The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

<p>Abstract</p> <p>Background</p> <p>Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate ³H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.</p> <p>Methods</p> <p>Melanoma cells were gamma- and/or UV-irradiated. ³H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression.</p> <p>Results</p> <p>UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100.</p> <p>Conclusion</p> <p>These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.</p

Meat and Nicotinamide:A Causal Role in Human Evolution, History, and Demographics

Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B 3 /nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital

Comparison of computer aided production system with the conventional production system in a yatch furniture manufacturing factory

YÖK Tez No: 309237Bu çalışmada; yat ve gezi teknelerine özel mobilyaların üretilmesinde bilgisayar destekli üretim (BDÜ) ve geleneksel üretim (GÜ) uygulamaları incelenmiştir. Mobilyaların CNC makinesinde üretilebilirliği, mobilya adedi, parça sayısı, levha miktarı ve işlem zamanı gibi parametreler esas alınarak değerlendirilmiştir.Araştırma kapsamında HardTop 78 (HT 78) teknesine ait 60 farklı mobilyanın üretimi gerçekleştirilmiştir. Elde edilen veriler MS Project ve Excel 2007 programında değerlendirilmiştir. BDÜ'de üretim için gerekli olan programlama ve diğer hazırlıklar CNC makinesi, WoodWOP 5.0 ve CutRiteV81 paket programları kullanılarak yapılmıştır.Araştırma sonucunda; HT 78 teknesine ait 60 farklı mobilyanın tamamı GÜ sisteminde üretilebilirken, BDÜ sisteminde ise %68'i (42 adet) %100 üretilebilmektedir. Tüm mobilyaların %32'si (19 adet) ise kısmen BDÜ'de üretilebilir olduğu ortaya çıkmıştır. HT 78 teknesine ait mobilyalar 943 adet parçadan oluşmaktadır. Tüm parçaların %95'i (894 adet) BDÜ'de üretilebilmektedir. %5'nin (49 adet) ise BDÜ'de üretimi yapılamamaktadır. Tekne mobilyaları toplam 277 m2 levhadan meydana gelmektedir. Tüm levha miktarının %91'i (253 m2) BDÜ'de üretilebilmektedir. %9'u (24 m2) ise GÜ sisteminde üretilmesi gerektiği ortaya çıkmıştır.Makinelerin işletmeye maliyetleri 2006 ile 2008 yılları arasındaki fiyatları baz alınarak karşılaştırılmıştır. GÜ'de kullanılan 13 adet konvansiyonel makinenin toplam yatırım maliyeti 106.993 ? iken BDÜ'de kullanılan 3 adet makinenin yatırım maliyeti 341.091 ? olduğu ortaya çıkmıştır. GÜ'de kullanılan makine maliyetleri incelendiğinde BDÜ'ye geçişte işletme için ilk yatırım maliyeti 3.18 kat arttığı tespit edilmiştir.Araştırma sonuçlarına göre yat mobilyalarının üretiminde BDÜ sistemlerinin kullanılmasının işletmeler için daha avantajlı olduğu ortaya çıkmıştır. Makine kapasitesinin ve esnekliğinin sağladığı avantajlar arasında; personel sayısının azalması ve üretilen ürün kalitesindeki standartların kalıcı olması, üretim süresinin kısalarak daha hızlı üretim yapılması ve müşteri taleplerinin hızlı bir şekilde karşılanabilmesi gibi üretimin farklı değişkenlerinde olumlu sonuçlar elde edilmiştir.Yat mobilyası gibi genel kullanıma ait mobilyalardan belirgin farklılıklar içeren mobilyaların tasarım sürecinde, mevcut üretim sisteminin yapısı ve üretilebilirlik değerlendirmesinin daha dikkatli yapılması gerekmektedir.Bu amaçla işletmeler Araştırma-Geliştirme çalışmalarına daha çok önem vermeli, CNC makinesi değerlendirme ve seçimleri daha hassas bir şekilde yapılması önerilmektedir.In this study; manufacturing of special furniture for yacht and cruise boats with computer aided manufacturing and conventional manufacturing systems and their manufacturability with CNC machines according to the quantity of furniture, piece and amount of boards were investigatedThe production of 60 different types of furniture for Hardtop 78 project is done with conventional machines. Data gained from this production are saved on Project and Excel 2007 software. As the selection of furniture for computer aided manufacturing, VIP cabin set identical to the 78 feet model and other test furniture were determined. Preparation for computer aided manufacturing is satisfied with CNC machines and its related software. Comparison is done with the data gained from two different manufacturing systems.As a result of study, 60 different furnitures of 78 hardtop project are 100% producible by traditional manufacturing system, but 68%(42 furniture) are producible compeletely by computer aided manufacturing. For all furniture only 32% (19 furniture) are participally producible by computer aided manufacturing system. The furnıture of 78 hardtop includes 943 components. When total number of furniture pieces is examined, 95% (894 pieces) is producible by computer aided manufacyuring system, 5% (49 pieces) is needed to be produced by traditional manufacturing system. Yacht furnitures include 277 m2 boards. 91% (253 m2) of all boards can be produced by computer aided manufacturing system, %9?u (24 m2 ) can be produced by traditional manufacturing system.The comparison between the costs of machines to the companies is based on the prices between 2006 to 2008. The total cost of 13 machines used in traditional manufacturing is 106.993 ? and 3 machines? used in computer aided manufacturing is 341.091 ?. It is identified that when the costs of machines are studied, the transition from traditional manufacturing to computer aided manufacturing is ricing up to the initial investment costs 3.18 times.In this study, it is determined that computer aided manufacturing system is advantageous for yacht furniture production. Beside the advantages of capacity and flexibility of machines, reduction in the number of employees, permanence in quality and standards of furniture, speeding up the manufacturing process and meeting customer demands more quickly are the other major advantages.At the phase of investment for the CNC and other machines that is needed to use for producing special furnitures such as yatch furnitures, the experts should study on construction of furnitures, materials is used and etc. for suitability to furnitures planned to manufacture.It is observed that CNC machine user companies should pay attention to design of furniture for manufacturability in CNC machines. Production development and manufacturing development departments should gain more importance in the companies. It is suggested to managers of such companies to have experts to make more feasibility studies on manufacturing