Interferometer for Co-operating Target Motion Detection

A correlation interferometer working with a cooperation target operating at 2.2GHz center frequency is presented. This simplified interferometer presented here uses a
lock-in amplifier to significantly increase system sensitivity when used in conjunction with a co-operating target signaling using amplitude modulation. The system is verified by detecting the angular velocity of passing tagged target. Experimental results show detectable range up over 110 meters in a multipath environment using a 10dBm EIRP tag.

TBX2 represses CST6 resulting in uncontrolled legumain activity to sustain breast cancer proliferation: a novel cancer-selective target pathway with therapeutic opportunities.

TBX2 is an oncogenic transcription factor known to drive breast cancer proliferation. We have identified the cysteine protease inhibitor Cystatin 6 (CST6) as a consistently repressed TBX2 target gene, co-repressed through a mechanism involving Early Growth Response 1 (EGR1). Exogenous expression of CST6 in TBX2-expressing breast cancer cells resulted in significant apoptosis whilst non-tumorigenic breast cells remained unaffected. CST6 is an important tumor suppressor in multiple tissues, acting as a dual protease inhibitor of both papain-like cathepsins and asparaginyl endopeptidases (AEPs) such as Legumain (LGMN). Mutation of the CST6 LGMN-inhibitory domain completely abrogated its ability to induce apoptosis in TBX2-expressing breast cancer cells, whilst mutation of the cathepsin-inhibitory domain or treatment with a pan-cathepsin inhibitor had no effect, suggesting that LGMN is the key oncogenic driver enzyme. LGMN activity assays confirmed the observed growth inhibitory effects were consistent with CST6 inhibition of LGMN. Knockdown of LGMN and the only other known AEP enzyme (GPI8) by siRNA confirmed that LGMN was the enzyme responsible for maintaining breast cancer proliferation. CST6 did not require secretion or glycosylation to elicit its cell killing effects, suggesting an intracellular mode of action. Finally, we show that TBX2 and CST6 displayed reciprocal expression in a cohort of primary breast cancers with increased TBX2 expression associating with increased metastases. We have also noted that tumors with altered TBX2/CST6 expression show poor overall survival. This novel TBX2-CST6-LGMN signaling pathway, therefore, represents an exciting opportunity for the development of novel therapies to target TBX2 driven breast cancers.

Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4+ T Cell Immunity

Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

Generation of high-energy-density ion bunches by ultraintense laser-cone-target interaction

A scheme in which carbon ion bunches are accelerated to a high energy and density by a laser pulse (∼10 W/cm) irradiating cone targets is proposed and investigated using particle-in-cell simulations. The laser pulse is focused by the cone and drives forward an ultrathin foil located at the cone's tip. In the course of the work, best results were obtained employing target configurations combining a low-Z cone with a multispecies foil transversely shaped to match the laser intensity profile. © 2014 AIP Publishing LLC.

Manganese Superoxide Dismutase Is a Promising Target for Enhancing Chemosensitivity of Basal-Like Breast Carcinoma

AIMS: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is significantly amplified in the aggressive breast carcinoma basal subtype, and targeting MnSOD could be an attractive strategy for enhancing chemosensitivity of this highly aggressive breast cancer subtype.

RESULTS: Using MDA-MB-231 and BT549 as a model of basal breast cancer cell lines, we show that knockdown of MnSOD decreased the colony-forming ability and sensitized the cells to drug-induced cell death, while drug resistance was associated with increased MnSOD expression. In an attempt to develop a clinically relevant approach to down-regulate MnSOD expression in patients with basal breast carcinoma, we employed activation of the peroxisome proliferator-activated receptor gamma (PPARγ) to repress MnSOD expression; PPARγ activation significantly reduced MnSOD expression, increased chemosensitivity, and inhibited tumor growth. Moreover, as a proof of concept for the clinical use of PPARγ agonists to decrease MnSOD expression, biopsies derived from breast cancer patients who had received synthetic PPARγ ligands as anti-diabetic therapy had significantly reduced MnSOD expression. Finally, we provide evidence to implicate peroxynitrite as the mechanism involved in the increased sensitivity to chemotherapy induced by MnSOD repression.

INNOVATION AND CONCLUSION: These data provide evidence to link increased MnSOD expression with the aggressive basal breast cancer, and underscore the judicious use of PPARγ ligands for specifically down-regulating MnSOD to increase the chemosensitivity of this subtype of breast carcinoma.

Enhanced target detection in clutter using dispersive delay lines and time reversal

On the basis of the technique of time reversal (TR), a new method for low dielectric contrast target detection in clutter by adding dispersive delay lines (DDLs) to each element of the TR mirror (TRM) is proposed. When compared with a conventional TR system, the proposed method improves refocusing to a target by reducing the impact of other scatterers in the environment. The proposed method makes it unnecessary to estimate the position of the target and removes the need for subsequent subtraction as traditionally required. Theoretical and numerical simulated results demonstrate the proposed method.

Enhancing Linear Programming with Motion Modeling for Multi-target Tracking

In this paper we extend the minimum-cost network flow approach to multi-target tracking, by incorporating a motion model, allowing the tracker to better cope with longterm occlusions and missed detections. In our new method, the tracking problem is solved iteratively: Firstly, an initial tracking solution is found without the help of motion information. Given this initial set of tracklets, the motion at each detection is estimated, and used to refine the tracking solution.
Finally, special edges are added to the tracking graph, allowing a further revised tracking solution to be found, where distant tracklets may be linked based on motion similarity. Our system has been tested on the PETS S2.L1 and Oxford town-center sequences, outperforming the baseline system, and achieving results comparable with the current state of the art.

New design of a multi-jet target for quasi phase matching

An improved dual-gas quasi-phase matching (QPM) foil target for high harmonic generation (HHG) is presented. The target can be setup with 12 individual gas inlets each feeding multiple nozzles separated by a minimum distance of 10 μm. Three-dimensional gas density profiles of these jets were measured using a Mach-Zehnder Interferometer. These measurements reveal how the jets influence the density of gas in adjacent jets and how this leads to increased local gas densities. The analysis shows that the gas profiles of the jets are well defined up to a distance of about 300 μm from the orifice. This target design offers experimental flexibility, not only for HHG/QPM investigations, but also for a wide range of experiments due to the large number of possible jet configurations. We demonstrate the application to controlled phase tuning in the extreme ultraviolet using a 1 kHz-10 mJ-30 fs-laser system where interference between two jets in the spectral range from 17 to 30 nm was observed.

Evidence of locally enhanced target heating due to instabilities of counter-streaming fast electron beams

The high-current fast electron beams generated in high-intensity laser-solid interactions require the onset of a balancing return current in order to propagate in the target material. Such a system of counter-streaming electron currents is unstable to a variety of instabilities such as the current-filamentation instability and the two-stream instability. An experimental study aimed at investigating the role of instabilities in a system of symmetrical counter-propagating fast electron beams is presented here for the first time. The fast electron beams are generated by double-sided laser-irradiation of a layered target foil at laser intensities above 10(19) W/cm(2). High-resolution X-ray spectroscopy of the emission from the central Ti layer shows that locally enhanced energy deposition is indeed achieved in the case of counter-propagating fast electron beams

Spitzer observations of the asteroid-comet transition object and potential spacecraft target 107P (4015) Wilson-Harrington

Context: Near-Earth asteroid-comet transition object 107P/ (4015) Wilson-Harrington is a possible target of the joint European Space Agency (ESA) and Japanese Aerospace Exploration Agency (JAXA) Marco Polo sample return mission. Physical studies of this object are relevant to this mission, and also to understanding its asteroidal or cometary nature. Aims: Our aim is to obtain significant new constraints on the surface thermal properties of this object. Methods: We present mid-infrared photometry in two filters (16 and 22 μm) obtained with NASA's Spitzer Space Telescope on February 12, 2007, and results from the application of the Near Earth Asteroid Thermal Model (NEATM). We obtained high S/N in two mid-IR bands allowing accurate measurements of its thermal emission. Results: We obtain a well constrained beaming parameter (η = 1.39±0.26) and obtain a diameter and geometric albedo of D = 3.46±0.32 km, and pV = 0.059±0.011. We also obtain similar results when we apply this best-fitting thermal model to single-band mid-IR photometry reported by Campins et al. (1995, P&SS, 43, 733), Kraemer et al. (2005, AJ, 130, 2363) and Reach et al. (2007, Icarus, 191, 298). Conclusions: The albedo of 4015 Wilson-Harrington is low, consistent with those of comet nuclei and primitive C-, P-, D-type asteorids. We establish a rough lower limit for the thermal inertia of W-H of 60 Jm-2s-0.5 K-1 when it is at r = 1 AU, which is slightly over the limit of 30 Jm-2 s-0.5 K-1 derived by Groussin et al. (2009, Icarus, 199, 568) for the thermal inertia of the nucleus of comet 22P/Kopff.

ESO observations of the Nucleus of Rosetta Target 67P/C-G

Rosetta is ESA's new comet orbiter mission, launched in March 2004 and currently en route to Jupiter-family comet 67P/Churyumov-Gerasimenko. The probe will rendezvous with the comet in 2014 and remain in orbit around the nucleus for on-going detailed physical and compositional analysis. Pre-encounter observations of the target are important for characterization of the heliocentric light-curve behaviour and the physical properties of the nucleus, information that is critical for mission planning. The nucleus was first characterized using HST observations in 2003 (Lamy et al. 2006) and observed directly in May 2005 by ground based telescopes (Lowry et al. 2006) when it was at 5.6 AU from the Sun. An extensive database of nucleus observations have since been acquired, not only from large ground-based telescopes like the ESO VLT (Tubiana et al. 2008 & 2011), but also from Spitzer (Kelley et al. 2006 & 2009; Lamy et al. 2008).

Mechanistic Rationale to Target PTEN-Deficient Tumor Cells with Inhibitors of the DNA Damage Response Kinase ATM

Ataxia telangiectasia mutated (ATM) is an important signaling molecule in the DNA damage response (DDR). ATM loss of function can produce a synthetic lethal phenotype in combination with tumor-associated mutations in FA/BRCA pathway components. In this study, we took an siRNA screening strategy to identify other tumor suppressors that, when inhibited, similarly sensitized cells to ATM inhibition. In this manner, we determined that PTEN and ATM were synthetically lethal when jointly inhibited. PTEN-deficient cells exhibited elevated levels of reactive oxygen species, increased endogenous DNA damage, and constitutive ATM activation. ATM inhibition caused catastrophic DNA damage, mitotic cell cycle arrest, and apoptosis specifically in PTEN-deficient cells in comparison with wild-type cells. Antioxidants abrogated the increase in DNA damage and ATM activation in PTEN-deficient cells, suggesting a requirement for oxidative DNA damage in the mechanism of cell death. Lastly, the ATM inhibitor KU-60019 was specifically toxic to PTEN mutant cancer cells in tumor xenografts and reversible by reintroduction of wild-type PTEN. Together, our results offer a mechanistic rationale for clinical evaluation of ATM inhibitors in PTEN-deficient tumors.

PET/CT imaging for target volume delineation in curative intent radiotherapy of non-small cell lung cancer: IAEA consensus report 2014

This document describes best practice and evidence based recommendations for the use of FDG-PET/CT for the purposes of radiotherapy target volume delineation (TVD) for curative intent treatment of non-small cell lung cancer (NSCLC). These recommendations have been written by an expert advisory group, convened by the International Atomic Energy Agency (IAEA) to facilitate a Coordinated Research Project (CRP) aiming to improve the applications of PET based radiation treatment planning (RTP) in low and middle income countries. These guidelines can be applied in routine clinical practice of radiotherapy TVD, for NSCLC patients treated with concurrent chemoradiation or radiotherapy alone, where FDG is used, and where a calibrated PET camera system equipped for RTP patient positioning is available. Recommendations are provided for PET and CT image visualization and interpretation, and for tumor delineation using planning CT with and without breathing motion compensation.