182
Archived Theses
0
DOIs Assigned
0%
DOI Rate
Discipline
Bina tasarımında aydınlatma ve renk olgusunun biyoharmoloji ve biyosüreç açısından incelenmesi
Bir insanın dış dünyayla bağlantı kurmasında, hafızasının çalışmasında, beyninin öğrenme görevini yerine getirmesinde rengin önemi büyüktür. Çünkü insan, olaylar ve mekanlar, kişiler ve nesneler arasında ancak dış görünüşleri ve renkleri sayesinde sağlıklı bir bağlantı kurar. Sadece ses ya da dokunma, cisimleri tanımlamada yeterli olmaz. İnsan için dış dünya ancak renkleriyle bir bütündür ve bir anlam ifade eder.Mimari aydınlatmanın en önemli amaçları, görüş keskinliği ve doğru renk algılamasını sağlamak, mekanın mimari özelliklerini ve içindeki eşyaların özelliklerini ortaya koymak, elektrik enerjisini en az harcayarak en çok randımanı almak, baskın bir etki yaratarak istenilen atmosferi sağlamak ve belirli noktalara dikkat çekebilmektir.Bu çalışmada, günümüzün %90'nı geçirdiğimiz yapılarda, yeterli aydınlatma ve psikolojimizi olumlu yönde etkileyecek, hastalık, yorgunluk, depresif vb etkiler oluşturmayacak renk ve aydınlatma tasarımları, biyoharmoloji ve biyosüreç açısından incelenecektir.Yapılarımızdaki mevcut durumun belirlenmesi ve gerekli çözüm önerileri getirilmesi için, ilköğretim okulları, özel eğitim ve rehabilitasyon merkezleri ve kütüphanelerde incelemeler yapılmış, mevcut durum çerçevesinde gerekli çözüm önerileri sunulmuştur.
Köpeklerde kortikal ve spongiyöz otogreftlerin uygulanması ile oluşan kallusun çekme ve basma dayanımlarının incelenmesi
Bu çalışma, ortopedik cerrahide büyük bir sorun olan kemik defektlerinin onarımında otojen kortikal ve spongiyöz kemik greftlerinin uygulanması sonucunda oluşacak kallusun biyomekaniksel yöntemlerle çekme ve basma dayanım değerlerinin saptanması amacıyla gerçekleştirildi.Çalışmada değişik ırktan, 2-3 yaşlarında, ağırlıkları 25-30 kg arasında değişen 12 adet dişi köpek kullanıldı. Genel anestezi altında, köpeklerin herhangi bir radius'unda 0.7 cm uzunluğunda segmental bir defekt oluşturuldu. Oluşturulan defektler köpeklerin 6 tanesinde otojen kortikal kemik grefti ile, 6 tanesinde ise otojen spongiyöz kemik grefti ile dolduruldu. Bütün olgularda ilk iki hafta görülen topallık daha sonraki incelemelerde tamamen ortadan kalktı. Hayvanlar iki, 4 ve 6. ayın sonunda sakrifiye edilerek greft uygulanan radiusları çıkarıldı ve çekme, basma testleri uygulandı.Uygulanan mekanik testlerin sonucunda otojen spongiyöz kemik greftinin çekme ve basma değerlerinin otojen kortikal kemik greftinde elde edilen değerlere göre daha yüksek olduğu saptandı.Sonuç olarak, otojen spongiyöz kemik greftlerinin çekme ve basmaya karşı dayanımlarının otojen kortikal kemik greftlerine göre daha yüksek olduğu ve elde edilen bu bulgular sonucunda otojen spongiyöz kemik greftlerinin kullanımının otojen kortikal kemik greftleri kullanımına göre daha avantajlı olduğu kanısına varıldı.Anahtar Kelimeler: Otogreft, Kortikal greft, Spongiyöz greft, Çekme testi, Basma testi.
Tıbbi verileri çizge bölütleme yöntemi ile sınıflandırma ve kümelendirme
Bilgisayar başta olmak üzere bilgi teknolojilerinin hızlı gelişiminin olumlu etkisiyle ?Bilgi Çağı? olarak tanımlanan günümüz dünyasında karmaşık biçimlerdeki büyük veri yığınları içinden değerli bilgi parçalarını ayıklamak ve kullanılır hale getirmek ?Veri Madenciliği? işlemleri ile olmaktadır. Bilgisayar mühendisliği ve biyomühendislik bilim dallarında veri miktarının artması sonucunda uzmanın yararlı bilgiyi çıkarması zorlaşmaktadır. Bu yararlı bilgiyi çıkarmada, veri toplanması veya üretilmesi için sinyali doğru algılama, verilerin doğru sınıflandırılması ve kümelendirilmesi ile çok boyutlu ilişkilerinin ortaya konularak analizi çok önemlidir.Bu çalışmada ?tıbbi verileri çizge bölütleme yöntemi ile sınıflandırma ve kümelendirme? için doğrusal cebir tabanlı bir hesapsal yöntem kullanılarak ve bu yöntemin başarımının ortaya konulması için veri madenciliği alanına uygulaması yapıldı.Çizge bölütleme yöntemi, başta tıbbi verilerde sınıflandırma ve kümelendirme problemleri olmak üzere bir çok bilimsel problemin çözümünün kolaylaştırılması veya bu çözümün bulunması amacıyla yapılan çalışmalar sonucunda ortaya çıkmıştır. Bundan dolayı çizgelerin analizi ve testi yöntemin geliştirilmesi çok önemlidir.Bu çalışmanın en önemli özelliği, tıbbi verileri çizge bölütleme yöntemi ile sınıflandırma ve kümelendirme algoritmalarının uygulamasının yapılmış olmasıdır.
Matlab görüntü işleme aracı kullanarak endometriozis hastalığının ultrason görüntülerinde tespiti
Günümüzde hızla gelişen teknolojiyle birlikte görüntü işleme yöntemleri yaygın bir şekilde kullanılmaktadır. Bu tez çalışmasında kadınlarda sık rastlanılan bir hastalık olan endometriozisin ultrason görüntülerinde, hastalıklı yerin tespit edilmesini kolaylaştırmaya yönelik olarak, görüntü işleme tekniklerini kullanan ve kitlenin sınırlarını yakalamaya çalışan bir yöntem üzerinde durulmuştur. Görüntü işleme tekniklerinin klasik yapısal programlama dilleri kullanılarak gerçekleştirilmesi zor olmaktadır. Bu zorluklar çoğunlukla yoğun matematiksel işlemlerin gerekliliği, işlenecek veri sayısının yüksek oluşu ve algoritma karmaşıklığının yanında oluşturulan uygulama programına ait doğruluğun her adımda test edilmesi şeklinde ortaya çıkmaktadır. Bu problemi aşmak için bu tez çalışmasında Matlab programı kullanılmıştır.Tez çalışmasında, ultrason görüntülerinde endometriozis hastalığının kitle sınırının bulunması için aktif sınır yakalama yöntemlerinden yararlanılmıştır. Yapılan çalışmada gri seviye ultrason görüntüleri kullanılmış, eğri uydurma için görüntüler üzerinde farklı yerlerde ve boyutlarda başlangıç sınırları denenerek algoritma farklı iterasyonlarda çalıştırılarak sonuçlar görüntülenmiştir. Gri seviye ultrason görüntülerinde sınır bulmanın zorluğu ve başlangıç eğrisinin yeri, boyutu ve algoritmanın iterasyon sayısının görüntü üzerindeki nesne sınırının bulunmasında önemi görülmüştür. Buna rağmen sonuçta algoritmanın çalıştırılmasıyla gri seviye ultrason görüntülerindeki endometriozis kistinin gerçek sınırlarına yakın sınırlar elde edilmiştir.Anahtar Kelimeler : Endometriozis, Görüntü İşleme, Bölütleme, Yılan Modeli, Geometrik Biçim Değiştirme Modeli, Aktif Yörünge Modeli
Çok amaçlı genetik algoritma kullanarak DNA mikrodizi verilerinin kümelenmesi
DNA mikrodizi teknolojisi, önemli biyolojik süreçlerdeki binlerce gen ifadesi seviyelerinin aynı anda izlenmesini olanaklı kılar. Gen ifadesi verilerinde saklı örüntüleri açıklama fonksiyonel genomu anlama için muazzam bir fırsat sunar. Bununla birlikte, biyolojik ağların karmaşıklığı ve çok büyük miktarlardaki genler, oluşan veriyi anlama ve yorumlamada bazı problemleri de beraberinde getirir. Bu problemlerin çözümü için sunulan bir alternatif, kümeleme tekniklerinin kullanılmasıdır. Kümeleme, mevcut verideki ilginç örüntüleri tanımlama ve doğal yapıları açığa çıkarmak için kullanılan veri madenciliği yöntemlerinden biridir. Kümeleme analizi verilen bir veri kümesini belirlenmiş özelliklere göre gruplara parçalama çabasıdır. Böylece bir grup içindeki veri noktaları, farklı gruptaki noktalara göre birbirine daha çok benzerdir.Kümeleme algoritmalarında küme sayıları genellikle önceden verilir. Fakat bir veri kümesi için uygun küme sayısının önceden tahmin edilmesi alanın uzmanı için zor bir işlemdir. Bu tez çalışmasında bu problemin üstesinden gelebilmek için çok-amaçlı genetik algoritma tabanlı bir kümeleme yöntemi önerilmiştir. Yöntem k-means kümeleme algoritmasıyla çok-amaçlı genetik algoritma sürecini birleştirir. Leukemia, Lymphoma ve Kolon kanseri veritabanlarına uygulanan yöntemin sonuçları literatürde çokça kullanılan Dunn, Davies Bouldien, Silhoutte, C, SD ve S-Dbw küme geçerlilik indeksleriyle karşılaştırılmış ve yüksek doğruluk oranlı etkin çözümler verdiğini göstermiştir.
Tıbbi veri kümeleri arasındaki birliktelik kurallarının çok amaçlı genetik algoritma ile çıkarılması
Tıbbi verilerin hacimlerinin artması nedeniyle bu verilerden bilgi çıkarmak oldukça zorlaşır. Günümüzde çok büyük miktarda bilgi sürekli bir biçimde hastaların fizyolojik parametreleri gözlemlenerek toplanılmaktadır. Artan veri miktarları tıp uzmanları tarafından yapılan manüel analizleri bıktırıcı ve bazen imkansız birer görev haline getirmiştir. Analiz yapanlar, potansiyel olarak faydalı olabilecek bazı bilgilerin farkına varamayabilmektedir. Veri miktarında meydana gelen hızlı artış sonucu faydalı bilginin çıkarımı konusunda otomatikleştirilmiş bir yola ihtiyaç duyulur. Bu problem için kullanılan yaklaşımlardan biri veritabanları üzerinde bilgi keşfi veya veri madenciliği yöntemidir.Bu tezin amacı, şizofreni hastalığına ait tıbbi verilerden çok amaçlı genetik algoritma kullanarak bağıntı ve sınıflandırma kurallarını çıkarmaktır. Bağıntı ve sınıflandırma kuralları özellikle tıbbi teşhis alanında uygulanan tıbbi problemler için faydalıdır. Bu tip kurallar tıbbi uzmanlar tarafından doğrulanabilir ve bu durum mevcut problemin daha iyi anlaşılmasını sağlar.Son on yılda veri madenciliğinde kural keşfi üzerine pek çok teknik uygulanmıştır. Bu tekniklere örnek olarak uzman sistemler, yapay sinir ağları, veritabanı sistemleri ve evrimsel algoritmalar verilebilir. Evrimsel algoritmalar doğal evrim sürecinden esinlenerek geliştirilen hesapsal tekniklerin bir sınıfıdır. Doğal evrim süreci, gerçek hayatta karşılaşılan problemleri çözmek için doğal seçim ve en iyinin hayatta kalması mekanizmalarını örnek alır. Çok amaçlı evrimsel algoritmalar, kıyaslanamayan ve çoğunlukla rekabet halinde olan amaçların eş zamanlı optimizasyonu ile uğraşır.Bu tezdeki amaç, çok amaçlı genetik algoritma kullanarak sınıflandırma ve birliktelik kurallarını etkin bir şekilde bulmaktır. Bu maksatla şizofreni hastalarının sosyodemografik ve biyokimya verilerine uygulanan yöntem, suç işleme durumları dikkate alındığında sosyodemografik verilere daha bağımlı olduğu gözlenmiştir.
Yapılarda huzur kriterlerinin incelenmesi
Son yıllarda gelişen teknoloji ile birlikte bireylerin kapalı mekânlarda kalma süreleriartmış ve buna paralel olarak da kapalı mekânlara bağlı sağlıklı problemleri ortayaçıkmıştır. İç hava kalitesi kullanıcıların sağlığı ve verimi ile doğrudan ilişkilidir ve bubakımdan temel yaşam alanı olan konutlardaki iç hava kalitesinin durumunun tespitedilmesi son derece önemlidir. Bu çalışmada, kapalı mekânlardaki huzur kriterleri ile ilgiliolan konfor şartları ve iç hava kalitesi alt başlıkları Elazığ'da 3 farklı merkezde hermerkezde yaklaşık 65'er anket uygulaması ve yaklaşık 30'ar evde eş zamanlı olaraksıcaklık, bağıl nem, hava hızı, gürültü, ışık şiddeti CO2, O2, CO ölçümleri yapılmıştır. Herev için misafir odası, oturma odası ve mutfakta gerekli ölçümler alınmıştır. Elde edilenanket ve ölçüm sonuçları literatürdeki çalışmalar, ulusal ve uluslararası standartlar ilekarşılaştırılmış ve çözüm önerileri geliştirilmiştir.
Biyoseramik kaplamanın MA8M ve AA6061-T4 alaşımlarında korozyon direncine etkisi
Kalsiyum fosfat esaslı bir seramik olan Hidroksiapatit [Ca10(PO4)6(OH)2] (HA), biyouyumlu oluşundan dolayı biyomedikal uygulamalarda kemik yerine geçebilen ve hasarlı kemik dokuların onarımında kullanılabilen biyoseramik bir malzemedir. Bu malzeme doğrudan greft veya daha iyi implant-kemik integrasyonu için metalik implantlar üzerine kaplama malzemesi olarak kullanılmaktadır. Bu tür kalsiyum fosfat esaslı malzemeler, kemik integrasyonu ve yeni kemik oluşumunu teşvik ederek implantların daha hızlı tespitini (osteointegrasyonunu) sağlamaktadırlar. İmplant malzemeler üzerine HA kaplamada elektroporetik, plazma sprey, magnetron sputter, CVD gibi metodların yanısıra Sol-Jel yöntemi de oldukça etkin bir metotdur. Bu yöntem; düşük işlem sıcaklığı, daha kompleks parçaların kaplama kolaylığı ve yüksek yüzey alanı ve serbest enerjiye sahip katıların daha düşük sıcaklıkta sinterlenmesi bakımından avantajlı sayılabilir.Bu çalışmanın amacı mevcut implant uygulamalarına alternatif olarak Mg alaşımı (MA8M) ve Al alaşımı (AA 6061-T4) malzemelerin yüzeylerini Sol-Jel yöntemi ile nano ve mikro-HA partikül boyutlarında, üç farklı kaplama kalınlığında (~30, ~60, ~85µm) biyoaktif-HA tabakası kaplayarak, adezyon dayanımı, HA tane boyutu ve kaplama kalınlığına bağlı olarak yapay vücut sıvısı içerisinde korozyon davranışlarını incelemektir. Bu amaçla, adezyon testleri ile Ringer sıvısı içinde korozyon deneyleri Potansiyostat cihazında yapılan numunelerin, karakterizasyonu taramalı elektron mikroskobu (SEM), X-ışınları difraktometresi ile gerçekleştirilmiştir. Yapılan incelemelerden, mikro-HA kaplı Mg alaşımı numunelerin korozyon ve adezyon direnci kaplama kalınlığı arttıkça azaldığı gözlenmiştir. Al alaşımı taban malzemelerin kullanıldığı HA kaplamaların aktivasyon kontrollü bir korozyon mekanizması ile korozyona uğradıkları görülmüştür. Al alaşımları için optimum düzeyde değerleri sağlayan numune ~30µm kaplama kalınlığına sahip nano-HA kaplı Al alaşımı numuneler, Mg alaşımları için optimum düzeyde değerleri sağlayan numuneler ise ~30µm kaplama kalınlığına sahip mikro-HA kaplı Mg alaşımı numunelerin olduğu görülmüştür.Anahtar sözcükler: Alüminyum ve Magnezyum, Biyoseramik kaplama, Hidroksapatit, Korozyon
Uzamsal bulanık c-ortalamalar kümeleme yöntemlerinin medikal imge bölütleme açısından değerlendirilmesi
Bu tez çalışmasında farklı bulanık c-ortalamalar (BcO) kümeleme algoritmaları incelenmiş ve bu yöntemlerin medikal görüntü bölütleme uygulamalarındaki başarımları test edilmiştir. Bu bağlamda, öncelikle standart BcO algoritması ve daha sonra standart BcO algoritmasından geliştirilmiş olan iki farklı BcO algoritması ayrıntılı olarak incelenmiştir. İncelenen yöntemlerin bilgisayar benzetimleri MATLAB ortamında gerçekleştirilmiş ve farklı görüntülerin bölütlenmesi sağlanmıştır. Yapılan uygulamalarda yapay görüntüler, gerçek görüntüler ve biyomedikal görüntüler (beyin MR) kullanılmıştır. Elde edilen sonuçlardan standart BcO algoritmasının, görüntü bölütleme uygulamalarında ki zayıflığı belirgin olarak görülmektedir. Bunda en büyük etken standart BcO algoritmasının görüntüyü bölütlerken piksellerin sadece parlaklık değerlerini göz önüne alması etkili olmaktadır. Zira bu standart BcO algoritmasının en büyük dezavantajıdır ve geliştirilmeye çalışılan tüm yeni algoritmalar bu zayıflığı gidermeye yöneliktir. Diğer taraftan değiştirilmiş BcO ve uzamsal BcO algoritmaları, standart BcO algoritmasından çok daha başarılı sonuçlar üretmiştir. Bunda en büyük etken, her iki geliştirilmiş BcO yönteminin, her bir piksel ile birlikte bu piksele komşu diğer piksellerin de göz önüne alınmasının sonucudur.Anahtar Kelimeler: görüntü bölütleme, bulanık c-ortalamalar, uzamsal bulanık c-ortalamalar, medikal görüntüler
Anatomi eğitiminde öğrenme nesnelerinin tasarlanması
Üniversitelerin tıp fakültelerinde okutulan anatomi dersinin anlatım ve anlama zorluğu karşısında her alanda ihtiyaç duyulduğu gibi eğitim içerikli bilgisayarlı öğrenme nesnelerinin hazırlanması kaçınılmaz olmuştur.Bu çalışmada. kulağın anatomisinin anlatımına yönelik bilgisayar tabanlı öğrenme nesneleri hazırlandı. Bu öğrenme nesneleri hazırlanırken anatomi resimleri ve bilgileri kullanıldı. Bilgisayar tabanlı öğrenme nesneleri, metinsel bilgiler ile görsel bilgileri belli bir konu sistematiği içerisinde, eğitici kontrollü sunumuna dayanmaktadır.Bu çalışmanın nihayetinde eğitimcilerin konusunu daha rahat anlatabileceği, öğrencilerin de daha kolay anlayıp kendilerinin tekrar edebilecekleri öğrenme nesneleri üretilmiştir.Anahtar Kelimeler: Kulak Anatomisi, Öğrenme Nesnesi, Photoshop, Flash, e-öğrenme
Sağlık yapılarının biyosüreç ve biyoharmoloji açısından incelenmesi: Fırat Tıp Merkezi örneklemi
ÖZETYüksek Lisans TeziSAĞLIK YAPILARININ B YOSÜREÇ VE B YOHARMOLOJ AÇISINDANNCELENMES : FIRAT TIP MERKEZ ÖRNEKLEMSadık Sezgin OZANFırat ÜniversitesiFen Bilimleri EnstitüsüBiyomühendislik Anabilim Dalı2006, Sayfa : 90Bu çalışmada, insan hayatının ve yapılaşmanın en önemli kurumlarından birisayılabilecek sağlık yapıları ve hastaneler; son yıllarda yeni gelişen bilim dalları olanbiyosüreç ve biyoharmoloji bakış açıları ile incelenmiştir. Bir ülkenin gelişmişlik düzeyinigösteren parametreler arasında genel sağlık hizmetleri yer almaktadır. Yaşamımızın büyünbölümlerinde görülen gelişmeler ve değişmeler her şeyden önce, temel bir toplumsal görevolacak şekilde sağlık işlerine değinmektedirler. Çünkü tekniğin ilerlemesi özelikle tıpalanında göze batacak, hatta heyecanlandıracak bir biçimde gerçekleşmektedir. Sağlıkyapılarının kısaca, insan-mekan, yapı-çevre ilişkisi demek olan, biyoharmolojiçerçevesinde değerlendirilmesinin bir bütünün çok önemli bir parçası olduğu göz ardıedilmemelidir.Anahtar Kelimeler: Biyoharmoloji, Biyosüreç, Sağlık Yapıları, Fırat Tıp MerkeziI
Veri madenciliği kullanarak biyokimya verilerinden hastalık teşhisi
ÖZETYÜKSEK LİSANS TEZİVERİ MADENCİLİĞİ KULLANARAK BİYOKİMYA VERİLERİ İLE HASTALIK TEŞHİSİŞengül DOĞANFırat ÜniversitesiFen Bilimleri EnstitüsüBiyomühendislik Anabilim Dalı2007, Sayfa: 91Elektronik değişimin yaşandığı günümüzde tıp, sanayi, eğitim gibi pek çok alanda verihacmi hızla artmaktadır. Bu veriler geniş veri havuzları oluşturmakta ve mevcut verilerdenamaçlanan verilere ulaşmak oldukça zorlaşmaktadır. Özelikle tıbbi veri tabanlarında verilerinanalizi, karar alma ve yönetim aşamalarında yeni bilgilerin keşfedilmesi ve bu bilgilerin etkilibir şekilde kullanılması işlemlerinin bilgisayar tarafından seri ve hızlı bir şekilde yaptırılmasıuzmanlara büyük kolaylık sağlamaktadır.Bu tez çalışmasında, Miyokard infarktüsü, Hiperlipidemi, Demir eksikliği anemisi veHipertiroidi-Hipotiroidi hastalıklarının teşhisinde kullanılacak bir karar destek sistemitasarlanmıştır. Karar destek sisteminde veri madenciliği tekniklerinden karar ağaçları yöntemikullanılmıştır. Sistemde belirlenen her bir hastalık için doktorların tanıda bulunurkenkullandıkları biyokimya verilerinden seçilen parametreler baz alınarak değerlendirmeyapılmıştır. Bu amaçla, delphi programlama dili kullanılarak bir paket program geliştirilmiştir.Sonuçta elde edilen veriler uzman bir doktorun verdiği kararla karşılaştırılmıştır.Anahtar kelimeler: Veri madenciliği, Örüntü tanıma, Uzman sistemler, Karar ağaçları, Karardestek sistemleri, Biyokimya parametreleri.VIII
COVID-19 patogenezinin moleküler düzeyde tanımlanması ve tahmini için spektrokimyasal ve açıklanabilir yapay zekâ yaklaşımlarının birlikte değerlendirilmesi
Bu tez çalışması, ATR-FTIR spektroskopisi ile spektrokimyasal ve açıklanabilir yapay zekâ (AYZ) yaklaşımlarının birleştirilmesiyle COVID-19 hastalarındaki moleküler değişiklikleri ve hastalık ilerlemesini incelemektedir. Entübe hastalardan (EC), hastane hizmetleri alan hastalardan (SC) ve iyileşen hastalardan (PC) alınan kan serumu örnekleri, olası spektrokimyasal serum biyobelirteçlerini belirlemek amacıyla analiz edilmiştir. Lipid, protein, nükleik asit konsantrasyonları ve IgG glikozilasyonu gibi spektrokimyasal parametreler kantifize edilerek hastalık şiddetini yansıtan önemli değişiklikler ortaya konmuştur. Özellikle, EC hastalarında SC ve PC gruplarına kıyasla artmış lipid içeriği, değişmiş protein konsantrasyonları ve artırılmış protein fosforilasyonu gözlemlenmiştir. Serum AGR (Albümin/Globulin Oranı) indeksi hasta grupları arasında belirgin farklılık göstermekte olup COVID-19 şiddeti için hızlı bir biyokimyasal belirteç olma potansiyeli taşımaktadır. Buna ek olarak, IgG glikozilasyonu ve glukoz konsantrasyonlarındaki değişikliklerin hastalık şiddeti ile ilişkili olduğu tespit edilmiştir. Ayrıca ağır hasta gruplarının (EC ve SC) serum IgG, IgM ve IgA antikor seviyelerinde PC gruba göre artış gözlemlenmiştir. Spektral analiz, EC hastalarında gözlemlenen belirgin değişikliklerle nükleik asit konsantrasyonlarını gösteren spesifik bantları vurgulamaktadır. AYZ teknikleri, COVID-19'un etkisinin heterojenliğini vurgulamakta ve hasta kategorileri arasında hastalık şiddetini tahmin etmede çeşitli spektral özelliklerin önemini daha belirgin hale getirmektedir. Genel olarak, bu kapsamlı yaklaşım COVID-19 patogenezinin altında yatan moleküler mekanizmalara dair önemli içgörüler sunmakta ve karar alma süreçlerine ve hasta yönetimine yardımcı olmak amacıyla şeffaf ve yorumlanabilir bir tahmin algoritması önerilmektedir.
Yeni doğan buzağılarda ishale bağlı ölümcül hastalığın teşhisine yönelik serum biyobelirteçleri temelinde makine öğrenimi ile hızlı teşhis yönteminin geliştirilmesi
Bu çalışma, ATR-FTIR spektroskopisi ve makine öğrenimi temelli öngörücü analizlerin entegre kullanımıyla, yenidoğan buzağı ishalinin hızlı, duyarlı ve invaziv olmayan biçimde teşhis edilmesine yönelik yenilikçi bir tanı platformu sunmaktadır. Yenidoğan buzağı ishalleri, sığır yetiştiriciliğinde ciddi ekonomik kayıplara ve hayvan refahı sorunlarına yol açan başlıca hastalıklardan biridir. Mevcut tanı yöntemlerinin zaman alıcı ve invaziv olması, erken teşhis ve müdahaleyi güçleştirmektedir. Çalışmada, sağlıklı (S), hasta (H) ve iyileşen (İ) buzağılardan elde edilen serum örneklerinin özgün biyokimyasal parmak izleri analiz edilmiştir. Spektral veriler ön işleme tabi tutulmuş, Temel Bileşen Analizi (PCA) ile indirgenmiş ve ardından Doğrusal Ayrım Analizi (LDA) ile Destek Vektör Makineleri (SVM) kullanılarak sınıflandırılmıştır. Bu öngörücü modeller, buzağıların fizyolojik durumlarını yüksek doğrulukla ayırt ederek önerilen sistemin güvenilir bir tanı aracı olabileceğini ortaya koymuştur. Çalışmanın bir diğer özgün katkısı, PO₂⁻ simetrik gerilme bandının Amide A bandına oranından türetilen yeni bir spektrokimyasal gösterge olan 1080 cm⁻¹/3300 cm⁻¹ indeksidir. Bu indeks, hastalığın ilerlemesi ve iyileşmesiyle ilişkili moleküler değişimleri yansıtarak tanısal doğruluğu güçlendirmekte ve erken müdahale için kantitatif bir parametre sunmaktadır. Ayrıca, serum kızılötesi spektroskopisi kullanılarak hastalık patogenezinde rol oynayan biyomoleküler işaretler tanımlanmış, 4000–650 cm⁻¹ aralığındaki kritik bantlar belirlenmiş ve lipit, protein ve nükleik asit düzeylerindeki değişimler nitel ve nicel olarak analiz edilmiştir. Bant alanı, bant genişliği ve ROC analizleri ile bu değişimlerin patogenez ile ilişkisi değerlendirilmiştir. Sonuç olarak, spektral verilerin kolay yorumlanabilir bir metriğe dönüştürülmesi, yenidoğan buzağı ishalinin erken teşhisini mümkün kılarak hayvan refahının iyileştirilmesine ve sürdürülebilir hayvancılık yönetimine önemli katkılar sağlamaktadır.
İndirgenmiş grafen oksit ve karbon kuantum nokta katkılı polikaprolakton nanofiber üretimi ve karakterizasyonu
Bu tez kapsamında, hem indirgenmiş grafen oksit (RGO) hem de karbon kuantumu nokta (CQDs) dolgulu poli(ɛ-kaprolakton) (PCL) esaslı nanofiberlerin morfolojisi, termal, mekanik, elektriksel iletkenlik ve biyolojik özellikleri arasında karşılaştırmalı bir çalışma gerçekleştirilmiştir. Katkısız PCL nanofiberi ile karşılaştırıldığında kristal boyutu değerleri, ağ. %1,5 ve %2,0 RGO içeriğinde %50,6 ve ağ. %1,5 CQDs içeriğinde %57,9 oranında arttığı tespit edilmiştir. Termal analiz sonuçları, hem RGO hem de CQDs dolgularının çekirdeklenme etkisi yarattığını ve termal kararlılığı arttırdığını göstermiştir. Elektron mikroskobu görüntülerinden RGO dolgu maddesi ilavesi ile ortalama nanofiber çapında artış, CQDs ilavesi ile ortalama nanofiber çapında azalma gözlenmiştir. PCL/RGO ve PCL/CQDs nanofiberlerin iletkenlik testi sonuçları yalıtkan özellikler sergilediklerini göstermiştir. Nanofiberlerin mekanik test sonuçları, PCL matriksinde RGO ve CQDs katkılarının homojen dağılımlarının yük aktarımını sağlayabilmelerine ve polimer-dolgu etkileşimi ile yapı içerisinde sıcaklık artarken bile boşluklar oluşmadan matrikste sertlik artışına sebep olduklarını göstermiştir. PCL/1.5CQDs nanofiberin katkısız PCL nanofiberi ile karşılaştırıldığında elastik modül %73 ve nanosertlik değerinde %160 artış, PCL/2CQDs nanofiberin depolama modülünde %210,79 ve kayıp modülünde %595,27 artışlar sergiledikleri tespit edilmiştir. Üretilen nanofiberlerin hidrofilik yapıları biyobozunurluğu arttırmıştır. 56 günün sonunda en yüksek % ağırlık kaybı değerleri ağ.% 2,0 RGO ve CQDs içeren nanofiberlerde sırasıyla %3,66 ve %3,75 değerlerinde gözlenmiştir. 7 günlük biyoaktivite testi sonucunda apatit kristallerinin mikroskop görüntüleri, EDS analiz sonuçlarında Ca/P oranları (1,48) ve 32,8° (211) ve 44,7° (222) düzlemlerine ait keskin pikler hidroksiapatit oluşumunu kanıtlamıştır. RGO ve CQDs dolgu maddelerinin oksidatif stres oluşturmaması nedeniyle nanofiberlerin antibakteriyel özellik göstermedikleri de belirlenmiştir.
Alıev-panfılov modeli kullanarak kalbin elektriksel aktivitesinin 3-boyutlu simülasyonu
Kalbin elektriksel aktivitesi ile ilgili veriler kalbin fonksiyonel durumu hakkında bilgiedinilmesini sağlar. Kalbin elektriksel aktivitesinin araştırılmasında deneysel ölçümyöntemleri en çok kullanılan yöntemler olmalarına rağmen ölçümlerin yapılmasısırasında girişimsellik, sınırlı konumsal çözünürlük ve etik problemler gibi sorunlarortaya çıkmaktadır. Bu problemleri ortadan kaldıran matematiksel modellere dayalıyöntemler ise deneysel ölçümleri baz olarak kalbin elektriksel aktivitesinimatematiksel ifadelerle ortaya koyarlar. Matematiksel modeller iyonik ve dokusalmodeller olmak üzere ikiye ayrılır. İyonik modeller iyonik akımların dinamikdavranışlarını ifade ederken dokusal modeller elektriksel yayılımı tanımlar. Buçalışmada, dokusal modellerden biri olan Aliev-Panfilov modeli kullanarak kalbinelektriksel aktivitesinin 3-Boyutlu (3B) simülasyonu gerçekleştirilerek deneyselverilerle karşılaştırılması ortaya koyulmaktadır. Deneysel ölçümler ve simülasyonlarfarklı köpek kalpleri üzerinde gerçekleştiği için köpek kalplerine geometri çakıştırmaişlemi uygulanır. Sonuç olarak simülasyon verileri ile deneysel veriler arasında hatakriterleri hesaplanır. Bu hesaplama sonucunda; ilinti katsayısı (İK) için 0,87 m 0,06 ,hata karelerinin ortalamalarının karekökü (HKOK) için 12,85 m 4,38 ve göreceli hata(GH) için 0,199 m 0,045 değerleri bulunmuştur. Deneysel veriler kendi içerisindekarşılaştırıldığında İK için 0,87 m 0,08 , HKOK için 20,8 m 4,37 ve GH için 0,335 m 0,095değerleri bulunmuştur. Bu sonuçlar Aliev-Panfilov modelinin kalbin 3B elektrikselfaaliyetinin simülasyonunda kullanılabilirliğini göstermektedir.ANAHTAR SÖZCÜKLER: Kalp haritalaması, Aliev-Panfilov modeli, geometriçakıştırma, kalbin elektriksel aktivitesinin simülasyonu.Danışman: Yrd. Doç. Dr. Bülent Yılmaz, Başkent Üniversitesi, BiyomedikalMühendisliği Bölümü.
PLLA membranların gözenek büyüklüğü belirlemesi ve mikroyapı analizi
PLLA MEMBRANLARIN GÖZENEK BÜYÜKLÜĞÜ BELİRLEMESİ VE MİKROYAPI ANALİZİ Çiğdem BOZDEMİR Dokuz Eylül Üniversitesi Sağlık Bilimleri Enstitüsü Biyomekanik Anabilim Dalı 35340 İnciraltı/İzmir Biyolojik olarak degrede olabilen materyallerin gelişimi; elde edilen ürünlerin protezlerdeki geçici materyaller olarak kullanımını uygun duruma getirmek amacıyla canlı organizma ile etkileşimlerini araştırmada yenilenen ilgiye neden olmuştur. Poli-L-laktik asit (PLLA) biyolojik olarak degrede olabilen bir poliester olup mükemmel biyouyumluluğu ve mekanik özellikleri nedeniyle son zamanlarda birçok araştırmanın konusu olmuştur ve rastgele veya blok kopolimerleri; ilaç dağıtım sistemleri, kemik fiksasyonu için implant materyalleri ve biyolojik olarak absorbe olabilen cerrahi dikişler gibi biyomedikal uygulamalar için kullanılmaktadır. Bu çalışmada PLLA membranların yüzey morfolojisi ve kemiğin trabeküler yapısına yatkınlığının araştırılması hedeflenmektedir. Metilen klorür çözeltisi ile hazırlanan %8'lik PLLA çözeltisinden elde edilen hem selülozik destek yapıya sahip hem de desteksiz membranlar oluşturulmuştur. Membranlar arasındaki temel fark değişen miktarlardaki PLLA içeriğidir. Bunun yanı sıra selülozik destek yapıya sahip membranlar etanol çözeltisinde koagule edilerek elde edilmiştir. Elde edilen PLLA membranların morfolojik özellikleri SEM, AFM ve IR gibi karakterizasyon teknikleriyle incelenmiştir. PLLA membran özellikleri üzerine yaptığımız araştırma sonucunda hücrelerin entegre olmasına olanak sağlayacak porozite yapısının çok uygun olduğu çalışmamızda da ortaya koyulmuştur. PLLA membran hücre kültürlerinde mekanik ve diğer stimülasyonlara bağlanmaya kolayca uyum ve olanak sağlayacak bir yapı olarak göz önüne alındığında, araştırmamız bu yöndeki çalışmalara teşvik edici nitelikte yol göstermektedir. Anahtar Kelimeler: Poli-L-laktik asit; Biyouyumluluk; Yüzey morfolojisi; Porozite.
Recognition of angiotensin II via molecularly imprinted polymers
Anjiyotensin-II (ANGII) molekülü, bazı enfeksiyonların, tümörlerin ve özellikle kardiyovasküler hastalıkların tanı ve takibi için önemli bir biyobelirteçtir. Anjiyotensin analizinin sağlık uygulamalarında rutin olarak yapılabiliyor olmasına rağmen, bu proteinin kandan tayini oldukça zahmetli ve pahalıdır. ANGII'nin, afinite sistemlerinin hazırlanması için güvenilir bir teknik olan moleküler baskılama tekniği ile doğrudan kandan saptanması için gerçekleştirilmiş bir çalışma bulunmamaktadır. Yapılan tez çalışmasında, ANGII baskılanmış polimerik süngerler (ANGIIMIP), ANGII'nin saptanması için mevcut yöntemlere alternatif olarak farklı oranlarda çapraz bağlayıcı, fonksiyonel monomer ve kalıp molekülü (ANGII) kullanılarak tasarlanmış ve üretilmiştir. Sentezlenen ANGII-MIP kolonları, yüzey alanı ölçümleri (BET), şişme testleri, taramalı elektron mikroskopisi (SEM) ile karakterize edilmiştir. Karakterizasyon çalışmalarında, ANGII-MIP kolonlarının yüzey alanı 52 m2 /g, kolonların şişme oranı %94.3 olarak bulunmuştur. ANGII-MIP kolonunda kalıp moleküle özgü boşluklar elde etmek için ANGII molekülleri, 0,5 M NaCl çözeltisi kullanılarak %80'in üzerinde başarı ile kolondan söküldü. ANGII molekülleri olmadan sentezlenen AngII baskılanmamış polimerler (ANGII-NIP) için de karakterizasyon çalışmaları gerçekleştirildi. ANGII-MIP kolonunun ANGII molekülü için seçiciliği, Arg8 Vasopressin ve Angiotensin-I (AngI) yarışmacı moleküllerine karşı incelendi. Son olarak, sentezlenen ANGII-MIP kolonunun tekrar kullanılabilirliği, tekrar eden adsorpsiyon-desorpsiyon çalışmalarında incelenmiştir. Anahtar Kelimeler: Anjiyotensin II, Polimerik Kriyojeller, Moleküler Baskılama
Integrative and comparative omic approaches to identify molecular signatures of rheumatoid arthritis
Rheumatoid arthritis (RA) frequently seen chronic synovial inflammation causing joint destruction, chronic disability, and reduced life expectancy. The pathogenesis of RA is not completely known. In this study, several gene expression data including synovial tissue and macrophages cells, blood cells, T cells, 〖CD4〗^+ T cells, 〖CD8〗^+ T cells, natural killer T (NKT) cells, natural killer (NK) cells, neutrophils, and monocyte cells were analyzed with a holistic perspective and the molecular targets and signatures in RA were determined. Differentially expressed genes (DEGs) were identified from each dataset by comparing diseased and healthy samples. Afterward, the RA-specific protein-protein interaction (PPI) and hub proteins were identified. Molecular signatures were determined through a statistical test employing the hypergeometric probability density function by using the physical interactions of transcriptional regulators and PPI. Reporter metabolites of each tissue with RA were determined by using genome-scale metabolic networks and DEGs. It was determined the common hub proteins, novel reporter biomolecules (i.e. receptor, transcription factors, and miRNAs), metabolites in two or more tissue types. It was identified SOCS2 Cullin family members CUL1 and CUL3, HDAC family members HDAC2, HDAC4, HDAC9, RAS members KRAS, HRAS and NRAS, OCS family members SOCS1 and SOCS2, as hub proteins, AR, FOXP3 and GATA2 as TFs, NADP^+ NADPH, ADP, pyruvate, and Acetyl-CoA members as a reporter biomolecule. Importantly, miR-155-5p is common miRNAs in all tissues. Our findings could be a crucial resource for the understanding of RA molecular mechanisms and may be considered as drug targets and development of novel diagnostic strategies. Corresponding genes and miRNAs should be validated via experimental studies.
Double-imprinted polymers for selective HSA depletion from human serum
Human Serum Albumin (HSA) is the most abundant protein in human blood plasma ̶ it constitutes about half of serum proteins. As in the all proteomic studies of the blood plasma, high-abundant proteins, i.e. albumin, hemoglobin, interfere with the analysis of low-abundant and disease-related proteins, so removal or depletion of these proteins is vital for proteomic studies. In this thesis study, it was aimed to deplete HSA from human serum in one step using double-imprinted cryogels, prior to use in proteomic analysis. For this purpose, HSA-imprinted cryogels were synthesized with 8% monomer concentration and a second imprinting step with 16% monomer concentration in presence of HSA was achieved on the first gel. Thereby, HSA double-imprinted cryogel columns (HSA-DIP) were obtained. Cryogel column synthesized by double-layer imprinting technique but not containing template molecule (DL-NIP) and monolayer HSA-specific polymers with monomer concentrations of 8% and 16% (called HSA-MIP8% and HSA-MIP16%, respectively) were synthesized as the control group. Synthesized columns were characterized by swelling tests, Scanning Electron Microscopy (SEM) and Micro Computed Tomography (Micro-CT) analysis. The water uptake ratios were calculated as 84% for HSA-DIP, 82% for DL-NIP, 89% for HSA-MIP8% and 88% for HSA-MIP16%. HSA adsorption capacity was investigated, and selectivity studies were performed against Human Hemoglobin (Hb) and Immunoglobulin G (IgG) molecules which occupy a significant portion of human serum. Obtaining results were investigated by kinetic analyses to determine adsorption properties of the system. Finally, depletion of HSA directly from human serum was studied. In addition, HSA-DIP columns were tested in terms of reusability, and it was demonstrated that they can be used up to 10 times without significant decrease in selective HSA adsorption capacity.
Investigation of the effect of B. spergulifolius extracts on insulin-resistant 3T3-L1 adipocytes
Diabetes mellitus (DM) is a metabolic disease with chronic hyperglycemia characterized by metabolic outcomes due to insufficient insulin secretion and/or insulin effect defect. DM often causes cardiovascular diseases and various complications on the eye, kidney and nervous system. Type 2 DM (T2DM) accounts for approximately 90% of the total DM. Therefore, it is very important to investigate new therapeutic approaches for T2DM and alternative, natural agents that target molecules in potential signal pathways. Medicinal plants are very significant resources in the research of alternative new drug active ingredients. Bolanthus spergulifolius (B. spergulifolius) is one of the genera of the family Caryophyllaceae. In the present study, it was aimed to investigate the potential anti-diabetic effects in-vitro of B. spergulifolius extracts on 3T3-L1 adipocytes. B. spergulifolius were extracted with methanol (MeOH), ethylacetate (EA) and Aqueous and evaluated for their total phenolic content (TPC) by Folin-Ciocalteu method. B. spergulifolius extracts showing highly TPC (Aqueous< MeOH< EA) and their different concentrations were caried out on preadipocytes differentiated in to mature 3T3-L1 adipocytes to investigate their half-maximal (50%) inhibitory concentration (IC50) by using MTT assay. The IC50 concentrations of MeOH, EA and Aqueous extracts were observed as 305.7 ± 5.583 µg/mL, 567.4 ± 3.008 µg/mL and 418.3 ± 4.390 µg/mL and were used for further experiments. A live/dead assay further confirmed the cytotoxic effect of MeOH, EA and Aqueous extracts (respectively, 69.75 ± 1.70%, 61.75 ± 1.70%, 70 ± 4.24% and for all P< 0.05). Also, effects of extracts on lipid accumulation in mature 3T3-L1 adipocytes were evaluated by Oil-Red O staining assay. The extracts effectively decreased lipid-accumulation compared to untreated adipocytes (for all P< 0.05). Morever, effect of extracts on apoptosis regulated by the Bax and Bcl-2 was investegated by qRT-PCR. The extracts significantly induced apoptosis by up-regulating pro-apoptotic Bax expression but down-regulating anti-apoptotic Bcl-2 gene expression compared to untreated adipocytes (for all P< 0.05). The Glut-4 expression linked with insulin resistance was determined by qRT-PCR, Western-blot and Immunofluorescence staining. In parallel, expression of Glut-4 in adipocytes treated with extracts was significantly lower compared to untreated adipocytes (for all P< 0.05). Extracts significantly supressed cell migration after 30 h of wounding in a scratch-assay (for all P< 0.05). Cell morphology and diameter were further evaluated by phase-contrast microscopy, Scanning electron microscope (SEM), Immunofluorescence (with F-Actin) and Giemsa staining. The adipocytes treated with extracts partially lost spherical morphology and showed smaller cell-diameter compared to untreated adipocytes (for all P< 0.05). In conclusion, these results suggest that extracts of B. spergulifolius causes to an induce apoptosis, a decrease lipid-accumulation, wound healing, Glut-4 level and migth contribute to the reducing of insulin-resistance in DM. Key Words: Bolanthus spergulifolius, diabetes mellitus, insulin-resistant, 3T3-L1 adipocytes, Glucose transporter-4, anti-diabetic
Drug repurposing in colorectal cancer by using transcriptomic data
Colorectal cancer (CRC) is one of the most fatal cancer types that people suffer from worldwide. In this study, we aimed to reveal the candidate drugs that may be usable in the treatment of CRC via a very popular approach known as drug repurposing (drug repositioning) and computational biology methods. Firstly, differentially expressed genes (DEGs) were identified in CRC via analyzing transcriptomic data. Then, differentially coexpressed gene modules were identified and prognostic significance of these module genes in CRC was demonstrated. Finally, based on the gene modules we uncovered, various treatment candidates that may alter the course of CRC were identified. These candidates include drugs or small molecules which were studied in experimental/clinical studies to demonstrate the effects on tumor growth or not used/studied originally in the treatment of CRC. In our study, we revealed a novel, differentially co-expressed, highly interconnected, and co-regulated prognostic gene module in CRC consisting of twenty two genes. We suggest fifteen drugs or small molecules comprising gallic acid, valinomycin, cysteamine, AZD8055, BRDK81473043, tyrphostin AG1478, BRD-A17065207, dovitinib, trametinib, HDAC6 inhibitor ISOX, AS605240, 480743.cdx, BRD-K03829970, L-6307 and NVP-TAE684 as repurposing candidates for CRC. We present HDAC6 inhibitor ISOX, AS605240, 480743.cdx, BRDK03829970, L-6307, and NVP-TAE684 as novel repuposing candidates whose anticarcinogenic effects on CRC tumorigenesis have not been investigated before. Clinical investigation of our findings is important in terms of creating new treatment options for CRC. Keywords: colorectal cancer, drug repurposing, transcriptomic data
DCNA: A tool for differential co-expression network analysis of gene expression data
A method was developed based on comparing gene expressions of tissues in two context-specific conditions (i.e. disease and normal samples or chemical applied and not applied samples), and differential-co-expression analysis was performed based on comparing the correlation relationships between the expression levels of genes in both states. Gene clusters (modules) with high interaction with each other in the created network structures were obtained. In this thesis, the web-based tool named DCNA was developed by using the new algorithm belonging to our research group. Codes and supplementary data are available in http://www.github.com/tyasird/differential-coexpression-network-analysis. Besides, the most important point of the study, a user-friendly web-based tool was designed, where researchers can easily analyze gene expression data (microarray & RNA-seq) without wasting time with coding. DCNA is accessible at http://dcna.computationalbiology.org/. Herewith method, gastric cancer microarray datasets were used as a case study and a cancer-specific correlation network was constructed. Significant gene modules were determined with the help of the DCNA web-based tool. We assert that disease-specific candidate gene modules found by the DCNA web-based tool will help to develop strategies for the prognosis and treatment of the disease.
AFB1 recognition from liver tissue via afb1 imprinted magnetic nanoparticles
Fungi grow rapidly depending on the increase in humidity and temperature, producing harmful toxins called "mycotoxins" in cereals, feed and almost all dry foods. The most important of these toxins is Aflatoxins which are produced mainly by Aspergillus flavus and Aspergillus parasiticus. Although there are more than 20 types of aflatoxins, types B1, B2, G1, G2 are the most important ones and Aflatoxin B1 is one of the most harmful among mycotoxins with its carcinogenic properties. As a result of consumption and metabolization of AFB1 contaminated food by animals, AFB1 and metabolites such as M1, M2, aflatoxicol can be found in meat and dairy products. People may be exposed to aflatoxicosis as a result of consumption of such contaminated animal products. Many of the methods used for the detection of aflatoxin require long extraction procedures which is time consuming, labourous and costly. In this thesis, AFB1 imprinted magnetic nanoparticles (magAFB1-MIP) were synthesized using molecular imprinting technology to be used in AFB1 recognition. Characterization studies of the synthesized polymers were carried out by swelling analysis, surface area measurements, scanning electron microscopy and particle size analysis. The effects of AFB1 concentration, temperature and interaction time on the adsorption capacity of magAFB1-MIPs from the aqueous solution were investigated. Selectivity of the magAFB1-MIP was analyzed calculating the selectivity coefficients against competitor molecules of AFB2, AFG1 and AFG2. Moreover as a final part of the thesis AFB1 recognition form liver tissue was investigated.
Controlled release of neurosin enzyme for alternative treatment of Parkinson's Disease
Parkinson's Disease (PD) is a common neurodegenerative disorder that shows the motor and non-motor symptoms. Misfolded alpha-synuclein aggregates (Lewy bodies) are found in the brain pathology of Parkinson's patients. As a result of studies, it has been determined that these alpha-synuclein aggregates were directly related to the degrees of neurodegeneration. Although these pathological aggregates are found inside the cell, they are able to pass to healthy neurons by a prion-like mechanism. In previous studies, neurosin (Kallikrein 6, KLK6) has been shown to destroy the alpha-synuclein by cleavage at the NAC (non Amyloid-β component) region of the enzyme. In controlled drug release systems, nanoparticles are preferred because of their nano size, allowing ease of uptake into cells. Human serum albumin (HSA), the most abundant protein in the body, is an important candidate for nanoparticle synthesis due to its easy purification, biocompatibility, biodegradability, and having many functional groups. The most common method in the synthesis of nanoparticles from HSA is the desolvation technique. In this method, generally glutaraldehyde, which has a toxic effect on cells, is used as a cross-linker. This study, it is aimed to encapsulate neurosin, which is a therapeutic agent candidate, into HSA nanoparticles by desolvation technique. Additionally, it is aimed to reduce the toxic effect by using natural crosslinker genipin instead of glutaraldehyde in the production of HSA nanoparticles. First of all, the optimum synthesis condition for genipin-crosslinked HSA nanoparticles was determined. Zetasizer, FTIR, SEM analyzes were performed for the characterization of the synthesized nanoparticles. Variables affecting nanoparticles production were estimated as HSA concentration, crosslinker concentration, crosslinking temperature, crosslinking time and speed of magnetic stirrer. According to the parameters examined, the optimum condition of nanoparticle synthesis was determined as 20 mg/ml HSA concentration and 0.2% w/w genipin per mg of HSA concentration. The condition of crosslinking was determined as 37°C for 2 hours at 600 rpm. Then, neurosin enzyme was loaded into HSA nanoparticles which were produced under optimum condition. Encapsulation efficiency was calculated using the ELISA kit. In vitro release study of neurosin loaded HSA nanoparticles was performed in PBS buffer using the dialysis membrane. As a result of the studies, genipin cross-linked HSA nanoparticles with desired properties were produced. In the release studies of neurosin loaded nanoparticles, it was observed that neurosin was released with burst effect in the first 30 minutes. Afterward, it was observed that the drug release continues slowly according to the samples taken for 7 days. It is predicted that neurosin loaded genipin-crosslinked HSA nanoparticles will contribute to the drug delivery systems and literature as an alternative drug system in Parkinson's disease.
Methods for increasing accuracy in modelling metal organic frameworks
High throughput screening of metal organic frameworks (MOFs) for gas mixture separations have produced large amounts of data. Reported gas permeabilities have been mainly calculated using an approximate approach. Permeability predictions of an alternative method (new method) have shown to significantly improve the predictions of the approximate method for noble gas mixtures. Permeabilities calculated using Onsager coefficients, detailed method, are accepted as correct answers, however constructing Onsager coefficient matrix is computationally cumbersome and not feasible especially for the high throughput screenings. Thus, new or approximate methods have been applied for calculating permeability and permeation selectivities of gas mixtures. However, permeability prediction accuracies of these methods for gas mixtures having dispersion and electrostatic interactions with the pores have not been discussed in the literature so far. In the first part of this thesis, we question the accuracy of permeability predictions for CO 2, H 2, CH 4 mixtures. Another perspective to increase the accuracy for screening MOFs is to determine the best net atomic charge calculation method. Density Derived Electrostatic and Chemical Charges (DDEC) method relies on optimizing the atomic electron density distribution to assign a chemically meaningful atomic charges. The method is considered to be the most reliable method, however it is computationally demanding. Non-DFT based Extended Charge Calculation (EQeq) method which is developed as an extended version of the Charge Equilibration Method assigns atomic charges by just requiring a reasonable assumption for the charge centre to compute all the ionization energies of electrons. In the second part of the thesis, we investigate the accuracy of charges assigned via EQeq with respect to the charges assigned using DDEC and discuss which method should be used for modelling MOFs.
Investigation effects of pterostilbene on differentiation and adipogenesis in 3T3-L1 cells
Diabetes mellitus (DM) is a chronic illness that occurs when there is inadequate insulin secretion and/or insulin action defect. DM is usually characterized by high blood sugar (hyperglycemia) above normal blood sugar levels. Having consistently high blood glucose causes general vascular damage that affects the kidneys, nerves, heart, eye vessels and can lead to a variety of health problems. In etiology, diabetes is divided into three main groups as gestational diabetes (GDM), type 1 diabetes and type 2 diabetes. Plant extracts are very important sources in the search for alternative new drug active ingredients. Pterostilbene is known as a naturally dimethylated analogue of resveratrol and its main source is grapes and blueberries. In this study, it was aimed to evaluate the effects of Pterostilbene on differentiation and adipogenesis in 3T3-L1 cells. For this purpose, Pterostilbene was treated to mature 3T3-L1 adipocytes at different concentrations and half-maximum inhibitory concentrations (IC50) were determined by MTT. Based on the results, 5 and 7.5 µM doses of Pterostilbene were chosen to apply to cells in subsequent experiments. In addition, Oil Red O was applied to determine the lipid accumulation and effects of Pterostilbene in preadipocytes and 3T3-L1 adipocytes, and it was observed that Pterostilbene treatment reduced lipid accumulation in adipocyte differentiation. The cytotoxic effect of Pterostilbene in 3T3-L1 adipocyte cells was confirmed by dead/live cell assay. Phase contrast microscopy and Giemsa staining, F-actin staining and DAPI staining were applied to investigate the effect of Pterostilbene on the morphology of 3T3-L1 adipocyte cells. According to the study result, adipocytes treated with a dose of 7.5 µM on day 14 showed less intense lipid deposition and a more spindle-like morphology compared to the other treatment group. Finally, the expression of Glucose transporter-4 (Glut-4) and Adinopectin associated with insulin resistance was evaluated by immunofluorescent staining and qRT-PCR. Especially on the 14th day, compared to the other treatment group, actin filaments were filamentous in adipocytes treated with Pterostilbene 7.5 µM compared to the other treatment group, the filaments were similarly oriented as in preadipocytes, and chromatin condensation was observed to be quite high. As a result of this study, it was observed that Pterostilbene induce apoptosis, reduce lipid accumulation but induce Glut-4 and Adiponectin level, and may conduce to the reduction of insulin resistance in diabetes. Keywords: Diabetes mellitus, Pterostilbene, 3T3-L1, Adipogenesis, Differentiation, Glucose transporter 4, Adiponectin.
Ab-initio modeling of cobalt based water reduction catalysts in aqueous solution and on surface
The common use of hydrogen as a renewable energy source has been one of today's challenges that, if resolved, could replace dependence on fossil fuels. One of the sustainable ways of H2 production is the photocatalytic water reduction reaction catalyzed by molecules with transition metals as reaction centers. Studies have shown that cobalt-based catalysts have an active and efficient effect in photocatalytic water reduction reactions and can be used instead of expensive transition metals such as ruthenium and platinum. In this study, we investigate Co-based water reduction catalysts in aqueous solution as well as on the TiO2 surface by means of Ab-initio Molecular Dynamics (AIMD), Metadynamics (MTD), Density Functional Theory (DFT) as well as Free Energy Perturbation Theory. Regarding homogeneous catalysis, we model the first and second electron injection intermediate steps of the EECC water reduction reaction mechanism. We analyze the solvent response following the electron injections as well as the behavior of the planar structure of the catalyst in the water solvent. The first and the second reduction free energies are calculated, AIMD trajectories are analyzed, and electronic structures of the selected snapshots are further evaluated using more sophisticated methods. For the heterogeneous catalysis, we compare the optimized geometries as well as adsorption energies of several cobalt-based catalysts on the rutile(110) surface. Electronic structures of the selected catalysts/TiO2 systems are further investigated by calculating electron density difference maps.
Theoretical modeling of heterolytic mechanism for H2 production: A detailed investigation of Cobalt(II)-polypyridyl catalyst
Hydrogen (H2) molecule is a remarkable carrier of energy that is found naturally in biomass, water, and hydrocarbon. Solar energy is the most abundant energy source, which plants inherently uses to feed their photosynthesis mechanisms. Hereupon, researchers gain inspiration of these nature's great event, the light reactions of impeccable H2 production pathway of photosynthesis. In order to mimick the water reduction mechanism of photosynthesis, various transition metals have been employed. However, a satisfactory solution couldn't been found in the terms of price/performance ratio. Recently, researchers have investigated photocatalytic water reduction by taking advantage of Cobalt based photocatalysts. In this connection, by applying Ab-initio Molecular Dynamics simulations as well as Density Functional Theory, and Free Energy Perturbation Theory, we investigate water reduction, also known as H2 production, mechanism of Co-based poly-pyridyl catalyst having perfect octahedral coordination. At this thesis, our aim is to clarify the effect of regulation at octahedral coordination and compare the two pathways of, ECEC and EECC, H2 production mechanism. Consequently, for the hydrogen production cycle, both ECEC and EECC mechanisms are utilized and each intermediate step is simulated in order to determine the allowed spin states as well as solvent response around the reaction center of Co-based water reduction catalyst investigated. Furthermore, by performing additional simulations the electronic structures of each intermediate step of both mechanisms have been analyzed. Reduction free energies have been calculated using Marcus theory of electron transfer.
Preparation of neopterin imprinted nanofilm coated surface plasmon resonance sensors for detection of neopterin from human serum
Neopterin (Neo) is produced by induction of macrophages by T-lymphocytes that activate interferon-gamma (IFN-ϒ) from guanosine triphosphate (GTP). Neo is synthesized only in activated macrophages of humans and primates, and from there it passes to plasma. Neopterin is present in serum and urine at pronounced constant rates. For this reason, it can be a useful marker for monitoring infectious disease activity during treatment and for estimating the extent of the disease and prognosis. Our aim in this study is to selectively detect Neo from body fluids by synthesizing Neopterin-imprinted nanofilms on the gold SPR chip surface. First, after cleaning the gold-coated chip surface with piranha solution, the surface will be modified by dropping allyl mercaptan. Then, using HEMA-EGDMA and AIBN, a molecularly imprinted polymer solution will be prepared and the SPR will be poured onto the chip surface to obtain a nanofilm surface under appropriate conditions. In addition, initial Neo concentration, interaction time and selectivity for chip surfaces will be investigated. SPR studies will be carried out using gold chips with a Neopterin imprinted nanofilm surface. For this, Neopterin imprinted SPR chips will be prepared and then the selective recognition of Neo will be tested using the SPR sensor. Keywords: Nanofilm, Molecular Imprinted Nanofilms, Neopterin.
Theoretical investigation of mixed metal organic frameworks as H2 adsorbents
Molecular hydrogen (H2) is an environmentally friendly, renewable, and sustainable energy carrier. One of the biggest reasons for the limited use of molecular hydrogen (H2) in energy required applications is the inability to fully develop safe and high-performance hydrogen storage systems. New generation nanoporous materials, in principle, can store H2 which could be solution of the H2 storage challenge. Metal Organic Frameworks (MOF), which are new generation nanoporous materials are shown to be promising candidates for the H2 storage applications. MOFs that contain at least two different metal ions in their structures are called as mixed-metal MOFs (MM-MOF) and they could adsorb H2 in higher amounts compared to structures containing single metal nodes. In this thesis, the H2 adsorption capacities of the 27 MM-MOFs having different topological and chemical features have been theoretically investigated using Grand Canonical Monte Carlo (GCMC) and Density Functional Theory (DFT) simulations. Materials under consideration are divided into two groups. While the 1st group materials have been experimentally synthesized before, the 2nd group materials are hypothetical MM-MOFs designed by You et al. (2020). To the best of our knowledge, H2 storage performances of the selected MM-MOFs have not been studied in the literature before. H2 adsorption isotherms of the MM-MOFs have been predicted by GCMC simulations carried out at 233 K and at pressures between 1 and 100 bar. 5-site (anisotropic) atomic modeling has been used for modeling H2. The atomic point charges of the MM-MOF atoms required for calculating electrostatic interactions have been determined by applying the DDEC method. Correlation between H2 storage capacity of the MM-MOFs and their topological and chemical features have been established and six materials are determined to be the best performing MM-MOFs that can adsorb H2 both volumetrically and gravimetrically. Electronic structure analysis has been carried out for the top H2 adsorbing materials by applying DFT simulations. Keywords: Grand Canonical Monte Carlo Simulations, Density Functional Theory
Investigation of potential inhibitory effects of natural compounds from Melissa officinalis L. in drug-resistant non-small cell lung carcinoma
In cancer treatment, the development of new generation drugs and innovations in surgery have significantly extended the life expectancy of patients. However, despite all these developments, the main obstacle in the treatment of lung cancer is the recurrence of the disease over time due to intrinsic or extrinsic resistance to the chemotherapeutic drugs used in the treatment. Alternative methods and new therapeutics are needed to cope with the development of chemoresistance. Due to their low cytotoxicity and good tolerability in the human body, natural plant compounds are very important sources that can be used to obtain drug active ingredients that have been used in the treatment of many diseases, including cancer, for many years. In this study, the anticarcinogenic effects of Melissa officinalis L., a well-known medicinal plant from the Lamiaceae family, widely grown in Turkey and known as lemongrass, on the non-small cell lung cancer cell line A549 and the erlotinib resistant A549 sub-cell line and its parallel parental sub cell-line were evaluated. In our study, four different extracts were obtained from the leaf parts of Melissa officinalis L. plant with different solvents. The cytotoxic effects of these extracts on each cell line were determined by MTT cell viability analysis. As a result, although each type of extract was cytotoxic on each sub-cell line, there was no significant difference between their inhibitory intensities. The remainder of the study was then continued with the total methanolic fraction, which includes all of the substance groups in the plant leaf. Afterwards, the effects of this extract on the migration of different sub-cell lines were determined by the wound healing assay, whereas tumorigenic capacities were determined by the soft agar colony formation test. Finally the effects of the total methanolic extract on the cell cycle progression were determined by flow cytometry analysis. According to the results, increasing concentration of total MeOH extract of M. officinalis L. decreases cell viability in a concentration dependent manner and prevents both migration capacity and colony formation in all types of sub-cell lines. A decrease was observed in the S-phase cell populations, where DNA replication takes place, compared to cells exposed to control in all three sub-cell lines. In the light of these findings, it is thought that Melissa officinalis L. plant may represent an alternative source of novel therapeutic compounds for treatment of non-small cell lung cancer. Keywords: Melissa officinalis L. , natural compounds, A549, anticancer , drug resistance
Engineering of a novel 3-dimensional glioblastoma cell culture system
Glioblastoma (GBM) is considerably aggressive, lethal, and has a poor prognosis. The therapies applying for GBM often fail because of the invasiveness and heterogeneity of the tumor. In addition, there are many molecular alterations responsible for the drug resistance mechanisms that hinder the success of treatment. Therefore, investigating these mechanisms and understanding GBM biology is crucial for developing new treatments. 3D GBM cell culture models can be used to study GBM biology and drug resistance mechanism. In this study, it is aimed to establish a novel 3D GBM cell culture model to investigate the drug resistance mechanism and to understand the tumor biology of GBM. For this purpose, pHEMA-gelatin-based cryogels were synthesized at 3 different cryogelation temperatures (-12 oC, -16 oC, and -20 oC) and with 3 different gelatin concentrations (0.2g, 0.3g, 0.4g). The characterization studies of cryogels and in vitro cell studies were performed. According to the analyses performed, all of the synthesized cryogels were found suitable for use as scaffolds in terms of porosity, swelling characteristics, and non-cytotoxicity. To investigate the drug responses of GBM cells, a pHEMA-gelatin-based cryogel synthesized at -16 oC with 0,4 g gelatin concentration was preferred because it gave the best cell viability results. It was observed that the GBM cells showed greater resistance to drugs than 2D cultured cells, similar to in vivo conditions.
Molecular modeling of Bio-MOF's for anesthetic Xe recovery from exhale gas mixtures
Designing an in expensive and highly efficient recovery process for Xenon (Xe) is gaining importance in the development of sustainable applications. Using metal organic frameworks (MOFs) for separating Xe from anesthetic gas mixtures has been a recent topic studied rarely and superficially in the literature. In this thesis, we theoretically investigate Xe recovery performances of 43 biological MOFs (Bio-MOFs) formed by biocompatible metal cations and biological endogenous linkers. Xe uptakes and Xe permeabilities in its binary mixtures with CO2, O2, and N2 are investigated by applying Grand Canonical Monte Carlo and Molecular Dynamics simulations. Materials having metalloporphyrin, hexacarboxylate, triazine, or pyrazole ligands, dimetallic paddlewheel units, relatively large pore sizes (PLD>5 Å and LCD>10 Å), large void fractions (≈0.8), and large surface areas (>2900 m2/g) are determined as top performing Bio-MOFs for Xe recovery. The results of this thesis show examples of rarely studied aerogen interactions that play a critical role in selective adsorption of Xe in nanoporous materials.
Valorisation of grape juice wastes to produce citric acid by Aspergillus niger
Citric acid, which is used as an additive in many industries, including food, beverage, and pharmaceutical, is commercially produced from microorganisms by fermentation. Although many types of bacteria, yeast, and fungi are used in the production of citric acid, the most preferred species in industrial production are Aspergillus niger species, also known as the black mold. Carbon sources with high sugar content are preferred in fermentation in the production of citric acid. Therefore, especially fruit wastes are suitable substrates for fermentation. Grape pomace, which is an important waste of wine and fruit juice factories, has a sugar content of 50-80%. For this reason, dried and ground grape pomace was chosen as the substrate in this study. In order to obtain citric acid in high yield, the fermentation parameters must be optimized. However, testing all parameters is a negative situation in terms of time and cost. For this reason, the optimum conditions of the parameters can be determined by some statistical methods. In this study, the optimum conditions of substrate concentration, initial pH, fermentation temperature, and time were investigated using the Response Surface Methodology Box Behnken Design. 30-120 g/L for substrate concentration, 2-8 for pH, 25-35⁰C for fermentation temperature, and 48-168 hours for fermentation time were determined for minimum and maximum values. Optimum conditions for substrate concentration, initial pH, fermentation temperature, and time were determined as 120 g/L, 5, 30⁰C, and 168 hours respectively, and the citric acid concentration was found to be 7.57 g/L. The statistical analysis showed that the created model was significant and the R2 was found to be 0.936. Keywords: Aspergillus niger, Box Behnken Design, citric acid optimization, grape pomace
The comparison of T98G cell response to trifluoperazine in 2D & 2.5D microenvironment
In cancer-drug interaction studies, 3D culture systems have been shown to mimic living organism conditions better than 2D culture environments. 2.5D cell culture environments have been developed to take advantage of 3D cell culture and mitigate its disadvantages. Trifluoperazine (TFP) is an FDA-approved antipsychotic and antiemetic drug used to treat schizophrenia. It has been shown to inhibit the proliferation and invasion of various cancer cells and to induce cell death in several cancer cell lines and animal models. T98G cells are a human glioblastoma cell line and are routinely used as an experimental model for the development of cancer therapies. There is a limited number of studies investigating the effect of TFP drug on T98G cell line in 2D culture. The aim of this thesis was to create an in vitro culture system for drug molecules that is cost-effective, efficient, and more similar to in vivo cell responses. The T98G glioblastoma cell line was evaluated for cell viability and morphology in the presence and absence of trifluoperazine (TFP) in 2.5D and 2D cell culture systems. For the 2.5D cell culture system, chitosan hydrogels cross-linked with genipin and glycerol phosphate were prepared and T98G cells were cultured directly on these wet hydrogels. The surface pore structure of the gels was examined by scanning electron microscopy. The response of the cells to Trifluoperazine (1 µM, 2 µM, 4 µM, 6 µM and 8 µM) drug molecule in 2D and 2.5D culture systems, cell viability was investigated by MTT assay and rezazurin methods. Changes in the cell nucleus were detected by DAPI staining. The IC50 concentrations of TFP on T98G cell line was calculated as 3.75 µM for 24 h and 2.57 µM for 48 h by MTT analysis for 2D culture on TCPS. IC50 concentrations of TFP on T98G cell line was calculated as 2.86 µM for 24 h and 2.64 µM for 48 h by resazurin analysis for 2D culture on TCPS. It was concluded that, IC50 concentrations calculated from MTT and resazurin analysis results were very close. DAPI staining also showed the condensed and small nuclei shape in T98G cells after 24 h application of TFP when compared to the control group. According to these results TFP doses were selected as 1-8 µM for 2.5D cell culture studies. 2.5D chitosan hydrogels were prepared using 0.5% acidic acid as a solvent, 100 µL glycerol phosphate (1 g/mL) and 1 mM genipin as physical and chemical crosslinkers. T98G cells were cultured on these hydrogels for 24 and 48 h. Viability of the cells were both determined by resazurin analysis. IC50 concentration of TFP for T98G cells cultured on 2.5D chitosan hydrogels were determined as 2.37 µM for 24 h culture and 1.94 µM for 48 h culture. In conclusion, it was observed that 2.5D chitosan hydrogels mimicked the 3D cell culture environment. The IC50 dose of cells cultured on 2.5D chitosan hydrogels was lower and closer to the IC50 value of cells cultured on 2D TCPS, indicating that T98G cells may be more sensitive to TFP drug on 2.5D hydrogels. The results showed that the hydrogels produced created in vitro and in vivo-like culture conditions for the cells and that the cell-drug response can be examined more closely than in vivo.
Development of angiotensin (II) imprinted nanoparticles
Angiotensin II (Ang II) is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin-angiotensin system that regulates blood pressure. The role of Ang II on cardiovascular balance is quite large. Due to its relationship with scientifically proven cardiovascular diseases, it is an important biomarker in blood serum for the detection of diseases. Molecularly imprinted polymers (MIPs) are affinity-based polymeric support materials that enable the recognition of a specific target molecule with high selectivity. Molecular imprinting method is a very frequently used reliable technique to quickly and with high selectivity recognize the desired molecule (eg protein, amino acid, peptide, ion, etc.) from a complex environment. Within the scope of this thesis, Ang II imprinted nanoparticles were synthesized by miniemulsion polymerization reaction for the determination of Ang II from aqueous solutions. For the preparation of hydroxyethyl methacrylate (HEMA) based nanoparticles (NPs), a binary phase mixture was prepared. After Ang II imprinted (Ang II-MIPnp) and non-imprinted nanoparticles (NIPnp) were synthesized, they were characterized by Zeta Size analysis, Scanning Electron microscopy (SEM), Transmission Electron Microscopy (TEM) and FTIR-ATR spectrophotometer. Specific surface areas were then calculated. The average particle size of the NPs was recorded as 50 nm. The specific surface areas of Ang II-MIPnp and NIPnp were calculated as 26903.4 and 25868.9 m2/g, respectively. Ang II molecules were successfully removed from the polymeric structure with a 98% success rate using 0.5 M NaCl solution to obtain template-specific cavities in Ang II-MIPnp. Then, the adsorption of Ang II molecules from their aqueous solutions was investigated in terms of their binding capacity to the recognition sites. It has been found that the Ang II adsorption of NPs can go down to 50 pg/mL sensitively. 0.5 M NaCl solution was used for desorption and 98% recovery was achieved. The adsorption-desorption cycle was repeated 10 times and no significant change was observed in the adsorption capacity. The selectivity of NPs was evaluated in the presence of Angiotensin I (Ang I) and Vasopressin (Vsp), which are competitive molecules similar to Ang II in terms of molecular structure, shape and size. The results show that Ang II-MIPnp have high selectivity and sensitivity for Ang II molecule and shows that the synthesized nanomaterial is reusable. Keywords: Angiotensin II, Nanoparticles, Molecular imprinted polymers, Renin-Angiotensin-Aldosterone system (RAAS).
Phyllanthus emblica yüklü yara örtüsü malzemeleri
Since ancient times, plants have played a vital role in therapeutic approaches for a variety of diseases and ailments. Phyllanthus emblica (P. emblica) has been described in many studies to have multiple therapeutic activities and is considered an important part of Ayurvedic and Unani medicinal systems. This study sought to examine the efficacy of synthesized Phyllanthus emblica loaded cryogels on wound healing and their potential in wound dressing applications. For this purpose, polyvinylalcohol/gelatin (PVA/Gel) based cryogels were synthesized containing 0.5% (PVA/Gel/P.emblica-0.5), 1% (PVA/Gel/P.emblica-1), 1.5% (PVA/Gel/P.emblica-1.5), 2% (PVA/Gel/P.emblica-2) P. emblica extract. Swelling tests, Brunauer-Emmett-Teller (BET) and morphology analysis were conducted within the scope of characterization studies. In-vitro cell culture studies were performed using HaCaT cells to illustrate the suitability of the synthesized cryogels as wound dressing material. The swelling tests and BET results revealed that P. emblica loaded PVA/Gel cryogels was increased with increasing the amounts of P. emblica. Morphological results displayed that the cryogels had an dense, interconnected pore morphology and a macroporous structure. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion and live-dead assay results revealed that adding of P. emblica into cryogels led to enhanced cell proliferation, increased cell number, and improved cell viability. Based on the phase contrast microscope, scanning electron microscope (SEM), immunofluorescence and giemsa images of the HaCaT cells on P. emblica loaded PVA/Gel cryogels, it was observed that P. emblica promoted cell attachment, proliferation and penetration. In conclusion, it has been shown that PVA/Gel/P.emblica cryogels are suitable for use as wound dressing materials and can be developed with further studies.
Identification of key biomolecules in adrenocortical cancer progression via bioinformatics and machine learning approaches
Adrenal Adenomas (ACA) are benign masses that form in the adrenal gland, while adrenocortical carcinoma (ACC) is a malignant aggressive tumor. In the present study, our aim is to investigate critical biomolecules from the onset of adrenocortical adenoma to the progression of carcinoma with bioinformatics and machine learning approaches. We will use a new analysis method to identify a statistically significant Spearman's gene correlation coefficient that have both a positive correlation in the case state and a negative correlation in the control state (or vice versa). Three RGEC networks were recontructed for ACA-Normal tissue (ACA-N), ACC-Normal tissue (ACC-N), and ACC-ACA and hub genes of RGEC networks were identified. PLA2G4A gene in ACA-N group, 14 genes (i.e: SAE1, ATRX, PNMT, RYBP, NCAPG2, PDK2, C7, RNF114, PTPRB, NPY1R, PARM1, PGK1, HMMR and ETC2) in ACC-N group, the FMO2 and UBE2S genes in the ACC-ACA group were determined. Diagnostic and prognostic performance of the resultant genes were performed through machine learning (ML) classification algorithms including K Neighbor Classifier, Logistic Regression, MLP Classifier, Decision Tree Classifier, Random Forest Classifier, Gradient Enhancement Classifier, Cat Enhancement Classifier, LGBM Classifier, and XGB Classifier. It was found that 14 central genes of RCEG network for ACC-N group efficiently discriminate the ACC tissues from the normal tissues compared to the performance of discriminating in the live and dead specimens. The discovery of these putative biomolecules may also be an important step in preventing a benign tumor from turning into a malignant one.
Designing of L-proline specific nanoparticles for L-proline detection from human serum
Processes such as the detection and quantification of amino acids hold significant importance in biochemical analyses, particularly in the diagnosis of metabolic disorders. Among these amino acids, L-Proline has been identified as having significant relevance to various metabolic disorders in living organisms, particularly in human. Hyperprolinemia is a metabolic disorder that arises when the L-proline molecule is not effectively broken down due to deficiencies in proline oxidase or pyrroline-5 carboxylate dehydrogenase enzymes, resulting in an accumulation of L-Proline within the body. In individuals with Hyperprolinemia, there is a noticeable increase in L-Proline levels in both blood and urine, underlining the importance of accurately measuring and monitoring these levels in body fluids. To address the challenge of recognizing target molecules, such as proteins, peptides, amino acids, or ions, in complex environments with high selectivity, molecular imprinting emerges as a dependable technique that accomplishes this in a single step. In this study, molecularly imprinted nanoparticles that can selectively recognize the L-Proline molecule were synthesized. Hydroxyethyl methacrylate (HEMA) based nanoparticles were synthesized via emulsion polymerization technique and were characterized by scanning electron microscopy, zeta-sizer particle size analysis, surface area calculations, and Fourier Transform Infrared Spectroscopy (FTIR). Based on zeta-sizer analysis, the estimated diameters of Pro-MIP and NIP nanoparticles were determined to be approximately 27.51 nm and 20.66 nm, respectively. The adsorption of L-Proline onto nanoparticles from aqueous solutions was investigated in a batch system, and the maximum L-Proline adsorption capacity was determined to be 26.58 mg/g for Pro-MIP and 4.65 mg/g for NIP. The selectivity of L-Proline imprinted nanoparticles was successfully confirmed via Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), in the presence of competing molecules (L-Histidine and L- Phenylalanine). Finally, Pro-MIPs were subjected to repeated adsorption-desorption cycles and it was demonstrated that Pro-MIPs can be used up to 10 times without significant decrease in selective adsorption capacity.
Identification of on intestinal microbiota associated with irritable bowel syndrome
The balance of microbial communities in the human gut is critical to maintaining good health. Irritable bowel syndrome (IBS) is a common digestive disorder characterized by chronic and recurrent abdominal pain and altered bowel habits. Genetic, epigenetic, and gender-related factors are known to influence the function of the higher nervous and immune-endocrine systems, as well as the regulation of brain-gut physiology, bile acid production, and absorption. The objective of this study is to investigate the diversity of gut microbiota in patients with IBS. The study aims to determine the impact of changes in microbial diversity (low or high) on IBS symptoms, as well as the effects of diseases that patients have on microbiota and IBS. A gastroenterologist at Balcalı Hospital collected samples by colonoscopy biopsy, obtaining a total of 10 gut samples from IBS patients. Bacterial biodiversity was analyzed using Illumina-based next-generation sequencing methods. Samples from 10 patients with IBS symptoms were compared, and bacterial communities were analyzed to interpret the relationships between symptoms.
Development of epitope imprinted antimicrobial cryogel discs for tannic acid release
The molecular imprinting method allows for the synthesis of polymers sensitive to the desired molecule. Cryogels, one of these polymers, are gel matrices produced below the freezing temperature of the solvent. In contrast to many polymers containing toxic organic compounds as pore-forming agents, cryogels utilize ice crystals as the pore-forming material. Cryogels supported structurally by natural materials offer advantages such as biocompatibility, flexibility, and high mechanical stability, making them suitable for various applications like wound healing, tissue scaffolding, and drug release. In this study, the aim is to take advantage of the antimicrobial effects of Tannic acid molecules by preparing epitope-imprinted cryogel discs. These discs are intended to introduce a biomaterial with acute wound healing and antimicrobial properties to the literature. Biocompatible cryogels imprinted with gallic acid were prepared, and the goal was to impart antimicrobial properties by incorporating Tannic acid at different concentrations into the structure of the cryogels. The synthesized cryogels were characterized using FTIR, swelling tests, and SEM. Additionally, the cumulative release of Tannic acid from cryogel discs at different concentrations and their antimicrobial properties against S. aureus and E. coli were evaluated. The studies revealed that as the drug loading rate in the polymer increased, the release rate also increased. According to the power law, the exponent "n" was found to be less than 0.5, suggesting that the release mechanism in the prepared cryogel discs is non-Fickian diffusion. Keywords: Epitope-imprinted polymers, cryogel discs, tannic acid, controlled drug release systems, wound healing
Development of wound/burn dressing material with astaxanthin-imprinted phema based polymer
Astaxanthin is a carotenoid pigment and is commonly found in nature in organisms such as algae, fungi, bacteria, algae and some marine creatures. Astaxanthin, which has high antioxidant properties, can be found in high amounts in seafood, especially algae, krill, shrimp and salmon. Astaxanthin belongs to the carotenoid family and has particularly red-pink hues. It has been researched that astaxanthin has antioxidant and anti-inflammatory effects on human health, and its potential benefits are known, especially for skin health, regarding wounds and burns. Its antioxidant and anti-inflammatory properties can promote healing by fighting free radicals in the skin and reducing inflammation. In this study, Astaxanthin imprinted HEMA based polymers were synthesized and cryogels were synthesized using these polymers containing different amounts of Astaxanthin. Hydroxyethyl methacrylate (HEMA)-based cryogels were characterized by swelling tests, scanning electron microscopy. Release kinetics were examined depending on the amount of Asx-MIP embedded into the cryogels; MTT assay was applied to examine the effect of astaxanthin on mouse embryonic fibroblast (MEF, (CF-1) (ATCC® SCRC-1040™)) cell line. As a result, it has been shown that astaxanthin contained in cryogels has a cell proliferation-enhancing effect, and it has been proven that MIP cryogels containing astaxanthin have the potential to facilitate wound healing and can be used as wound/burn dressing material.
Development of controlled etoposide release materials: Testing on glioblastoma cells
Etoposide is a chemotherapy drug used to treat cancer. This medicine works by preventing the growth and proliferation of cancer cells. Etoposide is often used to treat various types of cancer, such as solid tumors, lymphoma, and leukemia. Etoposide works by affecting the processes of DNA replication and cell division. The main mechanism of the drug is to inhibit the enzyme topoisomerase II, affecting the processes of unwinding and recombination of the DNA pair. Etoposide inhibits the normal function of this enzyme, preventing DNA from being properly replicated and cell division from completing. Etoposide is used by oncologists to treat certain types of cancer. The effect of etoposide may vary depending on the type of cancer for which it is used, the patient's general health condition, and other treatment methods. In this study, empty HSA particles were synthesized with HSA-nanoparticles loaded with etoposide at different concentrations, and molecularly imprinted HEMA/gelatin cryogels were synthesized using these particles. Hydroxyethyl methacrylate (HEMA)-based cryogels were characterized by scanning electron microscopy, zeta-sizer particle size analysis, and swelling tests. Release kinetics were examined depending on the amount of Etoposide-loaded into the cryogels; A cytotoxicity test was performed to examine the effect of Etoposide on Glioblastoma cells. As a result, it turned out that Etoposide-loaded into the gel was more effective than Etoposide applied directly to the cells.
Green synthesized silver nanoparticles embedded chitosan edible films for food packing materials
In this master's thesis, it is aimed to produce green synthesized silver nanoparticle doped, antimicrobial, environmentally friendly, sustainable, renewable chitosan-gelatin based edible films as food packaging material. For this purpose, silver nanoparticles were synthesized by green synthesis method using walnut (Juglans regia) leaf extract. XRD, SEM, FTIR and DLS methods were used to characterize the nanoparticles synthesized under four different conditions. The antimicrobial activity of silver nanoparticles was tested against 7 different microorganisms (Escherichia coli, Pseudomonas aeruginosa,, Staphylococcus aureus, Salmonella typhi, Candida albicans, Penicillium italicum, Aspergillus niger) using disk diffusion and MIC methods. According to the data obtained, the MIC values for AgNPs-4 were in the range of 3.9-15.625 µg/mL. According to these MIC values, AgNPs-4 showed more antimicrobial effect against yeasts and fungi than bacteria. Although the disk diffusion inhibition diameters of all synthesized AgNPs were in the range of 9-11 mm, the highest inhibition diameter against all microorganisms belongs to AgNP-4 sample. Therefore, AgNP-4s were incorporated into Chitosan-Jelatin based edible films as antimicrobial active agents. The produced edible films were characterized and antimicrobial tests were performed and according to the data collected, the mechanical and antimicrobial properties of the nanoparticle-added edible films were satisfactory. Keywords: Anticmicrobial, biodegredible, edible film, green syhntesized silver nanoparticles
Drug repositioning for neurodegenerative diseases based on bioinformatics and text mining analysis
Neurodegenerative diseases (NDDs) are a group of complex diseases with limited treatment options. This thesis presents a comprehensive bioinformatics approach to identify repurposed drug candidates for NDDs, focusing on Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Transcriptomic data including disease and healthy samples were selected and grouped. Differentially expressed genes were identified and co-expression network analysis was performed. Machine learning (ML) algorithms were applied to identify prominent gene clusters. These significant gene clusters were used for drug repositioning analysis. Five ML algorithms (Linear Regression, SVR, Random Forest, Gradient Boosting and Neural Network) were performed to predict the fold change of potential drug candidates. The novelty of these drugs was verified by text mining analysis. For AD, we identified 5 candidate drugs: Dmnq (2,3-dimethoxy-1,4-naphthoquinone), Interferon beta-1b, Cyfluthrin, Torcetrapib, and Vx. For PD, 9 candidate drugs: Interferon beta-1b, Aplidin, Androstanolone, Ribavirin, Dmnq, Natural alpha interferon, Interferon beta-1a, Clinafloxacin, and Bicalutamide. Lastly, for ALS, 5 candidate drugs: Nilotinib, Trovafloxacin, Apratoxin A, Carboplatin, and Clinafloxacin. Among these novel drugs, Dmnq and Interferon beta-1b drugs were common for AD and PD, while Clinafloxacin is common for ALS and PD. Validation of these findings with wet lab studies may provide new treatment options for NDDs. Keywords: drug repurposing, machine learning, neurodegenerative diseases
GSK2126458 loaded polycaprolactone (PCL)/ polyvinylpyrrolidone (PVP) electrospun membranes: Production, characterization and anticancer activity
Skin cancer is one of the most dangerous cancers. The mutations resulting from the failure to repair DNA damage in skin cells result in the formation of cancer tissue in the skin. Skin cancer is a type of cancer that can spread to different parts of the human body and is divided into two main groups: melanoma and non-melanoma. The data in the literature indicate that the type of melanoma cancer accounts for 1% of cases of skin cancer. Although the incidence of melanoma skin cancer is low, patients have high mortality rates. There are different methods of treating skin cancer. The most common of these methods are biopsy and resection. In recent years, interest in the use of nanotechnology in the treatment of skin cancer has increased. Materials produced by nanotechnology are used as molecular carriers. Membranes produced using nanotechnological methods are intended to enable the drug to be applied directly to a specific area, to faster treatment and to reduce side effects. In this study, it was aimed to load GSK2126458 (Omipalisib®), which is used as a cancer drug, into Polycaprolactone (PCL)/ Polyvinylprolidone (PVP) fiber membranes obtained by electrospinning method and to investigate its effects on melanoma cancer cell line. Within the scope of the study, PCL/PVP/50 (50 µL drug and 50 µL DMSO), PCL/PVP/75 (75 µL drug and 25 µL DMSO), PCL/PVP/100 (100 µL drug) and PCL/PVP/C fiber membranes containing GSK2126458 drug and PCL/PVP/C fiber membranes without drug were produced by electrospinning method. DMSO ratio was kept constant in all samples. The morphology of the produced fiber structures were analyzed by scanning electron microscopy (SEM) and their chemical structures were analyzed by Fourier Transform Infrared Spectroscopy (FTIR). Fiber diameters and diameter distributions were calculated from the images obtained by SEM analysis using ImageJ software. Water retention properties of the fiber membranes were determined by water contact angle analysis and mechanical properties were determined by tensile analysis. Antibacterial properties of the fiber membranes were determined using E. coli, S. aureus, P. aeruginosa and MRSA bacterial strains. The IC50 value of the GSK2126458 on B16-F10 cell line was determined by resazurin assay. The effect of the drug on melanoma cells after being added to the fiber membrane was determined by viability analysis, SEM analysis of cell morphology and spreading behavior and immunofluorescent staining. As a result of the thesis study, GSK2126458 drug molecule loaded and drug-free control fiber membranes were obtained in a smooth and bead-free fiber structure. The average diameters of the fibers of PCL/PVP/C, PCL/PVP/50, PCL/PVP/75 and PCL/PVP/100 membranes were calculated as 0.6820,316, 0.5880.240, 0.6370.208 ve 0.6110.196 µm, respectively. Hydrophilic structures of the membranes were shown by water contact angles of 76.028.06, 83.631.75, 66.982.83 ve 82.9212.82 degrees for PCL/PVP/C, PCL/PVP/50, PCL/PVP/75 and PCL/PVP/100 fiber membranes, respectively. FTIR analysis showed specific peaks for PCL and PVP polymers, but a specific peak for the drug molecule could not be obtained because the drug was embedded in the polymer structure. The IC50 value of GSK2126458 on B16-F10 cell line was determined as 49.21 µM. When cell viability in drug-loaded membranes was analyzed compared to drug-free fiber membranes, it was determined that cell viability in PCL/PVP/50, PCL/PVP/75 and PCL/PVP/100 fiber membranes were 72.25%, 64.61% and 57.82% (p<0.05) for 24 hours, respectively. The viabilities were changed to 74.76%, 70.85% (p<0.05) and 60.19% (p<0.01) for 48 h, respectively. SEM images showed that cell spreading was more prominent in the control group than in the other groups. Immunofluorescence staining images obtained by staining fibrous actin protein of cells cultured on fiber membranes with anti F-actin antibody and nuclei with DAPI showed that cell density decreased with increasing amount of drug molecule. No significant changes were observed in the cell nucleus. In conclusion, it was shown that GSK2126458 drug loaded PCL/PVP fiber membranes were successfully produced within the scope of the thesis study and were effective on B16-F10 mouse melanoma cell line.
Investigation of cytotoxic activity of βeta-caryophyllene on pancreatic cancer cells
Beta-Caryophyllene (BCP) is an organic sesquiterpene composite derived from multiple plants and authorized by the Food and Drug Administration (FDA). It interacts with cannabinoid receptors CB2, exhibiting analgesic and anti-inflammatory effects. Many researches have demonstrated that BCP exhibits a variety of biological effects in tumor cells, including inducing apoptotic cell death, exerting anti-inflammatory effects, and inhibiting clonogenicity, migration, and invasion. This special approach on cancer cells suggests that BCP is a hopeful therapeutic option for cancer treatment. Within this study, the influence of BCP on MIAPaCa-2 pancreatic cancer cells were examined in conjunction with the chemotherapeutic agent Etoposide to assess its potential to enhance therapeutic performance. The IC50 values of BCP for MIAPaCa-2 cell lines were 58 µg/mL, while etoposide had an IC50 of 10.7 µM. The combination of etoposide and BCP led to a higher occurrence of cell death in MIAPaCa-2 cells compared to either treatment alone. BCP additionally inhibited the levels of gene expression c-Myc and survivin, concurrently boosting the level of caspase-3 in MIAPaCa-2 cell lines, with these impacts being intensified when combined with etoposide. BCP demonstrated cytotoxic effects on MIAPaCa-2 cells and augmented the anti-growth effects of etoposide when combined, showing reduced unfavorable effects on normal cells.
Investigation of the cytotoxic activity of astaxanthin on glioblastoma cells
Glioblastoma is well known among cancer cells to be one of the most formidable and highly proliferative forms of brain tumors. Despite the fact that there are numerous significant milestones in treatment that include chemotherapy, surgery, and radiation, its rapid progression , invasive nature and resistance to conventional therapies characteristics make it difficult to manage the spread of this disease and to enhance the several rates in total. In other words, glioblastoma is thought to have a very complex cellular and molecular heterogeneity coupled with highly infiltrative nature and ability to control immune system mechanisms which present obstacles in achieving suitable treatment approaches. Astaxanthin (ASX) has received much attention for its anticancer, antioxidant, anti-inflammatory, and anti-aging properties. However, the studies that explore the cytotoxic effects of ASX on glioblastoma cells remain poor. To address this gab, this study aims to investigate the cytotoxic potential of ASX against glioblastoma cells as a standalone treatment and in combination with the chemotherapeutic drug Etoposide. In order to perform this , a series of in vitro experiments that include cell viability tests, colony formation assays, and molecular analyses was done. Additionally, it was examined whether combining ASX with Etoposide enhances the cytotoxic effects against these cancer cell lines. Furthermore, this research further study the antimicrobial properties of ASX to expand our understanding of its potential applications as relatively few studies were conducted in this area. The findings of this study indicated dose-dependent reductions in cell viability with ASX, etoposide, and their combination, supported by IC50 assessments. ASX and etoposide also prevented clonogenic potential and caused morphological changes in U87MG cells, while downregulating survivin and c-Myc and upregulating Caspase-3 expression, indicating potent apoptotic effects. Moreover, the antimicrobial activity of ASX against Bacillus subtilis, Bacillus, Staphylococcus aureus, and Escherichia coli, was demonstrated suggesting further studies into its antimicrobial effectiveness and mechanisms of action. Overall, this thesis offers new perspective in the use of ASX in treating glioblastoma, highlighting its therapeutic potential importance as a natural substance with promising anticancer properties.
Microrna - based drug repurposing analysis in glioblastoma multiforme via machine learning approaches
Glioblastoma (GBM) is the most common cancer among all brain tumours and has the worst prognosis. In this thesis, we applied various bioinformatic analyses and machine learning classification techniques to GBM data to illustrate and better understand the biomolecular mechanisms of GBM. First, GBM datasets to be analysed were selected. Then, expression analyses of transcriptome and miRNA data were performed. Differentially expressed genes and miRNAs were identified, gene clusters co-expressed with common genes and genes targeted by miRNAs were identified, and the co-expression network was drawn. The prognostic properties of these gene clusters were examined and performance analyses were performed with machine learning classification algorithms such as Random Forest (RF), Support Vector Machine (SVM), Naive Bayes (NB) and The K-Nearest Neighbours (KNN). As a result of the performance analyses, RF, SVM and KNN algorithms were found to be reliable and accurate classification algorithms that work with existing gene groups with accuracy scores above 80%. In addition, according to the results obtained by upward and downward feature selection, it was determined that SEPT4, VAMP1, MAP1A, KIF5C, NPTX1 and ATP8A1 genes give high interaction and may be important biomarker candidates in GBM disease. In addition, the gene clusters obtained were used for drug repositioning analyses. As a result of these tests, the gene groups with the highest interactions in the gene clusters belonging to the gene co-expression network module and miRNA-based co-expression network module data in machine learning analyses and their common drugs were determined. A large number of drug candidates such as Emetine Dihydrochloride Hydrate (74), 16beta Bromoandrosterone, AS605240, 480743.cdx, BRD K00627859, HDAC6 inhibitor ISOX, BRD-K12184916 and 16-HYDROXYTRIPTOLIDE were found for the treatment of GBM. It was determined that these drugs and small molecules can be tested in future clinical trials and may be new drug candidates for the treatment of GBM.