715 research outputs found
Mycobacterium Tuberculosis Klinik İzolatlarında Yeni Antitüberküloz İlaçlar Olan Bedaquiline ve Delamanid'in MİK Değerlerinin ve Dirence Neden Olan Mutasyonların Saptanması
No full textDoktora öğrencisi TÜBİTAK 2214A-Yurt Dışı Doktora Sırası Araştırma Programı kapsamında 4 ay süre ile İsviçre Zürih Üniversitesi’nde desteklenmiştir (Proje Kodu: 1059B141600355). Araştırma, Hacettepe Üniversitesi BAP. Kapsamlı Araştırma Projesiyle desteklenmiştir (Proje Kodu: TSA-2019-18169).The purpose of this study is to detect the minimum inhibitory concentration (MIC) values of these novel drugs against to 101 resistant-M.tuberculosis clinical isolates with MGIT 960 automatized liquid culture system integrated with TB/eXİST research software as phenotypically and detection of drug resistance related mutations on bacteria genome by Sanger DNA sequencing or whole genome sequencing (WGS) as genotypically. Thirty one strains were isolated in University of Zurich, Switzerland and 70 strains were isolated in Turkey. Cross resistance between bedaquiline and clofazimin was also investigated in Swiss isolates. According to phenotypic MGIT 960 system bedaquiline, delamanid and clofazimin MIC ranges were found as <0.2 µg/ml to ≥4.0 µg/ml (mean MIC=0.92 µg/ml), ≤0.01 µg/ml to ≥3.2 µg/ml (mean MIC=0.18 µg/ml) and ≤0.5 µg/ml to ≥2.0 µg/ml (mean MIC=1.11 µg/ml), respectively. Phenotypical susceptibility test results reveal that bedaquiline MIC values of Swiss isolates were found higher than those of Turkish isolates while delamanid MIC values of isolates from Turkey were found higher than those of Swiss isolates. According to World Health Organization Critical Drug Concentration Report, mean MIC values of all of the strains were classified as sensitive to bedaquiline while they were classified as resistant to delamanid and clofazimin. Some isolates had both bedaquiline and clofazimin high MIC values but we couldn’t detect any cross resistance related mutations in genome of these bacterial strains. Further studies are required to clarify new mutations related to resistance. In this study, we also tried to optimize the WGS protocol in order to detect all drug resistance profile in the genome of bacteria. The protocol could detect the resistance related variations in the genome of 25 strains. In conclusion, this study provides a preliminary AST results of M.tuberculosis strains isolated from Turkish patients for novel drugs which will be available in Turkey soon. Research software integrated MGIT 960 testing and optimized WGS protocol will be used for determination of individualised therapy of MDR-TB patients.Bu çalışmanın amacı, dirençli tüberküloz hastalarından izole edilen 101 M. tuberculosis klinik izolatının bedaquiline ve delamanid minimal inhibitör konsantrasyon (MİK) değerlerinin fenotipik olarak MGIT-960 otomatize sıvı kültür sisteminde bir araştırma yazılımı olan TB/eXİST ile saptanması ve dirence neden olan mutasyonların Sanger dizileme ve tüm genom analizi (WGS) yöntemleriyle genotipik olarak araştırılmasıdır. Suşların 31’i İsviçre Zürih Üniversitesi’nde, 70’i ise Türkiye’deki hastalardan izole edilmiştir. İsviçre suşlarında bedaquiline ve klofazimin arasında çapraz direnç varlığı da araştırılmıştır. Fenotipik duyarlılık sonuçlarına göre İsviçre ve Türkiye suşlarının bedaquiline, delamanid ve yalnızca İsviçre suşlarının klofazimin MİK dağılımları ve ortalama MİK değerleri sırasıyla <0,2 µg/ml ile ≥4,0 µg/ml arasında (ortalama MİK=0,92 µg/ml), ≤0,01 µg/ml ile ≥3,2 µg/ml arasında (ortalama MİK=0,18 µg/ml) ve ≤0,5 µg/ml ile ≥2,0 µg/ml arasında (ortalama MİK=1,11 µg/ml) saptanmıştır. İsviçre suşlarının bedaquiline MİK değerleri, Türkiye suşlarına göre daha yüksek bulunurken, Türkiye suşlarının delamanid MİK değerleri İsviçre suşlarına göre daha yüksek bulunmuştur. Dünya Sağlık Örgütü’nün Kritik İlaç Kosantrasyonları Raporu’na göre çalışmamızdaki tüm suşlar ortalama MİK değerlerine göre bedaquiline duyarlı bulunurken, delamanid ve klofazimine dirençli bulunmuştur. Bedaquiline ve klofazimin MİK değerleri yüksek suşlarda çapraz dirençten sorumlu olan mutasyon, Sanger dizileme ile saptanamamıştır, dirence neden olan yeni mutasyonun saptanması için ileri çalışmalar yapılması gerekmektedir. Bakteri genomunda bulunan ve tüm ilaçlara karşı gelişen direnç profillerini saptamak amacıyla bir WGS protokolü optimizasyon çalışması yapılmıştır. 25 suşun genomunda bulunan dirençle ilişkili varyantlar saptanabilmiştir. Sonuç olarak, bu çalışmada ÇİD-TB tedavisinde yakın zamanda ülkemizde de kullanıma girmesi beklenen yeni ilaçlar için Türkiye M. tuberculosis suşlarının ön duyarlılık verisi elde edilmiştir. MGIT-960 sistemiyle entegre edilen araştırma yazılımı ve optimize edilmiş WGS protokolünün ÇİD-TB hastalarının kişiselleştirilmiş tedavilerinin belirlenebilmesinde kullanılabileceği düşünülmektedir
Recent Advances in Molecular Point of Care Tests
No full textMolecular point of care tests has become promising methods for the global control of infectious diseases in recent years. Different kinds of point of care testing devices have been introduced into the market in the last decade. They are mainly based on miniaturization and integration of sample processing, nucleic acid amplification, and detection systems. These devices must offer a low-cost, sensitive, specific, and practical analysis to be used especially in low-resource settings. Microfluidics has high potential for handling very small volumes of fluids on a single platform. The key design features for molecular point of care tests in resource-limited settings include isothermal nucleic acid amplification methods to eliminate the need for a thermocycler, lyophilized reagents for long-term stability at high temperature and relatively simple test procedures. CRISPR-Cas-based new generation molecular point of care tests have been developed in recent years. In these tests Cas enzymes are used as highly specific target sequence recognition elements. Collateral cleavage activity of these enzymes cleaves both target sequence and labeled RNA in the mixture and a signal is generated. The ongoing Coronavirus 2019 pandemic has shown the importance of rapid diagnostic tests for the prevention of further spread. Although real-time polymerase chain reaction method was used successfully for the rapid diagnosis during the pandemic, additional rapid and practical tests that could be performed outside the laboratories would provide even faster diagnosis and lighten the burden of test load in large central laboratories. Molecular point of care tests are considered to be one of the best candidates to fill the this gap in the near future. The future technology challenges will be the standardization of the methods and further miniaturization of the system components. In this review article, point-of-care tests adapted from nucleic acid amplification methods with a large number of studies in the literature and tests based on the CRISPR-Cas system which constitutes the newest group and which is among the point-of-care molecular tests based on new next -generation sequencing have been discussed
QUANTITATIVE ANALYSIS OF SERUM BONE ALP (ALP Ⅲ) IN AFFlNITY ELECTROPHORESIS AND THE PRECIPITATION METHOD CONTAINING LECTIN
No full textFor decades, ALP had been interpreted as a marker enzyme of metabolic bone diseases and an isoenzyme specific for the osteoblast been widely known as ALP Ⅲ, too. Moreover, current tremendous advances in dialysis technology project an impact for the clinical significance of ALP Ⅲ, because of the advent of a new characteristic clinical entity formed renal osteodystrophy (ROD) which had been one of the inevitable complications in long term hemodialysis patients. So far, however, many conventional methods failed to separate clearly ALP Ⅲ from the liver specific ALP (ALP Ⅱ) and present determination of ALP Ⅲ by no means satisfied the clinical demand due to the lack of a direct quantitative method. On the other hand, lectin method, reported originally in 1984 by Rosalki, proved it to be possible to measure ALP Ⅲ directly as well as quantatively. So, the author performed this study to confirm more precisely several conditions of procedure of the lectin method, using established osteoblastic cell line ROS 17/2 as a marker, as well as the availability of its clinical application, and obtained the following results ; 1) The optimum concentration of Wheat-Germ lectin binded fully to ALP Ⅲ was 139 μmol/ml in distilled water. 2) The concentration of Triton X-100 preventing biliary ALP from ALP-lectin complex was 20%. 3) ALP Ⅲ activity incubated with lectin overnight at 4℃ after incubation for 30 min. at 37℃ was higher (mean±S.D, 24.0±15.2%) than that incubated with lectin for 30 min. at 37℃. 4) ALP Ⅲ was clearly separated from the liver fraction using affinity electrophoresis on polyacrylamide gel disc and isoelectric focusing on agarose gel. 5) ALP Ⅲ activity in precipitate showed good correlation (r=0.998) with the differential between total ALP activity and ALP Ⅱ activity in supernate
Factions in the ALP
No full textThis record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/317496Article or speech, unidentified author and audience, mostly likely created in 2001 owing to statements in text about the Labor Party's 100 year anniversary.280917
item: [2010.0053.01109] "Factions in the ALP
Maximum power point tracking algorithm based on inflection voltage for photovoltaic systems
No full textFen Bilimleri Enstitüsü, Elektrik-Elektronik Mühendisliği Ana Bilim DalıBu tez çalışmasında, Fotovoltaik sistemlerde, kısmi gölgelenme durumu altında Maksimum Güç Noktası İzleme (MGNİ) amacıyla, iki yeni arama algoritması literatüre kazandırılmıştır. Dönüm gerilimleri tabanlı bu iki algoritma; Alp yöntemi ve Alp tırmanma algoritmasıdır. Alp yöntemi öncelikle Fotovoltaik sistemin dönüm gerilimlerini hesaplayarak daha sonra bu dönüm gerilimlerinin her birine açık devre gerilimi yöntemi uygular ve yeni güç noktaları elde eder. Son olarak bu güç noktalarından en büyüğünü seçip bu noktayı maksimum güç noktası olarak belirler. Alp tırmanma algoritması ise Alp yöntemiyle bulunan en büyük güç noktasından itibaren tırmanma işlemi gerçekleştirerek dizinin maksimum güç noktasına %100 yakınsamayı amaçlar. Fotovoltaik dizinin farklı gölgelenme durumları altında Akım/ Gerilim karakteristikleri elde edilmiştir ve bu karakteristikler algoritmaların başarı karşılaştırması için veri seti olarak kullanılmıştır. Bu deney verileri kullanılarak Alp yöntemi ve Alp tırmanma algoritması, stokastik tepe tırmanma algoritması, açık devre gerilimi yöntemi, stokastik ışın arama algoritması ve benzetilmiş tavlama algoritması ile kıyaslanmıştır. Deneysel çalışmalar, Alp yöntemi ve Alp tırmanma algoritmasının kısmi gölgelenme durumu altındaki Fotovoltaik sistemlerde, maksimum güç noktasına başarıyla yakınsadığını göstermektedir. Alp tırmanma algoritması karşılaştırılan diğer algoritmalara göre çok daha yüksek başarı gösterdiği görülmüştür. Alp yöntemi ise uygulama kolaylığı ve çok az adım sayısı kullanarak maksimum güç noktasına yakınsamasıyla ön plana çıkmıştır.In this thesis study, two novel search algorithms have been added to the literature for the purpose of Maximum Power Point Tracking for photovoltaic systems under partial shading conditions. These two algorithms based on inflection voltage and named as Alp method and Alp climbing algorithm. The Alp method first calculates the inflection voltages of the photovoltaic system and then applies the open circuit voltage method to each of these voltages to obtain maximum power points. Finally, it chooses the biggest power point from these power points and determines that point as the global maximum power point. The Alp climbing algorithm aims to achieve a 100% convergence to the global maximum power point by climbing from the largest possible power point found by the Alp method. Current/voltage characteristics of the photovoltaic array were obtained under different shading conditions and these characteristics were used as data sets for the success comparison of the algorithms. Alp method and Alp climbing algorithm have been compared with the stochastic climbing algorithm, the open circuit voltage method, the stochastic beam search algorithm and the simulated annealing algorithm using these experimental data. Experimental studies show that the Alp method and the Alp climbing algorithm successfully converge to the global maximum power point under partial shading. Alp climbing algorithm has shown to be much more successful than other algorithms compared. The Alp method has come to the forefront in terms of ease of application and very close to the maximum power point using very few steps
Treatment with cucurbitacin B alone and in combination with gefitinib induces cell cycle inhibition and apoptosis via EGFR and JAK/STAT pathway in human colorectal cancer cell lines
No full textBayram, Cem/0000-0001-8717-4668; Elmazoglu, Zubeyir/0000-0003-4527-8834WOS: 000375574200007PubMed: 26183715The epidermal growth factor receptor (EGFR) associated with signaling pathways, such as Janus kinase (JAK)/signal transducer and activator of transcription (STAT), plays an important role in colorectal cancers (CRCs). Gefitinib (Gef) is an orally active inhibitor targeting the adenosine tri phosphate-binding domain of EGFR, and cucurbitacin B (CuB) is a selective inhibitor of JAK/STAT signaling with potent antitumor activity via suppression of STAT3 phosphorylation, but the underlying mechanism is not clear. We aimed to investigate the apoptotic and antiproliferative effects of CuB as a single agent and in combination with Gef on both HT-29 and HCT-116 cell lines. Cell proliferation, cell cycle distribution, and apoptosis were evaluated using viability assay, fluorescent microscopy, cytotoxicity assay, proliferation, DNA fragmentation, and cleaved caspase 3 levels. Real-time polymerase chain reaction and Western blot analyses were performed to determine the expression of relevant genes and proteins including antiapoptotic, proapoptotic, and cell cycle regulation. EGFR, phosphorylated EGFR (pEGFR), STAT3, and pSTAT3 proteins were evalutaed with Western blot analysis. Our results showed that, compared to CuB alone, CuB plus Gef treatment caused a significant growth and cell cycle inhibition and induced apoptosis in both cell lines. Also CuB plus Gef treatment decreased DNA synthesis rate more effectively than CuB alone. Treatment with CuB alone and in combination with Gef decreased the expression levels of B-Cell CLL/Lymphoma 2 (Bcl-2), BCL2-like 1 (BCL2L1), cyclin D1, pSTAT3, and pEGFR and increased the expression levels of Bcl-2-like protein 4, Bcl-2 homologous antagonist/killer, Bcl-2-associated death promoter, Bcl-2-like protein 11, and p27kip1 levels. Our results suggest that treatment with CuB alone and more likely in combination with Gef may be a considerable alternative therapeutic approach for CRC, at least in vitro.Gazi University Research FoundationGazi University [01/2011-56]The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by Gazi University Research Foundation, with the project code number 01/2011-56
Problems Of Contemporary Art Courses; Purpose, Content, Methods And Applıcatıons For The Students And Faculty Member Comments
No full textÇağdaş Sanatlar dünyada ve ülkemizde kendini sürekli güncelleyen ve geliştiren, geliştirmeye de devam eden kavramlardır. Bugün çağdaş sanat denilince, yalnızca bir sanat kavramı değil, eğitimi ve öğretimi de kapsayan geniş bir anlam bütünlüğü de akla gelmektedir. Birçok disiplini de içinde barındıran hatta birleştiren çağdaş sanatlar günümüz de Çağdaş Sanat Sorunları dersi içeriğinde ele alınmaktadır. Çağdaş sanat sorunları dersi, çağdaş sanatın ana sorunlarını ele alarak modernizimden postmodernizme geçiş sürecinde sanat, sanatçı, yapıt ve sanat ortamı ilişkilerini yeni estetik değerler bazında ele alıp analiz etmek amacındadır. Böylesine önemli kuramsal bir dersin yüksek lisans düzeyindeki etkililiği ve aynı zamanda öğrencilerin uygulamalarıyla olan ilişkiselliği araştırmaya değer bir konudur. Özellikle ders içerik, amaç, yöntem ve teknikleri tüm diğer eğitim alanlarında olduğu gibi sanat eğitiminde de etkililiğin ana bileşenlerini oluşturmaktadır. Çağdaş sanat sorunları derisi; öğrencilerin sanata bakış açılarını genişletirken, sanata yorum katma ve eleştirebilme yetisi kazandırmak, hayal gücünü geliştirmek, kendi tarz ve üslupları ile sanata yaklaşımlarını sağlamak, geçmiş ve gelecek arasında bir köprü oluşturmak, ileriye dönük araştırma teknikleri öğretmek dersin hedeflerindendir. Çağdaş sanatlar teknolojinin
ilerlemesi ile farklı anlamlar ve yollar ile kendini yenilemektedir. Bununla birlikte teknolojinin gelişmesiyle de bazı sorunları da beraberinde getirmiştir. Yapılan bu çalışmada Çağdaş Sanat Sorunları dersine ülkemizde öğrenciler ve öğretim elemanlarının bakış açısına, Çağdaş sanat sorunlarının anlaşılması ya da genel sorunların nasıl algılandığı, yapılan öğrenci anketi ve dersin öğretim elemanı ile diğer öğretim elemanlarının görüşleri ile tespit edilmeye çalışmıştır.Contemporary Arts, in the world and in our country continuous self-updating and renewing, concepts that continue to develop. Today, contemporary art is mentioned, not only an artistic concept, including education and training, it refers to a broad sense of integrity. Many disciplines within hosting, combining contemporary arts, today Contemporary Art Issues course go about. Contemporary art problems lesson, it discusses the main issues of contemporary art, the transition from modernism to postmodernism in the arts, artists, art works and media relations, in some aesthetic values and it aims to analyze. An important theoretical lessons, effectiveness in the master's level and at the same time, students practice interrelations is an issue worth investigating. Specifically, this course content, objectives, methods and techniques, as in all other education branch constitute the main component of the effectiveness of arts education. Contemporary art problems lessons; Students expand their vision of art to gain the ability to add art review and criticize, develop imagination, provide approaches and styles of art with their own style, to build a bridge between past and future, teach prospective research techniques, In lesson of the target.Contemporary arts advancement of technology with it renews itself through different means and ways. With the development of technology some issues have been brought up. Made in this study, Problems of Contemporary Art course students and lecturers of our country perspective, An understanding of the problems of contemporary art or the perception of the general problem, The student survey done and the course instructor with It has tried to determine the opinions of the other instructors
Advancement In Poct Molecular Testing: The Multiplex Pcr Poct Devices For Infectious Diseases
No full textRapid and accurate diagnostic tests are very important for the global control of infectious diseases. The point of care diagnosis has become a promising strategy in recent years. Different kind of point of care testing devices has been introduced into the market in the last decade. These devices must provide a low-cost, robust, sensitive, specific, and practical analysis in order to replace the conventional clinical laboratory diagnostic test algorithms when needed. The successful implementation of point of care diagnostics has a potential to increase the strength of infectious diseases surveillance programs. Finally, the rapid progress in point of care diagnosis can stimulate a shift from a centralized diagnostic model to a decentralized patient-centered approach.PubMe
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