A novel Monoclonal Antibody against Notch1 Targets Leukemia-associated Mutant Notch1 and Depletes Therapy Resistant Cancer Stem Cells in Solid Tumors

Higher Notch signaling is known to be associated with hematological and solid cancers. We developed a potential immunotherapeutic monoclonal antibody (MAb) specific for the Negative Regulatory Region of Notch1 (NRR). The MAb604.107 exhibited higher affinity for the ``Gain-offunction'' mutants of Notch1 NRR associated with T Acute lymphoblastic Leukemia (T-ALL). Modeling of the mutant NRR with 12 amino-acid insertion demonstrated ``opening'' resulting in exposure of the S2-cleavage site leading to activated Notch1 signaling. The MAb, at low concentrations (1-2 mu g/ml), inhibited elevated ligand-independent Notch1 signaling of NRR mutants, augmented effect of Thapsigargin, an inhibitor of mutant Notch1, but had no effect on the wild-type Notch1. The antibody decreased proliferation of the primary T-ALL cells and depleted leukemia initiating CD34/CD44 high population. At relatively high concentrations, (10-20 mu g/ml), the MAb affected Notch1 signaling in the breast and colon cancer cell lines. The Notch-high cells sorted from solid-tumor cell lines exhibited characteristics of cancer stem cells, which were inhibited by the MAb. The antibody also increased the sensitivity to Doxorubucinirubicin. Further, the MAb impeded the growth of xenografts from breast and colon cancer cells potentiated regression of the tumors along with Doxorubucin. Thus, this antibody is potential immunotherapeutic tool for different cancers.

Reduction of proton acceleration in high-intensity laser interaction with solid two-layer targets

Reduction of proton acceleration in the interaction of a high-intensity, picosecond laser with a 50-mu m aluminum target was observed when 0.1-6 mu m of plastic was deposited on the back surface (opposite side of the laser). The maximum energy and number of energetic protons observed at the back of the target were greatly reduced in comparison to pure aluminum and plastic targets of the same thickness. This is attributed to the effect of the interface between the layers. Modeling of the electron propagation in the targets using a hybrid code showed strong magnetic-field generation at the interface and rapid surface heating of the aluminum layer, which may account for the results. (c) 2006 American Institute of Physics.

Modeling target bulk heating resulting from ultra-intense short pulse laser irradiation of solid density targets

Isochoric heating of solid-density matter up to a few tens of eV is of interest for investigating astrophysical or inertial fusion scenarios. Such ultra-fast heating can be achieved via the energy deposition of short-pulse laser generated electrons. Here, we report on experimental measurements of this process by means of time-and space-resolved optical interferometry. Our results are found in reasonable agreement with a simple numerical model of fast electron-induced heating. (C) 2013 AIP Publishing LLC.

Application of Imaging to Study the Evolution and Dynamics of Laser Produced Plasma from Solid and Thin Film Li Targets

The present thesis report the results obtained from the studies carried out on the laser blow off plasma (LBO) from LiF-C (Lithium Fluoride with Carbon) thin film target, which is of particular importance in Tokamak plasma diagnostics. Keeping in view of its significance, plasma generated by the irradiation of thin film target by nanosecond laser pulses from an Nd:YAG laser over the thin film target has been characterized by fast photography using intensified CCD. In comparison to other diagnostic techniques, imaging studies provide better understanding of plasma geometry (size, shape, divergence etc) and structural formations inside the plume during different stages of expansion.

Mothers' perceptions of introducing solids to their infant at six months of age : identifying critical belief-based targets to promote adherence to current infant feeding guidelines

We investigated critical belief-based targets for promoting the introduction of solid foods to infants at six months. First-time mothers (N = 375) completed a Theory of Planned Behaviour belief-based questionnaire and follow-up questionnaire assessing the age the infant was first introduced to solids. Normative beliefs about partner/spouse (β = 0.16) and doctor (β = 0.22), and control beliefs about commercial baby foods available for infants before six months (β = −0.20), predicted introduction of solids at six months. Intervention programs should target these critical beliefs to promote mothers’ adherence to current infant feeding guidelines to introduce solids at around six months.

Chemotherapy and zoledronate sensitize solid tumour cells to Vγ9Vδ2 T cell cytotoxicity

Combinations of cellular immune-based therapies with chemotherapy and other antitumour agents may be of significant clinical benefit in the treatment of many forms of cancer. Gamma delta (γδ) T cells are of particular interest for use in such combined therapies due to their potent antitumour cytotoxicity and relative ease of generation in vitro. Here, we demonstrate high levels of cytotoxicity against solid tumour-derived cell lines with combination treatment utilizing Vγ9Vδ2 T cells, chemotherapeutic agents and the bisphosphonate, zoledronate. Pre-treatment with low concentrations of chemotherapeutic agents or zoledronate sensitized tumour cells to rapid killing by Vγ9Vδ2 T cells with levels of cytotoxicity approaching 90%. In addition, zoledronate enhanced the chemotherapy-induced sensitization of tumour cells to Vγ9Vδ2 T cell cytotoxicity resulting in almost 100% lysis of tumour targets in some cases. Vγ9Vδ2 T cell cytotoxicity was mediated by perforin following TCR-dependent and isoprenoid-mediated recognition of tumour cells. Production of IFN-γ by Vγ9Vδ2 T cells was also induced after exposure to sensitized targets. We conclude that administration of Vγ9Vδ2 T cells at suitable intervals after chemotherapy and zoledronate may substantially increase antitumour activities in a range of malignancies.

A Device to Crystallize Organic Solids: Structure of Ciprofloxacin, Midazolam, and Ofloxacin as Targets

The crystal structure determination of the anhydrous form of any organic compound has been a challenge because of solvent incorporation during crystallization. A device to grow anhydrous forms of low melting organic solids based on vaporization and condensation by a gradient cooling technique has been designed. Its utility has been evaluated by growing anhydrous forms of ciprofloxacin, midazolam, and ofloxacin. Ciprofloxacin crystallizes in triclinic P (1) over bar, midazolam in monoclinic P2(1)/n, and ofloxacin in the C2/c space group. Comparative studies on the conformational features with solvated structure show no significant variation in the aromatic moieties.

Process-kinetics in facing targets sputtering of multi-component oxide thin films

The kinetics of the processes in facing targets sputtering of multicomponent oxide films is presented. The novel configuration of the process exhibits an enhanced ionization efficiency. Discharge diagnostics performed using optical emission spectroscopy revealed strong dependence of plasma parameters on process conditions. Numerical simulation based on thermalization and diffusion of sputtered atoms has been performed to estimate the transport efficiency in off-axis mode. Composition, structure and epitaxial quality of YBa2Cu3O7-x films prepared was found to be strongly dependent on atomic flux ratios (of Cu/Y and Ba/Y) arriving at the substrate, resputtering effect and phase stability of YBa2Cu3O7-x These studies have been shown to be useful in understanding the complex processes that occur in sputtering of multicomponent films. (C) 1999 Elsevier Science S.A. All rights reserved.

Direct acceleration of solid-density plasma bunch by ultraintense laser

The interaction of a petawatt laser with a small solid-density plasma bunch is studied by particle-in-cell simulation. It is shown that when irradiated by a laser of intensity >10(21) W/cm(2), a dense plasma bunch of micrometer size can be efficiently accelerated. The kinetic energy of the ions in the high-density region of the plasma bunch can exceed ten MeV at a density in the 10(23)-cm(-3) level. Having a flux density orders of magnitude higher than that of the traditional charged-particle pulses, the laser-accelerated plasma bunch can have a wide range of applications. In particular, such a dense energetic plasma bunch impinging on the compressed fuel in inertial fusion can significantly enhance the nuclear-reaction cross section and is thus a promising alternative for fast ignition.

X-ray emission produced by interaction of highly ionized Arq+ ions with metallic targets

This paper studies the X-ray spectra produced by the interaction of highly charged ions of Arq+ (q = 16, 17, 18) with metallic surface of Be, Al, Ni, Mo and Au respectively. The experimental results show that the K alpha X-ray emerges from under the surface of solid in the interaction of ions with targets. The multi-electron excitation occurred in the process neutralization of the Ar16+ in electronic configuration of 1s(2) in metallic surfaces, which produces vacancy in the K shell. Electron from high n state transition to K vacancy gives off X-ray. We find that there is no obvious relation between the shape of X-ray spectra and the different targets. The X-ray yield of incident ions are associated with initial electronic configuration. The X-ray yield of target is related to the kinetic energy of the incident ions.

Enhanced He-α emission from ‘smoked’ Ti targets irradiated with 400nm 45fs 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.

Measurement of highly transient electrical charging following high-intensity laser-solid interaction

The multi-million-electron-volt proton beams accelerated during high-intensity laser-solid interactions have been used as a particle probe to investigate the electric charging of microscopic targets laser-irradiated at intensity similar to10(19) W cm(2). The charge-up, detected via the proton deflection with high temporal and spatial resolution, is due to the escape of energetic electrons generated during the interaction. The analysis of the data is supported by three- dimensional tracing of the proton trajectories. (C) 2003 American Institute of Physics.

Dynamics of nanometer-scale foil targets irradiated with relativistically intense laser pulses

In this paper we report on an experimental study of high harmonic radiation generated in nanometer-scale foil targets irradiated under normal incidence. The experiments constitute the first unambiguous observation of odd-numbered relativistic harmonics generated by the v x B component of the Lorentz force verifying a long predicted property of solid target harmonics. Simultaneously the observed harmonic spectra allow in-situ extraction of the target density in an experimental scenario which is of utmost interest for applications such as ion acceleration by the radiation pressure of an ultraintense laser.

Effect of laser intensity on fast-electron-beam divergence in solid-density plasmas

Metal foil targets were irradiated with 1 mu m wavelength (lambda) laser pulses of 5 ps duration and focused intensities (I) of up to 4x10(19) W cm(-2), giving values of both I lambda(2) and pulse duration comparable to those required for fast ignition inertial fusion. The divergence of the electrons accelerated into the target was determined from spatially resolved measurements of x-ray K-alpha emission and from transverse probing of the plasma formed on the back of the foils. Comparison of the divergence with other published data shows that it increases with I lambda(2) and is independent of pulse duration. Two-dimensional particle-in-cell simulations reproduce these results, indicating that it is a fundamental property of the laser-plasma interaction.

Measurements of energy transport patterns in solid density laser plasma interactions at intensities of 5x10(20) W cm(-2)

K-alpha x-ray emission, extreme ultraviolet emission, and plasma imaging techniques have been used to diagnose energy transport patterns in copper foils ranging in thickness from 5 to 75 mu m for intensities up to 5x10(20) Wcm(-20). The K-alpha emission and shadowgrams both indicate a larger divergence angle than that reported in the literature at lower intensities [R. Stephens , Phys. Rev. E 69, 066414 (2004)]. Foils 5 mu m thick show triple-humped plasma expansion patterns at the back and front surfaces. Hybrid code modeling shows that this can be attributed to an increase in the mean energy of the fast electrons emitted at large radii, which only have sufficient energy to form a plasma in such thin targets.