (Na(24)Y(23)Ln(1)F(96), Ln = La, Ce, Pr, Nd, Pm, Sm, Eu, Gd) were systematically studied by density functional theory (DFT) with a perturbative account for spin-orbit coupling. The simulated results, including the optimised molecular structures, electronic and magnetic properties, are compared to previous spin-polarised DFT studies in the same system. The spin-orbit coupling effects become significant with the increase in the number of unpaired 4f electrons in the doped lanthanide ions, particularly for the Sm3+-, Eu3+- and Gd3+-doped nanocrystals. Abnormal behaviour of Eu3+-doped nanocrystals was observed due to the Wybourne-Downer mechanism. A sandwich-like’ 2p-4f-4d,5d electronic structure for Na(24)Y(23)Ln(1)F(96) and the energies of the highest occupied 4f electrons from Ce3+ to Gd3+ are consistent with Dorenbos’s relationship. The energy difference between the first and second Russell-Saunders terms (L2S+1) of the lanthanide dopant is consistent with Carnall’s experimental results and with earlier spin-polarised DFT calculations.

Chemistry Department.


Zhang, Yuchi, Chao Qiu, & Dmitri S. Kilin. (2014). Electron dynamics in charged wet TiO2 anatase (001) surface functionalised by ruthenium ions. Molecular Physics, 112(3-4), 441-452.

The surface of charged wet TiO2 anatase (001) functionalised by ruthenium ion at ambient temperatures is studied by computational modelling. Response of this model to photoexcitations at ambient temperatures is explored with the Redfield density matrix equation of motion on the basis of Kohn-Sham orbitals. The parameters of the Redfield equation are on-the-fly non-adiabatic couplings for electronic degrees of freedom obtained along the ab initio molecular dynamics nuclear trajectories. The main results in this study are the following: (1) optical properties of the doped models such as light absorption intensity and transition energies can be tuned by modifying total charge; (2) electron and hole relaxation rates depend on the initial excitation; and (3) in the doped model, excitations of lower energy provide quicker relaxation. Results of computational modelling would benefit understanding of the mechanism of electron transfer processes on the surface of ruthenium-doped TiO2.

Chemistry Department.


Zhang, Z. L., M. Dubey, D. Galipeau, Q. H. Fan, James D. Hoefelmeyer, & I. Y. Al-Qaradawi. (2013). Creating textured surfaces using plasma electrolysis. Mrs Communications, 3(4), 255-258.

Plasma electrolysis (PE) is a combination of electrolysis and plasma discharge. Previous studies indicated that PE usually created porous surface with irregular morphology as a result of the plasma-cathode interaction that was dominated by physical reactions. This paper demonstrated that highly ordered textured silicon surfaces could be created using PE. This abnormal anisotropic etching phenomenon implied that the chemical reactions were decoupled from the physical processes and the physical reactions were suppressed. Raman spectra confirmed that the textured silicon surface created by PE conserved the crystalline structure. Therefore, PE may lead to new process regimes for surface engineering.

Chemistry Department.


May, P. A., B. G. Tabachnick, J. P. Gossage, …., H. Eugene Hoyme, & C. M. Adnams. (2013). Maternal Factors Predicting Cognitive and Behavioral Characteristics of Children with Fetal Alcohol Spectrum Disorders. Journal of Developmental and Behavioral Pediatrics, 34(5), 314-325.

Objective: To provide an analysis of multiple predictors of cognitive and behavioral traits for children with fetal alcohol spectrum disorders (FASDs). Method: Multivariate correlation techniques were used with maternal and child data from epidemiologic studies in a community in South Africa. Data on 561 first-grade children with fetal alcohol syndrome (FAS), partial FAS (PFAS), and not FASD and their mothers were analyzed by grouping 19 maternal variables into categories (physical, demographic, childbearing, and drinking) and used in structural equation models (SEMs) to assess correlates of child intelligence (verbal and nonverbal) and behavior. Results: A first SEM using only 7 maternal alcohol use variables to predict cognitive/behavioral traits was statistically significant (B = 3.10, p < .05) but explained only 17.3% of the variance. The second model incorporated multiple maternal variables and was statistically significant explaining 55.3% of the variance. Significantly correlated with low intelligence and problem behavior were demographic (B = 3.83, p < .05) (low maternal education, low socioeconomic status [SES], and rural residence) and maternal physical characteristics (B = 2.70,p < .05) (short stature, small head circumference, and low weight). Childbearing history and alcohol use composites were not statistically significant in the final complex model and were overpowered by SES and maternal physical traits. Conclusions: Although other analytic techniques have amply demonstrated the negative effects of maternal drinking on intelligence and behavior, this highly controlled analysis of multiple maternal influences reveals that maternal demographics and physical traits make a significant enabling or disabling contribution to child functioning in FASD.

May, Philip A. Tabachnick, Barbara G. Gossage, J. Phillip Kalberg, Wendy O. Marais, Anna-Susan Robinson, Luther K. Manning, Melanie A. Blankenship, Jason Buckley, David Hoyme, H. Eugene Adnams, Colleen M.


Bersamin, M. M., B. L. Zamboanga, S. J. Schwartz, M. B. Donnellan, …., & S. Jean Caraway. (2014). Risky Business: Is There an Association between Casual Sex and Mental Health among Emerging Adults? Journal of Sex Research, 51(1), 43-51.

A multiethnic sample of single, heterosexual, emerging-adult college students (N=3,907) ages 18 to 25, from 30 institutions across the United States, participated in a study about identity, culture, psychological well-being, and risky behaviors. Given ongoing debates about the connection between casual sex and psychological adjustment, in the current study we assessed the cross-sectional association of participation in casual sex with psychological well-being and distress. A greater proportion of men (18.6%) compared to women (7.4%) reported having had casual sex in the month prior to assessment. Structural equation modeling indicated that casual sex was negatively associated with well-being (ss=.20, p <.001) and positively associated with psychological distress (ss=.16, p <.001). Gender did not moderate these associations. For emerging-adult college students, engaging in casual sex may elevate risk for negative psychological outcomes.

Psychology Department.


Dezutter, J., A. S. Waterman, S. J. Schwartz, …., & S. Jean Caraway. (2014). Meaning in Life in Emerging Adulthood: A Person-Oriented Approach. Journal of Personality, 82(1), 57-68.

The present study investigated naturally occurring profiles based on two dimensions of meaning in life: Presence of Meaning and Search for Meaning. Cluster analysis was used to examine meaning-in-life profiles, and subsequent analyses identified different patterns in psychosocial functioning for each profile. A sample of 8,492 American emerging adults (72.5% women) from 30 colleges and universities completed measures on meaning in life, and positive and negative psychosocial functioning. Results provided support for five meaningful yet distinguishable profiles. A strong generalizability of the cluster solution was found across age, and partial generalizability was found across gender and ethnicity. Furthermore, the five profiles showed specific patterns in relation to positive and negative psychosocial functioning. Specifically, respondents with profiles high on Presence of Meaning showed the most adaptive psychosocial functioning, whereas respondents with profiles where meaning was largely absent showed maladaptive psychosocial functioning. The present study provided additional evidence for prior research concerning the complex relationship between Presence of Meaning and Search for Meaning, and their relation with psychosocial functioning. Our results offer a partial clarification of the nature of the Search for Meaning process by distinguishing between adaptive and maladaptive searching for meaning in life.

Psychology Department.


Ammann, E. M., J. V. Pottala, William S. Harris, M. A. Espeland, R. Wallace, N. L. Denburg, . . . J. G. Robinson. (2013). Omega-3 fatty acids and domain-specific cognitive aging Secondary analyses of data from WHISCA. Neurology, 81(17), 1484-1491.

Objective: To test the hypothesis that higher levels of red blood cell (RBC) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a protective association with domain-specific cognitive function in women aged 65 years and older. Methods: A total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years. In this retrospective cohort study, we assessed the relationship between prerandomization RBC DHA +/- EPA levels and a) cognitive measures at baseline, and b) cognitive change over time. Endpoints were composite cognitive function and performance in 7 cognitive domains: fine motor speed, verbal memory, visual memory, spatial ability, verbal knowledge, verbal fluency, and working memory. Results: After adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA +/- EPA tertiles in the rate of cognitive change over time. Conclusions: We did not find an association between RBC DHA +/- EPA levels and age-associated cognitive decline in a cohort of older, dementia-free women.

Sanford School of Medicine, Sioux Falls Campus.


Martin-Montalvo, A., I. Gonzalez-Mariscal, T. Pomares-Viciana, Sergio Padilla-Lopez, M. Ballesteros, L. Vazquez-Fonseca, . . . C. Santos-Ocana. (2013). The Phosphatase Ptc7 Induces Coenzyme Q Biosynthesis by Activating the Hydroxylase Coq7 in Yeast. Journal of Biological Chemistry, 288(39), 28126-28137.

The study of the components of mitochondrial metabolism has potential benefits for health span and lifespan because the maintenance of efficient mitochondrial function and antioxidant capacity is associated with improved health and survival. In yeast, mitochondrial function requires the tight control of several metabolic processes such as coenzyme Q biosynthesis, assuring an appropriate energy supply and antioxidant functions. Many mitochondrial processes are regulated by phosphorylation cycles mediated by protein kinases and phosphatases. In this study, we determined that the mitochondrial phosphatase Ptc7p, a Ser/Thr phosphatase, was required to regulate coenzyme Q(6) biosynthesis, which in turn activated aerobic metabolism and enhanced oxidative stress resistance. We showed that Ptc7p phosphatase specifically activated coenzyme Q(6) biosynthesis through the dephosphorylation of the demethoxy-Q(6) hydroxylase Coq7p. The current findings revealed that Ptc7p is a regulator of mitochondrial metabolism that is essential to maintain proper function of the mitochondria by regulating energy metabolism and oxidative stress resistance.

Sanford School of Medicine, Sioux Falls Campus.


May, P. A., J. Blankenship, A. S. Marais, …., H. Eugene Hoyme, B. Tabachnick, & S. Seedat. (2013). Maternal alcohol consumption producing fetal alcohol spectrum disorders (FASD): Quantity, frequency, and timing of drinking. Drug and Alcohol Dependence, 133(2), 502-512.

Background: Concise, accurate measures of maternal prenatal alcohol use are needed to better understand fetal alcohol spectrum disorders (FASD). Methods: Measures of drinking by mothers of children with specific FASD diagnoses and mothers of randomly-selected controls are compared and also correlated with physical and cognitive/behavioral outcomes. Results: Measures of maternal alcohol use can differentiate maternal drinking associated with FASD from that of controls and some from mothers of alcohol-exposed normals. Six variables that combine quantity and frequency concepts distinguish mothers of FASD children from normal controls. Alcohol use variables, when applied to each trimester and three months prior to pregnancy, provide insight on critical timing of exposure as well. Measures of drinking, especially bingeing, correlate significantly with increased child dysmorphology and negative cognitive/behavioral outcomes in children, especially low non-verbal IQ, poor attention, and behavioral problems. Logistic regression links (p < .001) first trimester drinking (vs. no drinking) with FASD, elevating FASD likelihood 12 times; first and second trimester drinking increases FASD outcomes 61 times; and drinking in all trimesters 65 times. Conversely, a similar regression (p = .008) indicates that drinking only in the first trimester makes the birth of a child with an FASD 5 times less likely than drinking in all trimesters. Conclusions: There is significant variation in alcohol consumption both within and between diagnostic groupings of mothers bearing children diagnosed within the FASD continuum. Drinking measures are empirically identified and correlated with specific child outcomes. Alcohol use, especially heavy use, should be avoided throughout pregnancy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.


Nagle, A. S., Matthew A. Barker, S. D. Kleeman, B. Haridas, & T. D. Mast. (2014). Passive biomechanical properties of human cadaveric levator ani muscle at low strains. Journal of Biomechanics, 47(2), 583-586.

The objective of this study was to measure and model the passive biomechanics of cadaveric levator ani muscle in the fiber direction at low strains with a moderately slow deformation rate. Nine levator ani samples, extracted from female cadavers aged 64 to 96 years, underwent preconditioning and uniaxial biomechanical analysis on a tensile testing apparatus after the original width, thickness, and length were measured. The load extension data and measured dimensions were used to calculate stress-strain curves for each sample. The resulting stress-strain curves up to 10% strain were fit to four different constitutive models to determine which model was most appropriate for the data. A power-law model with two parameters was found to fit the data most accurately. Constitutive parameters did not correlate significantly with age in this study; this may be because all of the cadavers were postmenopausal. (C) 2013 Elsevier Ltd. All rights reserved.

Sanford School of Medicine, Sioux Falls Campus.


Pradip, De, M. Bouzyk, Nandini Dey, & Brian Leyland-Jones. (2013). Dissecting GRB7-mediated signals for proliferation and migration in HER2 overexpressing breast tumor cells: GTP-ase rules. American Journal of Cancer Research, 3(2), 173-U126.

Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)=0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.

Sanford School of Medicine, Sioux Falls Campus.


Randall, Bradley B., D. S. Paterson, E. A. Haas, K. G. Broadbelt, J. R. Duncan, O. J. Mena, . . . H. C. Kinney. (2013). Potential Asphyxia and Brainstem Abnormalities in Sudden and Unexpected Death in Infants. Pediatrics, 132(6), E1616-E1625.

OBJECTIVE: Sudden and unexplained death is a leading cause of infant mortality. Certain characteristics of the sleep environment increase the risk for sleep-related sudden and unexplained infant death. These characteristics have the potential to generate asphyxial conditions. We tested the hypothesis that infants may be exposed to differing degrees of asphyxia in sleep environments, such that vulnerable infants with a severe underlying brainstem deficiency in serotonergic, g-aminobutyric acid-ergic, or 14-3-3 transduction proteins succumb even without asphyxial triggers (eg, supine), whereas infants with intermediate or borderline brainstem deficiencies require asphyxial stressors to precipitate death. METHODS: We classified cases of sudden infant death into categories relative to a “potential asphyxia” schema in a cohort autopsied at the San Diego County Medical Examiner’s Office. Controls were infants who died with known causes of death established at autopsy. Analysis of covariance tested for differences between groups. RESULTS: Medullary neurochemical abnormalities were present in both infants dying suddenly in circumstances consistent with asphyxia and infants dying suddenly without obvious asphyxia-generating circumstances. There were no differences in the mean neurochemical measures between these 2 groups, although mean measures were both significantly lower (P<.05) than those of controls dying of known causes. CONCLUSIONS: We found no direct relationship between the presence of potentially asphyxia conditions in the sleep environment and brainstem abnormalities in infants dying suddenly and unexpectedly. Brainstem abnormalities were associated with both asphyxia-generating and non-asphyxia generating conditions. Heeding safe sleep messages is essential for all infants, especially given our current inability to detect underlying vulnerabilities.

Sanford School of Medicine, Sioux Falls Campus.


Smythe, M. A., J. Fanikos, Michael P. Gulseth, A. K. Wittkowsky, S. A. Spinler, W. E. Dager, & E. A. Nutescu. (2013). Rivaroxaban: Practical Considerations for Ensuring Safety and Efficacy. Pharmacotherapy, 33(11), 1223-1245.

Rivaroxaban is the first agent available within a new class of anticoagulants called direct factor Xa inhibitors. Rivaroxaban is approved for use in the United States for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the prevention of deep vein thrombosis in patients undergoing total hip replacement and total knee replacement, for the treatment of deep vein thrombosis and pulmonary embolism, and for the reduction in risk of recurrence of deep vein thrombosis and pulmonary embolism (with additional indications under review). Rivaroxaban dose and frequency of administration vary depending on the indication. As of result of predictable pharmacokinetics and pharmacodynamics, a fixed dose of rivaroxaban is administered without routine coagulation testing. Rivaroxaban has a short half-life, undergoes a dual mode of elimination (hepatic and renal), and is a substrate for P-glycoprotein. Rivaroxaban has a lower potential for drug interactions compared with warfarin. Despite the advantages of a once/day fixed-dose oral agent, in many clinical situations limited evidence is available to guide optimal management of rivaroxaban therapy. In this article, we review the available evidence and provide recommendations where possible for such situations including the desire to monitor the anticoagulation intensity, use in special patient populations, managing drug interactions, and transitioning across anticoagulant agents. Potential strategies for reversing rivaroxaban’s anticoagulant effect are reviewed. Health systems will need to perform a systematic safety evaluation and ensure that numerous hospital policies related to anticoagulation are updated to include rivaroxaban. A comprehensive approach to education is needed for clinicians, patients, and technical support personnel involved in patient interactions to ensure safe use.

Sanford School of Medicine, Sioux Falls Campus.


Williams, Casey B., S. Kambhampati, W. Fiskus, J. Wick, C. Dutreix, S. Ganguly, . . . J. P. McGuirk. (2013). Preclinical and Phase I Results of Decitabine in Combination with Midostaurin (PKC412) for Newly Diagnosed Elderly or Relapsed/Refractory Adult Patients with Acute Myeloid Leukemia. Pharmacotherapy, 33(12), 1341-1352.

PURPOSE To determine the preclinical activity, clinical maximum tolerated dose (MTD), and recommended phase II dose of midostaurin (MS) combined either sequentially or concurrently with intravenous decitabine (DAC) in newly diagnosed patients 60 years or older or relapsed/refractory adult patients (18 years or older) with acute myeloid leukemia (AML). PATIENTS AND METHODS Cultured and primary AML cells were treated with DAC and/or MS and analyzed by flow cytometry and immunoblot analyses. In the phase I study, 16 patients were enrolled; 8 were newly diagnosed patients 60 years or older and 8 were 18 years or older with relapsed AML. Only 2 of 16 patients (13%) had FLT3-internal tandem duplication (ITD) mutations, and no patient had KIT mutations. RESULTS Compared with treatment with either agent alone, sequential treatment with DAC and MS exerted superior anti-AML activity in cultured and primary FLT3-ITD-expressing AML cells. In the subsequent phase I study, the MTD and schedule of administration of the combination was identified as DAC followed by MS. Three patients developed dose-limiting toxicities: two patients developed pulmonary edema requiring mechanical ventilation and one patient developed a prolonged QTc greater than 500 msec. Based on an intent-to-treat analysis, 57% of the patients achieved stable disease or better while enrolled in the trial; 25% had a complete hematologic response. Pharmacokinetic analysis revealed results similar to those previously reported for MS. CONCLUSION The in vitro combination of DAC and MS is synergistically active against FLT3-ITD mutations expressing AML cells. In a clinical setting, the combination of sequentially administered DAC followed by MS is possible without significant unexpected toxicity, but the concurrent administration of DAC and MS led to pulmonary toxicity after only a few doses. On the basis of these results, additional studies exploring the sequential combination of untreated AML in elderly patients are warranted to further evaluate this combination at the MTD.

Sanford School of Medicine, Sioux Falls Campus.


Beebe, Justin A., Roger W. Hines, Laura T. McDaniel, & Brenda L. Shelden. (2013). An Isokinetic Training Program for Reducing Falls in a Community-Dwelling Older Adult: A Case Report. Journal of Geriatric Physical Therapy, 36(3), 146-153.

Background: With the population older than 65 years, projected to double by the year 2030, falls in older adults are a substantial health concern. Muscle strength deficits are one of the multifactorial components linked to increased fall risk, and decreasing these deficits has been one of the goals of interventions designed to decrease fall risk. These interventions have traditionally focused on improving peak torque; however, recent research suggests that exercise protocols that focus on the rate of torque development (RTD) may be more effective in decreasing fall risk. Purpose: This case report examines clinical outcomes following implementation of an isokinetic strengthening protocol coupled with a balance program designed to reduce fall risk in a community-dwelling older adult. Methods: The individual was a 70-year-old woman with a history of 3 falls over the past 8 months and no related medical etiology who had self-limited her activities because of fear of another fall. She was classified as having substantial risk for future falls because of fall history, increased fear of falling, and below age norms on the Berg Balance Scale (BBS), and the Timed Up and Go (TUG). The treatment program consisted of 12 weeks of high-intensity isokinetic knee extensor training, high challenge dynamic gait and balance activities, and core strengthening. The isokinetic protocol consisted of 4 sets of 10 concentric-only repetitions at speeds of 240 degrees/sec and 300 /sec for a total of 8 work sets. Dynamic gait activities incorporating directional and obstacle drills, and rocker and balance boards were used for balance training activities. Progressive theraband exercises were used for core strengthening. As her home program, the participant was encouraged to return to line dancing twice per week. During the 12-week protocol, the participant completed two 90-minute therapy sessions and two 90-minute dance classes per week. Results: After the 12 weeks of treatment, knee extensor peak torque at 150 ms improved on the right from 67.8 N to 107.1 N (57.9% increase), and on the left from 65.1 N to 97.6 N (49.9% increase). The BBS score improved from 45 to 52; and the TUG improved from 14.0 to 8.6 seconds. Both final scores exceeded fall risk cutoffs (BBS = 48; TUG = 13.5 seconds) and the change score exceeded minimal detectable change (BBS = 7; TUG 5.4 seconds). Conclusions: The treatment program produced improvements in knee extensor peak torque and RTD, but more importantly, the final scores on the clinical outcome measures placed the participant above established fall-risk cutoff scores. Although future research with increased numbers of participants and a control group should be conducted to confirm this study’s results, these findings support the use of isokinetic training to reduce fall risk in older adults.

School of Health Sciences.

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