Seismic oceanography imaging of thermal intrusions in strong frontal regions

The Naval Research Laboratory and collaborating partners carried out two dedicated seismic oceanography field experiments in two very different strong frontal regions. ADRIASEISMIC took seismic oceanography measurements at the confluence of North Adriatic Dense Water advected along the Western Adriatic Current and Modified Levantine Intermediate Water advected around the topographic rim of the Southern Adriatic basin. ARC12 took seismic oceanography measurements in and around the Agulhas Return Current as it curved northwards past the Agulhas Plateau and interacted with a large anticyclone that had collided with the current. Despite one study focused on coastal boundary currents and the other focused on a major Western Boundary Current extension, the complex horizontal structures seen through seismic imaging are tied to the processes of thermal intrusions and interleaving in both systems. Seismic Oceanography provides a unique capability of tracking the fine-scale horizontal extent of these intrusions

The Vascular Basement Membrane as “Soil” in Brain Metastasis

Brain-specific homing and direct interactions with the neural substance are prominent hypotheses for brain metastasis formation and a modern manifestation of Paget's “seed and soil” concept. However, there is little direct evidence for this “neurotropic” growth in vivo. In contrast, many experimental studies have anecdotally noted the propensity of metastatic cells to grow along the exterior of pre-existing vessels of the CNS, a process termed vascular cooption. These observations suggest the “soil” for malignant cells in the CNS may well be vascular, rather than neuronal. We used in vivo experimental models of brain metastasis and analysis of human clinical specimens to test this hypothesis. Indeed, over 95% of early micrometastases examined demonstrated vascular cooption with little evidence for isolated neurotropic growth. This vessel interaction was adhesive in nature implicating the vascular basement membrane (VBM) as the active substrate for tumor cell growth in the brain. Accordingly, VBM promoted adhesion and invasion of malignant cells and was sufficient for tumor growth prior to any evidence of angiogenesis. Blockade or loss of the β1 integrin subunit in tumor cells prevented adhesion to VBM and attenuated metastasis establishment and growth in vivo. Our data establishes a new understanding of CNS metastasis formation and identifies the neurovasculature as the critical partner for such growth. Further, we have elucidated the mechanism of vascular cooption for the first time. These findings may help inform the design of effective molecular therapies for patients with fatal CNS malignancies

Electrophysiological activation by masked primes: Independence of prime-related and target-related activities

Visual stimuli that are made invisible by metacontrast masking (primes) have a marked influence on behavioral and psychophysiological measures such as reaction time (RT) and the lateralized readiness potential (LRP). 4 experiments are reported that shed light on the effects that masked primes have on the LRP. Participants had a go-nogo task in which the prime was associated with 1 of 2 responses even if the target required participants to refrain from responding. To analyze the electrophysiological responses, we computed the LRP and applied an averaging method separating the activation due to the prime and the target. The results demonstrated that (a) masked primes activate responses even in a nogo situation, (b) this prime-related activation is independent of masking, (c) and is also independent of whether prime and target require the same responses (congruent condition) or different responses (incongruent condition)

Top-down contingent feature-specific orienting with and without awareness of the visual input

In the present article, the role of endogenous feature-specific orienting for conscious and unconscious vision is reviewed. We start with an overview of orienting. We proceed with a review of masking research, and the definition of the criteria of experimental protocols that demonstrate endogenous and exogenous orienting, respectively. Against this background of criteria, we assess studies of unconscious orienting and come to the conclusion that so far studies of unconscious orienting demonstrated endogenous feature-specific orienting. The review closes with a discussion of the role of unconscious orienting in action control

Monitoring the oceanic flow between Africa and Antarctica: Report of the first GoodHope cruise

The southern ocean plays a major role in the global oceanic circulation role in the global oceanic circulation, as a component of the Meridional Overturning Circulation, and it is postulated that it has a great influence on present-day climate. However, our understanding of its complex three-dimensional dynamics and of the impact of its variability on the climate system is rudimentary. The newly constituted, international GoodHope research venture aims to address this knowledge gap by establishing a programme of regular observations across the Southern Ocean between the African and Antarctic continents. The objectives of this programme are fivefold: (1) to improve understanding of Indo-Atlantic inter-ocean exchanges and their impact on the global thermohaline circulation and thus on global climate change; (2) to understand in more detail the influence these exchanges have on the climate variability of the southern African subcontinent; (3) to monitor the variability of the main Southern Ocean frontal systems associated with the Antarctic Circumpolar Current; (4) to study air–sea exchanges and their role on the global heat budget, with particular emphasis on the intense exchanges occurring within the Agulhas Retroflection region south of South Africa, and (5) to examine the role of major frontal systems as areas of elevated biological activity and as biogeographical barriers to the distribution of plankton. We present here preliminary results on the physical and biological structure of the frontal systems using the first GoodHope transect that was completed during February–March 2004

Follow the sign! Top-down contingent attentional capture of masked arrow cues

Arrow cues and other overlearned spatial symbols automatically orient attention according to their spatial meaning. This renders them similar to exogenous cues that occur at stimulus location. Exogenous cues trigger shifts of attention even when they are presented subliminally. Here, we investigate to what extent the mechanisms underlying the orienting of attention by exogenous cues and by arrow cues are comparable by analyzing the effects of visible and masked arrow cues on attention. In Experiment 1, we presented arrow cues with overall 50% validity. Visible cues, but not masked cues, lead to shifts of attention. In Experiment 2, the arrow cues had an overall validity of 80%. Now both visible and masked arrows lead to shifts of attention. This is in line with findings that subliminal exogenous cues capture attention only in a top-down contingent manner, that is, when the cues fit the observer’s intentions

Targeting NKG2D ligands in glioblastoma with a bispecific T-cell engager is augmented with conventional therapy and enhances oncolytic virotherapy of glioma stem-like cells

Background: Glioblastoma (GBM) almost invariably becomes resistant towards conventional treatment of radiotherapy and temozolomide (TMZ) chemotherapy, partly due to subpopulations of intrinsically resistant glioma stem-like cells (GSC). The oncolytic herpes simplex virus-1 G207 is a promising approach for GBM virotherapy although its efficacy in patients with GBM is often limited. Natural killer group 2 member D ligands (NKG2DLs) are minimally expressed by healthy cells but are upregulated by the DNA damage response (DDR) and in malignant cells with chronic DDR signaling, resulting in innate immune activation. Methods: We have designed a bispecific T-cell engager (BiTE) capable of cross-linking CD3 on T cells with NKG2DL-expressing GBM cells. We then engineered the G207 virus to express the NKG2D BiTE and secrete it from infected cells. The efficacy of the free BiTE and BiTE delivered by G207 was evaluated in combination with conventional therapies in GBM cells and against patient-derived GSCs in the context of T-cell activation and target cell viability. Results: NKG2D BiTE-mediated cross-linking of GBM cells and T cells causes antigen-independent T-cell activation, pro-inflammatory cytokine release, and tumor cell death, thereby combining direct viral oncolysis with BiTE-mediated cytotoxicity. Surface NKG2DL expression was further elevated on GBM cells following pretreatment with sublethal doses of TMZ and radiation to induce the DDR, increasing sensitivity towards G207-NKG2D BiTE and achieving synergistic cytotoxicity. We also demonstrate a novel strategy for targeting GSCs that are non-permissive to G207 infection but remain sensitive to NKG2D BiTE. Conclusions: We propose a potential model for targeting GSCs in heterogeneous tumors, whereby differentiated GBM cells infected with G207-NKG2D BiTE produce NKG2D BiTE locally, directing T-cell cytotoxicity towards the GSC subpopulations in the tumor microenvironment

Multiparticle production in the model with antishadowing

We discuss the role of absorbtion and antishadowing in particle production. We reproduce power-like energy behavior of the mean multiplicity in the model with antishadowing and discuss physical implications of such behavior for the hadron structure.Comment: 11 pages, 3 figures, extended version of the talk at the XXXII International Symposium on Multiparticle Dynamics September 7-13, 2002 Alushta, Crimea, Ukrain