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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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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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Written Corrective Feedback: A Case Study of One Teacher's Feedback on ESL Students' Initial and Final Drafts

二语写作

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二语写作 2022年第2期 34-54页

作者： Peihong CAO Jeroen VAN DE weijer Northeast Normal University Shenzhen University

Despite the heated research of written feedback(WF), few studies have explored the actual practice of English writing instructors in situ and even fewer studies report teachers’ feedback practice on students’ initial draft and final draft separately. Therefore, this case study, through analyzing the WF provided on students’ initial and final drafts in situ in America and the data drawn from the interview, explores one writing teacher’s practice of providing WF and the(mis)match between her cognition and practice. The results show that the participant employed such WF strategies as underlining rubrics and written commentaries to provide positive feedback, negative feedback, and suggestions for improvement on both drafts. The feedback targeted students’ writing content, organization, and language on both drafts, but the feedback foci differed. The feedback on language changed from general to specific and the number increased significantly. Moreover, differing from most previous research, the teacher’s cognition matched with her practice. This current study may offer some insights into tailoring one’s feedback practice to students’ different drafts and into how to provide balanced and sufficient feedback for students.

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Interpenetrating structure for efficient Sb_(2)Se_(3) nanorod array solar cells loaded with CuInSe_(2) QDs sensitizer

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Journal of Energy Chemistry 2022年第5期31卷 521-528页

作者： Cong Liu Zhenxiao Pan Kai Shen Jianzha Zheng Xiaoyang Liang Hongbing Zhu Fei Guo Zhiqiang Li ruud E.I.Schropp Yaohua Mai Institute of New Energy Technology College of Information Science and TechnologyJinan UniversityGuangzhou 510632GuangdongChina Key Laboratory for Biobased Materials and Energy of Ministry of Education College of Materials and EnergySouth China Agricultural UniversityGuangzhou 510642GuangdongChina National-Local Joint Engineering Laboratory of New Energy Photoelectric Devices College of Physics Science and TechnologyHebei UniversityBaoding 071002HebeiChina

The strong anisotropic electrical properties of one-dimensional(1 D) nanostructure semiconductors,especially the anisotropic carrier transport, have a negative and significant influence on the performance of solar cells if the nanostructures have random orientation. Considering the advantages of nanorod solar cells in carrier transport, we have achieved growth of vertically aligned Sb_(2)Se_(3) nanorod array with highly(hk1) orientation on Cd S substrate, and constructed superstrate nanorod solar cells for the first time. The Sb_(2)Se_(3) nanorod array solar cells exhibit the more efficient and long-range carrier transport in vertical direction. Furthermore, in order to suppress interface recombination, a CuInSe_(2) quantum dots(QDs) sensitizer has been applied to fill the volume between the nanorods completely, thus forming an interpenetrating nanocomposite structure. The CuInSe_(2) QDs can harvest additional light by absorption of visible light and contribute photocurrent. Meantime, the QDs function as a hole transport material and thus reduce the dependence of lateral transport. Consequently, the interpenetrating nanocomposite CuInSe_(2) / Sb_(2)Se_(3) solar cells display a power conversion efficiency of 7.54% with significant enhancements in the short-circuit current density and open-circuit voltage over pure Sb_(2)Se_(3) nanorod cells. This is the highest efficiency for superstrate solar cells based on Sb_(2)Se_(3) nanorod arrays.

关键词： Superstrate solar cells Sb_(2)Se_(3)nanorod arrays Carrier transport Interpenetrating structure CuInSe_(2)QDs

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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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