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Inhibition of hypoxia-inducible factor 1 with acriflavine sensitizes hypoxic tumor cells to photodynamic therapy with zinc phthalocyanine-encapsulating cationic liposomes

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Nano Research 2016年第6期9卷 1639-1662页

作者： Mans Broekgaarden ruud weijer Massis Krekorian Bas van den IJssel Milan Kos Lindy K. Alles Albert C. van Wijk1 Zsolt Bikadi Eszter Hazai Thomas M. van Gulik Michal Heger Department of Experimental Surgery Academic Medical Center University of Amsterdam Meibergdreef 9 1105 AZ Amsterdam the Netherlands Virtua Drug Ltd. Csalogany 4C H-1015 Budapest Hungary

Photodynamic therapy （PDT） is a tumor treatment modality in which a tumor- localized photosensitizer is excited with light, which results in local production of reactive oxygen species, destruction of tumor vasculature, tumor hypoxia, tumor cell death, and induction of an anti-tumor immune response. However, pre-existing tumor hypoxia may desensitize tumors to PDT by activating the hypoxia-inducible factor 1 （HIF-1） survival pathway. Therefore, we hypothesized that inhibition of HIF-1 with acriflavine （ACF） would exacerbate cell death in human epidermoid carcinoma （A431） cells. PDT of A431 tumor cells was per- formed using newly developed and optimized PEGylated cationic liposomes containing the photosensitizer zinc phthalocyanine （ZnPC）. Molecular docking revealed that ACF binds to the dimerization domain of HIF-la, and confocal microscopy confirmed translocation of ACF from the cytosol to the nucleus under hypoxia. HIF-1 was stabilized in hypoxic, but not normoxic, A431 cells following PDT. Inhibition of HIF-1 with ACF increased the extent of PDT-induced cell death under hypoxic conditions and reduced the expression of the HIF-1 target genes VEGF, PTGS2, and EDN1. Moreover, co-encapsulation of ACF in the aqueous core of ZnPC-containing liposomes yielded an adjuvant effect on PDT efficacy that was comparable to non-encapsulated ACF. In conclusion, HIF-1 contributes to A431 tumor cell survival following PDT with liposomal ZnPC. Inhibition of HIF-1 with free or liposomal ACF improves PDT efficacy.

关键词： cancer therapy confocal microscopy drug delivery system glucose metabolism hypoxia

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Dietary supplementation of zinc oxide modulates intestinal functionality during the post-weaning period in clinically healthy piglets

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Journal of Animal Science and Biotechnology 2024年第1期15卷 313-328页

作者： Dirkjan Schokker Soumya K.Kar Els Willems Alex Bossers ruud A.Dekker Alfons J.M.Jansman Wageningen Bioveterinary Research LelystadThe Netherlands Wageningen Livestock Research Wageningen University&ResearchWageningenThe Netherlands Royal Agrifirm Group ApeldoornThe Netherlands Institute for Risk Assessment Sciences Utrecht UniversityUtrechtThe Netherlands

Background To improve our understanding of host and intestinal microbiome interaction,this research investigated the effects of a high-level zinc oxide in the diet as model intervention on the intestinal microbiome and small intestinal functionality in clinically healthy post-weaning *** study 1,piglets received either a high concentration of zinc(Zn)as zinc oxide(Zn O,Zn,2,690 mg/kg)or a low Zn concentration(100 mg/kg)in the diet during the post weaning period(d 14–23).The effects on the piglet's small intestinal microbiome and functionality of intestinal tissue were *** study 2,the impact of timing of the dietary zinc intervention was investigated,i.e.,between d 0–14 and/or d 14–23 post weaning,and the consecutive effects on the piglet's intestinal functionality,here referring to microbiota composition and diversity and gene expression *** Differences in the small intestinal functionality were observed during the post weaning period between piglets receiving a diet with a low or high concentration Zn O content.A shift in the microbiota composition in the small intestine was observed that could be characterized as a non-pathological change,where mainly the commensals *** the immediate post weaning period,i.e.,d 0–14,the highest number of differentially expressed genes(DEGs)in intestinal tissue were observed between animals receiving a diet with a low or high concentration Zn O content,i.e.,23 DEGs in jejunal tissue and 11 DEGs in ileal *** genes are involved in biological processes related to immunity and inflammatory *** example,genes CD59 and REG3G were downregulated in the animals receiving a diet with a high concentration Zn O content compared to low Zn O content in both jejunum and ileum *** the second study,a similar result was obtained regarding the expression of genes in intestinal tissue related to immune pathways when comparing piglets receiving a diet with a high concentration Zn O con

关键词： Immune system Intestinal functionality Microbiota Piglets Zinc oxide

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Drained rock volume around hydraulic fractures in porous media:planar fractures versus fractal networks

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Petroleum Science 2019年第5期16卷 1064-1085页

作者： Kiran Nandlal ruud weijermars Harold Vance Department of Petroleum Engineering Texas A&M University3116 TAMUCollege StationTX 77843-3116USA

This study applies the Lindenmayer system based on fractal theory to generate synthetic fracture networks in hydraulically fractured *** applied flow model is based on complex analysis methods,which can quantify the flow near the fractures,and being gridless,is computationally faster than traditional discrete volume *** representation of hydraulic fractures as fractals is a more realistic representation than planar bi-wing fractures used in most reservoir *** withdrawal from the reservoir with evenly spaced hydraulic fractures may leave dead zones between planar *** fractal networks will drain the reservoir matrix more effectively,due to the mitigation of stagnation flow *** flow velocities,pressure response,and drained rock volume(DRV)are visualized for a variety of fractal fracture networks in a single-fracture treatment *** major advancement of this study is the improved representation of hydraulic fractures as complex fractals rather than restricting to planar fracture *** models indicate that when the complexity of hydraulic fracture networks increases,this will suppress the occurrence of dead flow *** order to increase the DRV and improve ultimate recovery,our flow models suggest that fracture treatment programs must find ways to create more complex fracture networks.

关键词： Hydraulic fractures Drained rock volume Dead zones Fractals Branched fractures

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Visualization of drained rock volume(DRV) in hydraulically fractured reservoirs with and without natural fractures using complex analysis methods(CAMs)

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Petroleum Science 2019年第3期16卷 550-577页

作者： Aadi Khanal ruud weijermars Harold Vance Department of Petroleum Engineering Texas A&M University

The drainage areas(and volumes)near hydraulically fractured wells,computed and visualized in our study at high resolution,may be critically affected by the presence of natural *** a recently developed algorithm based on complex analysis methods(CAMs),the drained rock volume(DRV)is visualized for a range of synthetic constellations of natural fractures near hydraulic ***,flow interference effects near a single hydraulic fracture are systematically investigated for a variety of natural fracture *** permeability contrast between the matrix and the natural fractures is increased stepwise in order to better understand the effect on the ***,a larger-scale model investigates flow interference for a full hydraulically fractured well with a variety of natural fracture *** time of flight contours(TOFCs)outlining the DRV are for all cases with natural fractures compared to a base case without any natural *** natural fractures,with different orientations,hydraulic conductivity,and fracture density,may shift the TOFC patterns in the reservoir region drained by the hydraulically fractured well,essentially shifting the location of the well’s drainage *** CAM-based models provide a computationally efficient method to quantify and visualize the drainage in both naturally and hydraulically fractured reservoirs.

关键词： Natural fracture Drained rock volume Drainage area distortion Hydraulic fractures

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The Snakes of the Lesser Sunda Islands (Nusa Tenggara),Indonesia

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Asian Herpetological Research 2011年第1期2卷 46-54页

作者： ruud DE LANG Rotterdam The Netherlands

From the existing literature and data from museum specimens an overview is presented of all currently known terrestrial and semi-aquatic snakes of the Lesser Sunda Islands, in the Wallacean area of Indonesia. In total, twenty-nine species are known to inhabit the area. Of these eight are endemic to the area： Boiga hoeseli, Coelognathus subradiatus, Dendrelaphis inornatus, Stegonotus florensis, Cylindrophis opisthorhodus, Broghammerus timoriensis, Liasis mackloti and Typhlops schmutzi. Insular endemism is only found at the subspecific level, including Liasis mackloti dunni （Wetar）, Liasis mackloti savuensis （Sawu）, Ramphotyphlops polygrammicus brongersmai （Sumba）, Ramphotyphlops polygrammicus elberti （Lombok） and Ramphotyphlops polygrammicus florensis （Flores）. Such endemism may be due to the relatively young geological age of the Lesser Sunda Islands and that the snake fauna is still underestimated. Taxonomy of the genus Cylindrophis, the species Coelognathus subradiatus, Dendrelaphis inornatus, Cryptelytrops insularis, and the five subspecies of Ramphotyphlops polygrammicus need to be reviewed. Ecological studies are urgently required to establish if the species Broghammerus timoriensis and Liasis mackloti savuensis are endangered and which conservation measures should be taken. Telah dilakukan pengamatan ulang dari kepustakaan yang ada, data dari databank Western Australian Museum, maupun koleksi museum. Hasil tersebut dirangkum dalam suam tinjauan mengenai semua jenis ular yang hidup di darat maupun di air-tawar dari daerah Nusa Tenggara sebagai bagian dari daerah Wallacea. Jumlah jenis yang dapat dipastikan berjumlah dua puluh sembilan jenis, dan delapan di antaranya merupakan jenis yang endemik, yaitu Boiga hoeseli, Coelognathus subradiatus, Dendrelaphis inornatus, Stegonotus florensis, Cylindrophis opisthorhodus, Broghammerus timoriensis, Liasis mackloti dan Typhlops schmutzi. Jenis endemic dalam daerah pulau hanya meliputi anak jenis： Liasis mackloti dunni

关键词： Ophidia serpents Lesser Sunda Islands Nusa Tenggara Indonesia Timor-Leste checklist distribution

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An OT Analysis of Nasal-obstruent Clusters in English

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外国语 2013年第6期36卷 2-17页

作者： ZHENG Jizheng Jeroen van de weijer Shanghai Customs College Shanghai 201204 Shanghai International Studies University Shanghai 200083 China

This paper argues in favor of an Optimality Theory(OT)constraint hierarchy governing the phonotactics of nasal+obstruent clusters in *** paper shows that in careful speech English has a strong tendency favoring voiceless obstruents after nasals both in medial and coda positions,and retains a contrast between voiced and voiceless obstruents,as supported by statistical *** the paper proposes that,in English,the Optimality constraint IDENT-IO(ObsVce)dominates**** also show that in English voiced coronal stops are retained post-nasally,whereas voiced peripheral(labial and velar)stops are deleted(or,rather,not permitted).To explain this phenomenon,the paper proposes that the markedness constraint VOICED-CODA ranks between MAX-COR and MAX-PER,and the constraints IDENT-IO(ObsVce)and*VOICED-CODA work in tandem to result in the deletion of peripheral voiced *** shows that the same constraint hierarchy also applies to nasal+non-stop obstruent clusters,*** with fricatives and affricates,both medially and in final ***,It is pointed out that as language is changing,this is reflected in a changing constraint hierarchy as ****VOICEDCODA and*NO become higher ranked,this would cause either devoicing or deletion of voiced obstruents in the coda,or it would cause obstruents after nasals to become *** processes are found in faster,informal speech styles and may reflect change in progress.

关键词：英语学习阅读知识学习方法阅读材料

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Influence of oil viscosity on oil-water core-annular flow through a horizontal pipe

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Petroleum 2019年第2期5卷 199-205页

作者： Erik van Duin ruud Henkes Gijs Ooms m.burgerscentrum delft university of technologyfaculty of mechanicalmaritimeand materials engineering(3me)laboratory for aero-&hydrodynamicsmekelweg 22628 sc delftthe netherlands shell projects and technology po box 380001030 bn amsterdamthe netherlands

An experimental study has been made of oil-water core-annular flow in a horizontal pipe with special attention for the influence of the oil viscosity on the pressure *** that purpose a heating system has been installed and configured that is able to control the oil temperature,such that the oil viscosity could be varied between 3000 cSt at 20C and 400 cSt at 50*** oil flow rate was kept at a constant value of 0.35 l/s,whereas the watercut was varied between 9%and 25%.The measured pressure drop is scaled with the calculated pressure drop of only oil flowing at the same flow rate and *** main conclusion is that for a large oil viscosity the scaled pressure drop is almost independent of the watercut,whereas with decreasing viscosity the scaled pressure drop becomes strongly dependent on the *** of the oil-water interface shows a more irregular wave shape with smaller wave lengths when the viscosity is *** is very good agreement between the predictions of the model of Ullmann&Brauner for the scaled pressure drop and the measurements.

关键词： viscosity flow annular

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Advances in scalable gas-phase manufacturing and processing of nanostructured solids： A review

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Particuology 2017年第1期15卷 15-39页

作者： Samir Salameh Jesus Gomez-Hernandez Aristeidis Goulas Hao Van Bui J. ruud van Ommen Delft University ofTechnology Julianalaan 136 2628 BL Delft The Netherlands Carlos III University of Madrid Avda. de la Universidad 30 28911 Leganes Madrid Spain Delft IMP B.V. Mekelweg 2 2628 CD Delft The Netherlands

Although the gas-phase production of nanostructured solids has already been carried out in industry for decades, only in recentyears has research interest in this topic begun to increase. Nevertheless, despite the remarkable scientific progress made recently, many long-established processes are still used in industry. Scientific advancements can potentially lead to the improvement of existing industrial processes, but also to the development of completely new routes. This paper aims to review state-of-the-art synthesis and processing technologies, as well as the recent developments in academic research. Flame reactors that produce inorganic nanoparticles on industrial- and lab-scales are described, alongside a detailed overview of the different systems used for the production of carbon nanotubes and graphene. We discuss the problems of agglomeration and mixing of nanoparticles, which are strongly related to synthesis and processing. Finally, we focus on two promising processing techniques, namely nanoparticle fluidization and atomic layer deposition.

关键词： Nanoparticle synthesis Gas-phase process Nanoparticle fluidization Atomic layer deposition Agglomeration

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Scalable gas-phase processes to create nanostructured particles

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Particuology 2010年第6期8卷 572-577页

作者： J.ruud van Ommen Caner U.Yurteri Naoko Ellis Erik M.Kelder Delft University of Technology Department of Chemical EngineeringJulianalaan 1362628 BL DelftThe Netherlands University of British Columbia Department of Chemical and Biological Engineering2360 East MallVancouverB.C.Canada V6T 1Z3

The properties of nanoparticles are often different from those of larger grains of the same solid material because of their very large specific surface area. This enables many novel applications, but properties such as agglomeration can also hinder their potential use. By creating nanostructured particles one can take optimum benefit from the desired properties while minimizing the adverse effects. We aim at developing high-precision routes for scalable production of nanostructured particles. Two gas-phase synthesis routes are explored. The first one - covering nanoparticles with a continuous layer - is carried out using atomic layer deposition in a fluidized bed. Through fluidization, the full surface area of the nanoparticles becomes available. With this process, particles can be coated with an ultra-thin film of constant and well-tunable thickness. For the second route - attaching nanoparticles to larger particles - a novel approach using electrostatic forces is demonstrated. The micron-sized particles are charged with one polarity using tribocharging. Using electrospraying, a spray of charged nanoparticles with opposite polarity is generated. Their charge prevents agglomeration, while it enhances efficient deposition at the surface of the host particle. While the proposed processes offer good potential for scale-up, further work is needed to realize large-scale processes.

关键词： Nanoparticles Nanocomposite materials Coating Films Particle coating Atomic layer deposition Core-shell particles Electrospraying Electrohydrodynamic atomization Electrostatic forces Fluidization

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The Interplay of Gravity and Lorentz Transformation Collaborating with ChatGPT

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Journal of Applied Mathematics and Physics 2023年第12期11卷 4128-4152页

作者： ruud Loeffen Retired Faculty Member of Zuyd University of Applied Sciences Social Work Sittard and Life Sciences Heerlen Netherlands

This paper presents a short exploration of the phenomena of mass and heat increase, shedding light on the remarkable notion of an expanding universe. Aimed at physicists and mathematicians, this investigation draws on an innovative collaboration with ChatGPT, an AI language model trained using scientific knowledge, to enrich our understanding of these fundamental concepts. By delving into the Gravitational Constant, we unveil compelling evidence for an increase in mass and heat for all celestial objects within an isotropic and homogenous universe as a result of the Lorentz Transformation of mass energy (LTME). Traditionally, LTME has been considered relevant primarily for subatomic particles at high velocities. However, this study posits that LTME is equally applicable to celestial bodies, even at relatively low velocities. The journey commences with an examination of the Gamma Factor in the LTME, illuminating its significance in comprehending the expansion of the cosmos. Ultimately, this paper offers a comprehensive validation of “Expanding Matter” with responses from ChatGPT, illuminating the ever-growing nature of our universe. As physicists, embarking on this journey will lead to new perspectives on the profound mysteries that shape cosmic reality. This pursuit contemplates the possibility of an infinitely energetic universe, where energy metamorphoses into mass through M = E/c2. This interpretation proposes the existence of a Process of Continuously Created Matter, manifesting as an ongoing accretion, augmentation, and expansion, harmonizing with the universe’s ever-expansive nature. The study further incorporates state-of-the-art observational technologies to substantiate its claims, thereby opening new avenues for future research in both theoretical physics and cosmology.

关键词： Lorentz Transformation of Mass Energy Expanding Universe Gravitational Constant Protoplanetary Discs AI Collaboration

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