B-Zell-Lymphome des mukosaassoziierten lymphatischen Gewebes (MALT) entwickeln sich außerhalb des primären lymphatischen Gewebes und entstehen hauptsächlich im Magen aufgrund einer H. pylori-assoziierten chronischen Entzündung. Vorangegangene immunhisto-chemische und funktionelle Untersuchungen zeigten, daß die Tumorzellen phänotypisch Gedächtnis-B-Zellen entsprechen und Antigenrezeptoren auf ihrer Zelloberfläche exprimieren. In der vorliegenden Arbeit konnten mit Hilfe von molekulargenetischen Antigenrezeptor-analysen die Tumorzellpopulationen identifiziert und charakterisiert werden. Dabei wurde deutlich, daß sowohl mono- als auch biklonale B-Zell-Lymphome existieren. Im Vergleich zu neueren veröffentlichten Daten von MALT-Typ Lymphomen aus der Speicheldrüse, konnte jedoch bei den hier untersuchten gastralen Tumoren keine VH-Gen-restriktion nachgewiesen werden. Die tumorspezifischen VH-Mutationsanalysen zeigten, daß es sich bei den Tumor-B-Zellen auch genotypisch um Gedächtnis-B-Zellen handelt, die jedoch offensichtlich unter-schiedlich lange dem Mechanismus der Keimzentrumsmaturation ausgesetzt worden waren. Zudem konnte bei mono- und biklonale Lymphomen, im Gegensatz zu Fällen mit poly-klonalem Entzündungsinfiltrat die Translokation t(11;18)(q21;q21) nachgewiesen werden. Ausgehend von der Tatsache, daß die Tumorprogression dieser B-Zell-Lymphome anfangs noch abhängig von dem lokal vorhandenen Mikromilieu zu sein scheint, wurden die tumorinfiltrierenden T-Zellen (TITL) genauer charakterisiert. Es wurden überwiegend CD4+ TITLs nachgewiesen, die sowohl aktiviert (C69+) als auch immunkompetent (CD28+) waren und die für T/B-Zell-Kooperationen essentiellen Moleküle wie CD40-Ligand und Fas-Ligand exprimierten. Zudem konnten im Tumorgewebe vor allem TH2/3-Typ Cytokine (IL10, IL13, TGFb1) nachgewiesen werden, die ebenfalls das Tumorwachstum in vitro positiv beeinflussen können. Um in Zukunft spezifischere Untersuchungen zu den Wechselwirkungen zwischen Tumor-B-Zellen und TITLs durchführen zu können, wurde abschließend ein Zellkultursystem ent-wickelt, mit dessen Hilfe es möglich sein wird das Tumormikromilieu in vitro spezifisch zu simulieren, um so das Verhalten der Tumor-B-Zellen auch ex vivo beobachten und analysieren zu können. Die Daten dieser Arbeit geben einen vertieften und verbesserten Einblick in die tumorspezifischen Mechanismen und ermöglichen den Entwurf eines neuen detaillierteren Mo-dells zur Tumorentstehung und -progression von niedrig-maligne MALT-Typ Lymphomen. / B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) arise in sites primarily devoid of lymphoid tissue, preferentially in the stomach preceded by a chronic inflammation associated with H. pylori infection. Previous studies suggested that the tumor cells are the malignant counterpart of memory B-cells and express functional antigen receptors on their cell surfaces with autoantigenic reactivity. In the present work the molecular structure of the tumor antigen receptor was described more detailed in several cases of gastric MALT-type lymphomas and compared with recently published data from normal B-cells and different tumor entities. These findings clearly showed the existence of mono- as well as biclonal B-cell lymphomas. However, in contrast to recent molecular data derived from salivary gland MALT-type lymphomas, no VH-gene restriction was found. The tumorspecific VH-gene analyses confirmed the memory B-cell phenotype of the tumor cells at the DNA level. Furthermore, it is likely that the tumor B-cells passed several rounds of maturation cycles in the germinal centres because of their mutation pattern in the hypervariable region of the antigen receptor. By comparing clonality of the tumors it became obvious that those lymphomas showing the t(11;18)(q21;q21) translocation were directed towards (mono-)clonality. Therefore this translocation appears to represent a major progression event in tumor establishment. Because at least low-grade MALT-type B-cell lymphoma growth is depended on the local microenvironment, the tumorinfiltrating T-lymphocytes (TITL) were investigated in detail. In the tumor tissue CD4+ TITLs were found predominantly which were activated (CD69+) as well as immuncompetent (CD28+) and express CD40-Ligand and Fas-Ligand, two molecules which play a keyrole in T/B-cell interactions in germinal centre reaction. In addition, TH2/3 cytokines (IL10, IL13, TGFb1) were detected in the tumor tissue. These cytokines were shown to stimulate the tumor growth in vitro. Therefore it will be mandatory to engage CD40-Ligand and FAS-Ligand simultaneously for further detailed investigations of early steps of tumor development. An in vitro system will offer the possibility to investigate and analyse the behaviour of tumor B-cells ex vivo and compare t(11;18) positive and negative cases and thus lead to a biological based model of tumor-development and -progression of low-grade MALT-type lymphomas.

The purpose of this project is to demonstrate the market potential for a proposed micro-malt house in eastern Washington State through the development of a business plan. This plan looks at the history of the malted products industry, specifically barley. The industry is examined from a world, or macro view, down to a local (Tri-cities, WA) or micro view. The plan explains why there is currently a shift away from mass produced malted products in favor of a locally sourced malted cereal grain and how this shift can be capitalized on my aspiring maltsters and business owners. This plan includes all of the elements traditionally found in a modern business plan including startup costs, web plan summary, proposed product line, Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis of competitors and of the proposed business, management and ownership summaries, exit strategy, and perhaps most importantly, a full 5 year pro forma financial analysis. The researcher chose Tri-cities Washington (Richland, Pasco, and Kennewick) based on an existing relationship with a farmer local to that area. The farmer approached the researcher in the fall of 2013 and asked to partner in the research and development of the business plan. Should the business plan prove viable, it may be implemented to create the proposed micro-malt house as early as the spring of 2015.

B-Zell-Lymphome vom mukosa-assoziierten lymphatischen Gewebe (MALT)-Typ sind die größte Gruppe der extranodalen Lymphome. Sie enstehen vor dem Hintergrund einer chronischen Entzündung, wie etwa einer Helicobacter pylori-assoziierten Gastritis im Magen. Die Mechanismen der Lymphomgenese sind weitgehend unverstanden. Der Befund, dass die malignen B-Zellen der MALT-Typ Lymphome autoreaktiv sind und durch Antigen oder T-Zell-vermittelte Signale stimuliert werden, weist auf ein mögliches Ver-sagen der T-Zell-Kontrolle hin. Zur Prüfung dieser Hypothese wurden in der vorliegenden Arbeit sowohl tumor-infiltrierende T-Zellen als auch maligne B-Zellen aus MALT-Typ Lymphomen untersucht. Mit Hilfe von Expressionsanalysen der Vb -Kette des T-Zell-Rezeptors (TCR) wurden antigen-induzierte klonale Expansionen in den tumor-infiltrierenden T-Zellen nachgewiesen. Weiterhin wurden ähnliche antigen-erkennende Regionen (CDR3) des TCR in tumor-infiltrierenden T-Zellen aus zwei verschiedenen MALT-Typ Lymphomen gefunden. Diese Ergebnisse charakterisieren die T-Zellen als funktionell und auch als potenziell tumor-reaktiv. Um mögliche Defekte bei malignen B-Zellen zu untersuchen, wurde eine in vitro T/B-Zell-Kokultur entwickelt. Damit war es möglich, die Interaktion des apoptose-induzierenden Oberflächenmoleküls FasL auf aktivierten T-Zellen mit dem entsprechenden Todesrezeptor Fas auf malignen B-Zellen zu untersuchen. Drei von sieben MALT-Typ Lymphomen und vier von fünf DLBL erwiesen sich als resistent gegen FasL-vermittelte Apoptose. Meine Untersuchungen deuten darauf hin, dass hierfür eine mutationsbedingte funktionelle Inaktivierung des Fas-Rezeptors verantwortlich ist. In Fas-Transkripten aller untersuchten malignen B-Zellen wurden insgesamt 14 verschiedene Punktmutationen gefunden, die zu Aminosäureaustauschen bei der Translation führen. Zehn dieser Mutationen waren mit der Apoptose-Resistenz maligner B-Zellen assoziiert. Durch ergänzende Untersuchungen konnten alternative Mechanismen der Apoptose-Resistenz wie etwa reduzierte Fas-Expression, Produktion von löslichem Fas (sFas) oder Störungen in der Fas-Signalkaskade weitgehend ausgeschlossen werden. Aus diesen Ergebnissen lässt sich folgender Schluss ziehen: Resistenz gegen FasL/Fas-vermittelte Apoptose ist ein Mechanismus der frühen MALT-Typ Lymphomgenese und möglicherweise auf bestimmte Fas-Mutationen zurückzuführen. Durch Apoptose-Resistenz entkommen die malignen B-Zellen der MALT-Typ Lymphome der vorhandenen T-Zell-Kontrolle. Gleichzeitig nehmen sie die parakrin angebotene T-Zell-Hilfe solange in Anspruch, bis sie völlige Autonomie erreicht haben. Durch das abnorm verlängerte Überleben der B-Zellen steigt dann die Wahrscheinlichkeit, weitere Aberrationen wie etwa die in 50 Prozent aller Fälle auftretende Chromosomentranslokation t(11;18)(q21;q21) zu erwerben. / The largest group of extranodal lymphomas are B cell lymphomas of mucosa-associated lymphoid tissue (MALT)-type. They arise on the background of chronic inflammation, e.g. the Helicobacter pylori-associated gastritis in the stomach. The mechanism of MALT-type lymphomagenesis is still enigmatic. The finding of autoreactive malignant B cells which proliferate in response to antigen and T cell-mediated signals may suggest a failure of T cell control. For testing this hypothesis we examined both tumor-infiltrating T cells and malignant B cells of various MALT-type lymphomas. By expression analysis of the T cell receptor (TCR) Vb chain we showed clonal expansions of T cells due to antigenic stimulation. Furthermore we found similar antigen-binding regions (CDR3) in the TCR of tumor-infiltrating T cells in two different MALT-type lymphomas, that indicate potential antitumor-reactivity of the tumor-infiltrating T cells. Furthermore we established an in vitro T/B cell coculture assay for investigating the B cells and focused on the interaction of the pro-apoptotic molecule FasL on activated T cells with its corresponding death receptor Fas on malignant B cells. The malignant B cells from three out of seven MALT-type lymphomas and four out of five DLBL were resistant to FasL/Fas-mediated apoptosis. My results indicate that this is probably due to mutational inactivation of the Fas receptor. In Fas transcripts of malignant B cells from all cases investigated, 14 different point mutations leading to amino acid changes were found. Ten of these mutations were associated with resistance to apoptosis of malignant B cells. Additional investigations showed, that alternative mechanisms of resistance to apoptosis such as decreased expression of Fas, production of soluble Fas (sFas) or an impaired signalling cascade downstream of Fas were not operative. From the results we conclude the following: Resistance to FasL/Fas-mediated apoptosis is a mechanism of early MALT-type lymphomagenesis that could be due to certain Fas mutations. By this mechanism the B cells are able to escape T cell control while still receiving T cell help until they reach autonomous growth. The prolonged survival of the B cells might increase the risk of acquiring additional aberrations, such as the chromosomal translocation t(11;18)(q21;21) which is found in 50 per cent of all MALT-type lymphomas.

Barley is the second largest grain crop produced in Australia and has two primary end uses. The first use is the premium market for malt and beer production. The second use is animal consumption. The quality of barley for the range of end uses is influenced by the cultivar itself as well as the growing environment. A detailed understanding of these factors at the genetic and biochemical levels was required to enable breeding program to select for quality improvement. A number of grain and end product quality traits were assessed for genetic and environmental affects as well as their interaction.Grain size has an important impact on quality and large plump grain is desirable for malt and feed quality. The results from the research conducted in this study clearly show that grain size was affected by cultivar and environmental conditions. Using screenings (< 2.2 mm) and retention (> 2.5mm) data provided information on how cultivars performed under a range of environmental conditions, which included irrigated (water unlimited) to terminal moisture stress (no in crop rain). The results showed a strong genetic component in the variation in grain size and it would be possible to select for increased grain size but also stable grain size when considering cultivars grown under adverse environmental conditions.The husk content in barley impacts on malt and feed quality. The results in this studied showed there were significant genetic effects as well as environments effects on the level of husk. In addition, it was identified that the genetic regions controlled husk expression were associated with two other quality traits, namely, resistance to kernel discolouration and resistance to pre-harvest sprouting (dormancy). These regions on chromosome 4H and 6H are also associated with previously identified dormancy genes.Hardness is a trait not usually considered when assessing barley quality but the results from this study showed there are differences in the level of barley hardness, as measured by three methods, as well as differences in the hardness gene sequence. The three hardness methods used showed that barley hardness could be measured independently of the method used, but also that there were significant genetic and environmental effects on hardness. However, the results from sequencing for allelic variation in the hardness genes showed that while there was polymorphism, and hance the transcribed protein had little effect on variation in quality. The cultivars used were malting and feed cultivars and a set of iv breeding lines targeted at malt quality. It may be possible to identify diverse haplotypes from the use of wild relatives or landraces.This study also investigated the variation in barley for cattle feed quality. Feed quality was determined using an in-sacco dry matter digestibility (ISDMD) assay in fistulated cows as well as three other laboratory assays, namely acid detergent fibre, starch and particle size. These four traits are then used to calculate Net Energy (NE) and Average Daily Gain (ADG). The results show that there were genetic and environmental effects on feed quality. The key trait was the ISDMD assay and there were significant differences between the cultivars tested. The data suggested feed quality was a measurable and definable attribute that could be used in breeding selection.The final aspect of this study compared the feed data obtained with routine malt quality traits, of friability and hot water extract. There were strong genetic and environmental effects. The malting cultivars generally had the highest level of ADG and NE. The results also showed that there were negative correlations between extract and husk, ISDMD and ADG. Positive correlations were shown between friability and hardness, extract and test weight, and there was only a slight correlation between average daily gain and extract.An important aspect of this study was the calculation of the genetic component for each trait. This was carried using spatial analysis of mixed models. It was necessary to use this approach so a true estimation of the genetic component could be calculated which would then allow for the calculation of heritability. In plant breeding, the cultivar is not a fixed effect but rather a random variable, hence it was not possible to use normal analysis of variation (ANOVA) models. Rather models were written with cultivars, like environment and field position, as random effects which will allow the effect of each random variable to be accounted for in the analysis. Best Linear Unbiased Predictions (BLUPs) are calculated and presented for all traits.For all the traits measured in this study, heritability values were calculated to ascertain the level of success in improving these traits through breeding. The range in heritability for grain size was 40 to 90%, husk 30 to 60%, hardness, 40 to 90%, feed quality traits 20 to 80% and malt quality traits 40 to 90%. Generally most traits exhibited a moderate to high level of heritability which indicated genetic improvement was possible through the use of appropriate genetic material.

Short periods ( up to 5 days ) of high temperatures have been shown to reduce grain weight in barley although the specific effects on malting quality are still not clearly understood. Controlled environment conditions were used in this study to investigate the physiological and biochemical responses in Schooner barley to 5 days of elevated temperatures during grain filling. Control plants were maintained at 21 / 16 ° C ( 14th day ) from anthesis to harvest ripeness. Plants undergoing heat treatment experienced increasing temperatures for two days ( from 16 days after anthesis ) followed by 3 days at high temperatures (35 ° C day / 25 ° C night ). The period of high temperature reduced individual grain dry weight by 18 %. Schooner barley endosperm ( the grain storage tissue ) exhibited greater sensitivity to high temperatures than the whole grain ( 25 % reduction in dry weight ) in response to high temperatures. Grain development was accelerated by exposure to high temperatures and a reduction of approximately 8 % in the duration of grain filling was observed in heat treated compared with control grain. Changes in endosperm composition provided evidence that exposure to high temperatures altered overall grain metabolism. Reduction in starch, the single most important grain component contributing to final grain weight was the major factor lowering final grain dry weight, b - glucan deposition was also reduced following high temperature exposure. Little change was observed in the absolute amount of nitrogen accumulated per endosperm, although nitrogen concentration was higher in heat - treated grain, due mainly to reduced grain size and lower starch content. The results of this study confirmed other reports that the conversion of sucrose to starch was limiting in grain exposed to a period of high temperature. The amount of substrate, sucrose, within heat treated endosperms was not found to be limiting starch accumulation. The reduction in starch synthesis appeared to result from the combined effects of diminished catalytic activity of several enzymes in the committed pathway of starch synthesis and / or delayed recovery of enzyme activity during the cooler conditions which followed the heating period. Soluble starch synthase ( SSS ) showed an immediate loss of catalytic activity, even at moderate temperatures, while sucrose synthase and uridine 5 ' - diphosphoglucose pyrophosphorylase showed greatest reduction in activity only after plants were returned to cooler conditions. Individual enzymes showed variation in the level of recovery under the cooler temperature conditions which followed the heating period. The high temperature conditions which induced changes in the metabolism of grains following high temperature exposure, were associated with alterations to the appearance of the starchy endosperm cells, including the distribution of starch granules and their growth. Under elevated temperatures the synthesis of endosperm starch did not appear to keep pace with cell division and cell enlargement and peripheral endosperm cells remained relatively empty of starch granules. A reduction in Calcofluor fluorescent cell wall material was observed in both the endosperm and the crushed cell layer of heat treated grains. Microscopic observations revealed that the lower levels of starch observed in heat treated barley grains were not only associated with reduced accumulation of starch, but also localised degradation of the barley endosperm. Increased embryo growth, which was observed to take place in heat treated grains, may have been due to the nutrients thus generated although further investigations are required to elucidate the mechanisms involved. Structural observations of harvest ripe grain developing under control conditions also revealed changes in the grain associated with early germination events, and the possibility of a continuum between development and germination has been put forward. High temperature exposure resulted in an overall decrease in malt extract potential, but there was evidence that the effects of heat on individual malt parameters were both beneficial and detrimental. While DP, beta - amylase deposition, beta - glucan and viscosity were improved, heat treatment was associated with a reduced quantity of starch and increased protein concentration. Grain and malt beta - glucan levels were reduced as a result of high temperature exposure and beta - glucan degradation was enhanced in these grains. The overall reduction in the amount of ' maltable ' grain ( due to reduced grain size ) represented one of the most significant effects of heat treatment. The effects of a period of high temperature on grain growth and subsequent malting quality were examined for barley varieties Schooner and Arapiles and advanced breeding line WI - 2875 * 22. All showed reduced final grain dry weight in heat treated grains but the response to high temperature exposure with respect to starch, protein and ( b - glucan accumulation varied. The continued synthesis of starch by Arapiles and WI - 2875 * 22 under high temperature conditions warrants further investigation. Evidence has also been presented indicating that water loss may not have a decisive role in the termination of grain filling. The effect of high temperatures on the non - endosperm component of the grain showed both genotypic and environmental variation. Changes in the contribution made by the non - endosperm component to final grain weight was observed to lead to alterations in the relative concentration of important grain storage components. This was found to be crucial where potentially important heat stable quality characteristics, such as reduced accumulation of nitrogen, were masked by changes in the contribution to final grain dry weight by the non - endosperm component of the grain. / Meredith Anne Blesing Wallwork / Thesis (Ph.D.)--Department of Plant Science, 1997.

Bibliography: leaves 174-192. This research aims to obtain detailed knowledge on the effects of a period of high temperature on the accumulation of grain dry matter and endosperm starch, protein and B-glucan in the developing grain of the malting barley variety Schooner. Bbarley plants are exposed to high temperatures during mid grain filling for 5 days. Grain growth characteristics are measured prior to, during and following the high temperature period, with the aim of characterising the high temperature response in developing grain. The activities of several enzymes and metabolities of the pathway of starch synthesis are monitored and compared to those in grains maintained at a lower temperature. In addition, grain structure is also compared between control and heat treated grain during development, at maturity and following malting.

El mètode convencional utilitzat en el disseny d'un nou assecador o en la millora d'un existent consisteix a realitzar tota una sèrie d'experiments amb un assecador prototip (en planta pilot o utilitzant, fins i tot, el assecador industrial). Aquest mètode duu amb si normalment una despesa considerable en temps i diners (Nishiyama, 1982). La simulació per ordinador representa una eina cada vegada més potent per a realitzar aquestes tasques de disseny i optimització d'equips i operacions unitàries en la indústria agroalimentària en general. En particular, la simulació per ordinador tindrà gran interès en l'optimització de l'operació d'assecat que es porta a terme en la fabricació de malta per a cervesa (Bala, 1983). L'optimització de l'operació d'assecat de malta verda contribuiria a fer més competitiva la indústria espanyola de fabricació de malta, si s'assoleix reduir al mínim el consum energètic i el temps d'assecat (aconseguint així disminuir apreciablement els costos de fabricació). Això és realment interessant si es té en compte que aquesta indústria comença a exportar part de la seva producció de malta afavorint així la sortida de la producció agrícola d'ordi. En qualsevol cas per a tractar de modificar les condicions d'assecat de la malta verda també cal tenir en compte la influència d'aquestes condicions d'assecat sobre la qualitat de la malta, per a establir els límits d'actuació en aquest sentit. En general, sobre la qualitat de la malta influirà la qualitat de la matèria primera, l'ordi, i les condicions de procés que s'utilitzin durant la fabricació de malta. / El método convencional utilizado en el diseño de un nuevo secadero o en la mejora de uno existente consiste en realizar toda una serie de experimentos con un secadero prototipo (en planta piloto o utilizando, incluso, el secadero industrial). Este método lleva consigo normalmente un gasto considerable en tiempo y dinero (Nishiyama, 1982). La simulación por ordenador representa una herramienta cada vez más potente para realizar estas tareas de diseño y optimización de equipos y operaciones unitarias en la industria agroalimentaria en general. En particular, la simulación por ordenador tendrá gran interés en la optimización de la operación de secado que se lleva a cabo en la fabricación de malta para cerveza (Bala, 1983). Tal como se detalla a continuación, en los siguientes apartados, la optimización de la operación de secado de malta verde contribuiría a hacer más competitiva la industria española de fabricación de malta, si se logra reducir al mínimo el consumo energético y el tiempo de secado (consiguiendo así disminuir apreciablemente los costes de fabricación). Esto es realmente interesante si se tiene en cuenta que esta industria comienza a exportar parte de su producción de malta favoreciendo así la salida de la producción agrícola de cebada. En cualquier caso para tratar de modificar las condiciones de secado de la malta verde también es preciso tener en cuenta la influencia de estas condiciones de secado sobre la calidad de la malta, para establecer los límites de actuación en este sentido. En general, sobre la calidad de la malta influirá la calidad de la materia prima, la cebada, y las condiciones de proceso que se utilicen durante la fabricación de malta.

Texte remanié de: Thesis--Manchester university.

"May 2003" / Includes bibliographical references (leaves 216-225) / 225 leaves : ill., plates (col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, School of Agriculture and Wine, 2003

"May 2003" / Includes bibliographical references (leaves 216-225) / 225 leaves : ill., plates (col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, School of Agriculture and Wine, 2003