41 research outputs found
Vincristine cell resistance is accompanied by changes in integrins expression and adenovirus transduction efficiency
Kemoterapija se koristi za liječenje tumora, ali ĉesto dolazi do razvoja otpornosti stanica tumora. Razvoj otpornosti tumorskih stanica na protutumorske lijekove može dovesti do promjena u ekspresiji receptora za adnovirus tipa 5 (Ad5), kao i do promjena u ekspresiji transgena unesenog s Ad5 vektorom. Istražili smo postoji li razlika u Ad5–posredovanoj ekspresiji transgena između stanica karcinoma grkljana čovjeka (HEp2) i stanica VK2 otpornih na vinkristin, nastalih od HEp2 stanica. Mjerili smo ekspresiju transgena divljeg tipa Ad5wtRSVβgal, Ad5Δ639RSVβgal s kratkim vlaknom koji ulazi u stanice neovisno o primarnom receptoru CAR (coxsackie i adenovirus receptor), te Ad5RGD4CRSVβgal preusmjerenog na αv-integrine. Zapazili smo 4,5 puta povećanu ekspresiju transgena unesenog pomoću Ad5wtRSVβgal i Ad5RGD4CRSVβgal unesenog transgena u VK2 u odnosu na HEp2 stanice, dok je za Ad5Δ639RSVβgal ta razlika bila 10 puta. Izmjerili smo razlike između HEp2 i VK2 stanica u ekspresiji Ad5 receptora na površini stanica, ali te razlike nisu odgovorne za primijećenu povećanu Ad5-posredovanu ekspresiju transgena u VK2 stanicama. Vezanje i intenalizacija Ad5wtRSVβgal je 25-30% odnosno 15-30% manje u VK2 nego u HEp2 stanicama. Konačno, Ad5wtCMVβgal koji se razlikuje od Ad5wtRSVβgal samo u promotoru pod kojim je transgen, je pokazao jednaku ekspresiju transgena u HEp2 i VK2 stanicama. Zaključili smo da je povećana Ad5wtRSVβgal-posredovana ekspresija trangena u VK2 stanicama posljedica povećane aktivnosti promotora RSV. Naši rezultati pokazuju: (i) otpornost na protutumorske lijekove može biti popraćena promjenama u aktivnosti promotora i (ii) pravilan izbor promotora može doprinijeti smanjenju doze vektora potrebne za postizanje terapijskog učinka tijekom genske terapije tumora.Chemotherapy is regularly used for cancer treatment but often results in the development of drug resistance. The development of drug resistance could lead to differential expression of Adenovirus type 5 (Ad5) receptors as well as to changes in the expression of the transgene from Ad5 vector. We investigated whether there are differences in Ad5–mediated transgene expression between human laryngeal carcinoma (HEp2) cells and corresponding, HEp2-derived, vincristine resistant cell line VK2. We measured the transgene expression from wild type Ad5wtRSVβgal, short fibered Ad5Δ639RSVβgal which infects cells independent of primary Ad5 receptor CAR (coxsackie and adenovirus receptor) and Ad5RGD4CRSVβgal retargeted to αv-integrins. We observed 4,5-fold increase in Ad5wtRSVβgal and Ad5RGD4CRSVβgal transgene expression in VK2 cells comparing to HEp2 cells, while for Ad5Δ639RSVβgal this difference was 10-fold. We found differences between HEp2 and VK2 cells in cell surface expression of Ad5 receptors but these changes were not responsible for observed increased Ad5-mediated transgene expression in VK2 in comparison to HEp2 cells. The Ad5wtRSVβgal attachment and internalisation was 25-30% and 15-30% lower in VK2 than in HEp2 cells, respectively. Finally, Ad5wtCMVβgal differing from Ad5wtRSVβgal ony in promoter that drives transgene expression, showed equal transgene expression in HEp2 and VK2 cells. We conclude that the increased Ad5wtRSVβgal-mediated transgene expression in the VK2 cells is due to the increased RSV promoter activity. Our results point out that (i) drug-resistance may be accompanied with an alteration in promoter activity and (ii) the proper choice of promoter could contribute to a decrease in the vector dose required to achieve a therapeutic effect during tumor gene therapy
Optimalisasi Pelayanan Penumpang PT. Angkasa Pura Cabang I (Persero) Dari Sisi Darat (Landside) Terminal Domestik Bandara Juanda Surabaya
Pelayanan penumpang adalah hal utama yang diperhatikan dalam penyedia karena hal ini menjadi tolak ukur penilaian bagi pengguna jasa terhadap perusahaan, dalam kondisi pandemi penyedia jasa harus bisa bertahan dalam kondisi sulit dengan adanya batasan penggunaan transportasi umum. Keadaan tersebut terjadi di perusahaan jasa seperti PT. Angkasa Pura I Juanda Surabaya yang merupakan perusahaan penyedia jasa kebandarudaraan. Berdasarkan hal itu, penulis melakukan analisis kinerja dan optimalisasi pelayanan penumpang dengan cara melakukan survei penelitian dan pengolahan data berdasarkan peraturan kebandarudaraan. Tujuan penelitian ini adalah untuk mengetahui optimalisasi pelayanan penumpang, SOP alur pelayanan penumpang, dan fasilitas pelayanan penumpang dari sisi darat bandara Juanda Surabaya. Metode yang digunakan dalam penelitian ini adalah metode kualitatif untuk mendapatkan data berupa pengamatan dan asumsi dengan cara menilai tingkat kesesuaian prosedur melalui data. Hasil yang didapatkan dari penelitian ini adalah optimalisme yang dilakukan PT. Angkasa Pura I Bandar Udara Juanda dengan melakukan observasi keberlanjutan bandara saat ini. Dalam pelaksanaan pelayanan penumpang dari sisi terminal, digunakan SOP Surat Keputusan General Manager PT Angkasa Pura I (Persero) No. Kep.34/OB.01/GM.SUB Tahun 2018 Jenis pelayanan dari sisi terminal yaitu pemeriksaan keamanan, check-in, imigrasi keberangkatan, ruang tunggu penumpang, pelayanan bagasi, imigrasi kedatangan, pelayanan bea cukai, kedatangan penumpang, fasilitas yang memberikan nilai tambah
Vincristine cell resistance is accompanied by changes in integrins expression and adenovirus transduction efficiency
Kemoterapija se koristi za liječenje tumora, ali ĉesto dolazi do razvoja otpornosti stanica tumora. Razvoj otpornosti tumorskih stanica na protutumorske lijekove može dovesti do promjena u ekspresiji receptora za adnovirus tipa 5 (Ad5), kao i do promjena u ekspresiji transgena unesenog s Ad5 vektorom. Istražili smo postoji li razlika u Ad5–posredovanoj ekspresiji transgena između stanica karcinoma grkljana čovjeka (HEp2) i stanica VK2 otpornih na vinkristin, nastalih od HEp2 stanica. Mjerili smo ekspresiju transgena divljeg tipa Ad5wtRSVβgal, Ad5Δ639RSVβgal s kratkim vlaknom koji ulazi u stanice neovisno o primarnom receptoru CAR (coxsackie i adenovirus receptor), te Ad5RGD4CRSVβgal preusmjerenog na αv-integrine. Zapazili smo 4,5 puta povećanu ekspresiju transgena unesenog pomoću Ad5wtRSVβgal i Ad5RGD4CRSVβgal unesenog transgena u VK2 u odnosu na HEp2 stanice, dok je za Ad5Δ639RSVβgal ta razlika bila 10 puta. Izmjerili smo razlike između HEp2 i VK2 stanica u ekspresiji Ad5 receptora na površini stanica, ali te razlike nisu odgovorne za primijećenu povećanu Ad5-posredovanu ekspresiju transgena u VK2 stanicama. Vezanje i intenalizacija Ad5wtRSVβgal je 25-30% odnosno 15-30% manje u VK2 nego u HEp2 stanicama. Konačno, Ad5wtCMVβgal koji se razlikuje od Ad5wtRSVβgal samo u promotoru pod kojim je transgen, je pokazao jednaku ekspresiju transgena u HEp2 i VK2 stanicama. Zaključili smo da je povećana Ad5wtRSVβgal-posredovana ekspresija trangena u VK2 stanicama posljedica povećane aktivnosti promotora RSV. Naši rezultati pokazuju: (i) otpornost na protutumorske lijekove može biti popraćena promjenama u aktivnosti promotora i (ii) pravilan izbor promotora može doprinijeti smanjenju doze vektora potrebne za postizanje terapijskog učinka tijekom genske terapije tumora.Chemotherapy is regularly used for cancer treatment but often results in the development of drug resistance. The development of drug resistance could lead to differential expression of Adenovirus type 5 (Ad5) receptors as well as to changes in the expression of the transgene from Ad5 vector. We investigated whether there are differences in Ad5–mediated transgene expression between human laryngeal carcinoma (HEp2) cells and corresponding, HEp2-derived, vincristine resistant cell line VK2. We measured the transgene expression from wild type Ad5wtRSVβgal, short fibered Ad5Δ639RSVβgal which infects cells independent of primary Ad5 receptor CAR (coxsackie and adenovirus receptor) and Ad5RGD4CRSVβgal retargeted to αv-integrins. We observed 4,5-fold increase in Ad5wtRSVβgal and Ad5RGD4CRSVβgal transgene expression in VK2 cells comparing to HEp2 cells, while for Ad5Δ639RSVβgal this difference was 10-fold. We found differences between HEp2 and VK2 cells in cell surface expression of Ad5 receptors but these changes were not responsible for observed increased Ad5-mediated transgene expression in VK2 in comparison to HEp2 cells. The Ad5wtRSVβgal attachment and internalisation was 25-30% and 15-30% lower in VK2 than in HEp2 cells, respectively. Finally, Ad5wtCMVβgal differing from Ad5wtRSVβgal ony in promoter that drives transgene expression, showed equal transgene expression in HEp2 and VK2 cells. We conclude that the increased Ad5wtRSVβgal-mediated transgene expression in the VK2 cells is due to the increased RSV promoter activity. Our results point out that (i) drug-resistance may be accompanied with an alteration in promoter activity and (ii) the proper choice of promoter could contribute to a decrease in the vector dose required to achieve a therapeutic effect during tumor gene therapy
Interpolations : écriture de contraintes réactives pour improvisations pianistiques (démo)
National audienceDans le domaine des systèmes informatiques d'aide à la musique improvisée, nous proposons une série d'expérimentations dans lesquelles le musicien doit s'adapter aux retours automatiquement générés par l'ordinateur. Dans notre approche, ces « feedbacks » sont décrits à l'aide de fonctions algorithmiques de complexités croissantes, allant de l'ajout automatique de notes, à l'enregistrement et à la restitution transformé de séquences jouées par la musicien. Apparemment opposé aux approches par appren-tissages qui tentent de « comprendre » le style du mu-sicien pour lui proposer un feedback cohérent avec son jeu, nos expérimentations montrent que, sans doute dans les deux cas, le musicien arrive à adapter son jeu en s'appropriant les retours de l'ordinateur pour, in fine, faire de la musique
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The 'knowledge politics' of democratic peace theory
How do academic ideas influence US foreign policy, under what conditions and with what consequences? This article traces the rise, ‘securitisation’ and political consequences of democratic peace theory (DPT) in the United States by exploring the work of Doyle, Diamond and Fukuyama. Ideas influence US foreign policy under different circumstances, but are most likely to do either during and after crises when the policy environment permits ‘new thinking’, or when these ideas have been developed through state-connected elite knowledge networks, or when they are (or appear paradigmatically congenial to) foreign policymakers’ mindsets, or, finally, when they become institutionally-embedded. The appropriation of DPT by foreign policymakers has categorised the world into antagonistic blocs – democratic/non-democratic zones of peace/turmoil – as the corollary to a renewed American mission to make the world ‘safer’ through ‘democracy’ promotion. The roles of networked organic intellectuals – in universities and think tanks, for instance – were particularly important in elevating DPT from the academy to national security managers
Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection
The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrugresistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30–60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections
Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection
The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30–60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections
A comparison of robust polynomial fitting, global geopotential model and spectral analysis for regional–residual gravity field separation in the Doñana National Park (Spain)
Doñana National Park is a protected area of approximately 500 km2 located on the SW coast of Spain with
singular and interesting ecological and geological features. A gravimetric survey is presented where L&R
gravity metres were used in the gravimetric observations with GPS and high-precision levelling positioning.
Bouguer gravity anomalies were computed and least squares prediction was used for gross-error detection.
Robust polynomial fitting, the recent EGM2008 global geopotential model (complete to degree and order
2159), and spectral analysis were tested for regional–residual gravity field separation. A detailed description
of the gravimetric characteristics of the Doñana National Park is presented and the values of residual gravity
anomalies were correlated with geological features, where the use of the EGM2008 global geopotential model
has revealed an interesting tool for regional–residual gravity field separation. Finally, the interpretation of the
results is justified by the well-known geological aspects of the park, but some modifications in the boundaries
of the different geological features are needed in order to fit the modelled gravity with the residual gravity
anomalies in the two cross-sections analysed.The studies presented here were part of CICYT (Spanish Research Directorate) research project nos. HID 97-0321 and REN2001-1293. We would like to thank all UPC members participating in these projects and the staff from the Biological Station of Donana (CSIC), Palacio de Donana and Donana National Park. We remain deeply grateful for the fruitful discussion with Dr. Salvany and for the geological review of the manuscript.Martín Furones, ÁE.; Nuñez Andrés, M.; Gili, J.; Anquela Julián, AB. (2011). A comparison of robust polynomial fitting, global geopotential model and spectral analysis for regional–residual gravity field separation in the Doñana National Park (Spain). Journal of Applied Geophysics. 75(2):327-337. https://doi.org/10.1016/j.jappgeo.2011.06.037S32733775
