Ultrafast and nonlinear spectroscopy of brilliant green-based nanoGUMBOS with enhanced near-infrared emission

The synthesis, characterization, ultrafast dynamics, and nonlinear spectroscopy of 30 nm nanospheres of brilliant green–bis(pentafluoroethylsulfonyl)imide ([BG][BETI]) in water are reported. These thermally stable nanoparticles are derived from a group of uniform materials based on organic salts (nanoGUMBOS) that exhibit enhanced near-infrared emission compared with the molecular dye in water. The examination of ultrafast transient absorption spectroscopy results reveals that the overall excited-state relaxation lifetimes of [BG][BETI] nanoGUMBOS are longer than the brilliant green molecular dye in water due to steric hindrance of the torsional degrees of freedom of the phenyl rings around the central carbon. Furthermore, the second harmonic generation signal of [BG][BETI] nanoGUMBOS is enhanced by approximately 7 times and 23 times as compared with colloidal gold nanoparticles of the same size and the brilliant green molecular dye in water, respectively. A very clear third harmonic generation signal is observed from the [BG][BETI] nanoGUMBOS but not from either the molecular dye or the gold nanoparticles. Overall, these results show that [BG][BETI] nanoGUMBOS exhibit altered ultrafast and nonlinear spectroscopy that is beneficial for various applications including nonlinear imaging probes, biomedical imaging, and molecular sensing

Capturing Plasmon-Molecule Dynamics in Dye Monolayers on Metal Nanoparticles Using Classical Electrodynamics with Quantum Embedding

A multiscale hybrid quantum/classical approach using classical electrodynamics and a collection of discrete three-level quantum systems is used to simulate the coupled dynamics and spectra of a malachite green monolayer adsorbed to the surface of a spherical gold nanoparticle (NP). This method utilizes finite difference time domain (FDTD) to describe the plasmonic response of the NP within the main FDTD framework and a three-level quantum description for the molecule via a Maxwell/Liouville framework. To avoid spurious self-excitation, each quantum molecule has its own auxiliary FDTD subregion embedded within the main FDTD grid. The molecular parameters are determined by fitting the experimental extinction spectrum to Lorentzians, yielding the energies, transition dipole moments, and the dephasing lifetimes. This approach can be potentially applied to modeling thousands of molecules on the surface of a plasmonic NP. In this paper, however, we first present results for two molecules with scaled oscillator strengths to reflect the optical response of a full monolayer. There is good agreement with experimental extinction measurements, predicting the plasmon and molecule depletions. Additionally, this model captures the polariton peaks overlapped with a Fano-type resonance profile observed in the experimental extinction measurements. This technique can be generalized to any nanostructure/multichromophore system, where the molecules can be treated with essentially any quantum method

Accumulation of driver and passenger mutations during tumor progression

Major efforts to sequence cancer genomes are now occurring throughout the world. Though the emerging data from these studies are illuminating, their reconciliation with epidemiologic and clinical observations poses a major challenge. In the current study, we provide a novel mathematical model that begins to address this challenge. We model tumors as a discrete time branching process that starts with a single driver mutation and proceeds as each new driver mutation leads to a slightly increased rate of clonal expansion. Using the model, we observe tremendous variation in the rate of tumor development - providing an understanding of the heterogeneity in tumor sizes and development times that have been observed by epidemiologists and clinicians. Furthermore, the model provides a simple formula for the number of driver mutations as a function of the total number of mutations in the tumor. Finally, when applied to recent experimental data, the model allows us to calculate, for the first time, the actual selective advantage provided by typical somatic mutations in human tumors in situ. This selective advantage is surprisingly small, 0.005 +- 0.0005, and has major implications for experimental cancer research

Probing the colloidal gold nanoparticle/aqueous interface with second harmonic generation

a b s t r a c t The interface of 16 nm colloidal gold nanoparticles with the aqueous solution in which they are suspended is investigated using second harmonic generation. The population of malachite green freely adsorbing to the gold nanoparticle interface as a function of concentration is obtained. The experimental results are in good agreement with the modified Langmuir model, which includes depletion of the adsorbate bulk concentration. The free energy of adsorption is determined to be À15.4 ± 0.4 kcal/mol with 1.13 ± 0.04 Â 10 3 sites per nanoparticle. These results provide the first direct measurement of the isotherm of molecules adsorbing to colloidal metallic nanoparticles

A Pedagogical Review of Electroweak Symmetry Breaking Scenarios

We review different avenues of electroweak symmetry breaking explored over the years. This constitutes a timely exercise as the world's largest and the highest energy particle accelerator, namely, the Large Hadron Collider (LHC) at CERN near Geneva, has started running whose primary mission is to find the Higgs or some phenomena that mimic the effects of the Higgs, i.e. to unravel the mysteries of electroweak phase transition. In the beginning, we discuss the Standard Model Higgs mechanism. After that we review the Higgs sector of the Minimal Supersymmetric Standard Model. Then we take up three relatively recent ideas: Little Higgs, Gauge-Higgs Unification, and Higgsless scenarios. For the latter three cases, we first present the basic ideas and restrict our illustration to some instructive toy models to provide an intuitive feel of the underlying dynamics, and then discuss, for each of the three cases, how more realistic scenarios are constructed and how to decipher their experimental signatures. Wherever possible, we provide enough pedagogical details, which the beginners might find useful.Comment: 45 pages, Review based on a series of lectures; v2: 63 pages, substantially expanded, references added, to appear in `Reports on Progress in Physics

Evidence for Neutrino Oscillations from Muon Decay at Rest

A search for nu_bar_mu to nu_bar_e oscillations has been conducted at the Los Alamos Meson Physics Facility using nu_bar_mu from mu+ decay at rest. The nu_bar_e are detected via the reaction (nu_bar_e,p) -> (e+,n), correlated with the 2.2 MeV gamma from (n,p) -> (d,gamma). The use of tight cuts to identify e+ events with correlated gamma rays yields 22 events with e+ energy between 36 and 60 MeV and only 4.6 (+/- 0.6) background events. The probability that this excess is due entirely to a statistical fluctuation is 4.1E-08. A chi^2 fit to the entire e+ sample results in a total excess of 51.8 (+18.7) (-16.9) (+/- 8.0) events with e+ energy between 20 and 60 MeV. If attributed to nu_bar_mu -> nu_bar_e oscillations, this corresponds to an oscillation probability (averaged over the experimental energy and spatial acceptance) of 0.0031 (+0.0011) (-0.0010) (+/- 0.0005).Comment: 57 pages, 34 figures, revtex, additional information available at http://nu1.lampf.lanl.gov/~lsnd

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Radiative Electroweak symmetry breaking in the MSSM and Low Energy Thresholds

We study Radiative Electroweak Symmetry Breaking in the Minimal Supersymmetric Standard Model (MSSM). We employ the 2-loop Renormalization Group equations for running masses and couplings taking into account sparticle threshold effects. The decoupling of each particle below its threshold is realized by a step function in all one-loop Renormalization Group equations (RGE). This program requires the calculation of all wavefunction, vertex and mass renormalizations for all particles involved. Adapting our numerical routines to take care of the succesive decoupling of each particle below its threshold, we compute the mass spectrum of sparticles and Higgses consistent with the existing experimental constraints. The effect of the threshold corrections is in general of the same order of magnitude as the two-loop contributions with the exception of the heavy Higgses and those neutralino and chargino states that are nearlyComment: 39 pages, Latex, conclusions,description of numerical analysis expanded.References adde

Inhibition of Neuroblastoma Tumor Growth by Targeted Delivery of MicroRNA-34a Using Anti-Disialoganglioside GD2 Coated Nanoparticles

Neuroblastoma is one of the most challenging malignancies of childhood, being associated with the highest death rate in paediatric oncology, underlining the need for novel therapeutic approaches. Typically, patients with high risk disease undergo an initial remission in response to treatment, followed by disease recurrence that has become refractory to further treatment. Here, we demonstrate the first silica nanoparticle-based targeted delivery of a tumor suppressive, pro-apoptotic microRNA, miR-34a, to neuroblastoma tumors in a murine orthotopic xenograft model. These tumors express high levels of the cell surface antigen disialoganglioside GD2 (GD(2)), providing a target for tumor-specific delivery.Nanoparticles encapsulating miR-34a and conjugated to a GD(2) antibody facilitated tumor-specific delivery following systemic administration into tumor bearing mice, resulted in significantly decreased tumor growth, increased apoptosis and a reduction in vascularisation. We further demonstrate a novel, multi-step molecular mechanism by which miR-34a leads to increased levels of the tissue inhibitor metallopeptidase 2 precursor (TIMP2) protein, accounting for the highly reduced vascularisation noted in miR-34a-treated tumors.These novel findings highlight the potential of anti-GD(2)-nanoparticle-mediated targeted delivery of miR-34a for both the treatment of GD(2)-expressing tumors, and as a basic discovery tool for elucidating biological effects of novel miRNAs on tumor growth