1,018 research outputs found

    Oxidation-assisted alkaline precipitation : the effect of H2O2 on the size of CuO and FeOOH nanoparticles

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    H2O2 was demonstrated to narrow the size distribution and decrease the size of CuO and hydrous FeOOH (2-line ferrihydrite) nanoparticles under conditions of high supersaturation. We introduce oxidation-assisted alkaline precipitation (Ox-AP) and compare it to traditional alkaline precipitation (AP). While for AP, a metal salt solution (e.g., CuCl2) is mixed with an alkali (e.g., NaOH), for Ox-AP, the more reduced form of that metal salt solution (e.g., CuCl) is simultaneously mixed with that alkali and an oxidant (e.g., H2O2). The resulting precipitates were characterized with SEM, XRD, DLS and single particle ICP-MS and shown to be nanoparticles (NPs). Ox-AP CuO NPs were up to 3 times smaller than AP NPs. Ox-AP FeOOH NPs were up to 22.5% smaller than AP NPs. We discuss and propose a possible mechanism of Ox-AP through careful consideration of the known reaction chemistry of iron and copper. We propose that an increased monomer formation rate enhances the nucleation rate, which ultimately results in smaller particles with a more narrow distribution. The more distinct effect of Ox-AP on copper, was attributed to the fast formation of the stable CuO monomer, compared to AP, where the Cu(OH)(2) and/or Cu-2(OH)(3)Cl monomers are more likely formed. Although, the exact mechanism of Ox-AP needs experimental confirmation, our results nicely demonstrate the potential of using Ox-AP to produce smaller NPs with a more narrow distribution in comparison to using AP

    A GIS-based hydrographic resurvey strategy of the Belgian Continental Shelf

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    Using a GIS-based approach, bathymetric surveys and maritime traffic records were combined to determine resurvey priorities within the Belgian Continental Shelf (BCS). Four reference layers were produced: (1) water depth; (2) maximum absolute change in water depth; (3) ship traffic intensity; (4) maximum ship draught. The reference layers were reclassified and merged into a weighted overlay analysis. Two combinations of layers and weight factors were used and resulted in priority maps differing greatly from each other. The reliability of the analysis depends on the way weight factors are assigned, and on the availability and accuracy of the data. These are limited for bathymetric surveys. This empirical GIS-based methodology can be applied as a whole to a zone showing various morphodynamic patterns. It can also be automated: additional datasets can be included in the analysis, and different scenarios and assumptions can be easily tested

    Isolated limb perfusion with actinomycin D and TNF-alpha results in improved tumour response in soft-tissue sarcoma-bearing rats but is accompanied by severe local toxicity

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    Previously we demonstrated that addition of Tumour Necrosis Factor-α to melphalan or doxorubicin in a so-called isolated limb perfusion results in synergistic antitumour responses of sarcomas in both animal models and patients. Yet, 20 to 30% of the treated tumours do not respond. Therefore agents that synergise with tumour necrosis factor alpha must be investigated. Actinomycin D is used in combination with melphalan in isolated limb perfusion in the treatment of patients with melanoma in-transit metastases and is well known to augment tumour cell sensitivity towards tumour necrosis factor alpha in vitro. Both agents are very toxic, which limits their systemic use. Their applicability may therefore be tested in the isolated limb perfusion setting, by which the tumours can be exposed to high concentrations in the absence of systemic exposure. To study the beneficial effect of the combination in vivo, BN-175 soft tissue sarcoma-bearing rats were perfused with various concentrations of actinomycin D and tumour necrosis factor alpha. When used alone the drugs had only little effect on the tumour. Only when actinomycin D and tumour necrosis factor alpha were combined a tumour response was achieved. However, these responses were accompanied by severe, dose limiting, local toxicity such as destruction of the muscle tissue and massive oedema. Our results show that isolated limb perfusion with actinomycin D in combination with tumour necrosis factor alpha leads to a synergistic anti-tumour response but also to idiosyncratic locoregional toxicity to the normal tissues. Actinomycin D, in combination with tumour necrosis factor alpha, should not be explored in the clinical setting because of this. The standard approach in the clinic remains isolated limb perfusion with tumour necrosis factor alpha in combination with melphalan

    Histamine, a vasoactive agent with vascular disrupting potential, improves tumour response by enhancing local drug delivery

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    Tumour necrosis factor (TNF)-based isolated limb perfusion (ILP) is an approved and registered treatment for sarcomas confined to the limbs in Europe since 1998, with limb salvage indexes of 76%. TNF improves drug distribution in solid tumours and secondarily destroys the tumour-associated vasculature (TAV). Here we explore the synergistic antitumour effect of another vasoactive agent, histamine (Hi), in doxorubicin (DXR)-based ILP and evaluate its antivascular effects on TAV. We used our well-established rat ILP model for in vivo studies looking at tumour response, drug distribution and effects on tumour vessels. In vitro studies explored drug interactions at cellular level on tumour cells (BN-175) and Human umbilical vein endothelial cells (HUVEC). There was a 17% partial response and a 50% arrest in tumour growth when Hi was combined to DXR, without important side effects, against 100% progressive disease with DXR alone and 29% arrest in tumour growth for Hi alone. Histology documented an increased DXR leakage in tumour tissue combined to a destruction of the TAV, when Hi was added to the ILP. In vitro no synergy between the drugs was observed. In conclusion, Hi is a vasoactive drug, targeting primarily the TAV and synergises with different chemotherapeutic agents

    One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastases

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    OBJECTIVE: The aim of this study is to describe the experience with 100 TNF-based ILP for locally advanced melanoma and to determine prognostic factors for response, time to local progression, and survival. METHODS: One hundred TNF-based ILPs were performed between 1991 and 2003 in 87 patients for whom local control by surgery of in-transit melanoma metastases was impossible. In total, 62 iliac, 33 femoral, and 5 axillary ILPs were performed in mild hyperthermic conditions with 2 to 4 mg of TNF and 10 to 13 mg of melphalan per liter of limb volume. RESULTS: Overall response was 95%, with 69% complete response, 26% partial response, and 5% no change. Complete response rate differed significantly for patients with IIIA disease versus IIIAB and IV. Local and systemic toxicity was mild to moderate in almost all cases, with no treatment-related death and one treatment-related amputation. Five-year overall survival was 32%; local progression occurred in 55% after a median of 16 months. In complete response patients, 5-year survival was 42% with local progression in 52% at a median of 22 months. Response rate and survival were significantly influenced by stage of disease; (local progression free) survival was influenced by response rate. CONCLUSIONS: TNF-based ILP results in excellent response rates in this patient population with unfavorable characteristics. Response on ILP predicts outcome in patients and reflects aggressiveness of the tumor

    Independent Set Reconfiguration in Cographs

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    We study the following independent set reconfiguration problem, called TAR-Reachability: given two independent sets II and JJ of a graph GG, both of size at least kk, is it possible to transform II into JJ by adding and removing vertices one-by-one, while maintaining an independent set of size at least kk throughout? This problem is known to be PSPACE-hard in general. For the case that GG is a cograph (i.e. P4P_4-free graph) on nn vertices, we show that it can be solved in time O(n2)O(n^2), and that the length of a shortest reconfiguration sequence from II to JJ is bounded by 4n2k4n-2k, if such a sequence exists. More generally, we show that if XX is a graph class for which (i) TAR-Reachability can be solved efficiently, (ii) maximum independent sets can be computed efficiently, and which satisfies a certain additional property, then the problem can be solved efficiently for any graph that can be obtained from a collection of graphs in XX using disjoint union and complete join operations. Chordal graphs are given as an example of such a class XX

    Enhancement of electroporation facilitated immunogene therapy via T-reg depletion

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    Regulatory T cells (T-regs) can negatively impact tumor antigen-specific immune responses after infiltration into tumor tissue. However, depletion of T-regs can facilitate enhanced anti-tumor responses, thus augmenting the potential for immunotherapies. Here we focus on treating a highly aggressive form of cancer using a murine melanoma model with a poor prognosis. We utilize a combination of T-reg depletion and immunotherapy plasmid DNA delivered into the B16F10 melanoma tumor model via electroporation. Plasmids encoding murine granulocyte macrophage colony-stimulating factor and human B71 were transfected with electroporation into the tumor and transient elimination of T-regs was achieved with CD25-depleting antibodies (PC61). The combinational treatment effectively depleted T-regs compared to the untreated tumor and significantly reduced lung metastases. The combination treatment was not effective in increasing the survival, but only effective in suppression of metastases. These results indicate the potential for combining T-reg depletion with immunotherapy-based gene electrotransfer to decrease systemic metastasis and potentially enhance survival

    Semantic learning in autonomously active recurrent neural networks

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    The human brain is autonomously active, being characterized by a self-sustained neural activity which would be present even in the absence of external sensory stimuli. Here we study the interrelation between the self-sustained activity in autonomously active recurrent neural nets and external sensory stimuli. There is no a priori semantical relation between the influx of external stimuli and the patterns generated internally by the autonomous and ongoing brain dynamics. The question then arises when and how are semantic correlations between internal and external dynamical processes learned and built up? We study this problem within the paradigm of transient state dynamics for the neural activity in recurrent neural nets, i.e. for an autonomous neural activity characterized by an infinite time-series of transiently stable attractor states. We propose that external stimuli will be relevant during the sensitive periods, {\it viz} the transition period between one transient state and the subsequent semi-stable attractor. A diffusive learning signal is generated unsupervised whenever the stimulus influences the internal dynamics qualitatively. For testing we have presented to the model system stimuli corresponding to the bars and stripes problem. We found that the system performs a non-linear independent component analysis on its own, being continuously and autonomously active. This emergent cognitive capability results here from a general principle for the neural dynamics, the competition between neural ensembles.Comment: Journal of Algorithms in Cognition, Informatics and Logic, special issue on `Perspectives and Challenges for Recurrent Neural Networks', in pres
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