The importance of high-throughput cell separation technologies for genomics/proteomics-based clinical diagnostics

Gene expression microarray analyses of mixtures of cells approximate a weighted average of the gene expression profiles (GEPs) of each cell type according to its relative abundance in the overall cell sample being analyzed. If the targeted subpopulation of cells is in the minority, or the expected perturbations are marginal, then such changes will be masked by the GEP of the normal/unaffected cells. We show that the GEP of a minor cell subpopulation is often lost when that cell subpopulation is of a frequency less than 30 percent. The GEP is almost always masked by the other cell subpopulations when that frequency drops to 10 percent or less. On the basis of these results one should always assume that the GEP of a given cell subpopulation is probably seriously affected by, the presence of significant numbers of other "contaminating" cell types. Several methodologies can be employed to enrich the target cells submitted for microarray analyses. These include magnetic sorting and laser capture microdissection. If a cell subpopulation of interest is small, very high-throughput cell separation technologies are needed to separate enough cells for conventional microarrays. However, high-throughput flow cytometry/cell sorting overcomes many restrictions of experimental enrichment conditions. This technology can also be used to sort smaller numbers of cells of specific cell subpopulations and subsequently amplify their mRNAs before microarray analyses. When purification techniques are applied to unfixed samples, the potential for changes in gene levels during the process of collection is an additional concern. Since RNA rapidly degrades, and specific mRNAs turn over in minutes or hours, the cell separation process must be very rapid. Hence, high-throughput cell separation (HTS) technologies are needed that can process the necessary number of cells expeditiously in order to avoid such uncontrolled changes in the target cells GEP. In cases where even the use of HTS yields only a small number of cells, the mRNAs (after reverse transcription to cDNA's) must be amplified to yield enough material for conventional microarray analyses. However, the problem of using "microamplification" PCR methods to expand the amount of cDNAs (from mRNAs) is that it is very difficult to amplify equally all of the mRNAs. Unequal amplification leads to a distorted gene expression profile on the microarray. Linear amplifications is difficult to achieve. Unfortunately, present-day gene-chips need to be about 100 times more sensitive than they are now to be able to do many biologically and biomedically meaningful experiments and clinical tests

Biosensor-controlled gene therapy/drug delivery with nanoparticles for nanomedicine

Nanomedicine involves cell-by-cell regenerative medicine, either repairing cells one at a time or triggering apoptotic pathways in cells that are not repairable. Multilayered nanoparticle systems are being constructed for the targeted delivery of gene therapy to single cells. Cleavable shells containing targeting, biosensing, and gene therapeutic molecules are being constructed to direct nanoparticles to desired intracellular targets. Therapeutic gene sequences are controlled by biosensor-activated control switches to provide the proper amount of gene therapy on a single cell basis. The central idea is to set up gene therapy "nanofactories" inside single living cells. Molecular biosensors linked to these genes control their expression. Gene delivery is started in response to a biosensor detected problem; gene delivery is halted when the cell response indicates that more gene therapy is not needed

Thermal activation of ferroelectric switching

By applying the theory of thermally activated nucleation to the switching of ferroelectric domains, a method is developed to experimentally obtain the value of both the activation enthalpy, ΔH, and activation volume, V*, for the thermally activated process involved in ferroelectric switching. The method was applied to the switching of a soft lead zirconate titanate and values of ΔH = (0.16±0.02) eV and V* = (1.62±0.16)×10−25 m3 were obtained at the coercive field. These values imply that the energy, ΔU, required for the formation of switching nuclei is mainly supplied by the work done by the electric field. A comparison of these values with those obtained from theoretical considerations suggests that the switching is achieved by the sideways expansion of nuclei formed at the domain boundaries in the form of low amplitude and long wavelength fluctuations of the domain walls

Searching for the light dark gauge boson in GeV-scale experiments

We study current constraints and search prospects for a GeV scale vector boson at a range of low energy experiments. It couples to the Standard Model charged particles with a strength <= 10^-3 to 10^-4 of that of the photon. The possibility of such a particle mediating dark matter self-interactions has received much attention recently. We consider searches at low energy high luminosity colliders, meson decays, and fixed target experiments. Based on available data, searches both at colliders and in meson decays can discover or exclude such a scenario if the coupling strength is on the larger side. We emphasize that a dedicated fixed target experiment has a much better potential in searching for such a gauge boson, and outline the desired properties of such an experiment. Two different optimal designs should be implemented to cover the range of coupling strength 10^-3 to 10^-5, and < 10^-5 of the photon, respectively. We also briefly comment on other possible ways of searching for such a gauge boson.Comment: 33 pages, 5 figures; v2: corrected discussion of Upsilon decays, updates to discussion of fixed-target experiments and QED constraints, numerous minor changes, references added; v3: typo corrected relative to the JHEP published versio

Sensitivity of wide band detectors to quintessential gravitons

There are no reasons why the energy spectra of the relic gravitons, amplified by the pumping action of the background geometry, should not increase at high frequencies. A typical example of this behavior are quintessential inflationary models where the slopes of the energy spectra can be either blue or mildly violet. In comparing the predictions of scenarios leading to blue and violet graviton spectra we face the problem of correctly deriving the sensitivities of the interferometric detectors. Indeed, the expression of the signal-to-noise ratio not only depends upon the noise power spectra of the detectors but also upon the spectral form of the signal and, therefore, one can reasonably expect that models with different spectral behaviors will produce different signal-to-noise ratios. By assuming monotonic (blue) spectra of relic gravitons we will give general expressions for the signal-to-noise ratio in this class of models. As an example we studied the case of quintessential gravitons. The minimum achievable sensitivity to $h^2_{0} \Omega_{GW}$ of different pairs of detectors is computed, and compared with the theoretical expectations.Comment: 10 pages in Revtex style, 3 figure

Dark Force Detection in Low Energy e-p Collisions

We study the prospects for detecting a light boson X with mass m_X < 100 MeV at a low energy electron-proton collider. We focus on the case where X dominantly decays to e+ e- as motivated by recent "dark force" models. In order to evade direct and indirect constraints, X must have small couplings to the standard model (alpha_X 10 MeV). By comparing the signal and background cross sections for the e- p e+ e- final state, we conclude that dark force detection requires an integrated luminosity of around 1 inverse attobarn, achievable with a forthcoming JLab proposal.Comment: 38 pages, 19 figures; v2, references adde

Long-Lived Neutralino NLSPs

We investigate the collider signatures of heavy, long-lived, neutral particles that decay to charged particles plus missing energy. Specifically, we focus on the case of a neutralino NLSP decaying to Z and gravitino within the context of General Gauge Mediation. We show that a combination of searches using the inner detector and the muon spectrometer yields a wide range of potential early LHC discoveries for NLSP lifetimes ranging from 10^(-1)-10^5 mm. We further show that events from Z(l+l-) can be used for detailed kinematic reconstruction, leading to accurate determinations of the neutralino mass and lifetime. In particular, we examine the prospects for detailed event study at ATLAS using the ECAL (making use of its timing and pointing capabilities) together with the TRT, or using the muon spectrometer alone. Finally, we also demonstrate that there is a region in parameter space where the Tevatron could potentially discover new physics in the delayed Z(l+l-)+MET channel. While our discussion centers on gauge mediation, many of the results apply to any scenario with a long-lived neutral particle decaying to charged particles.Comment: 31 pages, 12 figure

Characterisation of polymorphic microsatellite loci in the western rock lobster

Nine microsatellite loci were identified in the western rock lobster (Panulirus cygnus) using two different methods. The first method involved the screening of a small, fragment, partial genomic library with a radioactive (CA) 6 probe. The second method, was based upon an enrichment method and used biotinylated, tetranucleotide microsatellite oligonucleotide capture probes. The nine loci described are all very polymorphic, with 11 to 34 alleles observed for each locus and heterozygosities ranging from 0.58 to 0.86. These microsatellite loci will be useful in analysing both the population structure and the mating systems used by this species and will add important information for the management of the wild stocks of this economically important species. © Springer Science+Business Media B.V. 2009

A slice of AdS_5 as the large N limit of Seiberg duality

A slice of AdS_5 is used to provide a 5D gravitational description of 4D strongly-coupled Seiberg dual gauge theories. An (electric) SU(N) gauge theory in the conformal window at large N is described by the 5D bulk, while its weakly coupled (magnetic) dual is confined to the IR brane. This framework can be used to construct an N = 1 MSSM on the IR brane, reminiscent of the original Randall-Sundrum model. In addition, we use our framework to study strongly-coupled scenarios of supersymmetry breaking mediated by gauge forces. This leads to a unified scenario that connects the extra-ordinary gauge mediation limit to the gaugino mediation limit in warped space.Comment: 47 Pages, axodraw4j.st

Production and detection of relic gravitons in quintessential inflationary models

A large class of quintessential inflationary models, recently proposed by Peebles and Vilenkin, leads to post-inflationary phases whose effective equation of state is stiffer than radiation. The expected gravitational waves logarithmic energy spectra are tilted towards high frequencies and characterized by two parameters: the inflationary curvature scale at which the transition to the stiff phase occurs and the number of (non conformally coupled) scalar degrees of freedom whose decay into fermions triggers the onset of a gravitational reheating of the Universe. Depending upon the parameters of the model and upon the different inflationary dynamics (prior to the onset of the stiff evolution) the relic gravitons energy density can be much more sizeable than in standard inflationary models, for frequencies larger than 1 Hz. We estimate the required sensitivity for detection of the predicted spectral amplitude and show that the allowed region of our parameter space leads to a signal smaller (by one 1.5 orders of magnitude) than the advanced LIGO sensitivity at a frequency of 0.1 KHz. The maximal signal, in our context, is expected in the GHz region where the energy density of relic gravitons in critical units (i.e. $h_0^2 \Omega_{GW}$) is of the order of $10^{-6}$, roughly eight orders of magnitude larger than in ordinary inflationary models. Smaller detectors (not necessarily interferometers) can be relevant for detection purposes in the GHz frequency window. We suggest/speculate that future measurements through microwave cavities can offer interesting perspectives.Comment: 24 pages in Revtex style, 7 figure