Slakkenschade in aardappelen : inventarisatie naar potentiële factoren die problemen met slakken in aardappelen veroorzaken (2009)

Veel telers in het zuidoosten van Nederland maakten in 2009 melding van gaten in aardappelen veroorzaakt door slakken. Ze gaven aan dat dit vaak pas wordt geconstateerd tijdens het inschuren van de aardappelen of zelfs pas in de bewaring. Het is echter nauwelijks bekend welke omstandigheden leiden tot dit probleem en wat voor soort slakken in dit gebied de schade veroorzaken. Verondersteld wordt dat een teelt van groenbemesters en al of niet kerende grondbewerking de problemen veroorzaken. Harde bewijzen ontbreken echter. Er zijn geen gefundeerde adviezen over effectieve maatregelen bekend die leiden tot het verminderen of voorkomen van slakkenschade in aardappelen. In dit onderzoek is het slakkenprobleem met betrekking tot aardappelen in kaart gebracht. Tegelijkertijd is getracht inzicht te krijgen in afhankelijke invloedsfactoren die bijdragen aan het probleem. Hiervoor zijn aardappeltelers benaderd om hun ervaringen met betrekking tot slakken in aardappelen tot uiting te brengen. Het doel is of via teelt- en/of beheersmaatregelen het probleem kan worden aangepakt

Delivering the power of nanomedicine to patients today

The situation of the COVID-19 pandemic reminds us that we permanently need high-value flexible solutions to urgent clinical needs including simplified diagnostic technologies suitable for use in the field and for delivering targeted therapeutics. From our perspective nanotechnology is revealed as a vital resource for this, as a generic platform of technical solutions to tackle complex medical challenges. It is towards this perspective and focusing on nanomedicine that we take issue with Prof Park's recent editorial published in the Journal of Controlled Release. Prof. Park argued that in the last 15 years nanomedicine failed to deliver the promised innovative clinical solutions to the patients (Park, K. The beginning of the end of the nanomedicine hype. Journal of Controlled Release, 2019; 305, 221\u2013222 [1]. We, the ETPN (European Technology Platform on Nanomedicine) [2], respectfully disagree. In fact, the more than 50 formulations currently in the market, and the recent approval of 3 key nanomedicine products (e. g. Onpattro, Hensify and Vyxeos), have demonstrated that the nanomedicine field is concretely able to design products that overcome critical barriers in conventional medicine in a unique manner, but also to deliver within the cells new drug-free therapeutic effects by using pure physical modes of action, and therefore make a difference in patients lives. Furthermore, the >400 nanomedicine formulations currently in clinical trials are expecting to bring novel clinical solutions (e.g. platforms for nucleic acid delivery), alone or in combination with other key enabling technologies to the market, including biotechnologies, microfluidics, advanced materials, biomaterials, smart systems, photonics, robotics, textiles, Big Data and ICT (information & communication technologies) more generally. However, we agree with Prof. Park that \u201c it is time to examine the sources of difficulty in clinical translation of nanomedicine and move forward \u201c. But for reaching this goal, the investments to support clinical translation of promising nanomedicine formulations should increase, not decrease. As recently encouraged by EMA in its roadmap to 2025, we should create more unity through a common knowledge hub linking academia, industry, healthcare providers and hopefully policy makers to reduce the current fragmentation of the standardization and regulatory body landscape. We should also promote a strategy of cross-technology innovation, support nanomedicine development as a high value and low-cost solution to answer unmet medical needs and help the most promising innovative projects of the field to get better and faster to the clinic. This global vision is the one that the ETPN chose to encourage for the last fifteen years. All actions should be taken with a clear clinical view in mind, \u201c without any fanfare\u201d, to focus \u201con what matters in real life\u201d, which is the patient and his/her quality of life. This ETPN overview of achievements in nanomedicine serves to reinforce our drive towards further expanding and growing the maturity of nanomedicine for global healthcare, accelerating the pace of transformation of its great potential into tangible medical breakthroughs

Ісак Мазепа: перші кроки у великій політиці

Досліджується становлення світоглядних позицій та формування політичних поглядів І. Мазепи.Исследуется становление мировоззренческих позиций и формирование политических взглядов И. Мазепы.Formation world outlook positions and formation of political views of I. Mazepa is investigated

Communicating Processes with Data for Supervisory Coordination

We employ supervisory controllers to safely coordinate high-level discrete(-event) behavior of distributed components of complex systems. Supervisory controllers observe discrete-event system behavior, make a decision on allowed activities, and communicate the control signals to the involved parties. Models of the supervisory controllers can be automatically synthesized based on formal models of the system components and a formalization of the safe coordination (control) requirements. Based on the obtained models, code generation can be used to implement the supervisory controllers in software, on a PLC, or an embedded (micro)processor. In this article, we develop a process theory with data that supports a model-based systems engineering framework for supervisory coordination. We employ communication to distinguish between the different flows of information, i.e., observation and supervision, whereas we employ data to specify the coordination requirements more compactly, and to increase the expressivity of the framework. To illustrate the framework, we remodel an industrial case study involving coordination of maintenance procedures of a printing process of a high-tech Oce printer.Comment: In Proceedings FOCLASA 2012, arXiv:1208.432

Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery

Tatiana A Slastnikova1,2, Andrey A Rosenkranz1,2, Pavel V Gulak1, Raymond M Schiffelers3, Tatiana N Lupanova1,4, Yuri V Khramtsov1, Michael R Zalutsky5, Alexander S Sobolev1,21Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Moscow, Russia; 2Department of Biophysics, Biological Faculty, Moscow State University, Vorobyevy Gory, Moscow, Russia; 3Laboratory for Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands; 4Department of Bioengineering, Biological Faculty, Moscow State University, Vorobyevy Gory, Moscow, Russia; 5Department of Radiology, Duke University Medical Center, Durham, NC, USABackground: Modular nanotransporters (MNT) are recombinant multifunctional polypeptides created to exploit a cascade of cellular processes, initiated with membrane receptor recognition to deliver selective short-range and highly cytotoxic therapeutics to the cell nucleus. This research was designed for in vivo concept testing for this drug delivery platform using two modular nanotransporters, one targeted to the α-melanocyte-stimulating hormone (αMSH) receptor overexpressed on melanoma cells and the other to the epidermal growth factor (EGF) receptor overexpressed on several cancers, including glioblastoma, and head-and-neck and breast carcinoma cells.Methods: In vivo targeting of the modular nanotransporter was determined by immunofluorescence confocal laser scanning microscopy and by accumulation of 125I-labeled modular nanotransporters. The in vivo therapeutic effects of the modular nanotransporters were assessed by photodynamic therapy studies, given that the cytotoxicity of photosensitizers is critically dependent on their delivery to the cell nucleus.Results: Immunohistochemical analyses of tumor and neighboring normal tissues of mice injected with multifunctional nanotransporters demonstrated preferential uptake in tumor tissue, particularly in cell nuclei. With 125I-labeled MNT{αMSH}, optimal tumor:muscle and tumor:skin ratios of 8:1 and 9.8:1, respectively, were observed 3 hours after injection in B16-F1 melanoma-bearing mice. Treatment with bacteriochlorin p-MNT{αMSH} yielded 89%–98% tumor growth inhibition and a two-fold increase in survival for mice with B16-F1 and Cloudman S91 melanomas. Likewise, treatment of A431 human epidermoid carcinoma-bearing mice with chlorin e6- MNT{EGF} resulted in 94% tumor growth inhibition compared with free chlorin e6, with 75% of animals surviving at 3 months compared with 0% and 20% for untreated and free chlorin e6-treated groups, respectively.Conclusion: The multifunctional nanotransporter approach provides a new in vivo functional platform for drug development that could, in principle, be applicable to any combination of cell surface receptor and agent (photosensitizers, oligonucleotides, radionuclides) requiring nuclear delivery to achieve maximum effectiveness.Keywords: drug delivery, nanobiotechnology, nanomedicine, cancer therapy, photosensitizers, multifunctional nanotransporte

Investigation into the Role of Tumor-Associated Macrophages in the Antitumor Activity of Doxil

Purpose. Our recent studies show specific localization of long-circulating liposomes (LCL) within the endosomal/lysosomal compartment of tumor-associated macrophages (TAM). Based on this finding, the present study aims to investigate whether clinically applied LCL formulations such as Doxil (LCLencapsulated doxorubicin), have alternative mechanisms of action additionally to direct drug-mediated cytotoxicity towards tumor cells. Methods. The antitumor activity of Doxil was evaluated in B16.F10 melanoma-bearing mice, in the presence and in the absence of TAM. To suppress TAM functions, liposomal clodronate (Lip-CLOD) was injected 24 h before the actual treatment. The effect of Doxil on the levels of angiogenic factors was determined using an angiogenic protein array. As positive control, the same experiments were conducted with LCL-encapsulated prednisolone phosphate (LCL-PLP), a tumor-targeted formulation with known strong anti-angiogenic/anti-inflammatory effects on TAM. Results. Our results show that the antitumor efficacy of Doxil was only partially attributed to the inhibition of TAM-mediated angiogenesis whereas LCL-PLP inhibited tumor growth through strong suppressive effects on pro-angiogenic functions of TAM. As described previously, the main mechanism of Doxil might be a cytotoxic effect on tumor cells. Conclusions. Our findings suggest that the antitumor activity of Doxil does not depend mainly on the presence of functional TAM in tumors

Een aanpak om schade door slakken in aardappelen te voorkomen : monitoring van Zuid-Limburgse percelen om in de bodem levende slakken te signaleren en schadelijke populaties vast te stellen voor middelenonderzoek en advisering praktijk (2010-2011)

Enkele slakkensoorten zijn verantwoordelijk voor vraatschade in aardappelen. Deze soorten behoren tot de wegslakken en de kielnaaktslakken. Van deze twee groepen slakken zijn in dit onderzoek vrijwel uitsluitend Zwarte wegslakken (Arion hortensis) in vooraf geselecteerde percelen aangetroffen. Dit zijn slakken die met het ingraven van een krop andijvie of kippenvoerprak afgedekt met slakkenmatjes in het najaar goed zijn vast te stellen. Met lokmiddel worden betrouwbaar hogere aantallen onder slakkenmatjes vastgesteld dan zonder lokmiddel. Deze slakken kunnen echter op gunstige momenten vroeg in de ochtend ook prima worden waargenomen. Dit in tegenstelling tot de kielnaaktslakken, die voornamelijk ondergronds actief zijn. Met de vallen zijn nauwelijks kielnaaktslakken aangetroffen, op de betreffende percelen werden deze slakken ook niet tijdens het doorzoeken van de grond waargenomen. Daarentegen werd een soort uit een andere groep in de bodem vastgesteld die niet eerder met vraatschade in de Nederlandse aardappelproductiepercelen in verband werd gebracht; de Slanke wormnaaktslak. Het doorzoeken van de grond leverde de hoogste aantallen op, met de geteste vallen zijn daarentegen in totaal maar twee wormnaaktslakken in de bodem vastgesteld. In het veld en in het lab werd vraatschade aan aardappelen door deze slakkensoort waargenomen. Of deze slakkensoort een bedreiging vormt voor de aardappelteelt is niet bekend. Dit onderzoek geeft aan dat het slakkenprobleem in aardappelen een sterk incidenteel karakter heeft. De uitdaging is om die percelen uit te selecteren waar slakkenschade in aardappelen tot afkeuring of prijskorting leidt, met als gevolg een financiële strop voor de individuele teler. In het proefveldonderzoek naar middelen ter bestrijding van ondergronds levende slakken werden zeer lage aantallen slakken waargenomen, dit leidde nauwelijks tot aangevreten knollen. Over de effectiviteit van de middelen kon hierdoor geen indicatie worden afgegeven

Physicochemical and Biological Evaluation of siRNA Polyplexes Based on PEGylated Poly(amido amine)s

PURPOSE: Use of RNA interference as novel therapeutic strategy is hampered by inefficient delivery of its mediator, siRNA, to target cells. Cationic polymers have been thoroughly investigated for this purpose but often display unfavorable characteristics for systemic administration, such as interactions with serum and/or toxicity. METHODS: We report the synthesis of a new PEGylated polymer based on biodegradable poly(amido amine)s with disulfide linkages in the backbone. Various amounts of PEGylated polymers were mixed with their unPEGylated counterparts prior to polyplex formation to alter PEG content in the final complex. RESULTS: PEGylation effectively decreased polyplex surface charge, salt- or serum-induced aggregation and interaction with erythrocytes. Increasing amount of PEG in formulation also reduced its stability against heparin displacement, cellular uptake and subsequent silencing efficiency. Yet, for polyplexes with high PEG content, significant gene silencing efficacy was found, which was combined with almost no toxicity. CONCLUSIONS: PEGylated poly(amido amine)s are promising carriers for systemic siRNA delivery in vivo