NK4, a four-kringle antagonist of HGF, inhibits spreading and invasion of human pancreatic cancer cells

Because of the highly aggressive behaviour, i.e. invasive, disseminative and metastatic properties, the outcome for patients with pancreatic cancer is morbid. A better understanding and interference with the malignant behaviour of pancreatic cancer may provide new directions for treatment. We report here the induction of highly motile and invasive properties in human pancreatic cancer cells by hepatocyte growth factor (HGF) and blockage of these properties by NK4, a newly identified antagonist for HGF. In all of eight human pancreatic cancer cell lines we used (AsPC-1, BxPC-3, H-48N, KP-1N, KP-2, KP-3, MIA PaCa-2 and SUIT-2 cells), the c-Met/HGF receptor was expressed at varying levels. Although weak mitogenic activity of HGF was seen only in SUIT-2 and KP-3 cells, HGF strongly stimulated migration and invasion of these pancreatic cancer cells, except for BxPC-3 and MIA PaCa-2 cells. In contrast, migration and invasion potently induced by HGF in KP-1N, KP-3 and SUIT-2 cells were inhibited by NK4. The invasion of SUIT-2 cells was also potently stimulated with the influence of cocultured pancreatic fibroblasts and by ascitic fluid obtained after pancreatic cancer resection, however, invasiveness of the cancer cells in such conditions was practically abolished by NK4. Consistently, the ascitic fluid in patients who had undergone pancreatic cancer surgery contained high levels of HGF. These findings mean that HGF is probably involved in invasion, dissemination, and metastasis of pancreatic cancer, particularly through tumour-stromal interaction and after resection of the pancreatic cancer. NK4, an effective antagonist of HGF, may prove to have the potential for anti-invasion/metastasis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Temporal Resolution Multiplexing: Exploiting the limitations of spatio-temporal vision for more efficient VR rendering.

Rendering in virtual reality (VR) requires substantial computational power to generate 90 frames per second at high resolution with good-quality antialiasing. The video data sent to a VR headset requires high bandwidth, achievable only on dedicated links. In this paper we explain how rendering requirements and transmission bandwidth can be reduced using a conceptually simple technique that integrates well with existing rendering pipelines. Every even-numbered frame is rendered at a lower resolution, and every odd-numbered frame is kept at high resolution but is modified in order to compensate for the previous loss of high spatial frequencies. When the frames are seen at a high frame rate, they are fused and perceived as high-resolution and high-frame-rate animation. The technique relies on the limited ability of the visual system to perceive high spatio-temporal frequencies. Despite its conceptual simplicity, correct execution of the technique requires a number of non-trivial steps: display photometric temporal response must be modeled, flicker and motion artifacts must be avoided, and the generated signal must not exceed the dynamic range of the display. Our experiments, performed on a high-frame-rate LCD monitor and OLED-based VR headsets, explore the parameter space of the proposed technique and demonstrate that its perceived quality is indistinguishable from full-resolution rendering. The technique is an attractive alternative to reprojection and resolution reduction of all frames.European Research Council; European Union Horizon 2020 research and innovation programm

Functional Coupling of Ca2+ Channels to Ryanodine Receptors at Presynaptic Terminals: Amplification of Exocytosis and Plasticity

Ca2+-induced Ca2+ release (CICR) enhances a variety of cellular Ca2+ signaling and functions. How CICR affects impulse-evoked transmitter release is unknown. At frog motor nerve terminals, repetitive Ca2+ entries slowly prime and subsequently activate the mechanism of CICR via ryanodine receptors and asynchronous exocytosis of transmitters. Further Ca2+ entry inactivates the CICR mechanism and the absence of Ca2+ entry for >1 min results in its slow depriming. We now report here that the activation of this unique CICR markedly enhances impulse-evoked exocytosis of transmitter. The conditioning nerve stimulation (10–20 Hz, 2–10 min) that primes the CICR mechanism produced the marked enhancement of the amplitude and quantal content of end-plate potentials (EPPs) that decayed double exponentially with time constants of 1.85 and 10 min. The enhancement was blocked by inhibitors of ryanodine receptors and was accompanied by a slight prolongation of the peak times of EPP and the end-plate currents estimated from deconvolution of EPP. The conditioning nerve stimulation also enhanced single impulse- and tetanus-induced rises in intracellular Ca2+ in the terminals with little change in time course. There was no change in the rate of growth of the amplitudes of EPPs in a short train after the conditioning stimulation. On the other hand, the augmentation and potentiation of EPP were enhanced, and then decreased in parallel with changes in intraterminal Ca2+ during repetition of tetani. The results suggest that ryanodine receptors exist close to voltage-gated Ca2+ channels in the presynaptic terminals and amplify the impulse-evoked exocytosis and its plasticity via CICR after Ca2+-dependent priming

Psychologizing indexes of societal progress: Accounting for cultural diversity in preferred developmental pathways

Since the Second World War, the dominating paradigm of societal development has focused on economic growth. While economic growth has improved the quality of human life in a variety of ways, we posit that the identification of economic growth as the primary societal goal is culture-blind because preferences for developmental pathways likely vary between societies. We argue that the cultural diversity of developmental goals and the pathways leading to these goals could be reflected in a culturally sensitive approach to assessing societal development. For the vast majority of post-materialistic societies, it is an urgent necessity to prepare culturally sensitive compasses on how to develop next, and to start conceptualizing growth in a more nuanced and culturally responsive way. Furthermore, we propose that cultural sensitivity in measuring societal growth could also be applied to existing development indicators (e.g. the Human Development Index). We call for cultural researchers, in cooperation with development economists and other social scientists, to prepare a new cultural map of developmental goals, and to create and adapt development indexes that are more culturally sensitive. This innovation could ultimately help social planners understand the diverse pathways of development and assess the degree to which societies are progressing in a self-determined and indigenously valued manner.info:eu-repo/semantics/acceptedVersio

The impact of metformin on the development and course of anaplastic thyroid cancer in comparison to other histologic types of thyroid cancer

Anaplastic thyroid cancer (ATC) is the rarest (1–2%) form of thyroid cancer, but also the most aggressive and associated with the worst prognosis. The survival median rate is 5–6 months, whereas only 20% of patients survive more than one year from the diagnosis, even though the usage of radiotherapy and surgical resection. The growing incidence rate of thyroid cancer and ATC determine the need for new prophylactic, diagnostic and therapeutic solutions. Metformin was first introduced as an oral antidiabetic drug. The beneficial effect of metformin on anaplastic thyroid cancer cells was confirmed, however, the mechanism of this interaction is still unclear. The usage of metformin in thyroid cancer prevention is still under discussion — nevertheless, studies conducted on larger groups support this beneficial impact, at least in patients with insulin resistance or metabolic syndrome. Both the synergistic effect of metformin in anaplastic thyroid cancer chemotherapy and its protective effect in radiotherapy are still concerns and need additional confirmation in randomized clinical trials. This review aims to sum up the recent knowledge on metformin usage in ATC

Fine-Scale Coral Connectivity Pathways in the Florida Reef Tract: Implications for Conservation and Restoration

Connectivity between coral reefs is critical to ensure their resilience and persistence against disturbances. It is driven by ocean currents, which often have very complex patterns within reef systems. Only biophysical models that simulate both the fine-scale details of ocean currents and the life-history traits of larvae transported by these currents can help to estimate connectivity in large reef systems. Here we use the unstructured-mesh coastal ocean model SLIM that locally achieves a spatial resolution of ~100 m, 10 times finer than existing models, over the entire Florida Reef Tract (FRT). It allows us to simulate larval dispersal between the ~1,000 reefs composing the FRT. By using different connectivity measures and clustering methods, we have identified two major connectivity pathways, one originating on the westernmost end of the outer shelf and the other originating on the inner shelf, North of the Lower Keys. We introduce new connectivity indicators, based on the PageRank algorithm, to show that protection efforts should be focused on the most upstream reefs of each pathway, while reefs best suited for restoration are more evenly spread between the Lower and Upper Keys. We identify one particular reef, North of Vaca Key, that is a major stepping stone in the connectivity network. Our results are the first reef-scale connectivity estimates for the entire FRT. Such fine-scale information can provide knowledge-based decision support to allocate conservation and restoration resources optimally