169 research outputs found

    Analysis of market areas of mega malls in Istanbul

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    After 1980?s, restructuring of Istanbul has occurred in many fields and the increased number of mega malls is one of the most interesting aspects of the transformation of business facilities. Increase in the number of products as a result of globalization, advantages of the multistore shopping supported by the recreational facilities and increase in the income of the people and car use results in the development of mega malls mostly in the periphery of the city. These shopping facilities have attractive environments and have many advantages with respect to street shopping. Downtown areas of Istanbul held their dominant positions by reasons of the pulling power built up during the mass transportation era. After the construction of the periphery highways, subcenters have started to develop and while some of the mega malls fill the gap in retail trade in these new centers, some others create new subcenters by themselves. This study investigates the market areas of the mega malls with respect to their location in different zones of Istanbul and by taking into consideration different variables such as distance, our ownership, socio-economic and demographic characteristics of customers. The results of the research are that several of the potential locations are not served by the existing malls. Further research is suggested by doing simulation studies in order to evaluate the alternative location for the new malls.

    The historical topography of a provincial Byzantine city in Thrace: Vize (Bizye)

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    This is a topographical study of an ancient settlement in southern Thrace. Located in the provincial district of the city Kırklareli in Turkey today, Vize (Bizye) was the residential capital of the Thracian kings from the 3rd century BC on, a prosperous Roman city under Trajan and Hadrian and a Late Antique and early Christian city with fortifications repaired and modified throughout the following centuries of the Byzantine period. Becoming a garrison regarding the Bulgarian threat especially from the 9th century on, the city survived, as proved by the 9th century church of Hagia Sophia. The city held strong in the years of intensive attacks in the 13th –14th centuries, until it was taken by the Ottomans in 1453. The Ottoman settlement lay mainly on the old Byzantine topography and extended with residential quarters on a small scale. After the Russian-Ottoman and Balkan Wars of the 19th and the early 20th centuries, the modern settlement of the Turkish Republic started developing towards the south on the plain, leaving the old acropolis to the small local houses and the ghosts of the Roman and Byzantine monuments. Although the archaeological significance of the site was known already at the beginning of the 20th century, neither a well-documented systematic excavation nor a comprehensive topographical study of the acropolis was made. Hitting the road with this motivation, we have undertaken a topographical survey throughout two summer campaigns in 2011 and 2012 on the Acropolis of Vize, which is the core of the settlement from the Roman until the end of the Ottoman period. The main purpose of the survey was primarily to document the fortifications in detail in order to produce a digital topographical plan. Other monuments on site have also been measured and inserted into this plan. This thesis discusses the results gained through the comprehensive analysis of the fortifications — their material, masonry and typology of the structural elements comparing with parallel examples from particularly the same administrative territory of Thrace. The presumable circuit of the walls half of which is missing and the extension and the changes of the urban structure are discussed while considering the construction periods of the walls together with the other remaining monuments and archaeological rests on site.Die vorliegende topographische Studie befasst sich mit einer antiken Siedlung im südlichen Thrakien. Vize (Bizye), das heute in der türkischen Provinz Kırklareli liegt, diente seit dem 3. Jahrhundert v. Chr. den Thrakerkönigen als Residenz. In römischer Zeit erlebte die Stadt unter den Kaisern Trajan und Hadrian eine Blüte. In der Spätantike wurde die Stadt ummauert. Diese Stadtbefestigung wurde in den darauffolgenden Jahrhunderten mehrfach repariert und verändert. Angesichts der bulgarischen Bedrohung, sprich besonders seit dem 9. Jahrhundert n. Chr. war in Vize eine byzantinische Garnison stationiert. Dieser Umstand sicherte auch das Fortbestehen der Siedlung, was wiederum durch die Errichtung der Sophienkirche im 9. Jahrhundert bestätigt wird. Die Siedlung überstand auch die Zeiten schwerer Angriffe im 13. und 14. Jahrhundert bis sie schließlich 1453 durch die Osmanen eingenommen wurde. Die osmanische Siedlung überlagert weitgehend den byzantinischen Siedlungsbereich und erweiterte diesen um Viertel, die von einfacher Wohnbebauung gekennzeichnet waren. Nach dem Krieg zwischen Russland und osmanischen Reich im 19. bzw. dem Balkankrieg im frühen 20. Jahrhundert entwickelte sich eine moderne türkische Siedlung in der Ebene südlich des historischen Siedlungshügels. Die Akropolis von Vize mit ihren römischen und byzantinischen Baudenkmälern überließ man dabei der lokalen Bevölkerung, die dort einfache Häuser errichteten. Obwohl die archäologische Bedeutung der Stätte bereits zu Beginn des 20. Jahrhunderts erkannt worden war, wurde sie weder systematisch ergraben und dokumentiert noch war der Bereich der Akropolis bislang Gegenstand einer umfassenden topographischen Studie. Um diese Forschungslücke zu schließen, wurde in den Jahren 2011 und 2012 auf dem Burgberg von Vize, der mit dem Siedlungskern von römischer bis osmanischer Zeit nahezu identisch ist, ein topographischer Survey durchgeführt. Hauptziel des Surveys war eine detaillierte Dokumentation der Befestigungsanlage um darauf aufbauend einen digitalen topographischen Plan erstellen zu können. Dabei wurden auch weitere Bauten im Surveybereich vermessen und in den Plan eingefügt. Die vorliegende Dissertation legt die Ergebnisse der umfassenden bauhistorischen Untersuchung der Befestigungsanlagen vor, wobei ein besonderes Augenmerk auf das verwendete Baumaterial, die Beschaffenheit des Mauerwerks und die typologische Analyse der Bauelemente gelegt wird. Hierfür werden die Baudenkmäler mit weiteren Verteidigungsanlagen verglichen, die hauptsächlich im selben Verwaltungsbezirk, also in Thrakien, liegen. Der mutmaßliche Verlauf der nur ungefähr zur Hälfte erhaltenen Akropolismauer werden ebenso diskutiert, wie die Erweiterung und die Veränderung der Siedlungsstruktur. Dabei werden die einzelnen Bauabschnitte der Befestigungsmauer in Bezug zu den übrigen Bauwerken und archäologischen Zeugnissen vor Ort gesetzt

    Methylierungsanalysen und Charakterisierung epigenetischer Regulationselemente bei Imprintingerkrankungen

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    Genomisches Imprinting ist ein epigenetischer Prozess, der zu einer monoallelischen elternspezifischen Expression bestimmter Gene führt. Die Prägung dieser Gene findet bereits in der jeweiligen elterlichen Keimbahn statt. Fehler bei diesem Prozess können zu Veränderungen von Genexpressionsmustern und somit zu Imprintingerkrankungen wie Angelman- oder Prader-Willi-Syndrom, Beckwith-Wiedemann- oder upd(14)pat-Syndrom führen. Die Rolle von cis- und transagierenden Faktoren bei diesen Prozessen ist bisher noch nicht vollständig aufgeklärt. Im Rahmen der vorliegenden Arbeit wurden daher patientenbezogene Ansätze verfolgt, um z.B. epigenetische Regulationsmechanismen näher zu untersuchen. Dabei wurde unter anderem die hier etablierte Methode der hochquantitativen DNA-Methylierungsanalyse genutzt. Ein Kollektiv von AS- und PWS-Patienten mit Imprintingdefekt wurde mittels Affymetrix SNP Array 6.0 genomweit auf Kopienzahlveränderungen untersucht. Es konnten dabei jedoch keine relevanten Veränderungen in cis oder in trans beobachtet werden. Im Rahmen dieser Arbeit war es möglich, ein Kind mit multiplen Imprintingdefekten zu untersuchen. Erste Analysen zeigten, dass der Patient eine Häufung aberranter DNA-Methylierung an geimprinteten und nicht geimprinteten Loci aufweist. Elf Kandidatengene wurden mittels der hier etablierten hochquantitativen Hochdurchsatz-Bisulfitsequenzierung auf dem Roche/454 GS Junior näher untersucht. Nur das Gen FAM50B wies dabei eine allelspezifische Methylierung auf. Außerdem konnte bei zwei hier untersuchten Genen (TSPO und CHP2) durch Trennung der Allele beim Patienten gezeigt werden, dass beide parentalen Allele von den Methylierungsveränderungen betroffen sind. Dies weist darauf hin, dass es zu einem Fehler bei der Aufrechterhaltung der Methylierungsimprints gekommen ist. Weiterhin konnte in der vorliegenden Arbeit bei einer BWS-Patientin mit einer Hypermethylierung der ICR1 auf Chromosom 11p15.5 eine Deletion in cis identifiziert und molekulargenetisch charakterisiert werden. Die 2,2 kb große Deletion führt zum Verlust von drei der sechs CTCF-Bindestellen innerhalb der ICR1 und konnte auch bei drei gesunden Familienmitgliedern nachgewiesen werden. Bei dieser und fünf weiteren Familien mit unterschiedlichen ICR1-Mikrodeletionen wurden Methylierungsanalysen mittels Hochdurchsatz-Bisulfitsequenzierung durchgeführt. Die Ergebnisse zeigten, dass die 2,2 kb große Deletion mit einer leichten Hypermethylierung der verbliebenen CTCF-Bindestellen oder auch einer normalen Methylierung einhergeht. Bei Patienten mit 1,4 und 1,8 kb großen Deletionen, die zum Verlust von einer oder zwei CTCF-Bindestellen führten, zeigte sich hingegen eine starke Hypermethylierung. Die Ergebnisse dieser in vivo Methylierungsanalyse sowie weiterer in vitro Untersuchungen, stützen die zuvor postulierte These, dass die räumliche Anordnung der verbliebenen CTCF-Bindestellen die Bindung von CTCF und damit die Aufrechterhaltung des unmethylierten Zustands des maternalen Allels beeinflusst. Bei einer weiteren Familie mit BWS aufgrund einer Punktmutation einer der OCT4-Bindestellen innerhalb der ICR1 wurde die Methylierung mittels hochquantitativer Hochdurchsatz-Bisulfitsequenzierung untersucht. Dabei konnte gezeigt werden, dass der Grad der Hypermethylierung über die Generationen hinweg zunimmt und mit der phänotypischen Ausprägung korreliert. Im Rahmen dieser Arbeit konnten bei zwei Patienten mit upd(14)pat-Syndrom Deletionen in der chromosomalen Region 14q32 mit einer Größe von 165 bzw. 5,8 kb identifiziert werden. Beide Deletionen führen dabei zum Verlust der MEG3-DMR, während die IG-DMR intakt bleibt. Die 5,8 kb große Deletion konnte auch bei einer ebenfalls betroffenen Schwester und der phänotypisch unauffälligen Mutter beobachtet werden, die diese Deletion im Mosaik auf ihrem paternalen Allel trägt. Wie erwartet konnten mittels Hochdurchsatz-Bisulfitsequenzierung bei allen Patienten nur methylierte Einzelsequenzen der MEG3-DMR detektiert werden. Bei der Mutter konnten aufgrund des Mosaikstatus der Deletion im Verhältnis weniger Einzelsequenzen vom methylierten paternalen Allel detektiert werden als vom unmethylierten maternalen Allel. Die IG-DMR hingegen zeigte, mit Ausnahme einiger bestimmter CpG-Dinukleotide, eine größtenteils normale Methylierung. Die hier gewonnenen Ergebnisse stützten die zuvor postulierte Hypothese der hierarchischen Interaktion der IG-DMR mit der ihr untergeordneten MEG3-DMR und liefern weitere Erkenntnisse über die heterogene Struktur der Methylierung an der IG-DMR.Genomic imprinting is an epigenetic process leading to a monoallelic parent-of-origin specific expression of certain genes. The imprint of these genes is already set in the parental germline. Mistakes during this process can lead to changes in gene expression, and thus, to imprinting diseases like Angelman, Prader-Willi, Beckwith-Wiedemann or upd(14)pat syndrome. The role of cis- and trans-acting factors in these processes is not completely elucidated. In the work at hand, patient-based approaches were pursued to investigate these mechanisms of epigenetic regulation using state-of-the-art methods and a here newly established highly quantitative DNA methylation analysis. A group of AS and PWS patients with an imprinting defect was screened for genome-wide copy number variations using the Affymetrix SNP Array 6.0. No relevant changes in cis or in trans could be identified by this approach. As another part of this thesis a patient with multiple imprinting defects could be investigated. First analyses showed that the patient harboured an accumulation of methylation changes at imprinted and non-imprinted loci. Eleven candidate genes were chosen for further investigation via the here established deep bisulfite sequencing on the Roche/454 GS Junior system. Only the FAM50B gene exhibited allele-specific methylation. Furthermore, allele separation was possible for two genes (TSPO and CHP2) in the patient. The result showed that both parental alleles were equally affected by the methylation changes in the patient, pointing to a defect in imprint maintenance. Additionally in a BWS patient with an imprinting control region 1 (ICR1) hypermethylation on chromosome 11p15.5, a deletion in cis could be identified. Further analyses revealed that the 2.2 kb deletion leads to the loss of three of the six CTCF-binding sites within the ICR1, and it is also present in three healthy family members. Methylation analyses in this and five further families with different ICR1 microdeletions were conducted via deep bisulfite sequencing. The results showed that the 2.2 kb deletion can lead to a mild hypermethylation or a normal methylation of the remaining CTCF-binding sites in ICR1. In contrast, smaller 1.4 and 1.8 kb deletions that abolished only one or two CTCF-binding sites, respectively, led to a severe hypermethylation of the remaining sites within the ICR1. The results of this in vivo methylation analysis as well as further in vitro analyses support the previously postulated hypothesis that the spatial arrangement of the remaining CTCF-binding sites plays an important role in the binding of CTCF, and thus, in the maintenance of the unmethylated state of the maternal allele. In another family with BWS caused by a point mutation within an OCT binding site in the ICR1 methylation analyses were also conducted using deep bisulfite sequencing. It could be shown that the degree of hypermethylation increases over generations and correlates to the phenotypical outcome. As a further part of this thesis, two patients with a upd(14)pat syndrome caused by deletions within the chromosomal region 14q32 could be identified. The deletions have sizes of 165 kb and 5.8 kb and lead to loss of the MEG3-DMR, but the IG-DMR remains intact. The 5.8 kb deletion was also detected in the affected sister and in the phenotypically unremarkable mother, who carries the deletion in a mosaic state on her paternal allele. As expected, only completely methylated deep bisulfite sequencing reads could be obtained for the MEG3-DMR for all upd(14)pat syndrome patients. For the mother with the mosaic deletion, a smaller proportion of reads was obtained from the methylated paternal allele than from the unmethylated maternal allele. In all upd(14)pat patients the methylation at the IG-DMR was mostly normal with the exception of a few certain CpG dinucleotides. These results support the previously postulated hypothesis of a hierarchical interaction of the two DMRs where the IG-DMR governs the MEG3-DMR and yield new insights into the heterogeneous methylation at the IG-DMR

    From Clutter to Cash: Online Book Sales at the University of Maryland’s Engineering and Physical Sciences Library (EPSL)

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    In 2003 the University of Maryland's Engineering and Physical Sciences Library conducted a pilot project selling gift books on the internet resulting in gross sales totaling 9,326,anetprofitof9,326, a net profit of 6,917, for only 96 calculated staff hours. This article describes this project from inception through conclusion summarizing the detailed processes needed to get started and make it profitable, while also giving step-by-step advice on running an online book sale. After three years of operation (over $18,000 in sales), the Library Administration Earned Income Committee recommended retail sales such as this not be part of the Libraries Mission

    Analysis for main toolkits of urban regeneration focused on earthquake: Case of IETT Blocks

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    İstanbul’un son 20 yıl içinde hızlı bir dönüşüm yaşamış olması, bu süreç içinde İstanbul’un gayrimenkul ve rant odaklı büyüme içerisinde olması, yapı stoğunun yaklaşık %60’ının depreme karşı mukavemet gösterecek sağlamlıkta olmaması gibi nedenler ile İstanbul için, kentsel dönüşüm kavramının yoğun olarak tartışılması kaçınılmaz olmuştur. Bununla birlikte İstanbul’da halen kentsel dönüşüm ve depreme hazırlık politikalarının üretilmesinde önemli eksiklikler bulunmaktadır. Bu tespitleri dikkate alarak, yeni dönemin gündemini doğru belirlememiz gerekmektedir. Özellikle deprem beklentisi ve yapı stoğunun yeterli sağlamlıkta olmadığı gerçeği, afet odaklı kentsel dönüşüm planlamasındaki ön koşulların neler olması gerektiğini sorgulamayı zorunlu kılmaktadır. İstanbul’da son yıllarda gerçekleştirilen kentsel dönüşüm çalışmaları, yerel yönetimlerin bireysel çabaları ile uygulanan tekil projelerden ibaret iken, depreme hazırlık çalışmalarının kentsel planlama ile ilişkilendirilme çabaları sınırlı kalmıştır. Bu süreç içinde ‘Kentsel dönüşüm ne olmalıdır? Neleri kapsamalıdır? İstanbul’a özgü koşullar ve stratejiler nelerdir?’ gibi sorulara cevap aranmış ve birtakım kavramsal kargaşa da yaşanmıştır. Bu karmaşa, ancak süreç içinde uygulamalı örneklerle ortadan kalkacaktır. Bu yönde atılan tüm adımlar değerlidir ve ülkesel politikalara ışık tutmalı, öncü olmalıdır. Bu makalenin amacı, deprem odaklı kentsel dönüşüm etki projelerinin araçlarının ve uygulanabilirliğinin değerlendirilmesi ve ileriye dönük kanıta dayalı kentsel dönüşüm politikalarının oluşturulmasıdır. Makalede, deprem odaklı kentsel dönüşüm etki projelerinin anahtar bileşenleri incelenmektedir. Deprem odaklı kentsel dönüşüm etki projesinin uygulanabilirliği örnek alan üzerinde SWOT analizi yöntemi ile sınanmaktadır. Makale, depreme odaklı çözüm ve etki yaratacak kentsel dönüşüm politikalarının önemini vurgulamakta ve kentsel dönüşüm tartışmalarına pilot alan sınaması ile kanıt sunmaktadır. Anahtar Kelimeler: Ateşleyici proje, deprem, İstanbul, dönüşüm, finansal fizibilite.It has been inevitable to discuss the concept of urban transformation intensively for Istanbul due to some reasons like having experienced the rapid transformation for the last 20 years, being in real estate and annuity based growth in this process, approximately % 60 of building stock not being strong and sound enough to resist earthquake. 1999 Marmara earthquake experience has introduced the necessity to plan earthquake preparation studies in Turkey within an integrated system. Designation of a provisional settlement area, associate the reserved places with the urban plans, provision of equipment in neighborhood unit at provisional housing areas and inter-association of the design of prefabricated housing units that form the neighborhood unit and the performance of earthquake preparation studies within this process must be adopted as a new approach. The results of 1999 Marmara earthquake has entailed the formation of "planning, design and management" systematic of earthquake preparation studies in Turkey. While the sensitivity of Turkey and Marmara to earthquake preparation studies increases, another issue of cooperation is reinforcement and the determination of areas that will start "urban regeneration acceleration" rapidly in areas where reinforcement is not sufficient, and the use of urban transformation as a tool in damage reduction studies. However, there are still important deficiencies for the urban regeneration and the production of preparation policies for earthquake. It is necessary to establish sustainable and well qualified urban living spaces for the public prepared for disaster. In other words, on one hand, disaster preparation activities have to be performed quickly and integrated with urban planning on the other hand, approaches on urban regeneration models have to be developed and application  /implementation areas for these models have to be determined. By considering these findings, we have to determine the agenda of the new period in a right way. Especially, the earthquake expectation and the fact that building stock is not sound and strong enough necessitate the questioning of what prerequisites have to be in disaster focused urban regeneration planning. While urban regeneration activities, which have been realized in Istanbul recently is made up of singular projects implemented by the efforts of the local authorities, the efforts to associate preparation activities for the earthquake with urban planning has been limited. In this process, the efforts were made to find answers for the questions like what should urban regeneration be? What should it cover? What are the conditions and strategies special for Istanbul? and several conceptual confusions were experienced. This confusion or chaos will be removed with practical examples in the process. The steps taken to this effect is valuable and should light the way for national policies, they should be pioneer in this way. The aim of this article is to evaluate the toolkits for flagship regeneration projects based on earthquake and their applicability and to build up evidence based urban regeneration policies for future. In the article, after literature investigation on flagship urban regeneration projects, toolkits for flagship urban regeneration projects based on earthquake are examined. By testing the applicability of the toolkits for flagship urban transformation projects based on earthquake on case area with SWOT analysis method, important urban regeneration policies are developed for Istanbul. The article emphasizes the importance of urban regeneration policies which will create flagship development based on earthquake and submits the proof for urban regeneration by pilot area test. In the 2nd section following the introduction section of the article, it is emphasized the main components of an earthquake based urban regeneration project. In the third section, selection of case / sample area and its importance is stated in the context of methodology of the study. In the fourth section of the article, in the framework of key components of an earthquake based regeneration project, the applicability of earthquake based regeneration model is questioned / interrogated on the area taken as a case / sample in Istanbul and the components of regeneration project are evaluated. In Conclusion section, pilot project proofs based strategies and policies are developed in earthquake based regeneration model. Keywords: Flagship, regeneration, Istanbul, disaster mitigation, financial feasibility

    No evidence for intervention-associated DNA methylation changes in monocytes of patients with posttraumatic stress disorder

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    DNA methylation patterns can be responsive to environmental influences. This observation has sparked interest in the potential for psychological interventions to influence epigenetic processes. Recent studies have observed correlations between DNA methylation changes and therapy outcome. However, most did not control for changes in cell composition. This study had two aims: first, we sought to replicate therapy-associated changes in DNA methylation of commonly assessed candidate genes in isolated monocytes from 60 female patients with post-traumatic stress disorder (PTSD). Our second, exploratory goal was to identify novel genomic regions with substantial pre-to-post intervention DNA methylation changes by performing whole-genome bisulfite sequencing (WGBS) in two patients with PTSD. Equivalence testing and Bayesian analyses provided evidence against physiologically meaningful intervention-associated DNA methylation changes in monocytes of PTSD patients in commonly investigated target genes (NR3C1, FKBP5, SLC6A4, OXTR). Furthermore, WGBS yielded only a limited set of candidate regions with suggestive evidence of differential DNA methylation pre- to post-therapy. These differential DNA methylation patterns did not prove replicable when investigated in the entire cohort. We conclude that there is no evidence for major, recurrent intervention-associated DNA methylation changes in the investigated genes in monocytes of patients with PTSD

    Recommendations for a nomenclature system for reporting methylation aberrations in imprinted domains

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    The analysis of DNA methylation has become routine in the pipeline for diagnosis of imprinting disorders, with many publications reporting aberrant methylation associated with imprinted differentially methylated regions (DMRs). However, comparisons between these studies are routinely hampered by the lack of consistency in reporting sites of methylation evaluated. To avoid confusion surrounding nomenclature, special care is needed to communicate results accurately, especially between scientists and other health care professionals. Within the European Network for Human Congenital Imprinting Disorders we have discussed these issues and designed a nomenclature for naming imprinted DMRs as well as for reporting methylation values. We apply these recommendations for imprinted DMRs that are commonly assayed in clinical laboratories and show how they support standardized database submission. The recommendations are in line with existing recommendations, most importantly the Human Genome Variation Society nomenclature, and should facilitate accurate reporting and data exchange among laboratories and thereby help to avoid future confusion
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