23 research outputs found
Simulation Study of an LWFA-based Electron Injector for AWAKE Run 2
The AWAKE experiment aims to demonstrate preservation of injected electron
beam quality during acceleration in proton-driven plasma waves. The short bunch
duration required to correctly load the wakefield is challenging to meet with
the current electron injector system, given the space available to the
beamline. An LWFA readily provides short-duration electron beams with
sufficient charge from a compact design, and provides a scalable option for
future electron acceleration experiments at AWAKE. Simulations of a shock-front
injected LWFA demonstrate a 43 TW laser system would be sufficient to produce
the required charge over a range of energies beyond 100 MeV. LWFA beams
typically have high peak current and large divergence on exiting their native
plasmas, and optimisation of bunch parameters before injection into the
proton-driven wakefields is required. Compact beam transport solutions are
discussed.Comment: Paper submitted to NIMA proceedings for the 3rd European Advanced
Accelerator Concepts Workshop. 4 pages, 3 figures, 1 table Changes after
revision: Figure 2: figures 2 and 3 of the previous version collated with
plots of longitudinal electric field Line 45: E_0 = 96 GV/m Lines 147- 159:
evaluation of beam loading made more accurate Lines 107 - 124: discussion of
simulation geometry move
Organically Modified Silica Nanoparticles Are Biocompatible and Can Be Targeted to Neurons In Vivo
The application of nanotechnology in biological research is beginning to have a major impact leading to the development of new types of tools for human health. One focus of nanobiotechnology is the development of nanoparticle-based formulations for use in drug or gene delivery systems. However most of the nano probes currently in use have varying levels of toxicity in cells or whole organisms and therefore are not suitable for in vivo application or long-term use. Here we test the potential of a novel silica based nanoparticle (organically modified silica, ORMOSIL) in living neurons within a whole organism. We show that feeding ORMOSIL nanoparticles to Drosophila has no effect on viability. ORMOSIL nanoparticles penetrate into living brains, neuronal cell bodies and axonal projections. In the neuronal cell body, nanoparticles are present in the cytoplasm, but not in the nucleus. Strikingly, incorporation of ORMOSIL nanoparticles into the brain did not induce aberrant neuronal death or interfered with normal neuronal processes. Our results in Drosophila indicate that these novel silica based nanoparticles are biocompatible and not toxic to whole organisms, and has potential for the development of long-term applications
Assessment of viral and non-viral gene transfer into adult rat brains using HSV-1, calcium phosphate and PEI-based methods
CNS gene transfer could provide new approaches to the modelling of neurodegenerative
diseases and devising potential therapies. One such disorder is Parkinson’s
disease (PD), in which dysfunction of several different metabolic processes
has been implicated. Here we review the literature on gene transfer systems
based on herpes simplex virus type 1 (HSV-1) and non-viral
polyethyleneimine (PEI) and calcium phosphate nanoparticle methods. We also
assess the usefulness of various CNS gene delivery methods and present some
of our own data to exemplify such usefulness. Our data result from vectors
stereotaxically introduced to the substantia nigra (SN) of adult rats and evaluated
1 week and/or 1 month post injection using histochemical methods to assess
recombinant Ă-galactosidase enzyme activity. Gene transfer using PEI or calcium
phosphate-mediated transfections was observed for both methods and PEI was
comparable to that of HSV-1 amplicon. Our data show that the amplicon delivery
was markedly increased when packaged with a helper virus and was similar
to the expression profile achieved with a full-size replication-defective HSV-1
recombinant (8117/43). We also examine whether PEI or HSV-1 amplicon-mediated
gene transfer could facilitate assessment of the biological effects induced
by a dominant negative FGF receptor-1 mutant to model the reduced FGF signalling
thought to occur in Parkinson’s disease
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Regulation of targeted chemotherapy with cytotoxic lutenizing hormone-releasing hormone analogue by epidermal growth factor.
Targeting chemotherapy selectively to cancers can reduce the toxic
side effects. AN-152, a conjugate of doxorubicin and[
d-Lys6]-luteinizing hormone-releasing
hormone (LH-RH), is more potent against LH-RH receptor-bearing cancers
and produces less peripheral toxicity than doxorubicin. Many cancers,
e.g., 50% of breast cancers, but few normal tissues
express these receptors, providing a selective target for this
cytotoxic conjugate. In this study, the effectiveness of AN-152 was
heightened by receptor up-regulation. The cytotoxic effect of AN-152
can be regulated by the number of active LH-RH receptors on cancer
cells. LH-RH receptor-positive (MCF-7) and -negative (UCI-107) cancer
cells were treated with epidermal growth factor (EGF) or the
somatostatin analogue, RC-160. EGF and RC-160 have been shown
previously to regulate LH-RH receptors through phosphorylation. The
effect of receptor regulation, by hormone exposure, on the cytotoxicity
of AN-152 and doxorubicin and on the cellular uptake of AN-152,[
d-Lys6]LH-RH, or doxorubicin was assessed by
the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
and by two-photon laser scanning microscopy. The results demonstrated
that the cellular entry of the conjugate was: (a)
specific for cancers with LH-RH receptors; (b)
up-regulated by EGF; (c) down-regulated by RC-160; and
(d) the cytotoxicity of the AN-152 paralleled the
efficiency of entry. This study illustrates the potential use of
receptor regulation for increasing the efficacy of chemotherapeutic
approaches that are directed to cell surface receptors
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Studies on the mechanism of action of a targeted chemotherapeutic drug in living cancer cells by two photon laser scanning microspectrofluorometry
In this study, we present a spectroscopic study of the entry pattern of a chemotherapeutic drug (AN-152) and its carrier hormone
into living cancer cells, with the help of our two-photon probes and a home-built localized microspectrofluorometer coupled with two photon laser scanning microscope (TPLSM). Due to the inherent localization ability of TPLSM, we were able to identify the drug and carrier location in different compartments of the cancer cells
. The apparent doxorubicin-assisted nucleic accumulation of AN-152 suggests a possible nuclear action of the drug on cell proliferation.
The short-term survival of dissected living larvae is not affected by ORMOSIL nanoparticles.
<p>Dissected living larvae were treated with <sup>R</sup>ORM (1 mg/ml and 0.2 mg/ml are shown) or buffer and larval survival was quantified by evaluating the twitching phenotype. We assigned âsurvivalâ values or survival points according to the extent of twitching observed when the larva was stimulated with a forceps. As described in the text, the more the larva twitched, the higher the âsurvivalâ value, indicating that the dissected larva was alive <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029424#pone.0029424-Gunawardena3" target="_blank">[43]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029424#pone.0029424-Gunawardena4" target="_blank">[44]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029424#pone.0029424-Hurd1" target="_blank">[45]</a>. The extent of twitching was recorded every 15 minutes for a total of 60 minutes. No significant difference was seen between the survival of ORMOSIL treated or buffer treated dissected living larvae.</p
Physiochemical properties of ORMOSIL nanoparticles.
<p>(<b>A</b>) The absorption and emission spectra for rhodamine-ORMOSIL (<sup>R</sup>ORM) particles. The typical emission band of rhodamine is λ<sub>max</sub> 600 nm. (<b>B</b>) The ORMOSIL nanoparticle size distribution profile as measured by the dynamic light scattering (DLS) method indicates that the diameter of ORMOSIL nanoparticles are on average 20 nm. (C) A transmission electron microscope (TEM) image of ORMOSIL nanoparticles. Barâ=â100 nm.</p