Interrogating Cancer Metabolism using Novel Imaging Techniques

Altered metabolism is one of the hallmarks of cancer and is known to enable the proliferation and survival of cancer cells in changing microenvironments. Metabolic changes can be interrogated using non-invasive metabolic imaging techniques, which enable the investigation of tumour metabolism in vivo and the identification of imaging biomarkers. Hyperpolarised 13C Magnetic Resonance Spectroscopic Imaging (MRSI) is a metabolic imaging technique that enables dynamic imaging of isotopically labelled metabolites in vivo, with [1-13C]pyruvate being the most widely used substrate in pre-clinical studies and the only substrate used so far in clinical studies. In the first part of this thesis, hyperpolarised 13C pyruvate MRSI was directly compared to mass spectrometry imaging in a murine lymphoma model, cross-validating both methods for providing information on the relative spatial distribution of 13C-labelled lactate. In the second part, the potential of hyperpolarised [1-13C]Ketoisocaproic Acid as a substrate for hyperpolarised imaging was investigated. Ketoisocaproic acid is a substrate for Branched Chain Aminotransferase 1 (BCAT1), the first enzyme in the catabolic pathway of Branched Chain Amino Acids. This enzyme is upregulated in many cancers and is linked to cancer progression. In this project, the role of BCAT1 in cell proliferation was confirmed in glioblastoma patient derived cells and tumours and BCAT1 was shown to regulate the cells’ metabolic and transcriptional profiles through regulation of alpha-ketoglutarate metabolism. In vivo imaging of BCAT1 activity is therefore suggested as a potential technique for patient stratification and potentially treatment monitoring. [1-13C]Ketoisocaproic acid was successfully hyperpolarised and showed fast uptake into subcutaneous EL4 lymphoma tumours, healthy rat brain and orthotopic gliomas in rat brain, following intravenous injection. Sufficient 13C leucine signal was generated in the lymphoma tumour models enabling in vivo imaging of BCAT activity but the reaction was found to be significantly slower in the healthy rat brain and in the glioma tumours. This was explained by low levels of glutamate, a co-substrate for the reaction, in the glioma tumours, which is a potential limiting factor for this reaction.Cancer Research UK Rosetrees Trus

User interface enhancement report

The existing user interfaces to TEMPUS, Plaid, and other systems in the OSDS are fundamentally based on only two modes of communication: alphanumeric commands or data input and grapical interaction. The latter are especially suited to the types of interaction necessary for creating workstation objects with BUILD and with performing body positioning in TEMPUS. Looking toward the future application of TEMPUS, however, the long-term goals of OSDS will include the analysis of extensive tasks in space involving one or more individuals working in concert over a period of time. In this context, the TEMPUS body positioning capability, though extremely useful in creating and validating a small number of particular body positions, will become somewhat tedious to use. The macro facility helps somewhat, since frequently used positions may be easily applied by executing a stored macro. The difference between body positioning and task execution, though subtle, is important. In the case of task execution, the important information at the user's level is what actions are to be performed rather than how the actions are performed. Viewed slightly differently, the what is constant over a set of individuals though the how may vary

KEMANDIRIAN PENGKONSUMSI MINUMAN BERALKOHOL

Penelitian ini dilakukan dengan tujuan untuk mengetahui kemandirian pengkonsumsi minuman beralkohol dilihat dari aspek kognitif, emosi, sosial dan psikomotor. Penelitian ini menggunakan pendekatan penelitian kualitatif deskriptif dengan metode penelitian studi kasus. Subyek dalam penelitian ini adalah 3 orang pengkonsumsi minuman beralkohol, dengan kriteria seseorang usia 18 – 24 tahun yang mengkonsumsi minuman beralkohol dan berdomisili di Yogyakarta. Setting penelitian ini dilakukan di Depok Kabupaten Sleman. Metode pengumpulan data dalam penelitian ini menggunakan wawancara dan observasi, Instrumen yang digunakan adalah pedoman wawancara dan pedoman observasi. Uji keabsahan data dilakukan dengan triangulasi metode dan triangulasi sumber. Teknik analisis data yang digunakan yaitu model interaktif yang terdiri dari reduksi data, penyajian data(display data), dan penarikan kesimpulan. Hasil penelitian terhadap 3 pengkonsumsi minuman beralkohol ini menunjukkan bahwa kemandirian seorang seseorang yang mengkonsumsi minuman beralkohol dapat dilihat dari beberapa aspek, yaitu; (1) Aspek kemandirian Kognitif, kurang dapat mengambil keputusan dan memiliha hal yang penting dengan yang tidak, (2) aspek kemandirian emosi yang dimiliki kurang, hal ini dikarenakan kurangnya hubungan yang harmonis dengan orang tuanya, (3) Aspek kemandirian sosial yang dimiliki tergolong kurang, hal ini dikarenakan kurangnya komunikasi dengan orang-orang disekitarnya, (4) aspek kemandirian psikomotor yang dimiliki tergolong kurang, hal ini dikarenakan seseorang yang mengonsusmsi alkohol kurang dapat berinisiatif, cenderung menunggu instruksi dari orang lain dan kurang dapat memecahkan permasalhan sendiri. Kata kunci : kemandirian, kemandirian seseorang, pengkonsumsi alkoho

Optimalisasi Fungsi Masjid Pendekatan Superimposisi (Desain Masjid Bulak)

Masjid memiliki peran penting dalam kemajuan peradaban manusia pada masa kejayaan islam. Namun saat ini di Indonesia masjid mengalami penyempitan makna dan fungsi. Jumlahnya banyak namun tidak berkualitas dan tidak makmur. Menghadirkan peran fungsi masjid yang sebenarnya diharapkan dapat menjadikan masjid pusat kegiatan masyarakat dan menyelesaikan masalah kemiskinan di kelurahan kedung cowek. Permasalahan desain yang timbul adaalah bagaimana masjid dapat menjadi pusat dari beragam kegiatan dan ibadah masyarakat kecamatan kedung cowek. Untuk mewujudkan itu berarti masjid harus mewadahi berbagai aktivitas dengan beragam program, berarti menggabungkan tempat ibadah yang diharuskan kondusif dengan tempat umum yang kurang kondusif. Untuk menjawab permasalahan desain tersebut digunakan pendekatan desain superimposisi. Program di eksplorasi sedemikian rupa untuk menimbulkan event-event baru yang tidak terduga agar masjid hidup dan makmur. Metode desain yang dipakai adalah programmatic dissociations yang dipakai Bernard tschumi dalam mendesain Tokyo opera house. Hasil rancangan berupa masjid yang terbuka dan menjadi wadah pusat kegiatan masyarakat

Risks to the Agri-food Sector of Republic of Moldova Associated with Restrictions Imposed by the Russian Federation on Moldovan Imports

AbstractAfter Republic of Moldova has declared its firm decision to sign the Association Agreement with the European Union, Russia has tightened Moldovan products’ access on its market. It has imposed a series of bans on Moldovan agri-food imports starting with the end of last year – wines (September 2013), pork meat (April 2014), fresh and canned fruits and vegetables (July 2014), all kinds of meat (October 2014). On July 31, a resolution on the introduction of import duties in respect of imported products whose country of origin is the Republic of Moldova, especially beef, pork, chicken, vegetables, some fruits, cereals, sugar, wine grapes, alcohol, and furniture has been adopted. This situation increases tension among domestic farmers and food producers and sparks concerns among decision makers, due to the high concentration of some of these products on the Russian market. The present paper aims to offer: an alternative vision on the effects these measures may have on different segments of the Moldovan agri-food sector; some attempts to estimate losses in revenue from exports in the most exposed to risk sectors. Some recommendations of measure to overcome the possible negative effects have been formulated. Despite the existence of trade preferential regime between CIS countries since the early 90s of the past century, nontariff barriers remain to be a major impediment to trade among them. Particularly severe are trade embargoes applied by Russia Federation. Although, the experience showed that some of these measures have strong negative impact, other effects appear to be sometimes overstated. This does motivate Russian authorities to use them as a leverage to solve non-economic disagreements, maintaining the dependence of the country and hindering its initiative to promote proper policies to develop its national competitiveness

A Study on Workload Assessment and Usability of Wind-Aware User Interface for Small Unmanned Aircraft System Remote Operations

This study evaluates pilots' cognitive workload and situational awareness during remote small unmanned aircraft system operations in different wind conditions. To complement the urban air mobility concept that envisions safe, sustainable, and accessible air transportation, we conduct multiple experiments in a realistic wind-aware simulator-user interface pipeline. Experiments are performed with basic and wind-aware displays in several wind conditions to assess how complex wind fields impact pilots' cognitive resources. Post-hoc analysis reveals that providing pilots with real-time wind information improves situational awareness while decreasing cognitive workload

Temporomandibular disorders: perspective clinical usage of acupuncture

Department of Alternative and Complementary Medicine, Department of Therapeutic Dentistry, Nicolae Testemițsanu State University of Medicine and Pharmacy, Chisinau, the Republic of MoldovaBackground: One of the oldest medical practices is acupuncture, which was developed for about 3 thousand years. It includes also methods of treatment for various diseases and disorders of the stomatognathic region. Currently, there is an increased interest for the usage of these alternative methods of treatment. Acupuncture methods are widespread worldwide and are endorsed by WHO. The use of alternative medicine methods in dental practice has more positive aspects than negative ones, attracting the attention of patients and doctors and even of countries with different economic levels of development. The most important indications of acupuncture in dentistry are: 1) glossodynia; 2) stomatodynia; 3) primary trigeminal neuralgia; 4) spasm/contracture of the masticatory muscles; 5) myogenous dysfunction of the temporomandibular joint; 6) salivary disorders. For the treatment of various pathologies in dentistry, various stimulation of acupuncture points is being used (needling, electro-puncture, laser-puncture, pressopuncture, thermo-puncture, magneto-puncture, etc.). Currently, there is ongoing research on defining differential indications for these methods, based on the highest efficiency for particular pathologies. Conclusions: Currently, there is ongoing research on defining differential indications for these methods, based on the highest efficiency for particular pathologies. It is not concluded yet which acupuncture treatment is more efficient: the one based on the reflexogenic theory (local, regional, distal points) or the one based on Traditional Chinese Medicine (meridian theory, etc.). There are being developed complex treatment protocols for dental pathologies, with the inclusion of various acupuncture methods (magneto-puncture, laser-puncture, etc.)

Optimalisasi Fungsi Masjid Pendekatan Superimposisi (Desain Masjid Bulak)

Masjid memiliki peran penting dalam kemajuan peradaban manusia pada masa kejayaan islam. Namun saat ini di Indonesia masjid mengalami penyempitan makna dan fungsi. Jumlahnya banyak namun tidak berkualitas dan tidak makmur. Menghadirkan peran fungsi masjid yang sebenarnya diharapkan dapat menjadikan masjid pusat kegiatan masyarakat dan menyelesaikan masalah kemiskinan di kelurahan kedung cowek. Permasalahan desain yang timbul adaalah bagaimana masjid dapat menjadi pusat dari beragam kegiatan dan ibadah masyarakat kecamatan kedung cowek. Untuk mewujudkan itu berarti masjid harus mewadahi berbagai aktivitas dengan beragam program, berarti menggabungkan tempat ibadah yang diharuskan kondusif dengan tempat umum yang kurang kondusif. Untuk menjawab permasalahan desain tersebut digunakan pendekatan desain superimposisi. Program di eksplorasi sedemikian rupa untuk menimbulkan event-event baru yang tidak terduga agar masjid hidup dan makmur. Metode desain yang dipakai adalah programmatic dissociations yang dipakai Bernard tschumi dalam mendesain Tokyo opera house. Hasil rancangan berupa masjid yang terbuka dan menjadi wadah pusat kegiatan masyarakat ============================================================================ The mosque has an important role in the human civilization improvement in islamic glory age. However, currently in Indonesia mosque narrowing the meaning and function. Polynomial but are not qualified and not prosper. Presenting the mosque actual function role is expected to make a mosque as community center to solve the poverty problem in the village kedung Cowek. Design issues is how mosques can be the center of various kedung Cowek activities and community worship. To realize it means that the mosque should accommodate the various programs activities, means combining the required worship place is conducive to the public areas less conducive. To answer that ,the design used the design approach superimposition. The programs is explored to make unexpeted events. The design method used is programmatic dissociations that Bernard Tschumi used in designing the Tokyo opera house. The design results is an open mosque and community center to societ

Correlations between the quantitative indices of the Schneiderian membrane, the indentation degree and the clinical manifestations of chronic generalized periodontitis

Catedra de stomatologie terapeutică, Universitatea de Stat de Medicină și Farmacie ”Nicolae Testemiţanu”, Chișinău, Republica MoldovaRezumat. Introducere. Pentru optimizarea procesului diagnostic la pacienții cu parodontită cronică generalizată, se studiază implicarea țesuturilor și structurilor adiacente parodonțiului în realizarea și menținerea procesului patologic. În acest aspect, un interes deosebit prezintă studierea interrelațiilor dintre semnele parodontitei cronice generalizate, gradul de indentație și grosimea membranei Schneider. Material și metode. A fost realizat un studiu prospectiv, pe serie de cazuri (48 de pacienți, ambele sexe, vârsta între 18 și 65 de ani). Pacienții au fost examinați clinic și paraclinic (tomografia computerizată cu fascicul conic) Rezultate. La pacienții cu parodontită cronică generalizată gravă, în 78,6% cazuri, este prezentă sinuzita preclinică, confirmată prin îngroșarea membranei Schneider mai mult de 2 mm. Frecvența de indentație este aproximativ egală la pacienții cu parodontită cronică generalizată ușoară (55%), medie (57,1%) și gravă (64,3%); odată cu creșterea frecvenței indentației bilaterale crește și gravitatea parodontitei cronice generalizate. Premolarul II, molarii II și III au dinamica de creștere a gradului de indentație în paralel cu creșterea gravității parodontitei; gradul de indentație a molarului I nu se deosebește statistic semnificativ în dependență de gravitatea parodontitei cronice generalizate. Gradul de indentație în sinusul maxilar a rădăcinilor dentare corelează cu grosimea membranei Schneider – valori maximale (Rxy=0,891, p0,05) pentru premolarul II. La pacienții cu parodontită cronică generalizată, durata maladiei are corelații mai puternice cu procesul inflamator (Rxy=0,58, p<0,001), comparativ cu vârsta pacienților (Rxy=0,31, p<0,001). Concluzii. La pacienții cu parodontită cronică generalizată, durata maladiei are corelații mai puternice cu procesul inflamator, comparativ cu vârsta pacienților. Frecvența de indentație este aproximativ egală la pacienții cu parodontită cronică generalizată ușoară, medie și gravă. Gravitatea parodontitei cronice generalizate se asociază cu anumite particularități a gradului de indentație a premolarul II, molarii I, II și III. La pacienții cu parodontită cronică generalizată gravă, în 78,6% cazuri, este prezentă sinuzita preclinică, confirmată prin îngroșarea membranei Schneider. Gradul de indentație în sinusul maxilar a rădăcinilor dentare corelează cu grosimea membranei Schneider. Monitorizarea în dinamică a parametrilor cantitativi ale membranei Schneider în corelație cu manifestările clinice ale parodontitei cronice generalizate și gradul de indentație, conduce la optimizarea diagnosticului complex al pacienților cu parodontită cronică generalizată.Abstract. Introduction. In order to optimize the diagnostic process for patients with chronic generalized periodontitis, there are studied the involvement of tissues and structures, adjacent to the periodontium, in the initiating and maintaining the periodontal disease process. In this regard, of special interest is modifithe studying of the interrelations between signs of chronic generalized periodontitis, the degree of indentation and the thickness of the Schneiderian membrane. Material and methods. There has been conducted a prospective study, on case series. There were enrolled 48 patients (both genders, aged between 18-65 years, mean age 39.5 years). Patients were examined clinically paraclinically (cone beam computer tomography). Results. In patients with severe chronic generalized periodontitis, in 78.6% of cases, preclinical sinusitis is present, which is confirmed by a thickening of the Schneiderian membrane more than 2 mm. The indentation frequency is approximately equal for all the patients with mild (55%), moderate (57.1%) or severe (64.3%) chronic generalized periodontitis; with the increase of the bilateral indentation frequency, the severity of periodontitis also increases. The 2nd premolar, the 2nd and 3rd molar show trends of increase for the indentation degree at the same rate with the increase of periodontitis severity; the indentation degree of the first molar doesn’t present any statistically significantly differences, depending on the severity of chronic generalized periodontitis. The indentation degree of dental roots in the maxillary sinus correlates with the thickness of the Schneiderian membrane – maximal values were seen for the 2nd molar (Rxy=0.891, p0.05). In patients with chronic generalized periodontitis, the disease duration has stronger correlation with the inflammatory process (Rxy=0.58, p<0.001), in comparison to patient’s age (Rxy=0.31, p<0.001). Conclusions. In patients with chronic generalized periodontitis, the duration of disease has stronger correlation with the inflammatory process, in comparison to the patient’s age. Indentation frequency is approximately equal in patients with mild, moderate or severe chronic generalized periodontitis. The severity of chronic generalized periodontitis is associated with certain peculiarities of the indentation degree of the 2nd premolar, 1st molar, 2nd molar and 3rd molar. In patients with severe chronic generalized periodontitis in 78.6% of cases, preclinical sinusitis is present, this being confirmed by the thickening of the Schneiderian membrane. The indentation degree of dental roots in the maxillary sinus, correlated with the Schneiderian membrane thickness. Monitoring the dynamics of the quantitative parameters of the Schneiderian membrane based on the clinical manifestations of chronic generalized periodontitis and the degree of indentation, leads to the optimization of the complex diagnosis of patients with chronic generalized periodontitis

Analysis of fixed-wing stall-type accidents in the United States

Spin training has not been required for students working towards their private or commercial certificates for the past 70 years. Switching to a stall-prevention mindset within training aimed to make spin recovery unnecessary; however, stall-type accidents, consisting of stalls, spins, and spirals, still occur and are highly fatal. Although past studies have analyzed accidents, interviewed pilots at different levels, and made recommendations for changes in the industry, stall-type accidents are no less fatal now, at a fatality ratio of approximately 40-50% yearly. The research discussed in this paper aims to summarize and present accident stall-type statistics in aggregate over the past five decades and motivate future pilot- and training-centered research to address the high presence of stall-type accidents in aviation. Specifically, this article uses NTSB accident reports to answer the research question of whether there have been changes in the prevalence of spins among both fatal and non-datal fixed-wing accidents in the United States over the past sixty years. The methodology breaks down the accident analysis in three groups, based on the time period in which they occurred, due to differences in the reporting methods used. This paper finds that the prevalence and fatality ratio of stall-type accidents has remained high over the past six decades and that stall-type accidents are more than twice as fatal as an average accident. To remedy the high accident count, we recommend experimental ground and simulator-based training to improve pilot knowledge, skill, and performance.Peer reviewedMechanical and Aerospace Engineerin