Netted LPI radars

A significant number of Low Probability of Intercept (LPI) radars are used in various military applications, from guided weapons (such anti-ship missile), to large platforms (aircrafts, ships), to large systems (Integrated Air Defense Systems - IADS). The purpose of this thesis is to evaluate the performance of netted LPI radar systems. To do so, it commences with establishing the theoretical background for the LPI radar techniques and detection methods. Additionally, it presents existing LPI assets along with their operational characteristics to provide the reader with a useful tool for comparative analysis of the LPI radar market. As this work focuses on LPI radar networks, specific emphasis is given to clarifying the notion of a netted system; the conceptual and mathematical background for such are presented in a separate chapter.http://archive.org/details/nettedlpiradars109455601Approved for public release; distribution is unlimited

The efficacy of epidermal growth factor receptor-specific antibodies against glioma xenografts is influenced by receptor levels, activation status, and heterodimerization

Purpose: Factors affecting the efficacy of therapeutic monoclonal antibodies (mAb) directed to the epidermal growth factor receptor (EGFR) remain relatively unknown, especially in glioma. Experimental Design: We examined the efficacy of two EGFR-specific mAbs (mAbs 806 and 528) against U87MG-derived glioma xenografts expressing EGFR variants. Using this approach allowed us to change the form of the EGFR while keeping the genetic background constant. These variants included the de2-7 EGFR (or EGFRvIII), a constitutively active mutation of the EGFR expressed in glioma. Results: The efficacy of the mAbs correlated with EGFR number; however, the most important factor was receptor activation. Whereas U87MG xenografts expressing the de2-7 EGFR responded to therapy, those exhibiting a dead kinase de2-7 EGFR were refractory. A modified de2-7 EGFR that was kinase active but autophosphorylation deficient also responded, suggesting that these mAbs function in de2-7 EGFR–expressing xenografts by blocking transphosphorylation. Because de2-7 EGFR–expressing U87MG xenografts coexpress the wild-type EGFR, efficacy of the mAbs was also tested against NR6 xenografts that expressed the de2-7 EGFR in isolation. Whereas mAb 806 displayed antitumor activity against NR6 xenografts, mAb 528 therapy was ineffective, suggesting that mAb 528 mediates its antitumor activity by disrupting interactions between the de2-7 and wild-type EGFR. Finally, genetic disruption of Src in U87MG xenografts expressing the de2-7 EGFR dramatically enhanced mAb 806 efficacy. Conclusions: The effective use of EGFR-specific antibodies in glioma will depend on identifying tumors with activated EGFR. The combination of EGFR and Src inhibitors may be an effective strategy for the treatment of glioma

Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR

We report the generation of a chimeric monoclonal antibody (ch806) with specificity for an epitope on the epidermal growth factor receptor (EGFR) that is different from that targeted by all other anti-EGFR therapies. Ch806 antibody is reactive to both de2-7 and overexpressed wild-type (wt) EGFR but not native EGFR expressed in normal tissues at physiological levels. Ch806 was stably expressed in CHO (DHFR −/−) cells and purified for subsequent characterisation and validated for use in preliminary immunotherapy investigations. Ch806 retained the antigen binding specificity and affinity of the murine parental antibody. Furthermore, ch806 displayed enhanced antibody-dependent cellular cytotoxicity against target cells expressing the 806 antigen in the presence of human effector cells. Ch806 was successfully radiolabelled with both iodine-125 and indium-111 without loss of antigen binding affinity or specificity. The radioimmunoconjugates were stable in the presence of human serum at 37°C for up to 9 days and displayed a terminal half-life (T1/2β) of approximately 78 h in nude mice. Biodistribution studies undertaken in BALB/c nude mice bearing de2-7 EGFR-expressing or amplified EGFR-expressing xenografts revealed that 125I-labelled ch806 failed to display any significant tumour retention. However, specific and prolonged tumour localisation of' 111In-labelled ch806 was demonstrated with uptake of 31%ID g−1 and a tumour to blood ratio of 5 : 1 observed at 7 days postinjection. In vivo therapy studies with ch806 demonstrated significant antitumour effects on established de2-7 EGFR xenografts in BALB/c nude mice compared to control, and both murine 806 and the anti-EGFR 528 antibodies. These results support a potential therapeutic role of ch806 in the treatment of suitable EGFR-expressing tumours, and warrants further investigation of the potential of ch806 as a therapeutic agent

Seasonal Phytoplankton Blooms in the North Atlantic Linked to the Overwintering Strategies of Copepods

The North Atlantic Ocean contains diverse patterns of seasonal phytoplankton blooms with distinct internal dynamics. We analyzed blooms using remotely-sensed chlorophyll a concentration data and change point statistics. The first bloom of the year began during spring at low latitudes and later in summer at higher latitudes. In regions where spring blooms occurred at high frequency (i. e., proportion of years that a bloom was detected), there was a negative correlation between bloom timing and duration, indicating that early blooms last longer. In much of the Northeast Atlantic, bloom development extended over multiple seasons resulting in peak chlorophyll concentrations in summer. Spring bloom start day was found to be positively correlated with a spring phenology index and showed both positive and negative correlations to sea surface temperature and the North Atlantic Oscillation in different regions. Based on the characteristics of spring and summer blooms, the North Atlantic can be classified into two regions: a seasonal bloom region, with a well-defined bloom limited to a single season; and a multi-seasonal bloom region, with blooms extending over multiple seasons. These regions differed in the correlation between bloom start and duration with only the seasonal bloom region showing a significant, negative correlation. We tested the hypothesis that the near-surface springtime distribution of copepods that undergo diapause (Calanus finmarchicus, C. helgolandicus, C. glacialis, and C. hyperboreus) may contribute to the contrast in bloom development between the two regions. Peak near-surface spring abundance of the late stages of these Calanoid copepods was generally associated with areas having a well-defined seasonal bloom, implying a link between bloom shape and their abundance. We suggest that either grazing is a factor in shaping the seasonal bloom or bloom shape determines whether a habitat is conducive to diapause, while recognizing that both factors can re-enforce each other

Seasonal Phytoplankton Blooms in the North Atlantic Linked to the Overwintering Strategies of Copepods

The North Atlantic Ocean contains diverse patterns of seasonal phytoplankton blooms with distinct internal dynamics. We analyzed blooms using remotely-sensed chlorophyll a concentration data and change point statistics. The first bloom of the year began during spring at low latitudes and later in summer at higher latitudes. In regions where spring blooms occurred at high frequency (i. e., proportion of years that a bloom was detected), there was a negative correlation between bloom timing and duration, indicating that early blooms last longer. In much of the Northeast Atlantic, bloom development extended over multiple seasons resulting in peak chlorophyll concentrations in summer. Spring bloom start day was found to be positively correlated with a spring phenology index and showed both positive and negative correlations to sea surface temperature and the North Atlantic Oscillation in different regions. Based on the characteristics of spring and summer blooms, the North Atlantic can be classified into two regions: a seasonal bloom region, with a well-defined bloom limited to a single season; and a multi-seasonal bloom region, with blooms extending over multiple seasons. These regions differed in the correlation between bloom start and duration with only the seasonal bloom region showing a significant, negative correlation. We tested the hypothesis that the near-surface springtime distribution of copepods that undergo diapause (Calanus finmarchicus, C. helgolandicus, C. glacialis, and C. hyperboreus) may contribute to the contrast in bloom development between the two regions. Peak near-surface spring abundance of the late stages of these Calanoid copepods was generally associated with areas having a well-defined seasonal bloom, implying a link between bloom shape and their abundance. We suggest that either grazing is a factor in shaping the seasonal bloom or bloom shape determines whether a habitat is conducive to diapause, while recognizing that both factors can re-enforce each other

Circadian profiles in young people during the early stages of affective disorder

Although disturbances of the circadian system are strongly linked to affective disorders, no known studies have examined melatonin profiles in young people in early stages of illness. In this study, 44 patients with an affective disorder underwent clinical and neuropsychological assessments. They were then rated by a psychiatrist according to a clinical staging model and were categorized as having an ‘attenuated syndrome' or an ‘established disorder'. During the evening, salivary melatonin was sampled under dim light conditions over an 8-h interval and for each patient, the time of melatonin onset, total area under the curve and phase angle (difference between time of melatonin onset and time of habitual sleep onset) were computed. Results showed that there was no difference in the timing of melatonin onset across illness stages. However, area under the curve analyses showed that those patients with ‘established disorders' had markedly reduced levels of melatonin secretion, and shorter phase angles, relative to those with ‘attenuated syndromes'. These lower levels, in turn, were related to lower subjective sleepiness, and poorer performance on neuropsychological tests of verbal memory. Overall, these results suggest that for patients with established illness, dysfunction of the circadian system relates clearly to functional features and markers of underlying neurobiological change. Although the interpretation of these results would be greatly enhanced by control data, this work has important implications for the early delivery of chronobiological interventions in young people with affective disorders

Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses.

G protein-coupled receptor (GPR) 55 is sensitive to certain cannabinoids, it is expressed in the brain and, in cell cultures, it triggers mobilization of intracellular Ca(2+). However, the adaptive neurobiological significance of GPR55 remains unknown. Here, we use acute hippocampal slices and combine two-photon excitation Ca(2+) imaging in presynaptic axonal boutons with optical quantal analysis in postsynaptic dendritic spines to find that GPR55 activation transiently increases release probability at individual CA3-CA1 synapses. The underlying mechanism involves Ca(2+) release from presynaptic Ca(2+) stores, whereas postsynaptic stores (activated by spot-uncaging of inositol 1,4,5-trisphosphate) remain unaffected by GPR55 agonists. These effects are abolished by genetic deletion of GPR55 or by the GPR55 antagonist cannabidiol, a constituent of Cannabis sativa. GPR55 shows colocalization with synaptic vesicle protein vesicular glutamate transporter 1 in stratum radiatum. Short-term potentiation of CA3-CA1 transmission after a short train of stimuli reveals a presynaptic, Ca(2+) store-dependent component sensitive to cannabidiol. The underlying cascade involves synthesis of phospholipids, likely in the presynaptic cell, but not the endocannabinoids 2-arachidonoylglycerol or anandamide. Our results thus unveil a signaling role for GPR55 in synaptic circuits of the brain

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal