DUAL ASSEMBLY NANOPARTICLES ACHIEVE SUSTAINED SILENCING OF ZNF304: A NOVEL TRANSCRIPTION FACTOR FOR Β1 INTEGRIN

Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to this process currently are known. Here, an integrated computational analysis of The Cancer Genome Atlas ovarian cancer dataset coupled with experimental validation identified a novel zinc finger transcriptional factor 304 (ZNF304) as one of the key factors for ovarian cancer metastasis. High tumoral ZNF304 expression was associated with poor overall survival in ovarian cancer patients. Through reverse phase protein array analysis, we demonstrated that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration, and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase and paxillin and prevents anoikis. Targeting ZNF304 using small interfering RNA (siRNA) reduces cell survival, anoikis and migration in vitro. A novel dual assembly nanoparticle system (DANP) was designed for in vivo delivery and sustained gene silencing. DANP-ZNF304 siRNA led to sustained ZNF304 silencing for 14 days, increased anoikis, and reduced tumor growth in orthotopic murine models of ovarian cancer. Taken together, ZNF304 is a novel transcriptional regulator of β1 integrin, promotes cancer cell survival, and protects against anoikis in ovarian vi cancer; DANP is a safe and efficient delivery system that provides prolonged gene silencing following systemic administration

Legal processes on trademark

101 pagesFikri ve sınai hakların zaman içerisinde gelişmesi neticesinde bunun bir parçası olan marka işletmeden bağımsız kimlik kazanmıştır. Marka işletmeden ayrı olarak devir, rehin haciz gibi 556 sayılı Kararnamede belirtilmiş hukuki işlemlere ayrıca Kararnamede belirtilmeyen başka hukuki işlemlere de konu olabilmektedir. Giriş bölümünde markaya ilişkin genel bilgiler verilmek sureti ile markaya özgü bir takım özelliklerden bahsedilmiştir. Birinci bölümde Markaların Korunması Hakkında Kanun Hükmünde Kararnamede ayrı olarak düzenlenmiş markanın konu olduğu hukuki işlemlerden devir, rehin ve haciz incelenmiştir. Tez çalışmamızda kararname ile düzenlenen hukuki işlemlerden olan markanın lisans sözleşmesine konu olması inceleme dışında bırakılmıştır. Çalışma yapılırken yeri geldikçe 40/94 sayılı Avrupa Birliği Marka Tüzüğü, Alman ve İsviçre Markalar Kanunu ile ilgili düzenlemelerden de yararlanılmış ve Yargıtay Kararlarına yer verilmiştir. İkinci bölümde kararnamede düzenlenmemiş hukuki işlemlerden olan marka üzerinde intifa hakkının tesisi ve markanın miras yolu ile intikali incelenmiştir.As a result of intellectual and industrial property evolved within time, a part of this“Trademark” became independent identity. Trademark has been subject to legal processes,separate than enterprise, expressed by Decree-Law no. 556 and also not expressed by Decree-Law like assignment, pledge, seizure etc.In the instruction part of this thesis, on the prompting of giving general information abouttrademark we have mentioned some special properties of trademark.In first part of the thesis, our legal search is about legal processes like assignment, pledge andseizure that related legally to other legal sources than Decree-Law No. 556 Pertaining to theProtect of Trademarks. In our thesis we have not researched on trademark license agreementthat is regulated in Decree-Law. During our research, we will give information aboutEuropean Union trademark regulations no. 40/94, Germany and Switzerland trademark lawsand decisions of Court of Appeal.In second part, legal processes, settlement of usufruct rights and transfer of trademark byheritage that are not regulated by Decree-Law has been researched.Özet........................................................................................................................................III İçindekiler............................................................................................................................ V Kısaltmalar....................................................................................................................... X Giriş MARKAYA İLİŞKİN GENEL BİLGİLER I. ÇALIŞMANIN SINIRLANDIRILMASI...............................................................1 II. MARKANIN TANIMI................................................................................................2 III. MARKANIN İŞLEVLERİ.......................................................................................4 A. Malın Menşeini (Kökenini) Gösterme İşlevi..................................................................5 B. Ayırt Etme İşlevi................................................................................................................5 C. Garanti İşlevi.....................................................................................................................6 D. Reklam İşlevi.....................................................................................................................6 IV. MARKANIN TÜRLERİ...........................................................................................7 A. Ticaret Markası................................................................................................................7 B. Hizmet Markası................................................................................................................8 C. Bireysel (Ferdi) Marka....................................................................................................8 D. Ortak Marka ve Garanti Markası..................................................................................9 E. Tanınmış Markalar.........................................................................................................12 V. MARKA ÜZERİNDEKİ HAKKIN HUKUKİ NİTELİĞİ...........................13 VI. KAVRAM SORUNU.................................................................................................15 Birinci B ö l ü m MARKALARA İLİŞKİN KANUN HÜKMÜNDE KARARNAME ÇERÇEVESİNDE ÖZELLİKLE DÜZENLENMİŞ OLAN MARKAYA İLİŞKİN HUKUKİ İŞLEMLER (MARKANIN DEVRİ- REHNİ- HACZİ) VI I. GENEL OLARAK MARKANIN HUKUKİ İŞLEMLERE KONU OLMASI...............................................................................16 II. MARKANIN DEVRİ..................................................................................................18 A. Genel Olarak....................................................................................................................18 B. Devrin Hukuki Niteliği Ve Hükümleri..........................................................................21 C. Markanın Devrinde Şekil Ve Tescilin Hükümleri.......................................................25 1. Markanın Devir Şekilleri.............................................................................................25 a. Markanın Sözleşme İle Devri................................................................................25 b. Markanın, Ticari İşletmelerin Devri veya Birleşmesi ya da Ortaklıkların Birleşmesi Yoluyla Devri..............................................................27 c. Markanın Mahkeme Kararı veya İcra Yolu İle İktisabı...................................33 2. Tescil...........................................................................................................................34 D. Markanın Bir Ortaklığa Sermaye Olarak Taahhüt Edilmesi.....................................36 E. Garanti Markasının ve Ortak Markanın Devri...........................................................37 F. Devrin Hüküm ve Sonuçları...........................................................................................37 G. Ticari Vekil veya Temsilci Adına Tescilli Markanın Devri........................................40 III. MARKANIN REHNİ................................................................................................41 A. Genel Olarak....................................................................................................................41 B. Marka Üzerindeki Rehin Hakkının Hukuki Niteliği...................................................42 C. Taşınır Rehnine Hakim Olan Genel Prensiplerin Marka Rehninde Uygulanması.................................................................43 1. Fer’ ilik (Alacağa Bağlılık) İlkesi.................................................................................43 2. Kamuya Açıklık İlkesi..................................................................................................44 3. Kamu Güveni İlkesi......................................................................................................44 4. Belirlilik İlkesi...............................................................................................................45 a. Rehin Konusunun Belirli Olması...........................................................................46 b. Rehinli Alacağın Belli Olması................................................................................46 5. Rehin Yükünün Bölünmezliği İlkesi...........................................................................47 VII 6. Öncelik İlkesi.................................................................................................................48 D. Marka Üzerinde Rehin Hakkının Tesisi..........................................................................49 1. Borçlandırıcı İşlem..........................................................................................................50 2. Tasarruf İşlemi................................................................................................................50 E. Tescil ve Etkisi....................................................................................................................51 F. Marka Üzerinde Rehnin Hükümleri.................................................................................52 G. Markanın Ticari İşletme İle Rehni...................................................................................53 H. Marka Üzerindeki Rehin Hakkının Sona Ermesi...........................................................57 I. Marka Üzerindeki Rehnin Paraya Çevrilmesi.................................................................58 IV. MARKANIN HACZİ VE MARKAYA ETKİSİ (İFLAS VE KONKORDATO DAHİL)...............................................................61 A. Markanın Haczi...............................................................................................................61 1. Genel Olarak.................................................................................................................61 2. Marka Haczinin Sınırları.............................................................................................66 3. Marka Haczinde Uygulanan Usul...............................................................................68 4. Haczedilen Markanın Paraya Çevrilmesi...................................................................71 5. Markanın Açık Arttırma Yolu İle Satışı.....................................................................74 a. Açık Arttırmaya Hazırlık.......................................................................................74 (1) Arttırma İlanı.....................................................................................................74 (2) Arttırma Şartnamesi..........................................................................................75 (3) Mükellefiyetler Listesi........................................................................................76 (4) Kıymet Takdiri...................................................................................................77 b. Arttırmanın Yapılması...........................................................................................77 c. Satış Bedelinin Ödenmesi ve Satışın Sonuçları.....................................................78 6. Marka Üzerindeki Haczin Etkisi.................................................................................79 7. Marka Değerinin Ölçülmesi.........................................................................................80 a. Marka Değerinin Ölçülmesinin Gerekli Olduğu Haller.......................................80 b. Marka Değerini Ölçme Yöntemleri........................................................................81 VIII B. Marka Üzerinde İflasın Etkisi........................................................................................83 1. Genel Olarak.................................................................................................................83 2. İflasın Marka Sahibi Müflisin Markasına Etkileri....................................................85 a. Borçlunun Haczedilebilen Tüm Malları İflas Masasına Girer...........................85 b. Üzerinde Rehin Tesis Edilmiş Markanın Masaya Girmesi................................86 c. Üzerinde Haciz Olan Markanın Masaya Girmesi................................................87 C. Marka Üzerinde Konkordatonun Etkisi.......................................................................88 1. Genel Olarak.................................................................................................................88 2. Konkordato Türleri......................................................................................................88 a. İflas Dışı Konkordato..............................................................................................88 b. İflastan Sonra Konkordato....................................................................................89 İkinci Bölüm MARKALARA İLİŞKİN KANUN HÜKMÜNDE KARARNAME ÇERÇEVESİNDE DÜZENLENMEMİŞ OLAN MARKAYA İLİŞKİN DİĞER HUKUKİ İŞLEMLER I. MARKANIN MİRAS YOLU İLE İNTİKALİ....................................................90 A. Genel Olarak....................................................................................................................90 B. Markanın Külli Halefiyet Yolu İle İktisabı...................................................................91 C. Markanın Cüz’i Halefiyet Yolu İle İktisabı..................................................................92 II. MARKA ÜZERİNDE İNTİFA HAKKI..............................................................93 A. Genel Olarak....................................................................................................................93 B. Marka Üzerinde İntifa Hakkının Özellikleri................................................................95 1. İntifa Hakkı Sahibine Sadece Yararlanma Yetkisi Verir.........................................95 2. İntifa Hakkının Devredilemezliği................................................................................96 3. Marka Sahibinin Marka Üzerindeki Tasarruf Yetkisinin Devam Etmesi..............96 C. İntifa Hakkının Kurulması.............................................................................................97 1. Hukuki İşlem Yolu İle İktisap......................................................................................97 a. Borçlanma İşlemi....................................................................................................97 b. Tasarruf İşlemi........................................................................................................97 2. Mahkeme Kararı İle İktisap........................................................................................97 D. Marka Üzerinde İntifa Hakkının Hükümleri...............................................................98 E. İntifa Hakkının Sona Ermesi..........................................................................................99 Sonuç....................................................................................................................................100 KAYNAKÇA.....................................................................................................................10

An Examination of the Activities in the Unit "Solar System And Eclipses" in the 6th Grade Science Textbook in Terms of Critical Thinking Standards

The science curriculum aims to provide students with the identity of a researcher, thinking skills, and scientific process skills. Critical thinking skill emerges as one of the skills that should be emphasized in the teaching process in terms of its structural features and the qualities aimed to be given to individuals. For individuals to gain critical thinking skills, they must first gain critical thinking standards. The main purpose of this research is to examine the activities in the "Solar System and Eclipses" unit in the sixth-grade science textbook in terms of critical thinking standards. The qualitative research model was used in the research. The data source of the research is the sixth-grade science textbook used in the province of Isparta. The data of the research were collected using the document analysis method. In the analysis of the data, the analysis was made by applying the descriptive analysis method, one of the qualitative data analyses. In line with the analysis, in terms of critical thinking standards, the secondary school sixth-grade science textbook has been determined to meet the standards of clarity, accuracy, significance/relevance, sufficiency, breadth/depth, and precision at a high rate. Based on the research results, suggestions have been developed that textbooks from different disciplines should be examined in line with critical thinking standards and that the activities of different grade-level units in the science curriculum should be examined in terms of critical thinking standards

Evaluation of stroke risk factors and characteristics in the comorbidity of cancer

Aim: Stroke and cancer can be followed together and in the presence of cancer, there may be changes in classical stroke characteristics. The aim of this study was to determine the effect of cancer on stroke risk factors, radiological and clinical features. Materials and Methods: Patients who were hospitalized with the diagnosis of stroke between 2014-2020 were included in the study retrospectively. By examining the stroke and cancer characteristics of the patients; The differences in demographic findings, stroke risk factors, and radiological features of stroke between patients with and without cancer were examined. The anti-cancer treatments used and the characteristics of cancer were evaluated in stroke patients. Results: 281 stroke patients were evaluated and cancer was detected in 52 patients. There was no significant difference in terms of demographic characteristics of the patients. No significant difference was observed in stroke patients with cancer in terms of risk factors except smoking and alcohol use. Multiple ischemic lesions were more evident on magnetic resonance imaging (MRI) in stroke patients with cancer. The most common cancer was lung cancer. Conclusion: Stroke and cancer are increasingly common comorbidities. As the time between stroke and cancer development decreases, while the risk factors for cancer are more prominent, classical risk factors for stroke are observed less frequently

A proteomic analysis for profiling NeuroD2 related changes in N2A neuroblastoma cell line

Aim: NeuroD2 transcription factor is a key regulator of neurogenin-NeuroD signaling network and induces neuronal development, differentiation, neurogenesis and calcium de- pendent signaling. NeuroD2 regulates expression of survival and plasticity related proteins in neurons. Surprisingly, inhibition of NeuroD2 causes an increase in apoptotic cell death. Even though previous studies found out important data about NeuroD2 function, molec- ular interactions of NeuroD2 behind all of these impacts remains elusive. For this reason, it was aimed to shed light on the proteome profile of NeuroD2 based changes in the N2A cell line. Materials and Methods: NeuroD2 over-expression and NeuroD2 inhibition groups were constructed via lentiviral vectors. Mouse N2A cell line was transfected with the given vectors and incubated for 6 hours. After incubation samples were prepared for proteomic analyses with Filter Aided Sample Preparation (FASP) protocol and LC-MS/MS analysis was carried out. Results: Under conditions of overexpression and inhibition, detected proteins were fil- tered according to significant cut off values. The filtered proteins were further investigated to exhibit a coherent expression in each situation. Eventually, increased NeuroD2 activity was accompanied by an increase in N-alpha-acetyltransferase 25 (NAA25), and Synapto- brevin homolog (YKT6). On the other hand, when NeuroD2 was suppressed, expression of Cytoplasmic Dynein 1 Light Intermediate Chain 1, Kinesin-Like Protein (KIF-11), Leucine-tRNA Ligase (LARS1), and Ubiquitin-Associated Protein 2 (UBA2) were found to be upregulated with a reverse action. Conclusion: Up-regulations of the proteins Cytoplasmic Dynein 1, KIF11, LARS1, and UBA2 suggested that these proteins might be controlled by inhibition of NeuroD2. In this contex it can be said that, axonal transport, neuronal signaling, and activity of PI3K/AKT pathway can be indirectly regulated by NeuroD2

Hydrogels in Regenerative Medicine

Polymer scaffolds have many various applications in the field of tissue engineering, drug delivery, and implantation. They are applied as dispensing devices for bioactive molecules and as three-dimensional (3D) structures that provide stimulants that organize cells and direct desired original tissue formation. Hydrogels are preferred scaffolding material because they are structurally similar to the extracellular matrix of many tissues, often processed under mild conditions, and can be delivered in a minimally invasive manner. Hydrogel materials formed a group of polymeric materials. The hydrophilic structure allows them to hold large amounts of water in their three-dimensional backbone. As a result, hydrogels are used as scaffolding material for drug and growth factor transmission, tissue engineering modifications, and many other applications. In this chapter, we describe the physical and chemical structure of hydrogels, side groups, cross-linkings, swelling properties, types of polymers and fabrication methods, and application fields

Effects of Force Constancy on the Distribution of Interleukin-1 Beta and Tumor Necrosis Factor-Alpha Levels

Objective:The purpose of this study was to evaluate levels of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF) with hybrid and PG retractors, which have differences in constancy of force.Materials and Method:Forty canine teeth of 10 orthodontic patients were distalized with hybrid or PG retractors. The GCF was sampled from the distal sides of the canines at baseline, hour 1, day 1, month 1, and month 2. In the PG group, samples were re-collected 1 hour and 1 day after reactivation at month 1. Two-way ANOVA, paired t test, and Friedman and Wilcoxon tests were used for statistical analysis.Results:The IL-1β level increased at hour 1 and month 2 in the upper and lower hybrid groups, whereas upper PG group increased at hour 1, month 1 + 1 hour, and month 2. The TNF-α level increased at hour 1 and declined afterward in the upper hybrid group. The only difference between the 2 retractors was found in TNF-α levels, which were higher at day 1 and month 2 in the upper PG group.Conclusion:Continuous but diminishing forces produced by PG mechanics enhanced levels of TNF-α significantly at day 1 and month 2 compared with the constant and continuous forces applied by the hybrid retractor in the upper arch. Despite this difference, both retractors induced similar effects in IL-1β and TNF-α production and in the amount of tooth movement

Analysis of the psychiatric consultations for inpatients and from the emergency room in a university hospital: A comparison with studies from Turkey

Objective: The aim of this research was to assess the characteristics of the consultations required in a psychiatric department of a university hospital, and the distribution of psychiatric disorders in hospitalized patients and patients admitted to the emergency room. Method: In the study, the data of 539 patients 18 years or older (48.67 ± 20.91 years) (46.8% women) who were hospitalized and who presented to the emergency room between 01/01/2015 and 31/12/2015, and for whom a psychiatric consultation was requested were recorded onto a structured form. Patients' electronic databases were reviewed retrospectively for the specified date range. Descriptive statistical analyzes (frequency of data, distribution, mean, standard deviation) were performed for the data examined in the study. Results: Medical departments (42.9%), surgical departments (31.7%) and the emergency medicine department (25.4%) were the most frequently psychiatric consultation requesting departments. The most frequent requests for consultation were agitation (15.4%), depressive symptoms and signs (14.7%) and suicide attempts (12.2%). The most frequent psychiatric diagnoses were depressive disorders (19.5%), delirium (18.2%) and schizophrenia and other psychotic disorders (7.4%). Musculoskeletal diseases (17.4%), mental disorders (15.0%), oncologic diseases (14.1%) and suicide attempts (12.2%) were the primary diagnoses of patients. Discussion: Consultation and liaison psychiatry services have an important role in our relationship with other departments in medicine. Priority to training of depressive disorders, delirium and suicide attempts should be offered to healthcare providers working in these departments

Epicardial fat thickness is associated with retinopathy in patients with newly diagnosed hypertension

OBJECTIVE: Hypertensive retinopathy develops based on endothelial dysfunction, inflammation, and atherosclerosis. Epicardial fat secretes various cytokines associated with endothelial dysfunction, oxidative stress, inflammation, and atherosclerosis. We aimed to evaluate whether epicardial adipose tissue (EAT) thickness is a marker for retinopathy in newly diagnosed hypertensive patients. METHODS: A total of 73 newly diagnosed hypertension (HT) patients were included in the study. Transthoracic echocardiography (TTE) was used to measure EAT thickness. To evaluate the presence of retinopathy in HT patients, hypertensive retinopathy staging was performed by ophthalmologists, according to Scheie classification. RESULTS: Retinopathy was detected in 27 (37.0%) of 73 patients. EAT thickness in HT patients with retinopathy was higher than the group without retinopathy (5.07 +/- 1.45 mm vs. 4.19 +/- 1.20 mm, p=0.007). Low-density lipoprotein cholesterol (LDL-C) levels in HT patients with retinopathy were higher than the group without retinopathy (162.4 +/- 41.2 mg/dl vs. 138.1 +/- 35.6 mg/dl, p=0.010). As a result of the regression analysis, LDL-C (OR=1.016, 95% CI 1.001-1.031, p=0.043) and EAT thickness (OR=1.674, 95% CI 1.069-2.626, p=0.043) were the independent predictors of retinopathy. CONCLUSION: Increased EAT thickness is associated with the presence of retinopathy in hypertensive patients