1,720,985 research outputs found
Overview of in vitro-in vivo extrapolation approaches for the risk assessment of nanomaterial toxicity
No full textNanomaterials are increasingly used in many applications due to their enhanced properties. To ensure their safety for humans and the environment, nanomaterials need to be evaluated for their potential risk. The risk assessment analysis on the nanomaterials based on animal or in vivo studies is accompanied by several concerns, including animal welfare, time and cost needed for the studies. Therefore, incorporating in vitro studies in the risk assessment process is increasingly considered. To be able to analyze the potential risk of nanomaterial to human health, there are factors to take into account. Utilizing in vitro data in the risk assessment analysis requires methods that can be used to translate in vitro data to predict in vivo phenomena (in vitro-in vivo extrapolation (IVIVE) methods) to be incorporated, to obtain a more accurate result. Apart from the experiments and species conversion (for example, translation between the cell culture, animal and human), the challenge also includes the unique properties of nanomaterials that might cause them to behave differently compared to the same materials in a bulk form. This overview presents the IVIVE techniques that are developed to extrapolate pharmacokinetics data or doses. A brief example of the IVIVE methods for chemicals is provided, followed by a more detailed summary of available IVIVE methods applied to nanomaterials. The IVIVE techniques discussed include the comparison between in vitro and in vivo studies, methods to rene the dose metric or the in vitro models, allometric approach, mechanistic modeling, Multiple-Path Particle Dosimetry (MPPD), methods using organ burden data and also approaches that are currently being developed.This work was supported by European Union's Horizon 2020 research and innovation programme under grant agreement No 814426 – NanoInformaTIX
Testing for in vitro genetic toxicity in high dimensional nanomaterial dose-response experiments
No full textThe application of nanomaterials in various fields has both benefits and risks. While the unique physico-chemical properties of nanomaterials are valuable for diverse applications, they may also alter how nanomaterials are taken up in the body, thus affecting their potential toxicity to humans. To ensure their safety, the potential risk of nanomaterials needs to be assessed. The risk of a given nanomaterial is typically evaluated through in vitro and in vivo studies. The H2020 NanoInformaTIX project, that is conducted under the European Union's Horizon 2020 research and innovation programme is focusing on the study of nanomaterials. One of its objectives includes the identification of nanomaterial toxicity, of which the first step consists of the detection of a nanomaterial dose-response relationship. In this paper, we focus on this step, which can be done for a given nanomaterial toxicity endpoint of interest, using statistical tests for a monotone dose-response trend, i.e., monotone relationship between the increasing concentration of the nanomaterial and the toxicity endpoint. The significance of the monotone trend is tested using a likelihood ratio test and t-tests. An R package and a Shiny App were developed to perform the analysis. As an illustration, data extracted from the H2020 NanoInformaTIX platform is presented as a case study. This data consists of genetic toxicity studies with DNA strand breaks as the toxicity endpoint of interest. Significant trends were found for 12 out of 26 nanomaterials after adjusting for multiplicity by applying the False discovery rate (FDR) method.This work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 814426 – NanoInformaTIX
Dose-response analysis of nanomaterial toxicity
No full textdexamethasone therapy, we apply physiologically-based pharmaco-kinetic (PBPK) modelling to predict foetal exposure after maternal dosing. Methods: To characterize the placental handling of dexametha-sone ex vivo, we performed dual-side perfused isolated human cotyledon experiments (n = 3) with term placenta in closed-closed setting. The tissue was perfused for 3 hours with 70 ng/mL dexamethasone in Krebs-Henseleit buffer. Next, intrinsic unbound placental transfer values were derived from the perfusion data using a physiologically-based semi-mechanistic placenta (PBMP) model in Matlab. Values were used for parameterization of Simcyp's pregnancy-PBPK (p-PBPK) model to predict maternal and foetal exposure. In addition, to evaluate whether placental exposure to the drug may result in adverse effects on placental syncytiotrophoblasts, a toxicity screening exposing BeWo cells to dexamethasone concentrations in a range of 5-25.000 nM for 24 hours was executed. Results: Perfusion experiments showed that dexamethasone extensively crosses the placenta. The PBMP model adequately described the perfusion data. The intrinsic unbound transfer values derived, were estimated to be 1033.5 mL/min and 15.2 mL/min for the maternal placental uptake and efflux, and 1311.1 mL/min and 10.7 mL/ min for foetal placental uptake and efflux, respectively. For an intramuscular dose of 8 mg at 28 weeks of gestation, whole body p-PBPK modelling predicted a C max and AUC 0−∞ of 46.09 ng/mL and 230.46 ng/ml*h in maternal plasma and a C max and AUC 0−∞ of 18.60 ng/mL and 100.25 ng/ml*h in the umbilical vein, respectively. Umbilical vein plasma concentrations derived from literature (range 5.5-23.7 ng/mL) are in accordance with the estimated C max concentration. None of the drug concentrations studied affected placental cell viability or progesterone production in BeWo cells. Conclusion: Ex vivo placenta perfusion in combination with p-PBPK modelling is a relevant approach for foetal exposure predictions. Outcomes can be used in re-evaluation of current dosing regimens of dexamethasone during pregnancy. It is expected that this approach can be used to predict foetal exposure to other pharmaceutical drugs as well, even in absence of umbilical vein concentrations of a drug. As nanomaterials are increasingly used in many different products, it becomes important to know their potential toxicity. In the risk assessment of nanomaterials, in vitro-in vivo extrapolation (IVIVE) techniques are interesting to be explored since they have advantages of maximizing the use of in vitro studies, and reducing the financial and time costs, especially when high numbers of nanomaterials are to be analyzed. The H2020 NanoInformaTIX project is a research project that partly focuses on the study of nanomaterial toxicity, with our goal being, implementing IVIVE methods for use in a strategy for risk assessment of nanomaterials. The initial step of our research includes building a software program (the R package NMTox) to explore the data gathered through the project and to perform preliminary analysis on the dose-response relationship of nanomaterial toxicity. Methods available in this package, such as the Likelihood ratio test, are used to test for the monotonic trend in dose-response relationships, and thus to screen for potential significant dose-response relationships of nanomaterials toxicity, that can be analyzed further. To identify the toxic concentrations, dose-response models are fitted on the subsets of data with a significant trend. The risk assessment strategy will involve applying IVIVE methods described in the literature and will use the estimated in vitro toxic concentration as the basis for the risk calculation. The current stage of our research is focusing on PBPK models to estimate in vivo toxic doses of nanomaterials and to aid the risk assessment strategy. The feasibility of applying this strategy is currently being investigated. We will illustrate this approach using data available in the NanoInformaTIX database and in the literature. Most studies assess the possible adverse effects of exposure to airborne nanomaterials (NMs) using submerged culture systems; however, air-liquid interface (ALI) exposure systems are far better suited for the assessment of in vitro pulmonary effects of NMs as they are more representative of the in vivo respiratory system. Although ALI exposure is preferred over submerged conditions, it is not known how toxicity, uptake and intracellular fate of NMs in cells may be influenced when ALI is compared with submerged exposure conditions. The aim of this study was to compare the distribution, toxicity, and cellular uptake of 14 nm citrate stabilised gold nanoparticles (AuNPs) exposed to human alveolar basal epithelial (A549) cells at the ALI (0.13, 0.21 and 0.443 μg/cm 2), using the VITROCELL ® Cloud 12 in vitro exposure system, to submerged conditions (10, 20, 40 μg/cm 2 , a 10-fold increase to account for sedimentation and diffusion). The toxicity of A549 cells was monitored using the lactate dehydrogenase (LDH) assay as this assay has previously shown to not be affected by interference of AuNPs. The distribution and intracellular uptake were assessed using conventional inverted microscopy and the CytoViva 3D Enhanced Darkfield Imaging System. The AuNPs were shown to be relatively non-toxic under both ALI and submerged conditions, however the cells showed increased sensitivity at the ALI. The distribution and intracellular uptake of the AuNPs were found to be more uniformly distributed, over the exposure area of the transwell insert, at the ALI whereas submerged conditions resulted in agglomerated NPs, outside cells as well as intracellularly. The use of the CytoViva 3D system has shown to be beneficial when assessing uptake of non-labelled NPs within a three-dimensional space. S198 Abstracts / Toxicology Letters 368S1 (2022) S84-S283Supported by European Union’s Horizon 2020 research and innovation programme under grant agreement No 814426 – NanoInformaTIX
Pilot-Scale Cultivation of the Snow Alga Chloromonas typhlos in a Photobioreactor
No full textThe most studied and cultivated microalgae have a temperature optimum between 20 and 35°C. This temperature range hampers sustainable microalgae growth in countries with colder periods. To overcome this problem, psychrotolerant microalgae, such as the snow alga Chloromonas typhlos, can be cultivated during these colder periods. However, most of the research work has been carried out in the laboratory. The step between laboratory-scale and large-scale cultivation is difficult, making pilot-scale tests crucial to gather more information. Here, we presented a successful pilot-scale growth test of C. typhlos. Seven batch mode growth periods were compared during two longer growth tests in a photobioreactor of 350 L. We demonstrated the potential of this alga to be cultivated at colder ambient temperatures. The tests were performed during winter and springtime to compare ambient temperature and sunlight influences. The growth and CO(2) usage were continuously monitored to calculate the productivity and CO(2) fixation efficiency. A maximum dry weight of 1.082 g L(−1) was achieved while a maximum growth rate and maximum daily volumetric and areal productivities of 0.105 d(−1), 0.110 g L(−1) d(−1), and 2.746 g m(−2) d(−1), respectively, were measured. Future tests to optimize the cultivation of C. typhlos and production of astaxanthin, for example, will be crucial to explore the potential of biomass production of C. typhlos on a commercial scale
Aktualisasi Life Skills (Kecakapan Hidup) di Pondok Pesantren An-Najiyah L3ngkong Sukorejo Ponorogo
No full textRafidatul Azizah, Rahma. 2022.Aktualisasi Life Skills (Kecakapan Hidup) di Pondok
Pesantren An-Najiyah Lengkong Sukorejo Ponorogo. Skripsi. Jurusan Pendidikan
Agama Islam Fakultas Tarbiyah dan Ilmu Keguruan Institut Agama Islam Negeri
Ponorogo. Pembimbing Skripsi: Dr. Kharisul Wathoni, M.Pd.I.
Kata Kunci: Aktualisasi, Life Skills, Pondok Pesantren
Lembaga pendidikan Islam mempunyai andil yang besar untuk proses menjalani hidup.
Pendidikan Islam harus menyiapkan sumber daya manusia yang tidak hanya sebagai penerima
arus informasi global namun juga memberikan bekal untuk mengolah, menyesuaikan, dan
mengembangkan segala hal yang diterima melalui arus informasi yaitu menjadi manusia yang
kreatif dan produktif. Pondok pesantren An-Najiyah Lengkong Sukorejo sebagai salah satu
lembaga pendidikan Islam berupaya membuka wacana global yang terjadi di masyarakat sekitar
pondok pesantren ataupun masyarakat umum dan berbagai masalah yang muncul di kalangan
santri setelah lulus dari pondok pesantren, seperti kurang kreatifnya santri setelah lulus dalam
artian santri tidak tahu apa yang harus dilakukan, sehingga dikatakan santri kurang cakap dalam
menyelesaikan permasalahan hidupnya. Atas hal ini pondok pesantren An-Najiyah
mengintrogasikan pola pendidikannya melalui berbagai latihan-latihan dan pola pembiasaan
hidup mandiri yang melekat pada kehidupan keseharian para santri yang mengarah pada
pengembangan life skills.
Pada saat ini masih banyak pengangguran dikalangan terdidik baik yang berasal dari lulusan
lembaga pendidikan formal maupun non formal yang belum bisa menguasai keterampilan. Oleh
karena itu perlu diadakan penelitian tentang “Aktualisasi Life Skills (Kecakapan Hidup) di
Pondok Pesantren An-Najiyah Lengkong Sukorejo Ponorogo”. Penelitian ini bertujuan untuk (1)
Mendeskripsikan aktualisasi kecakapan personal (Personal Skills) di pondok pesantren AnNajiyah Lengkong Sukorejo Ponorogo (2) Mendeskripsikan aktualisasi kecakapan sosial (Social
Skills) di pondok pesantren An-Najiyah Lengkong Sukorejo Ponorogo (3) Mendeskripsikan
aktualisasi kecakapan akademik (Academic Skills) di pondok pesantren An-Najiyah Lengkong
Sukorejo Ponorogo (4) Mendeskripsikan aktualisasi kecakapan vokasional (Vocational Skills) di
pondok pesantren An-Najiyah Lengkong Sukorejo Ponorogo (5) Mendeskripsikan aktualisasi
kecakapan berpikir (Thinking Skills) di pondok pesantren An-Najiyah Lengkong Sukorejo
Ponorogo.
Dalam penelitian ini peneliti menggunakan metode penelitian kualitatif yaitu penelitian yang
memberikan hasil data deskriptif berupa kata-kata tertulis atau lisan dari orang-orang dan
perilaku yang diamati. Metode pengumpulan data menggunakan metode wawancara, observasi,
dan dokumentasi.
Dari hasil penelitian yang dilakukan oleh peneliti di Pondok Pesantren An-Najiyah
Lengkong Sukorejo dapat ditarik kesimpulan bahwa (1) Aktualisasi kecakapan personal di
pondok pesantren An-Najiyah dibentuk melalui kegiatan pengajian rutin kitab kuning tiap ba‟da
subuh dan isya‟, kemudian dengan kegiatan ibadah sunah seperti sholat duha, sholat tahajud,
tadaraus Al-qur‟an, dan lain-lain. Selain itu juga melalui pola pembiasaan hidup mandiri bagi
para santri dengan berbagai kegiatan yang dilakukan sehari-hari. (2) Aktualisasi kecakapan
sosial di pondok pesantren An-Najiyah dibentuk melalui kegiatan organisasi yang dikelola oleh
santri. Tujuannya adalah untuk melatih jiwa kepemimpinan (Leadership) bagi para santri. (3)
Aktualisasi kecakapan akademik di pondok pesantren An-Najiyah dibentuk melalui kegiatan
belajar formal dan non formal seperti madrasah Tsanawiyah, madrasah Aliyah, dan madrasah
Diniyah. (4) Aktualisasi kecakapan vokasional di pondok pesantren An-Najiyah dibentuk
melalui kegiatan ekstrakurikuler seperti Qiroah, Hadroh Al-Banjari, Kaligrafi, Futsal, Arabic
Club, English Club, dan Enterpreneurs Club. (5) Aktualisasi kecakapan berpikir di pondok
pesantren An-Najiyah dibentuk melalui kegiatan pengajian kitab dengan metode sorogan dan
wektonan, forum keilmuan santri, kegiatan muhadhoroh, syawir, dan Bahtsu Masail
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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