Force-dependent focal adhesion assembly and disassembly: A computational study

Cells interact with the extracellular matrix (ECM) via cell–ECM adhesions. These physical interactions are transduced into biochemical signals inside the cell which influence cell behaviour. Although cell–ECM interactions have been studied extensively, it is not completely understood how immature (nascent) adhesions develop into mature (focal) adhesions and how mechanical forces influence this process. Given the small size, dynamic nature and short lifetimes of nascent adhesions, studying them using conventional microscopic and experimental techniques is challenging. Computational modelling provides a valuable resource for simulating and exploring various “what if?” scenarios in silico and identifying key molecular components and mechanisms for further investigation. Here, we present a simplified mechano-chemical model based on ordinary differential equations with three major proteins involved in adhesions: integrins, talin and vinculin. Additionally, we incorporate a hypothetical signal molecule that influences adhesion (dis)assembly rates. We find that assembly and disassembly rates need to vary dynamically to limit maturation of nascent adhesions. The model predicts biphasic variation of actin retrograde velocity and maturation fraction with substrate stiffness, with maturation fractions between 18–35%, optimal stiffness of ∼1 pN/nm, and a mechanosensitive range of 1-100 pN/nm, all corresponding to key experimental findings. Sensitivity analyses show robustness of outcomes to small changes in parameter values, allowing model tuning to reflect specific cell types and signaling cascades. The model proposes that signal-dependent disassembly rate variations play an underappreciated role in maturation fraction regulation, which should be investigated further. We also provide predictions on the changes in traction force generation under increased/decreased vinculin concentrations, complementing previous vinculin overexpression/knockout experiments in different cell types. In summary, this work proposes a model framework to robustly simulate the mechanochemical processes underlying adhesion maturation and maintenance, thereby enhancing our fundamental knowledge of cell–ECM interactions

Endüstri Mirasının Evrensel Tasarım İlkeleri Kapsamında İncelenmesi: İzmit Seka Kağıt Müzesi Örneği

Tarihten hız alarak gelişen endüstrileşme ile başlayan üretim dönemi; endüstri kentlerini, yapılı fiziksel çevreyi, sosyoekonomik özellikleri büyük ölçüde dönüştürmüştür. Toplumun her alanında meydana gelen bu dönüşüm pek çok etkileşime sebep olmuştur. Bu etkileşimin en büyük yansıması ise toplumsal emeğin tekniğini ve sanatsal yaratma gücünü yansıtan endüstri yapıları üzerinde olmuş ve bu da kültürel miras kavramını doğurmuştur. Kültürel miras kavramı genel itibariyle toplumların kimliğini var eden somut ve soyut oluşumlar olarak tanımlanmıştır. Kültürel mirasın somut oluşumları sitler, tarihi yapılar, endüstri alanları; toplumların zengin yaşam kültürünü, özgünlüklerini yansıtmaktadır. Geçmişe ait anıları, yaşanmışlıkları biriktiren, bireysel ve kolektif kimliğin zeminini oluşturan bu mekanların geleceğe aktarımı kültürel kimliğin sürekliliği için büyük bir önem taşımaktadır. Bu aktarım koruma ve yeniden işlevlendirme ile sağlanmaktadır. Bu bağlamda yeniden işlevlendirme ve toplumdaki tüm kullanıcı gruplarının gündelik yaşama aktif olarak katılabilmesi, sürdürülebilir bir toplum ve gelecek için vazgeçilmez bir unsurdur. Bireylerin gündelik yaşama aktif olarak katılımı için mekânsal olarak pek çok sorunla karşılaşılmaktadır. Söz konusu katılımın en sorunlu alanı ise kültürel ve doğal miras içinde gündelik yaşama dahil edilen endüstriyel alanlardır. Bu alanların koruma politikalarında evrensel tasarımın bir ölçüt olarak dahil edilmemesi, korunması gerekli taşınmaz kültür ve tabiat varlıklarının tespit ve tescili hakkında yönetmeliğe göre yalnızca yapının tescilli olup olmamasının dikkate alınması bu alanı sorunlu hale getiren başlıca nedenlerdir. Ancak kültürel mirasın korunması ve yeniden işlevlendirmesi ile evrensel tasarım, erişilebilirlik ve eşitlik kavramları birbirini tamamlayan süreçlerdir. Kültürel miras yapılarının geleceğe aktarımı, kullanımı, değerinin korunması evrensel tasarım yaklaşımı ile mümkündür ve insanın var oluşundan bu yana tasarlanan tüm yapıların, çevrelerin ortak hedefi kullanıcılara hizmet etmektir. Bu doğrultuda koruma kapsamında yer alan endüstriyel alanların koruma - yeniden işlevlendirme - kullanım sürecinde evrensel tasarımın bir ölçüt olarak değerlendirilmemesi sorunu çalışmanın çıkış noktası olmuştur. Bu sorundan hareketle eski ve yeni birlikteliğinden doğan mekanların en büyük göstergelerinden biri olan, kültürel miras niteliği kazanmış ve çağdaş yaklaşımlar ile müze işlevine adapte edilmiş olan SEKA Kağıt müzesi evrensel tasarım kapsamında incelenmiştir. Bu çalışmada, fotoğraf - video çekimleri, yerinde gözlem ve inceleme, literatür araştırması, yeniden işlevlendirme proje çalışmaları ile geniş bir alana yayılan SEKA alanı ve Kağıt Müzesi‟nin evrensel tasarım standartlarına uygunluğu; ulaşım ağından yapı çevresine, mekânsal organizasyonundan iç mekan donatılarına kadar evrensel tasarım ilkelerine göre ayrı alt başlıklar halinde değerlendirilmiştir.İncelemeler sonucunda evrensel tasarıma ilişkin bazı önlemlerin alındığı fakat eksik ve/veya hatalı olduğu için bu uygulamaların engelsiz erişim için yeterli olmadığı saptanmıştır.The production period, which started with the industrialization that accelerated from history; It has transformed industrial cities, physical environment and socio-economic characteristics to a great extent. This transformation, which has occurred in all areas of society, has led to many interactions. The greatest reflection of this interaction has been on the industrial structures that reflect the technique of social labor and the power of artistic creation, and this has given birth to the concept of cultural heritage. The concept of cultural heritage is generally defined as concrete and abstract formations that create the identity of societies. Concrete formations of cultural heritage sites, historical buildings, industrial areas; reflects the rich life culture and originality of societies. The transfer of these spaces, which accumulate memories and experiences of the past and form the basis of individual and collective identity, to the future is of great importance for the continuity of cultural identity. This transfer is ensured by protection and re-functioning. In this context, re-functioning and the active participation of all user groups in the society are an indispensable element for a sustainable society and the future.Many spatial problems are encountered for the active participation of individuals in daily life. The most problematic area of participation in question is the industrial areas included in daily life within the cultural and natural heritage. Not including universal design as a criterion in the conservation policies of these areas, and considering only whether the building is registered according to the regulation on the determination and registration of immovable cultural and natural assets to be protected are the main reasons that make this area problematic. However, the protection and re-functioning of cultural heritage and the concepts of universal design, accessibility and equality are processes that complement each other. The transfer of cultural heritage structures to the future, their use and preservation of their value is possible with a universal design approach, and the common goal of all structures and environments designed since the existence of man is to serve the users. In this direction, the starting point of the study is the problem of not evaluating the universal design as a criterion in the protection - re-functioning - use process of industrial areas within the scope of protection. Based on this problem, SEKA Paper museum, which is one of the biggest indicators of the spaces born from the unity of the old and the new, has gained the quality of cultural heritage and has been adapted to the museum function with contemporary approaches, has been examined within the scope of universal design. In this study, the compliance of the SEKA area and Paper Museum with universal design standards, which is spread over a wide area with photography - video shootings, on-site observation and examination, literature research, re-functioning project studies; From the transportation network to the building environment, from the spatial organization to the interior furnishings, they have been evaluated in separate sub-headings according to the universal design principles. As a result of the examinations, it was determined that some precautions regarding universal design were taken, but these applications were not sufficient for barrier-free access since they were incomplete and/or faulty

Bölgesel Kalkınmada Turizm Girişimciliğinin Rolü: Akçakoca Örneği

Bu araştırmanın amacı, Cittaslow (Sakin Şehir) olma yoluna giren Akçakoca ilçesinin kırsal turizm kapsamında değerlendirilebilecek alanlarında faaliyet gösteren turizm girişimcilerinin bölgesel kalkınmadaki rollerinin belirlenmesi ve bölgesel kalkınmaya katkı sağlayıp sağlamadıklarının değerlendirilmesidir. Çalışmanın alt amaçları; turizm girişimcilerinin temel sorunlarının ele alınması, turizm girişimciliğini tehdit eden unsurların belirlenmesi ve Akçakoca ilçesindeki turizm girişimcilerinin geliştirilmesine ve sayılarının arttırılmasına yönelik öneriler sunulmasıdır. Çalışmada veriler, yarı yapılandırılmış mülakat tekniğiyle 18 turizm girişimcisi ile görüşülerek elde edilmiştir. Araştırma sonucunda, turizm girişimcilerinin hem bölgesel kalkınmada hem de bölgede turizmin gelişmesinde etkin rol oynadığı belirlenmiştir. Turizm girişimcileri kurmuş oldukları işletmeler sayesinde bölgede gelir artışına, yeni istihdam olanaklarının oluşumuna ve ziyaretçi memnuniyet düzeyinin artış göstermesine katkı sağlamaktadırlar. Ortaya çıkarılan bu olumlu sonuçlara karşıt olarak yerel yönetimlerin turizm girişimciliğinin teşvik edilmesi ve geliştirilmesi kapsamında yeterli olmadığı sonucuna ulaşılmıştır. Bu bağlamda, turizm potansiyeli olan bölgelerde turizm sektörüne yapılan yatırımların bölge için önem arz etmesi bakımından turizm sektöründe faaliyette bulunan girişimcilerin tespit edilmesi ve bölgesel kalkınmaya katkısının belirlenmesi bu çalışmayı önemli kılmaktadır.The aim of this research is to determine the roles of tourism entrepreneurs operating in areas that can be evaluated within the context of rural tourism in the district of Akçakoca, which is on the way of becoming Cittaslow, and to assess whether it contributes to regional development. Sub objectives of the study; addressing the main problems of tourism entrepreneurs, identifying the elements threatening tourism entrepreneurship and to offer suggestions for the development of tourism entrepreneurs in Akçakoca district and increasing their number. The data in the study was obtained by interviewing 18 tourism entrepreneurs using a semi-structured interview technique. As a result of the research, it has been determined that tourism entrepreneurs play an active role both in regional development and in the development of tourism in the region. Thanks to the businesses they have established, tourism entrepreneurs contribute to the increase in income in the region, the creation of new employment opportunities and an increase in visitor satisfaction. Contrary to these positive results, it has been concluded that local governments are not sufficient within the scope of promoting and developing tourism entrepreneurship. In this context, in terms of the importance of investments made in the tourism sector in regions with tourism potential for the region; Identifying the entrepreneurs operating in the tourism sector and determining their contribution to regional development makes this study important

Evaluation of infection resistance of biological implants through CMP based micro-patterning

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Biomaterials are widely used for dental implants, orthopedic devices, cardiac pacemakers and catheters. One of the main concerns on using bio-implants is the risk of infection on the materials used. In this study, our aim is to quantify the effect of controlled surface roughness on the infection resistance of the titanium based bio-materials which are commonly used for orthopedic devices and dental implants. To modify the surface roughness of the surfaces in a controlled manner, Chemical Mechanical Polishing (CMP) technique, which is extensively used in semiconductor industry for the planarization of the interlayer dielectrics and metals, is utilized. To determine the infection resistance of the created films with varying surface roughness, bacteria growth response was studied on titanium plates after CMP.European Commissio

Evaluation of infection resistance of biological implants through CMP based micro-patterning

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Biomaterials are widely used for dental implants, orthopedic devices, cardiac pacemakers and catheters. One of the main concerns on using bio-implants is the risk of infection on the materials used. In this study, our aim is to quantify the effect of controlled surface roughness on the infection resistance of the titanium based bio-materials which are commonly used for orthopedic devices and dental implants. To modify the surface roughness of the surfaces in a controlled manner, Chemical Mechanical Polishing (CMP) technique, which is extensively used in semiconductor industry for the planarization of the interlayer dielectrics and metals, is utilized. To determine the infection resistance of the created films with varying surface roughness, bacteria growth response was studied on titanium plates after CMP.European Commissio

Metal oxide nano film characterization for CMP optimization

Due to copyright restrictions, the access to the full text of this article is only available via subscription.This paper focuses on the planarization of metallic films in microelectronics manufacturing by CMP through investigation of metal oxide thin films forming as a result of the chemical component of the process. Tungsten planarization is discussed as a model to establish the role of metal oxide nano-films in achieving material removal through their formation characteristics during polishing. The findings indicate a protective oxide film formation on tungsten, which tends to nucleate at high concentrations of oxidizers and enables material removal through the interaction of nano-particles in the slurry with the surface oxide hillocks

Metal oxide nano film characterization for CMP optimization

Due to copyright restrictions, the access to the full text of this article is only available via subscription.This paper focuses on the planarization of metallic films in microelectronics manufacturing by CMP through investigation of metal oxide thin films forming as a result of the chemical component of the process. Tungsten planarization is discussed as a model to establish the role of metal oxide nano-films in achieving material removal through their formation characteristics during polishing. The findings indicate a protective oxide film formation on tungsten, which tends to nucleate at high concentrations of oxidizers and enables material removal through the interaction of nano-particles in the slurry with the surface oxide hillocks

Characterization of chemically modified thin films for optimization of metal CMP applications?

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Metal CMP applications necessitate the formation of a protective oxide film in the presence of surface active agents, oxidizers, pH regulators and other chemicals to achieve global planarization. Formation and mechanical properties of the chemically modified metal oxide thin films in CMP determine the stresses develop at the interfaces delineating the stability and protective nature of the chemically altered films on the surface of the metal wafer. The balance between the stresses built in the film structure versus the mechanical actions provided during the process can be used to optimize the process variables and furthermore help define new planarization techniques for the next generation microelectronic device manufacturing. In this study, the preliminary studies were concentrated on the very well established tungsten CMP applications and furthermore, titanium CMP applications were presented as a part of surface nano-structuring methodology for biomedical applications by stressing the synergistic effect of protective metal oxide film of titanium in this advanced application

Advanced slurry formulations for new generation chemical mechanical planarization (CMP) applications

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Chemical Mechanical Planarization (CMP) is widely used to ensure planarity of metal and dielectric surfaces to enable photolithography and hence multilevel metallization in microelectronics manufacturing. The aim of this study is to establish a fundamental understanding on the dynamic growth of nano-scale protective oxide thin films during CMP to enable the selection of proper oxidizer concentrations for slurry formulations. Tungsten was selected as the model metal film to study the formation of these metal oxide films in various oxidizers and Atomic Force Microscope (AFM) was used to measure the surface roughness of the samples conditioned in the oxidizer environment before and after the CMP was conducted. The affect of surface roughness on wettability of the surfaces were also studied through contact angle measurements on the treated tungsten films. Fourier Transform Infrared Spectroscopy with Attenuated Total Reflectance FTIR/ATR technique in combination with the X-Ray Reflectivity (XRR) were utilized to determine the thicknesses of the oxidized nano films on the tungsten surface. The results were evaluated through the material removal responses reported in the literature for the W-CMP in addition to the comparison of the Pilling-Bedworth ratios of the oxidized nano films to determine the ability of the created oxide film as a self-protective oxide

The Role of Women Entrepreneurs in Regional Development: Akçakoca District Example

Günümüzde gelişmekte olan girişimcilik faktörü teknolojik gelişmelerin ve ekonomikbeklentilerin yardımıyla önem kazanmıştır. Buna bağlı olarak girişimcilerin sayısı artmaktave kadınların da birer girişimci olarak çalışma hayatına atıldıkları görülmektedir. Kadın girişimcilerbölge ekonomisinin kalkınmasına ve büyümesine destek sağlamaktadır. Ancak kadıngirişimciler bu konuda ekonomik şartlarla birlikte çevresel etkenlerden kaynaklanan birçoksorunla karşı karşıya kalmaktadırlar. Girişimci kadınların bölge ekonomisine katkı sağlamalarıbu sorunların nedenlerinin belirlenmesi ve çözüm önerileri ile gerçekleşebilecektir.Bu çalışma, kadın girişimcilerin girişimcilik özellikleri, girişimci olma nedenleri, başarı vebaşarısızlıklarına etki eden faktörleri ve bölge kalkınmasına sağladıkları katkıları belirlemektir.Bu amaçla araştırmada nitel araştırma deseni kullanılmıştır. Araştırma verileri iseAkçakoca ilçesinde faaliyet gösteren kadın girişimcilere uygulanmış olan yapılandırılmışgörüşme tekniği ile elde edilmiştir. Bu bağlamda çalışma Akçakoca Esnaf ve SanatkârlarOdaları Birliği ile Akçakoca Ticaret ve Sanayi Odasına kayıtlı olan 23 kadınla yapılan görüşmeleredayanmaktadır. Yapılan görüşmeler kapsamında girişimci kadınların Akçakoca’nın bölge kalkınmasına sağladığı katkılar bakımından, işletme kurulması, istihdam oluşturulması,misafirlere bölgenin tanıtılması, çevre illere mevcut müşteri potansiyelinin gönderilmemesive diğer kadınların da girişimciliğe teşvik edilmesi sonuçlarına ulaşılmıştır.Today, the developing entrepreneurship factor has gained importance withthe help of technological developments and economic expectations. In parallel with this, itis seen that the number of entrepreneurs is increasing, and women are engaged in workinglife as entrepreneurs. These women entrepreneurs provide support for the development andgrowth of the regional economy. However, entrepreneur women face many challenges andproblems from environmental factors, along with economic conditions. The contributionof entrepreneur women to the regional economy can only be achieved by determining thecauses of these problems and proposing solutions to these problems.This study aims to reach personal views of women by learning the entrepreneurshipcharacteristics and reasons for being an entrepreneur of women entrepreneurs, the factorsthat affect their successes and cause their failures and their contributions to regionaldevelopment. For this purpose, qualitative research design will be used in the research.The research data have been obtained by structured interview technique applied to femaleentrepreneurs operating in the district of Akçakoca. In this context, the study is basedon interviews conducted with 23 women registered in Akçakoca Union of Chamber ofMerchants and Craftsmen and Akçakoca Chamber of Commerce and Industry. As a resultof the interviews conducted, it has been achieved that entrepreneur women can providecontribution to the regional development of Akçakoca by introducing their region to theincoming customers with their enterprises they established and their employees theyemployed, preventing the customer potential to visit the nearby cities and encouragingother women to become entrepreneurs