22 research outputs found
The Changing Political Role of the Turkish Military since the Advent of the Justice and Development Party (AKP)
The Turkish military has had a large role in Turkish politics since the foundation of the Turkish Republic in 1923. It has seen itself, and has been seen by the Turkish public, as a guardian of the Republic and its guiding principles, especially those of secularism and republicanism. This guardianship role has led not only to a high degree of military involvement in politics, but also to four interventions, which overthrew the sitting Turkish government in times when the military deemed it unable or unwilling to protect the values of the nation. However, the military’s power has gradually decreased since the beginning of the 21st century, due to two factors: pressure to comply with the political criteria necessary for membership in the European Union, which requires civilian control and oversight of the military, and the emergence of a strong political party, the Justice and Development Party (AKP), which has increased its own power at the expense of the Turkish Armed Forces.The Turkish military has had a large role in Turkish politics since the foundation of the Turkish Republic in 1923. It has seen itself, and has been seen by the Turkish public, as a guardian of the Republic and its guiding principles, especially those of secularism and republicanism. This guardianship role has led not only to a high degree of military involvement in politics, but also to four interventions, which overthrew the sitting Turkish government in times when the military deemed it unable or unwilling to protect the values of the nation. However, the military’s power has gradually decreased since the beginning of the 21st century, due to two factors: pressure to comply with the political criteria necessary for membership in the European Union, which requires civilian control and oversight of the military, and the emergence of a strong political party, the Justice and Development Party (AKP), which has increased its own power at the expense of the Turkish Armed Forces
The Muslim Arc and Greece's Support for Serbia During the Bosnian War of 1992-1995
This thesis explores how Ontological Security Theory can be used to explain Greece's support for Serbia during the Yugoslav Wars, specifically during the Bosnian War of 1992-1995. I argue that Greece's sense of self and stability was disrupted by two concurrent crises in the early 1990s: the changing geopolitical role of Greece following the end of the Cold War, and the country's evolving position in the European Community's transition to the European Union. To recover a sense of ontological security, Greece relied on two historic relationships, one with a foe (Turkey) and one with a friend (Serbia), which were restored through the manipulation and mobilization of cultural memory via media, the Greek Orthodox Church, public speeches, the Greek education system, and commemorations and public holidays. I contend that Greece's support for Serbia during the Bosnian War was a way for Greece to reestablish ontological security and reemphasize its historical animosity toward Turkey, with the added element of the perceived threat of a Muslim Arc.Master of Art
Acoustic cell concentration, washing & perfusion for cellular therapy manufacturing
A major wave of promising cellular therapies is progressing through clinical trials, such that engineers and scientists need to address the challenges of economically ensuring the manufacture of safe and efficacious cell therapy products. These processes often depend on devices and methods that were developed for only related blood cell processing or vaccine manufacturing. Thus, we are in a window of opportunity to tailor innovative technologies to address the emerging specialized needs of cell therapy manufacturing. Concentrating and washing cells between stages is a repeated bioprocess unit operation, such as to transfer cells from culture medium to cryopreservation medium. Especially for small-scale autologous therapies, cell washing is not well performed by closed-system centrifuges or filters, including due to the loss of potentially lifesaving cells. We previously developed an acoustic cell separation device that has been widely used for 20 years as part of mammalian cell perfusion bioreactors. This non-fouling filter technology uses gentle ultrasonic standing wave forces to separate cells from medium based on density and compressibility differences. We have now adapted this technology to concentrate and then wash cells at high concentrations, so as to reduce the wash volumes by an order of magnitude, thereby reducing the process cost of goods compared to centrifuge washing. The device operation has been optimized to obtain greater than 99.9% washing with 95% washed cell recoveries, such that this acoustic technology could become the method of choice for cell therapy bioprocessing. We also have recently enhanced automated acoustic devices to perfuse over 140 million cell/mL cultures, maintaining \u3e99% cell separation efficiencies. With the simplicity of no physical filter barrier or mechanical moving parts, this tailored technology provides a high performance closed manufacturing device, to perfuse, concentrate and wash cells. The development of robust and economical means of mammalian cell manufacturing is on the critical path to ensuring that promising innovative therapies can become widely available to innumerable patients in dire need
Concentric double hollow grid cathode discharges
A new cathode system, consisting of two concentric spherical hollow grids with two aligned orifices, is investigated by space-resolved Langmuir probe measurements and non-linear dynamics analysis. Negative biases of this spherical hollow grids arrangement lead to the formation of two complex space charge structures in the regions of the orifices. The overall dynamics of the current-voltage characteristic (I–V characteristic) of each discharge is characterized by strong oscillatory behaviour with various waveforms correlated with jumps in the static I–V characteristics. Space-resolved measurements through the two aligned orifices of the two grids show a peak increase of the electron temperature and particle density in the regions of the two space-charge structures. The effects of the biases and Ar pressure on the overall spatial distribution of all plasma parameters are investigated. Two important working points of the concentric double hollow grid cathode discharges are revealed which could make this configuration suitable as an electron source
Oscillatory behavior of hollow grid cathode discharges
Multiple complex space-charge structures in unmagnetized low-temperature plasmas arise from ionization phenomena near additional negatively or positively biased electrodes or due to local constraints. Because of their usually spherical form, such structures are called fireballs. If they appear inside hollow grids, they are called inverted fireballs or plasma bubbles. The temporal evolution of such structures is often accompanied by strong plasma instabilities. The dynamics of complex space-charge structures have been investigated by using single spherical grid cathode with an orifice. Langmuir probe and optical emission spectroscopy were used to diagnose the structures. Measurements delivered the axial profiles of the plasma potential, electron temperature and density, and the densities of excited atoms and ions, that confirmed the formation of a fireball in the region near the orifice (also evidenced by visual observation). Inside the grid, a plasma bubble has developed, with a high ion density inside due to the hollow cathode effect. Information on the nonlinear dynamics of the complex space charge structures was obtained from the analysis of the oscillations of the discharge current
Acoustic cell washing and raman spectroscopy technologies To address cell therapy bioprocess challenges
Many organizations are confronting the challenges of economically ensuring the manufacture of safe and efficacious cell therapy products. These processes often depend on devices and methods that were developed for only related applications, such as blood cell processing or scientific research. Thus, we are in a window of opportunity to tailor innovative technologies to address the emerging specialized needs of cell therapy manufacturing.
The most frequent unit operation is to wash cells between process stages, such as from DMSO containing cryopreservation medium to culture expansion medium. In particular for relatively small-scale autologous cell therapy processing, cell washing is imperfectly performed by closed system blood cell centrifuges or filters. We previously developed an acoustic cell separation device, widely used for over 15 years in CHO cell perfusion cultures. This technology acts as a non-fouling filter for months of operation, by using the forces generated in ultrasonic standing wave fields. These forces separate cells from medium based on differences in density and compressibility. Greater than 99.9% cell washing with 95% washed cell recovery efficiencies have been provided by our device. We also have recently enhanced the acoustic technology to perfuse 100 million cell/mL cultures, maintaining \u3e99% cell separation efficiencies. This provides an alternative high performance closed manufacturing system, to perfuse, concentrate and wash cells, with no physical filter barrier or mechanical moving parts.
While many clinical trials have had few adverse events, the great promise of cellular therapies comes with grave risks, such as from potentially oncogenic pluripotent cells present in embryonic stem cell derived populations. There is an urgent need for process analytical technologies to non-invasively monitor mammalian cell populations and improve the reliability of manufactured cell products. This includes to monitor both the expected differentiation as well as to detect unexpected cells in the process. Recently, technological advances have led to an explosive growth in the capabilities of Raman spectroscopy, increasing the potential for novel applications. We are developing the use of this spectroscopic technique to track cell development, by measuring macromolecular changes in cell samples from cultures where stem cells are differentiated towards insulin-producing cells for the treatment of diabetes. Raman spectroscopy has great potential to provide continuous on-line assessment of cell quality during the manufacture of cell-derived therapeutic cells
Advantages of Graphene Biosensors for Human Stem Cell Therapy Potency Assays
Regenerative medicine is challenged by the need to conform to rigorous guidelines for establishing safe and effective development and translation of stem cell-based therapies. Counteracting widespread concerns regarding unproven cell therapies, stringent cell-based assays seek not only to avoid harm but also to enhance quality and efficacy. Potency indicates that the cells are functionally fit for purpose before they are administered to the patient. It is a paramount quantitative critical quality attribute serving as a decisive release criterion. Given a broad range of stem cell types and therapeutic contexts the potency assay often comprises one of the most demanding hurdles for release of a cell therapy medicinal product. With need for improved biomarker assessment and expedited measurement, recent advances in graphene-based biosensors suggest that they are poised to be valuable platforms for accelerating potency assay development. Among several potential advantages, they offer versatility for sensitive measurement of a broad range of potential biomarker types, cell biocompatibility for direct measurement, and small sample sufficiency, plus ease of use and point-of-care applicability
Liposomal-Based Formulations: A Path from Basic Research to Temozolomide Delivery Inside Glioblastoma Tissue
Glioblastoma (GBM) is a lethal brain cancer with a very difficult therapeutic approach and ultimately frustrating results. Currently, therapeutic success is mainly limited by the high degree of genetic and phenotypic heterogeneity, the blood brain barrier (BBB), as well as increased drug resistance. Temozolomide (TMZ), a monofunctional alkylating agent, is the first line chemotherapeutic drug for GBM treatment. Yet, the therapeutic efficacy of TMZ suffers from its inability to cross the BBB and very short half-life (~2 h), which requires high doses of this drug for a proper therapeutic effect. Encapsulation in a (nano)carrier is a promising strategy to effectively improve the therapeutic effect of TMZ against GBM. Although research on liposomes as carriers for therapeutic agents is still at an early stage, their integration in GBM treatment has a great potential to advance understanding and treating this disease. In this review, we provide a critical discussion on the preparation methods and physico-chemical properties of liposomes, with a particular emphasis on TMZ-liposomal formulations targeting GBM developed within the last decade. Furthermore, an overview on liposome-based formulations applied to translational oncology and clinical trials formulations in GBM treatment is provided. We emphasize that despite many years of intense research, more careful investigations are still needed to solve the main issues related to the manufacture of reproducible liposomal TMZ formulations for guaranteed translation to the market