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The accessibility of airports and the airport preference of users are significant criteria for the competitiveness of airports. When passengers choose a route, they actually expect the completion of the transportation chain and they want to travel to the door from the door. For this reason, the factors that affect the passenger's decision for a significant option go beyond the price and quality of air services. The decision for a specific air service and a particular airport depends on the accessibility of the airport to a considerable extent. Factors affecting the choice of the airport can simply be divided into two categories. The category that reflects the number of air fares, frequencies and served destinations is defined as "air side". The category of airport accessibility, namely access, is also called "land side". The locations of the airports are usually set up around the periphery of the city’s with a reasonable length such as 50 km. The access of the airports may affect the passenger demands, so this study investigate the Turkish airport coverage in length of 50, 75 and 100 km radius from city centers. The main purpose of this study thus investigates whether a new airport construction is needed or not for domestic flights. Results showed that if 100 km radius length is used as a criterion for building new airport, only 10 cities with total population of about 2.5 million people will be outside the airport access. Socio-economical features are highly related with the location choice of airports. Therefore, accessibility properties are compared with the special properties of the cities and possible new airport locations have been determined.

Havaalanlarının erişilebilirliği ve kullanıcıların havaalanlarının tercihi, havaalanlarının rekabet edebilirliği için önemli kriterlerdir. Yolcular bir rota seçtiklerinde, aslında taşıma zincirinin tamamlanmasını beklemekte ve kapıdan kapıya seyahat etmek istemektedirler. Bu nedenle, yolcuların belli bir seçenek için kararını etkileyen faktörler, hava hizmetlerinin fiyat ve kalitesinin ötesine geçmektedir. Belirli bir hava hizmeti ve belirli bir havaalanı için verilen karar, havaalanının büyük ölçüde erişilebilir olmasına bağlıdır. Havaalanı seçimini etkileyen faktörler sadece iki kategoriye ayılmaktadır. Uçuş ücretlerini, frekansları ve sunulan varış noktalarının sayısını yansıtan kategori "hava tarafı" olarak tanımlanmaktadır. Havaalanına erişilebilirlik kategorisine de, yani erişime, "kara tarafı" denir. Havaalanlarının yerleri genellikle kentin çevresine 50 km gibi makul bir uzunlukta kurulmaktadır. Havaalanlarının erişimi yolcu taleplerini etkileyebilir, bu nedenle bu çalışma, Türk havaalanlarının şehir merkezlerinden 50, 75 ve 100 km yarıçapı uzunluğunu araştırmaktadır. Bu çalışmanın temel amacı, iç hat uçuşları için yeni bir havaalanı inşaatının gerekli olup olmadığını incelemektir. Sonuçlar, 100 km yarıçap uzunluğunun yeni bir havalimanı inşa edilmesinde bir kriter olarak kullanılması durumunda, toplam nüfusu yaklaşık 2,5 milyon olan sadece 10 kentin havaalanına erişimin dışında olacağını göstermiştir. Sosyo-ekonomik özelliklerin havalimanlarının yer seçimi ile yakından ilgili olduğu görülmektedir. Bu nedenle erişilebilirlik özellikleri şehirlerin diğer özellikleri ile karşılaştırılmış ve olası yeni havalimanı yerleri belirlenmiştir.

Transit planning scenarios may lead to the different Objective Function (OF) values since each scenario has different transit travel times, frequencies and fleet sizes. Change on those variables leads to the different accessibility values for each route set. Therefore, the actual performance of a route set may be unforeseen since the accessibility values are out of evaluation criteria. This study tries to generate techniques, which handle the relation between accessibility and transportation in the scope of public transit. The accessibility measures, which have direct relation with land use and transportation, are utilized in transit route set decision. Accessibility measures have been utilized in the decision-making process of transit network design. Conventional OFs, which are used to determine the most effective route sets are combined with accessibility based OFs and the decision-making process of transit network design is strengthened. In this context, the effects of accessibility measures in decision-making process of transit network design have been represented on an 8-node example transit network. The results showed the accessibility measures could effectively improve the planners’ decision accuracy. First published online 12 April 2017

Ülkemizde ulaşım alt türler arasındaki dengesizlik ve entegrasyon en önemli problem olarak karşımıza çıkmaktadır. Çalışmada son yıllarda içhat hava taşımacılığı alt türünde gözlenen talebin aylık değişimini yansıtabilen indeksleme yöntemi kullanılarak modellemesi yapılmış, geleceğe yönelik tahminler yapılarak alt türlerdeki dengesizliğin giderilmesi yönünde önerilerde bulunulmuştur. Modelleme çalışmasında bağımsız değişkenler olarak Satın alma Gücü Paritesi ve jet yakıt fiyatları kullanılmıştır. Kullanılan yöntem ile aylık ve mevsimsel değişmelere duyarlı bir model geliştirilmiştir. Yapılan hesaplamalar sonucunda gelir seviyesinde iyimser gelişmeler gözlenmesi ve jet yakıt fiyatlarında düşük seyrin gözlenmesi durumunda karayolu ulaşım sisteminin ardından hava taşımacılığının demiryolu sistemi ile ciddi bir rekabet içinde olacağı belirlenmiştir. Bu nedenle ücret politikalarında gerekirse jet yakıt fiyatlarında vergi düzenlemesi ile talep gelişiminin desteklenmesinin gerekli olduğu düşünülmektedir.

Policy makers and planners evaluate the implementation of the urban public transport (UPT) planning studies in terms of some objective measures such as load factor, mean volume per trip, capacity usage ratio and total capacity. In some cases, improving these measures may lead an unforeseen decrease on accessibility to the opportunities in terms of UPT users. Thus, this study aims to evaluate Potential Accessibility (PA) as an efficiency measure in decision stage of UPT planning. It widely depends on fieldwork, surveys, data inventories and existing plans. In this context, a comprehensive UPT planning has been carried out through VISUM traffic simulation software by taking the PA into account, and a four-step UPT planning procedure has been proposed. The results showed that PA may alternatively be used as an evaluation instrument in decision stage of UPT planning while the objective measures are insufficient to represent the effectiveness of alternative scenarios.

Bu çalışmada geliştirilen yaklaşık hesaplama metodu (YHM) ile sinyalize kavşaklardaki ortalama taşıt gecikmelerinin bileşenleri, koordinat transformasyon tekniği kullanılarak çözülmüştür. Kavşak performans göstergeleri doygunluk üstü durumlar için iki farklı yaklaşım ile ve doygunluk altı linkler için kuyruk oluşup oluşmaması durumlarına göre incelenmiştir. Yapılan hesaplamalarda, kararlı denge ve deterministik kuyruk irdelenerek zamana bağlı dönüşümler yapılarak yaklaşık matematiksel ifadeler çıkarılmıştır. Geliştirilen YHM örnek sinyalize kavşak üzerine uygulanmış ve YHM'nin performansı mevcut durum ile Webster metoduna göre test edilmiştir. Geliştirilen metot ile seçilen kavşağın ortalama performansının % 500 oranında arttığı bulunmuştur. Ayrıca sinyal parametrelerinin mevcut durum ve Webster sinyal kontrolünden oldukça büyük farklılık gösterdiği belirlenmiştir.

This study develops approximate mathematical expressions for delay components at signalized intersections. Delay components are solved with the coordinate transformation method. The performance indicators for the signalized intersection are determined as an oversaturated and under saturated cases. During the analysis, the steady-state and the deterministic queuing theory are investigated first, and then time-dependent transformation is made. Developed model, called YHM, is applied to an example signalized intersection. Results are compared with the current situation and the Webster method. YHM is improved the intersection performance by about 500 % for this example. Moreover, signal parameters are significantly differs from the current and Webster signal control.

In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal cells called the epithelial to mesenchymal transition (EMT). The cytoskeleton is an active network of three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These filaments play a central role in the structural design and cell behavior and are necessary for EMT. During EMT, epithelial cells undergo a cellular transformation as manifested by cell elongation, migration, and invasion, coordinated by actin cytoskeleton reorganization. The actin cytoskeleton is an extremely dynamic structure, controlled by a balance of assembly and disassembly of actin filaments. Actin-binding proteins regulate the process of actin polymerization and depolymerization. Microtubule reorganization also plays an important role in cell migration and polarization. Intermediate filaments are rearranged, switching to a vimentin-rich network, and this protein is used as a marker for a mesenchymal cell. Hence, targeting EMT by regulating the activities of their key components may be a potential solution to metastasis. This review summarizes the research done on the physiological functions of the cytoskeleton, its role in the EMT process, and its effect on multidrug-resistant (MDR) cancer cells-highlight some future perspectives in cancer therapy by targeting cytoskeleton.

Signal transducer and activator of transcription (STAT) proteins, and in particular STAT3, have been established as heavily implicated in cancer. Recently, the involvement of STAT5 signalling in the pathology of cancer has been shown to be of increasing importance. STAT5 plays a crucial role in the development of the mammary gland and the homeostasis of the immune system. However, in various cancers, aberrant STAT5 signalling promotes the expression of target genes, such as cyclin D, Bcl-2 and MMP-2, that result in increased cell proliferation, survival and metastasis. To target constitutive STAT5 signalling in cancers, there are several STAT5 inhibitors that can prevent STAT5 phosphorylation, dimerisation, or its transcriptional activity. Tyrosine kinase inhibitors (TKIs) that target molecules upstream of STAT5 could also be utilised. Consequently, since STAT5 contributes to tumour aggressiveness and cancer progression, inhibiting STAT5 constitutive activation in cancers that rely on its signalling makes for a promising targeted treatment option.

Cytoskeletal proteins, which consist of different sub-families of proteins including microtubules, actin and intermediate filaments, are essential for survival and cellular processes in both normal as well as cancer cells. However, in cancer cells, these mechanisms can be altered to promote tumour development and progression, whereby the functions of cytoskeletal proteins are co-opted to facilitate increased migrative and invasive capabilities, proliferation, as well as resistance to cellular and environmental stresses. Herein, we discuss the cytoskeletal responses to important intracellular stresses (such as mitochondrial, endoplasmic reticulum and oxidative stresses), and delineate the consequences of these responses, including effects on oncogenic signalling. In addition, we elaborate how the cytoskeleton and its associated molecules present themselves as therapeutic targets. The potential and limitations of targeting new classes of cytoskeletal proteins are also explored, in the context of developing novel strategies that impact cancer progression., Competing Interests: The authors declare no conflicts of interest.

Oxymatrine (OMT) is a quinolizidine alkaloid derived from the roots of the Sophora genus plants. It has been widely used as a treatment for chronic hepatitis infections and inflammatory diseases due to its effective immunomodulatory and anti-inflammatory properties. Recently, the potential anti-cancer effects of OMT have been actively studied in various cancers. It can induce apoptosis and inhibit the proliferation of tumor cells, including those of colorectal cancer, gall bladder carcinoma, and leukemia. Moreover, it reduces tumor growth in different in vivo models as well as augments the anti-cancer effects of existing chemotherapeutics on tumor cells. OMT regulates various oncogenic signaling pathways such as the Akt, epidermal growth factor receptor (EGFR), and nuclear factor kappa B (NF-κB) cascades to exert its cytotoxicity against cancer cells. This review provides an overview of the current knowledge on the potential of OMT as an anti-cancer therapeutic through the modulation of diverse oncogenic molecular targets., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

: The FBXW7 (F-box with 7 tandem WD40) protein encoded by the gene FBXW7 is one of the crucial components of ubiquitin ligase called Skp1-Cullin1-F-box (SCF) complex that aids in the degradation of many oncoproteins via the ubiquitin-proteasome system (UPS) thus regulating cellular growth. FBXW7 is considered as a potent tumor suppressor as most of its target substrates can function as potential growth promoters, including c-Myc, Notch, cyclin E, c-JUN, and KLF5. Its regulators include p53, C/EBP-δ, Numb, microRNAs, Pin 1, Hes-5, BMI1, Ebp2. Mounting evidence has indicated the involvement of aberrant expression of FBXW7 for tumorigenesis. Moreover, numerous studies have also shown its role in cancer cell chemosensitization, thereby demonstrating the importance of FBXW7 in the development of curative cancer therapy. This comprehensive review emphasizes on the targets, functions, regulators and expression of FBXW7 in different cancers and its involvement in sensitizing cancer cells to chemotherapeutic drugs.

Cancer is still a major risk factor to public health globally, causing approximately 9.8 million deaths worldwide in 2018. Despite advances in conventional treatment modalities for cancer treatment, there are still few effective therapies available due to the lack of selectivity, adverse side effects, non-specific toxicities, and tumour recurrence. Therefore, there is an immediate need for essential alternative therapeutics, which can prove to be beneficial and safe against cancer. Various phytochemicals from natural sources have been found to exhibit beneficial medicinal properties against various human diseases. Zerumbone is one such compound isolated from Zingiber zerumbet Smith that possesses diverse pharmacological properties including those of antioxidant, antibacterial, antipyretic, anti-inflammatory, immunomodulatory, as well as anti-neoplastic. Zerumbone has shown its anti-cancer effects by causing significant suppression of proliferation, survival, angiogenesis, invasion, and metastasis through the molecular modulation of different pathways such as NF-κB, Akt, and IL-6/JAK2/STAT3 (interleukin-6/janus kinase-2/signal transducer and activator of transcription 3) and their downstream target proteins. The current review briefly summarizes the modes of action and therapeutic potential of zerumbone against various cancers.

A leaching model was developed using the United States Geological Survey public domain PHREEQC geochemical package to simulate the leaching of Pb, Cd, As, and Cr from cementitious wastes. The model utilises both kinetic terms and equilibrium thermodynamics of key compounds and provides information on leachate and precipitate speciation. The model was able to predict the leaching of Pb, Cd, As, and Cr from cement in the presence of both simple (0.1 and 0.6M acetic acid) and complex municipal landfill leachates. Heavy metal complexation by the municipal landfill leachate was accounted for by the introduction of a monoprotic organic species into the model. The model indicated Pb and As were predominantly incorporated within the calcium silicate hydrate matrix while a greater portion of Cd was seen to exist as discrete particles in the cement pores and Cr (VI) existed mostly as free CrO4(2-) ions. Precipitation was found to be the dominant mechanism controlling heavy metal solubility with carbonate and silicate species governing the solubility of Pb and carbonate, silicate and hydroxide species governing the solubility of Cd. In the presence of acetic acid, at low pH values Pb and Cd acetate complexes were predominant whereas, at high pH values, hydroxide species dominated. At high pH values, the concentration of As in the leachate was governed by the solubility of Ca3(AsO4)2 with the presence of carbonate alkalinity competing with arsenate for Ca ions. In the presence of municipal landfill leachate, Pb and Cd organic complexes dominated the heavy metal species in solution. The reduction of As and Cr in municipal landfill leachate was crucial for determining aqueous speciation, with typical municipal landfill conditions providing the reduced forms of As and Cr.

Soil contamination is a major environmental problem due to the ecological threat it poses. In this work, electron probe microanalysis (EPMA), X-ray diffraction (XRD), and leaching studies were employed to explain the different leaching behaviors of non-stabilized and stabilized soils. The applicability of the leaching fluids used in the toxicity characteristic leaching procedure (TCLP) and Australian Standards, AS 4439.1-1997 for assessing the hazards of contaminated soils was investigated as was the leaching of lead from soil stabilized by cement and buffered phosphate techniques. The results showed Pb speciation in the soil highly influenced metal leaching. The synthetic leaching fluids were unable to provide a reliable estimation of Pb concentration in the municipal landfill leachate (ML) due to the absence of organic ligands capable of forming stable complexes with the lead. Water provided the closest representation of lead leaching from the non-stabilized and phosphate stabilized soils while sodium tetraborate buffer was found to be suitable for cement-stabilized soil in a non-putrescible landfill leachate system. A comparison of stabilization methods revealed that the buffered phosphate technique was more suitable for stabilizing the lead in the soil relative to cement stabilization.

The Toxicity Characteristic Leaching Procedure (TCLP) has been widely used to characterize the suitability of solid wastes for disposal in landfills. However, the widespread application of this test for the assessment of wastes disposed in different landfill types is often questionable. This paper investigates the leaching profiles of cement-stabilized heavy metal ions, namely, Pb (II), Cd (II), As(V), and Cr(VI), using acetic acid and leachates from municipal and nonputrescible Australian landfill sites. The leaching profiles of Pb, Cd, As, and Cr using acetic acid were found to be similar to the nonputrescible landfill leachate and differed markedly from the municipal solid waste (MSW) leachate. The additional presence of high amounts of organic and inorganic compounds in the municipal landfill leachate influenced the leaching profiles of these metal ions as compared to the acetic acid and the nonputrescible systems. It is postulated that the organic compounds present in the municipal landfill leachate formed complexes with the Pb and Cd, increasing the mobility of these ions. Moreover, the organic compounds in the municipal landfill leachate induced a reducing environment in the leachate, causing the reduction of Cr(VI) to Cr(III). It was also found that the presence of carbonates in the municipal landfill leachate affected the stability of calcium arsenate, with the carbonate competing with arsenate for calcium at high pH, forcing arsenate into the solution.

Having the toxicity characteristic leaching procedure (TCLP) as a starting point, this study examined the effect of the various leaching parameters on the leaching of Pb and Cd from cementitious wastes. Using modified TCLP procedures, the parameters investigated were the acid concentration, leaching duration, particle size of the crushed waste, liquid to solid ratio, and the acid type. The main finding was that the final leachate pH controls the leachability of metals due to its influence on their solubility. The high alkalinity of cementitious waste buffers the leachate at a pH where most metals become insoluble. The TCLP was found to result in an unrealistic condition for cementitious wastes due to the high resultant leachate pH.