The Tff gene cluster encoding gastroprotective trefoil peptides and targeted disruption of the Tff2 gene in mouse

Kleeblattpeptide (TFF) sind kleine sezernierte Proteine, die eine wichtige Rolle bei Wund-heilungsprozessen und dem Schutz des Verdauungstraktes spielen. Das Ziel dieser Arbeit war es, Grundlagen für das Verständnis der Funktion des Tff2 Gens zu schaffen. Für die humanen Kleeblattproteine sind keine natürlich vorkommenden Mutationen, welche zu konstitutionellen Krankheiten führen könnten, bekannt. Daher sind die sogenannten 'Knockout-Mäuse' für die Grundlagenforschung von großer Bedeutung, um neue Einblicke in die Wirkungsweise der Kleeblattproteine zu erlangen. In dieser Arbeit sollte das natürlich vorhandene Tff2 Gen ausgeschaltet werden, um pathologische Situationen zu simulieren und dadurch die physiologische Funktion des Genproduktes aufzuklären. Durch homologe Rekombination wurde ein Allel des Tff2 Gens in den embryonalen Stammzellen der Maus ersetzt. Dazu wurde ein Zielvektor (pL2-?m2) konstruiert, in welchem das murine Kleeblattgen Tff2 deaktiviert vorliegt. Darüber hinaus wurde das mutierte Allel in die Keimbahn der heterozygoten (Tff2+/-) Tiere erfolgreich integriert. Basierend auf diesen Charakterisierungen werden nun die heterozygoten (Tff2+/-) Tiere untereinander gekreuzt, um letztendlich die Tff2 (-/-) Knockout-Maus zu züchten. Die Erzeugung dieser Maus wird die Familie der bereits bestehenden Kleeblatt-Knockout-Mäuse komplettieren. Als Grundlage für diese Arbeit wurde die genomische Struktur der murinen Kleeblattfamilie bestimmt. Drei bakterielle und eine von der Hefe abstammende Rekombinante (BACs und YAC) wurden identifiziert und für die detaillierte Charakterisierung durch PCR, Restriktionskartierung, Hybridisierung, und Fluoreszenz in situ Hybridisierung (FISH) verwendet. Daraus ergab sich, dass in der Maus die drei Tff Gene ähnlich wie im menschlichen TFF Gen-Cluster angeordnet sind. Sie erstrecken sich über eine Länge von ca. 40 kb in der transkriptionellen Anordnung Tff1-Tff2-Tff3 auf Chromosom 17.Trefoil peptides (TFFs) are a group of small secreted proteins, which play an important role in the protecting and healing processes of the stomach and intestine. The aim of these experiments was to create a basic foundation for understanding the exact function and/or the mode of action of the Tff2 gene. Since in the case of human trefoil peptides, no naturally occurring chance mutations leading to constitutional diseases had been discovered, a straight forward experimental approach for new insight into this trefoil peptide function is to engineer a strain of so-called knock-out mice, in which Tff2 is missing. By employing a replacement strategy, one allele of Tff2 was substituted in ES cells by homologous recombination in order to create the Tff2 knock-out mouse. The primary aim of this project was to construct the targeting vector (pL2-?m2), whereby the mouse trefoil gene Tff2 was disrupted, and to characterise the germline transmission of the mutant allele in heterozygous (Tff2+/-) animals. Indeed, this goal was realised within the scope of this work. In the near future, the mice will be mated inter se to generate the mutant Tff2 (-/-) knockout mice, completing the family of already existing trefoil knockout mice. To obtain fundamental information about the mouse trefoil gene cluster, the genomic structure was determined. Three bacterial and one yeast artificial chromosome recombinants (BACs and YAC) were identified and used for detailed characterisation by PCR, restriction mapping, hybridisation, and fluorescence in situ hybridisation (FISH). In a similar fashion to the TFF gene cluster in humans, the mouse Tff genes cover a region of approximately 40 kb in the transcriptional order Tff1-Tff2-Tff3 and are localised on chromosome 17

Trefoil factor 2 (Tff2) deficiency in murine digestive tract influences the immune system

Background & Aims: The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency. Methods: TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry. Results: On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. Expression of proteasomal subunits genes (LMP2, LMP7 and PSMB5) involved in the MHC class I presentation pathway were modulated indicating the formation of immunoproteasomes improving antigen presentation. Expression of one subunit of a transporter (TAP1) responsible for importing degraded antigens into ER was increased, similarly to the BAG2 gene that modulates chaperone activity in ER helping proper loading on MHC class I molecules. Several mouse defensin (cryptdin) genes coding important intestinal microbicidal proteins were up-regulated as a consequence of TFF2 deficiency. Normally moderate expression of TFF3 was highly increased in stomach

MODERN ÖLÇME ALETLERİ KULLANILARAK CAMİİ KUBBELERİNİN ÖLÇÜLMESİ (Maltepe/ANKARA CAMİİ ÖRNEĞİ)

Bu çalışmada jeodezik yöntemle reflektörsüz ölçüm yapabilen total station kullanılarak örnek olarak seçilen bir camii kubbesi üzerinde ölçüm yapılmıştır. Cihaz ile alınan koordinatlar güncel programlar kullanılarak sayısal verilere dönüştürülmüş ve autocad ve surfer programlarında modelleme yapılmıştır. Uygulama alanı olarak kullanılan Maltepe Camii kubbesinin çap ve yükseklik ölçüleri tespit edilmiştir.Within the scope of this study, a measurement has been conducted on a selected mosque dome with geodesic methods by using total station which is able to measure without reflector. Coordinates acquired via the device have been converted to digital by using recent softwares and modelings have been made in AutoCAD and Surfer. The height and the diameter of Maltepe Mosque's dome, which is the study of interest, have been determined

Die mittelfristige produktionsplanung und eine anwendung in einer textilgesellschaft

Building up a production planning in a textile firm is complicated problem. The most important reason of this is the existence that very large scale of products with different costs and capacity uses. In most companies of the industry, the production is planed and applied for a short range of time. In this way the overtime and supplier alternatives are used unconsciously so that the costs rise. In this work, a solution is presented with Aggregate Planning and Linear Programming. The goal is to make a midterm production planning to minimize the costs for apply all operations according this plan. To achieve this goal the elements of the production were aggregated in groups, a mathematical model was established and solved with Linear Optimization. After achieving the plan more alternatives were examined to reduce costs. Bir Tekstil işletmesinde tatminkar bir üretim planlaması yapmak oldukça komplike bir problemdir. Bunun en önemli nedeni farklı maliyet ve kapasite kullanımlarına sahip çok çeşitli sayıda mamulün olmasıdır. Çoğu işletmede üretim kısa vadeli olarak planlanır ve uygulanır. Bu şekilde de üretim aşamasında fazla mesai ve de fason üretim maliyetleri de arttıracak şekilde bilinçsizce kullanılır. Bu çalışmada bir Tekstil işletmesinde Orta Vadeli Üretim Planlaması problemini Lineer Programlama metodu ile bir çözüm sunuluyor. Amaç, tüm alt operasyonların uyucağı, maliyetleri düşürmeye yönelik optimal bir çözüm bulmaktır. Bunun için planlanan dönem için üretim elemnları gruplandırılımış, matematiksel bir model kurulmuş ve Lineer Optimizasyon uygulanmıştır. Sonuca ulaşıldıktan sonra da bu maliyeleri daha düşürmeye yönelik diğer yöntemler üzerinde durulmuştur

5-Carboxylato-5-hydroxy-4-(4-methoxybenzoyl)-3-(4-methoxyphenyl)-1,1-dimethyl-4,5-dihydro-1H-pyrazol-1-ium monohydrate

In the title compound, C21H22N2O6 center dot H2O, the pyrazolium ring is in an envelope conformation. In the crystal structure, intermolecular O-H center dot center dot center dot O hydrogen bonds form molecular tapes along [001]. In addition, weak C-H center dot center dot center dot O and a C-H center dot center dot center dot pi interaction link molecules into a three-dimensional network

ジゾクテキ キョクショ レーザー ショウシャ ト オンド カンジュセイ リポソーム ニ ヨル ミャクラクマク ジュンカン パターン ノ ヒョウカ

京都大学0048新制・課程博士博士(医学)甲第11383号医博第2806号新制||医||884(附属図書館)23026UT51-2005-D134京都大学大学院医学研究科外科系専攻(主査)教授 福山 秀直, 教授 富樫 かおり, 教授 橋本 信夫学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA