Lyconadin A (1) is a structurally unique Lycopodium alkaloid with antitumor properties, isolated from the club moss Lycopodium complanatum. We are developing a synthetic route to 1 based on a novel 7-exo-trig/6-exo-trig acyl radical cascade cyclization. The synthesis of model acyl radical cascade precursor 23 will be presented. Key features of this synthesis include the suppression of competing elimination during the alkylation of a hindered phenethyl bromide and the use of a lactone as a precursor to a compound bearing two differentially protected primary alcohols. An account of our studies on the model acyl radical cascade cyclization (23 to 24 above) will also be given, including a stereochemical analysis of the product. Our findings have been applied to develop a more detailed stereoselective synthetic plan for Lyconadin A (1).

This study shows the results of testing previous research that used remote sensing techniques to determine chlorophyll-a concentrations in turbid surface waters, and developing similar methods and models for Utah Lake using Landsat 7 ETM+ satellite imagery and field measured concentrations of chlorophyll-a. The data for the study included images acquired on June 22 and July 8, 2009. The field data included ground measurements taken on June 22 and July 6, 2009 from seven water quality sampling locations. The 48 hour time difference between the Landsat image acquisition (July 8) and the field measurement (July 6), and the small sample size for the data analysis were potential sources of error. The log transformation of red/near-infrared reflectance (i.e. ln[Band3/Band4]) had a high correlation with the field measured chlorophyll-a concentrations (R^2 = 0.9337). With this relationship, a model and 19 contour maps showing the spatial distribution of chlorophyll-a concentrations over Utah Lake was developed for the spring, summer, and fall seasons of 2003 to 2010. Generally about 90% of the Lake area had chlorophyll-a concentrations lower than 20µg/L. High concentrations of Chlorophyll-a (355µg/L and over) were observed mostly at the Provo Bay and Goshen Bay areas of the Lake. Occasionally, elevated levels of chlorophyll-a were observed at the northeastern, middle, and western sections of the lake. Utah Lake's average chlorophyll-a concentration is declining over time. In spring, the Lake average chlorophyll-a concentration reduced from 30.51µg/L in 2004 to 7.08µg/L in 2010. In summer, this average reduced from 132.13µg/L in 2003 to 36.58µg/L in 2010. Finally, in fall, the Lake average chlorophyll-a concentration reduced from 273.40µg/L in 2006 to 33.59µg/L in 2010. Field measured concentrations of phosphorus and model estimates for chlorophyll-a concentrations were highly correlated (R^2 = 0.9046). This suggests that the elevated levels of chlorophyll-a might be a result of the point and non-point discharge of phosphorus-laden wastewater from treatment plants, municipal storm drains, and agricultural activities.

Aim: Obesity is a risk factor for the development of cardiovascular diseases. Recently it was shown that overexpression of the Mas-receptor antagonist angiotensin(1-7) could prevent from diet-induced obesity. However, it remained unclear whether diet-induced obesity and angiotensin(1-7) overexpression might also have effects on the cardiovascular system in these rats. Methods:Twenty three male Sprague Dawley rats were fed with standard chow (SD+chow, n = 5) or a cafeteria diet (SD+CD, n = 6) for 5 months. To investigate the effect of angiotensin(1-7) transgenic rats, expressing an angiotensin(1-7)-producing fusion protein in testis were used. These transgenic rats also received a 5 month's feeding period with either chow (TGR+chow, n = 6) or cafeteria diet (TGR+CD, n = 6), respectively. Hemodynamic measurements (pressure-volume loops) were carried out to assess cardiac function and blood pressure. Subsequently, hearts were explanted and investigated according to the Langendorff technique. Furthermore, cardiac remodeling in these animals was investigated histologically. Results:After 5 months cafeteria diet feeding rats showed a significantly increased body weight, which could be prevented in transgenic rats. However, there was no effect on cardiac performance after cafeteria diet in non-transgenic and transgenic rats. Moreover, overexpression of angiotensin(1-7) deteriorated cardiac contractility as indicated by impaired dp/dt. Furthermore, histological analysis revealed that cafeteria diet led to myocardial fibrosis in both, control and transgenic rats and this was not inhibited by an overproduction of angiotensin(1-7). Conclusion:These results indicate that an overexpression of circulating angiotensin(1-7) prevents a cafeteria diet-induced increase in body weight, but does not affect cardiac performance in this experimental rat model of obesity. Furthermore, overexpression of angiotensin(1-7) alone resulted in an impairment of cardiac function.

Dagens arbetsklimat kännetecknas av konstanta förändringar, vilket sätter en stor press på företag att anpassa sig för att inte hamna efter. För att bibehålla konkurrenskraft tvingas därför företag att hitta nya sätt att utvecklas inom organisation och produktion, för att bemöta de kontinuerliga förändringar som sker. Tillverkning under tjugohundratalet kännetecknas av specialanpassade produkter där många tillverkande företag har komplexa produktionsplaneringar och affärssystem. Detta har lett till att företag söker sig alltmer mot koncept och metoder av ständiga förbättringar, något som gjort att tillämpningen av lean bland mindre tillverkande företag blivit alltmer framträdande.  Syftet med denna studie är att undersöka hur ett mindre tillverkande företag kan implementera koncept, verktyg, värderingar och principer inom lean för att bemöta sina nuvarande problem, och att långsiktigt kunna fortsätta arbeta vidare med det som en del i det dagliga arbetet. Målet är att ta fram ett ramverk för implementering av lean hos ett mindre tillverkande företag. Ramverket syftar till att visualisera de olika steg ett företag behöver gå igenom för att lyckas inkorporera förbättringskoncept/verktyg i sin verksamhet och därmed standardisera arbetet och minimera slöserier.  Studien är av kvalitativ karaktär där intervjuer, observationer och en litteraturstudie stod för insamlingen av data. Totalt genomfördes åtta intervjuer där en blandning av ledningen och anställda i produktionen var intervjuade. Observationerna utfördes genom att vandra omkring i produktionen för att skapa sig en bild för hur arbetet faktiskt går till idag. Litteraturstudien behandlar relevanta artiklar inom lean, SME:S och ständiga förbättringar. Genom att analysera den insamlade data mot den befintliga litteraturen kunde slutsatser om vilka verktyg/koncept som krävs för att bemöta respektive slöserier inom ett producerande SME göras. Även vilka faktorer som är viktiga för företag att ta i beaktning vid införandet av förbättringskoncept. Detta visualiseras genom ett ramverk som är framtaget genom denna studie. Fumex rekommenderas använda detta ramverk som ett stöd till implementering av lean i sin verksamhet. Detta syftar till att lösa de identifierade problemen med dokumentation, otydliga manualer/instruktioner och kommunikation mellan ledning och produktion.

Syftet med detta arbete är att studera hur elevers uppfattning av variabelbegreppet utvecklas mellan årskurs 7 till 9. Internationella tester visar att svenska elever i årskurs 8 har svårt för det matematiska begreppet variabler samtidigt som skolverket har konstaterat att variabelbegreppet är viktigt för förståelsen av matematiken på gymnasienivå. Inom forskningsprojektet Concepts in Secondary Mathematics gjorde forskaren D. E. Küchemann på 1980-talet en klassificering av elevers uppfattning av variabelbegreppet. Denna klassificering i 6 stadier används av bland annat skolverket och har även använts i denna studie. Küchemann ansåg att de flesta elever i åldrarna 13-15 inte hade möjlighet att helt uppfatta variabelbegreppets korrekta innebörd, en slutsats som blivit kritiserad. Jag ville således undersöka om jag kunde klassificera och mäta en utveckling i elevers uppfattning av variabelbegreppet enligt Küchemanns stadier. Jag studerade elever i årskurs 7 till 9 och använde mig av en enkätundersökning.Resultatet visade på en mycket tydlig utveckling av elevernas uppfattning av variabelbegreppet. I motsats till Küchemanns undersökning visade eleverna i årskurs 8 och 9 att de hade en uppfattning av variabelbegreppet som hör hemma i klassificeringens tre högre stadier. Däremot visade det sig att vara mycket svårt att klassificera uppfattningen hos de elever, övervägande från årskurs 7, som hade en uppfattning som representeras av de tre lägre stadierna. Jag anser att dessa tre lägre stadier är missuppfattningar och studiens resultat har fått mig att reflektera över hur konkretiseringar som används inom matematikundervisningen påverkar elevers förståelse.

The aim of this dissertation is to investigate how culture is represented in the Wings 7 blue textbook and workbook and what implications this may have on learners’ cultural understanding. The research questions are: How is culture represented in the textbook and workbook Wings 7 blue?, and What cultural understanding is promoted through the task design of the learning material Wings 7 blue?The analysis of the learning material draws on the theoretical framework of the Swedish researcher Ulrika Tornberg. The result of our analysis, and first research question, displays that the main focus of the cultural content in the Wings 7 blue textbook is on the mainstream national culture of Britain, typical British behavior, and linguistic readiness.Cultural understanding may be seen as either general cultural understanding, based on Tornberg’s two first perspectives, or as intercultural understanding which can be found in Tornberg’s third and final perspective. The result of the analysis of the tasks shows that both types of cultural understanding are promoted in the workbook, but the possibility for learners to develop their own intercultural understanding is limited, which is the answer to our second research question. This leads to the conclusion that the learning material, by itself, does not cover the complete aim for cultural understanding in the National Syllabus.One might argue that the material should only be seen as a complement to the other tools of the teacher, who can compensate for any missing information in his or her communication with the class. However, according to the large National survey for English, teachers of English mostly use published learning materials and tend to trust that these correspond to the aims of the steering documents.

Atherosclerosis is an inflammatory disease in which an accumulation of fatty acids and cholesterol occurs to form a plaque in small and large arteries. Monocyte polarization to classic M1 macrophages or alternative M2 macrophages is an important area of research that can determine the severity of disease progression. BMP-7 is a key growth factor responsible for directing differentiation of mesenchymal stem cells into brown fat cells, suggesting a role of BMP-7 in cellular plasticity; however, its role in monocyte polarization is yet to be revealed. In the current study, we hypothesize that monocyte treatment with BMP-7 will significantly result in increased polarization of monocytes into M2 macrophages and increased expression of anti-inflammatory cytokines. To that effect, we have established a stress induced cell culture system with monocytes (THP-1 cells) and apoptotic conditioned medium (ACM), simulating injury, to understand the effects of BMP-7 on M2 macrophage polarization from monocytes. Our data demonstrates that the BMP type 2 receptor (BMPR2) is found on monocytes and its activation is significantly (p

This thesis contains the design, manufacturing, and testing of a functional eight-legged robotic transporter based on the concept design laid out in U.S. Patent 7,246,671. The device is intended to achieve three different sequences of motion: regular driving, obstacle climbing, and stair climbing. The prototype was carried through concept design, analysis, selection of materials and components, manufacturing, software development, and final assembly and testing. The device can be assembled under multiple configurations, which harbor certain advantages and disadvantages. The results of the testing encourage the continuation of a second iteration of this concept.

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付記する学位プログラム名: 京都大学卓越大学院プログラム「メディカルイノベーション大学院プログラム」 / 京都大学 / 新制・課程博士 / 博士(薬科学) / 甲第24547号 / 薬科博第164号 / 新制||薬科||18(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 生田 宏一, 教授 橋口 隆生, 教授 木村 郁夫 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM