Selection Of A Novel Aptamer Against Vitronectin Using Capillary Electrophoresis And Next Generation Sequencing

Breast cancer (BC) results in ≃40,000 deaths each year in the United States and even among survivors treatment of the disease may have devastating consequences, including increased risk for heart disease and cognitive impairment resulting from the toxic effects of chemotherapy. Aptamer-mediated drug delivery can contribute to improved treatment outcomes through the selective delivery of chemotherapy to BC cells, provided suitable cancer-specific antigens can be identified. We report here the use of capillary electrophoresis in conjunction with next generation sequencing to develop the first vitronectin (VN) binding aptamer (VBA-01; Kd 405 nmol/l, the first aptamer to vitronectin (VN; Kd = 405 nmol/l), a protein that plays an important role in wound healing and that is present at elevated levels in BC tissue and in the blood of BC patients relative to the corresponding nonmalignant tissues. We used VBA-01 to develop DVBA-01, a dimeric aptamer complex, and conjugated doxorubicin (Dox) to DVBA-01 (7:1 ratio) using pH-sensitive, covalent linkages. Dox conjugation enhanced the thermal stability of the complex (60.2 versus 46.5°C) and did not decrease affinity for the VN target. The resulting DVBA-01-Dox complex displayed increased cytotoxicity to MDA-MB-231 BC cells that were cultured on plasticware coated with VN (1.8 × 10⁻⁶mol/l) relative to uncoated plates (2.4 × 10⁻⁶ mol/l), or plates coated with the related protein fibronectin (2.1 × 10⁻⁶ mol/l). The VBA-01 aptamer was evaluated for binding to human BC tissue using immunohistochemistry and displayed tissue specific binding and apparent association with BC cells. In contrast, a monoclonal antibody that preferentially binds to multimeric VN primarily stained extracellular matrix and vessel walls of BC tissue. Our results indicate a strong potential for using VN-targeting aptamers to improve drug delivery to treat BC

Void elimination in screen printed thick film dielectric pastes

The problem is to understand the mechanisms for the formation and evolution of defects in wet screen printed layers. The primary objective is to know how best to alter the properties of the paste (rather than the geometry of the screen printing process itself) in order to eliminate the defects. With these goals in mind the work done during the Study Group reported here was as follows; to describe a simple model for the closure of craters, a model for the partial closure of vias, a possible mechanism for the formation of pinholes and finally a more detailed consideration of the screen printing process

Simulating quantum-optical phenomena with cold atoms in optical lattices

We propose a scheme involving cold atoms trapped in optical lattices to observe different phenomena traditionally linked to quantum-optical systems. The basic idea consists of connecting the trapped atomic state to a non-trapped state through a Raman scheme. The coupling between these two types of atoms (trapped and free) turns out to be similar to that describing light-matter interaction within the rotating-wave approximation, the role of matter and photons being played by the trapped and free atoms, respectively. We explain in particular how to observe phenomena arising from the collective spontaneous emission of atomic and harmonic oscillator samples such as superradiance and directional emission. We also show how the same setup can simulate Bose-Hubbard Hamiltonians with extended hopping as well as Ising models with long-range interactions. We believe that this system can be realized with state of the art technology

Enhanced He-alpha emission from "smoked" Ti targets irradiated with 400nm, 45 fs laser pulses

We present a study of He-like 1s(2)-1s2p line emission from solid and low-density Ti targets under similar or equal to 45 fs laser pulse irradiation with a frequency doubled Ti: Sapphire laser. By varying the beam spot, the intensity on target was varied from 10(15) W/cm(2) to 10(19) W/cm(2). At best focus, low density "smoked" Ti targets yield similar to 20 times more He-alpha than the foil targets when irradiated at an angle of 45 degrees with s-polarized pulses. The duration of He-alpha emission from smoked targets, measured with a fast streak camera, was similar to that from Ti foils

Time-dependent effects in melting and phase change for laser-shocked iron

Using the Linac Coherent Light Source facility at the Stanford Linac Coherent Light Source National Accelerator Laboratory, we have observed X-ray scattering from iron compressed with laser-driven shocks to earth-core-like pressures above 400 GPa. The data show cases where melting is incomplete and we observe hexagonal-close-packed crystal structure at shock compressed densities up to 14.0 g cm-3 but no evidence of a double-hexagonal-close-packed crystal. The observation of a crystalline structure at these densities, where shock heating is expected to be in excess of the equilibrium melt temperature, may indicate superheating of the solid. These results are important for equation of state modeling at high strain rates relevant for impact scenarios and laser-driven shock-wave experiments

ASCR/HEP Exascale Requirements Review Report

This draft report summarizes and details the findings, results, and recommendations derived from the ASCR/HEP Exascale Requirements Review meeting held in June, 2015. The main conclusions are as follows. 1) Larger, more capable computing and data facilities are needed to support HEP science goals in all three frontiers: Energy, Intensity, and Cosmic. The expected scale of the demand at the 2025 timescale is at least two orders of magnitude -- and in some cases greater -- than that available currently. 2) The growth rate of data produced by simulations is overwhelming the current ability, of both facilities and researchers, to store and analyze it. Additional resources and new techniques for data analysis are urgently needed. 3) Data rates and volumes from HEP experimental facilities are also straining the ability to store and analyze large and complex data volumes. Appropriately configured leadership-class facilities can play a transformational role in enabling scientific discovery from these datasets. 4) A close integration of HPC simulation and data analysis will aid greatly in interpreting results from HEP experiments. Such an integration will minimize data movement and facilitate interdependent workflows. 5) Long-range planning between HEP and ASCR will be required to meet HEP's research needs. To best use ASCR HPC resources the experimental HEP program needs a) an established long-term plan for access to ASCR computational and data resources, b) an ability to map workflows onto HPC resources, c) the ability for ASCR facilities to accommodate workflows run by collaborations that can have thousands of individual members, d) to transition codes to the next-generation HPC platforms that will be available at ASCR facilities, e) to build up and train a workforce capable of developing and using simulations and analysis to support HEP scientific research on next-generation systems.Comment: 77 pages, 13 Figures; draft report, subject to further revisio

Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic

Reproduction numbers, defined as averages of the number of people infected by a typical case, play a central role in tracking infectious disease outbreaks. The aim of this paper is to develop methods for estimating reproduction numbers which are simple enough that they could be applied with limited data or in real time during an outbreak. I present a new estimator for the individual reproduction number, which describes the state of the epidemic at a point in time rather than tracking individuals over time, and discuss some potential benefits. Then, to capture more of the detail that micro-simulations have shown is important in outbreak dynamics, I analyse a model of transmission within and between households, and develop a method to estimate the household reproduction number, defined as the number of households infected by each infected household. This method is validated by numerical simulations of the spread of influenza and measles using historical data, and estimates are obtained for would-be emerging epidemics of these viruses. I argue that the household reproduction number is useful in assessing the impact of measures that target the household for isolation, quarantine, vaccination or prophylactic treatment, and measures such as social distancing and school or workplace closures which limit between-household transmission, all of which play a key role in current thinking on future infectious disease mitigation

Symmetry Breaking in Few Layer Graphene Films

Recently, it was demonstrated that the quasiparticle dynamics, the layer-dependent charge and potential, and the c-axis screening coefficient could be extracted from measurements of the spectral function of few layer graphene films grown epitaxially on SiC using angle-resolved photoemission spectroscopy (ARPES). In this article we review these findings, and present detailed methodology for extracting such parameters from ARPES. We also present detailed arguments against the possibility of an energy gap at the Dirac crossing ED.Comment: 23 pages, 13 figures, Conference Proceedings of DPG Meeting Mar 2007 Regensburg Submitted to New Journal of Physic

Reactor-based Neutrino Oscillation Experiments

The status of neutrino oscillation searches employing nuclear reactors as sources is reviewed. This technique, a direct continuation of the experiments that proved the existence of neutrinos, is today an essential tool in investigating the indications of oscillations found in studying neutrinos produced in the sun and in the earth's atmosphere. The low-energy of the reactor \nuebar makes them an ideal tool to explore oscillations with small mass differences and relatively large mixing angles. In the last several years the determination of the reactor anti-neutrino flux and spectrum has reached a high degree of accuracy. Hence measurements of these quantities at a given distance L can be readily compared with the expectation at L = 0, thus testing \nuebar disappearance. While two experiments, Chooz and Palo Verde, with baselines of about 1 km and thus sensitive to the neutrino mass differences associated with the atmospheric neutrino anomaly, have collected data and published results recently, an ambitious project with a baseline of more than 100 km, Kamland, is preparing to take data. This ultimate reactor experiment will have a sensitivity sufficient to explore part of the oscillation phase space relevant to solar neutrino scenarios. It is the only envisioned experiment with a terrestrial source of neutrinos capable of addressing the solar neutrino puzzle.Comment: Submitted to Reviews of Modern Physics 34 pages, 39 figure