Prognostic importance of the tumour microenvironment in follicular lymphoma patients treated with immunochemotherapy

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma. It is an indolent and clinically heterogeneous disease, which is generally considered incurable. Currently, immunochemotherapy has significantly improved the outcome of FL patients. This is based on the combination of rituximab, a monoclonal anti-CD20 antibody, with chemotherapy, and is used at present as a standard first-line therapy in FL. Thus far, however, patients have been selected for treatment based on clinical risk factors and indices that were developed before the rituximab era. Therefore, there is a growing need to understand the molecular mechanisms underlying the disease, which would not only provide information to predict survival in the rituximab era, but also enable the design of more targeted therapeutic strategies. In this study, our aim was to identify genes predicting the outcome in FL patients treated with immunochemotherapy. Thus, we performed a cDNA microarray with 24 FL patients. When gene expression differences from diagnostic tumour samples were related to the clinical outcome, we identified novel genes with a prognostic impact on survival. The expression of selected genes was further characterized with quantitative PCR and immunohistochemistry (IHC). Interestingly, the prognostic influence of these genes was often associated with their expression in non-malignant cells instead of tumour cells. Based on the observed gene expression patterns, we analyzed the abundance and prognostic value of non-malignant immune cells in 95-98 FL patients treated with immunochemotherapy. We observed that a high content of tumour-associated macrophages was a marker of a favourable prognosis. In contrast, the accumulation of mast cells correlated with a poor outcome and was further associated with tumour vascularity. Increased microvessel density also correlated with an inferior outcome. In addition, we used the same microarray data with a systems biology approach to identify signalling pathways or groups of genes capable of separating patients with favourable or adverse outcomes. Among the transcripts, there were many genes associated with signal transducers and activators of the transcription (STAT5a) pathway. When IHC was used as validation, STAT5a expression was mostly observed in T-cells and follicular dendritic cells, and expression was found to predict a favourable outcome. In cell cultures, rituximab was observed to induce the expression of STAT5a-associated interleukins in human lymphoma cell lines, which might provide a possible link for the cross-talk between rituximab-induced FL cells and their microenvironment. In conclusion, we have demonstrated that the microenvironment has a prognostic role in FL patients treated with immunochemotherapy. The results also address the importance of re-evaluating the prognostic markers in the rituximab era of lymphoma therapies.

The Saintly Madman : A Study of the Scholarly Reception History of Buile Shuibhne

This study examines the scholarly reception history of an early Irish text, Buile Shuibhne (The Frenzy of Suibhne), by focusing on the various theoretical and methodological presuppositions which have determined the scholars’ understanding of the text’s religious allegorical significance in the course of the 20th century. The reception-oriented inquiry takes the intersubjective aspect of literary interpretation as the basis for accentuating the importance of communally shared presumptions and reading strategies in the explication of interpretive variety. The materials of the study have been divided into four frameworks of interpretation: historical, pre-Christian, Christian and anthropological. This heuristic division does not denote mutually exclusive paradigms, but rather refers to perceived similarities within each group regarding the questions posed, and the evidence adduced, in textual analysis. The historical framework concentrates on the issues of the origins of the tale and the possible historicity of its main protagonist. The pre-Christian framework covers the theories of the shamanic, Indo-European and Celtic elements in the text, whereas the Christian framework includes readings emphasising the biblical, monastic and ascetic aspects of the tale. The anthropological framework in turn focuses on the parallels drawn between the narrative and the universal structure of the rites of passage. In addition to the examination of these four frameworks, the study also links the question of methodology with wider issues of authorship and textual integrity, and critically reconsiders the manner in which J.G. O'Keeffe's 1913 edition of the text has been reified in previous scholarship as a representation of a 12th century authorial original. The overall objective of the present case-study is to relate theoretical conceptions of literary theory, comparative religion and historiography to the study of early Irish narrative material by considering the communal and institutional dimension of meaning-making, and the implications of comparative methodology for historical research. In this aim, the prevailing methodological presuppositions informing the scholarly discourse on Buile Shuibhne are set against the wider context of Celtic Studies scholarship, in order to draw attention to the need to critically reflect upon the operations of knowledge production in future research.

The Reorganisation of Provincial Territories in Light of the Imperial Decision-Making Process : Later Roman Arabia and Tres Palaestinae as Case Studies

The dissertation examines Roman provincial administration and the phenomenon of territorial reorganisations of provinces during the Imperial period with special emphasis on the provinces of Arabia and Palaestina during the Later Roman period, i.e., from Diocletian (r. 284 305) to the accession of Phocas (602), in the light of imperial decision-making. Provinces were the basic unit of Roman rule, for centuries the only level of administration that existed between the emperor and the cities of the Empire. The significance of the territorial reorganisations that the provinces were subjected to during the Imperial period is thus of special interest. The approach to the phenomenon is threefold: firstly, attention is paid to the nature and constraints of the Roman system of provincial administration. Secondly, the phenomenon of territorial reorganisations is analysed on the macro-scale, and thirdly, a case study concerning the reorganisations of the provinces of Arabia and Palaestina is conducted. The study of the mechanisms of decision-making provides a foundation through which the collected data of all known major territorial reorganisations is interpreted. The data concerning reorganisations is also subjected to qualitative comparative analysis that provides a new perspective to the data in the form of statistical analysis that is sensitive to the complexities of individual cases. This analysis of imperial decision-making is based on a timeframe stretching from Augustus (r. 30 BC AD 14) to the accession of Phocas (602). The study identifies five distinct phases in the use of territorial reorganisations of the provinces. From Diocletian s reign there is a clear normative change that made territorial reorganisations a regular tool of administration for the decision-making elite for addressing a wide variety of qualitatively different concerns. From the beginning of the fifth century the use of territorial reorganisations rapidly diminishes. The two primary reasons for the decline in the use of reorganisations were the solidification of ecclesiastical power and interests connected to the extent of provinces, and the decline of the dioceses. The case study of Palaestina and Arabia identifies seven different territorial reorganisations from Diocletian to Phocas. Their existence not only testifies to wider imperial policies, but also shows sensitivity to local conditions and corresponds with the general picture of provincial reorganisations. The territorial reorganisations of the provinces reflect the proactive control of the Roman decision-making elite. The importance of reorganisations should be recognised more clearly as part of the normal imperial administration of the provinces and especially reflecting the functioning of dioceses.

Approaching Sacred Pregnancy : The Cult of the Visitation and Narrative Altarpieces in Late Fifteenth-Century Florence

The study focuses on the Visitation as a narrative subject of altarpieces in late fifteenth-century Florence. Although the Visitation was a well-known story in both verbal and visual representations since the early medieval period, it became a popular subject of altarpieces only towards the end of the fifteenth century. In this study, the first part provides an overview of the complex religious and historical background to an emerging cult of the Visitation. Devotional practices focusing on the Visitation belong in a context of late medieval Marian devotion and in 1389 a new feast of the Visitation was introduced into the liturgical calendar of the Catholic Church. Because of the ongoing schism within the Catholic Church, the feast was not unanimously accepted across Western Europe until the later part of the fifteenth century. Contrary to a widely disseminated view, the feast of the Visitation cannot be associated with Franciscan spirituality, but was rather a clearly defined Dominican project that primarily emphasised the importance of peace and unity within the Christian Church. Simultaneously with the gradual acceptance of the new feast, visual representations of the Visitation began to appear at the centre of altarpieces. The Visitation exemplifies an increasing preference for narrative subjects within the genre of the altarpiece. The second part of the study presents an analysis of the concept of the narrative altarpiece and highlights the complexities involved in combining a narrative content with the traditional devotional function of the altarpiece. In detailed case studies some prominent art works produced in Florence between 1490 and 1503 are discussed within a framework of contextual analysis, narrative theory and iconography. Altarpieces by Domenico Ghirlandaio, Piero di Cosimo and Mariotto Albertinelli represent visual manifestations of a cult of the Visitation with roots in late medieval devotional practices. At the same time, the altarpieces highlight the multiple functions of altarpieces in a culture where art works responded to a variety of social and religious needs. Building on earlier studies, each case study presents new insights and evidence not considered in previous art historical research.

Evaluation of driving ability of the disabled persons in the context of the psychological activity theory

In the future the number of the disabled drivers requiring a special evaluation of their driving ability will increase due to the ageing population, as well as the progress of adaptive technology. This places pressure on the development of the driving evaluation system. Despite quite intensive research there is still no consensus concerning what is the factual situation in a driver evaluation (methodology), which measures should be included in an evaluation (methods), and how an evaluation has to be carried out (practise). In order to find answers to these questions we carried out empirical studies, and simultaneously elaborated upon a conceptual model for driving and a driving evaluation. The findings of empirical studies can be condensed into the following points: 1) A driving ability defined by the on-road driving test is associated with different laboratory measures depending on the study groups. Faults in the laboratory tests predicted faults in the on-road driving test in the novice group, whereas slowness in the laboratory predicted driving faults in the experienced drivers group. 2) The Parkinson study clearly showed that even an experienced clinician cannot reliably accomplish an evaluation of a disabled person’s driving ability without collaboration with other specialists. 3) The main finding of the stroke study was that the use of a multidisciplinary team as a source of information harmonises the specialists’ evaluations. 4) The patient studies demonstrated that the disabled persons themselves, as well as their spouses, are as a rule not reliable evaluators. 5) From the safety point of view, perceptible operations with the control devices are not crucial, but correct mental actions which the driver carries out with the help of the control devices are of greatest importance. 6) Personality factors including higher-order needs and motives, attitudes and a degree of self-awareness, particularly a sense of illness, are decisive when evaluating a disabled person’s driving ability. Personality is also the main source of resources concerning compensations for lower-order physical deficiencies and restrictions. From work with the conceptual model we drew the following methodological conclusions: First, the driver has to be considered as a holistic subject of the activity, as a multilevel hierarchically organised system of an organism, a temperament, an individuality, and a personality where the personality is the leading subsystem from the standpoint of safety. Second, driving as a human form of a sociopractical activity, is also a hierarchically organised dynamic system. Third, in an evaluation of driving ability it is a question of matching these two hierarchically organised structures: a subject of an activity and a proper activity. Fourth, an evaluation has to be person centred but not disease-, function- or method centred. On the basis of our study a multidisciplinary team (practitioner, driving school teacher, psychologist, occupational therapist) is recommended for use in demanding driver evaluations. Primary in a driver’s evaluations is a coherent conceptual model while concrete methods of evaluations may vary. However, the on-road test must always be performed if possible.

The Development of the Concept of Music Education in Estonian Kindergartens, 1905-2008 : a Historical–Critical Overview

The dissertation focuses on the development of music education in Estonian kindergartens and the factors influencing it, analysed in the historical perspective relying on post-positivist paradigm. The study is based on the factors and subjects’ views on kindergarten music education from 1905 to 2008, recorded in written sources or ascertained by means of questionnaire and interview. The dissertation deals with music’s functions, music education in retrospective, factors influencing child’s musical aptitude and development and teacher’s role in it through the prism of history. The formation of Estonian kindergarten music education and the phenomenon of its development have been researched by stages: the first manifestations of music in kindergarten in 1905 - 1940; the formation of the concept of music education in 1941 - 1967 and the application of a unified system in 1968 - 1990. The work also outlines innovative trends in music education at the end of the last millennium and the beginning of this century, in 1991 - 2008. The study relies on a combined design and an analysis of historical archival material and empirical data. The empirical part of the study is based on the questionnaire (n=183) and interviews (n=18) carried out with kindergarten music teachers. The data has been analysed using both qualitative and quantitative methods. The subject of the research is the content and activity types of kindergarten music education and the role of music teacher in their implementation. The study confirmed that fundamental changes took place in Estonian kindergarten music education due to the change in political power in the 1940s. Following the example of the Soviet system of education, music in kindergarten became an independent music educational orientation and the position of a professionally trained music teacher was established (1947). It was also confirmed that in the newly independent Estonian Republic under the influence of innovative trends a new paradigm of music education arose from the traditional singing-centred education towards the more balanced use of music activity types (attaching importance to the child-centred approach, an increase in the number and variety of activity types). The most important conclusions made in the dissertation are that there has been improvement and development deriving from contemporary trends in the clear concept that has evolved in Estonian kindergarten music education over a century; professionally trained music teachers have had a crucial role in shaping it; and kindergarten music education is firmly positioned as a part of preschool education in Estonian system of education. Key words: early childhood music education, history of music education, kindergarten music education, early childhood music teachers

Smoking from Adolescence to Adulthood : A 15-year Follow-up of the North Karelia Youth Project

The aim of the study was to examine the effects of a smoking prevention program and smoking from early adolescence to early adulthood by using longitudinal data. In addition, predictors of smoking, smoking cessation, and associations of smoking with socio-economic factors and other health behaviours were assessed. The data was gathered in connection with the North Karelia Youth Project follow-up study during 15 years. A two-year cardiovascular disease risk factor prevention program was carried out among students from grades seven to nine in four schools in North Karelia. Two schools were selected from Kuopio province for the control schools. The North Karelia Project, a community-based cardiovascular disease prevention program, was implemented in the same area. At the baseline in 1978 the subjects were 13-year-olds (n=903) and in the following surveys 15-, 16-, 17-, 21- and 28-year-olds. The parents of the subjects were studied twice, in 1978 and 1980. A two-year intervention based on social influence approach prevented the onset of smoking for several years. The continuity of smoking from adolescence to adulthood was strong: most adolescent smokers were still smoking in adulthood. Moreover, approximately half of the 28-year-old smokers had started smoking after the age of 15. Previous smoking status and smoking by friends were the most important predictors of smoking. One third of all adolescent smokers had stopped smoking before the age of 28, averaging at 2.3 % annual decline. The socioeconomic status of the subject and, especially, education were strongly related to smoking, the lower socioeconomic groups smoking the most. Parental socioeconomic status and intergenerational social mobility were not significantly related to the smoking of the subject in adolescence or adulthood. Smoking was associated positively with the use of alcohol and negatively with physical activity from adolescence to adulthood. The results support the feasibility of a school-based social influence program with a community-based program in smoking prevention among adolescents. Strong continuity of smoking from adolescence to adulthood supports the importance of preventing the onset of smoking in adolescence. It would be useful to continue prevention programs also after the comprehensive school, since so many young start smoking after that. It would likewise be important to develop cessation programs tailor-made for adolescents and young adults. Additionally, the results support the importance of using methods based on social influence in smoking prevention and cessation programs, targeting especially such risk groups as those with low socioeconomic status as well as those with other unhealthy behaviours.

Molecular basis of the kidney filtration barrier : Role of the nephrin protein complex

The kidney filtration barrier consists of fenestrated endothelial cell layer, glomerular basement membrane and slit diaphragm (SD), the specialized junction between glomerular viscelar epithelial cells (podocytes). Podocyte injury is associated with the development of proteinuria, and if not reversed the injury will lead to permanent deterioration of the glomerular filter. The early events are characterized by disruption of the integrity of the SD, but the molecular pathways involved are not fully understood. Congenital nephrotic syndrome of the Finnish type (CNF) is caused by mutations in NPHS1, the gene encoding the SD protein nephrin. Lack of nephrin results in loss of the SD and massive proteinuria beginning before birth. Furthermore, nephrin expression is decreased in acquired human kidney diseases including diabetic nephropathy. This highlights the importance of nephrin and consequently SD in regulating the kidney filtration function. However, the precise molecular mechanism of how nephrin is involved in the formation of the SD is unknown. This thesis work aimed at clarifying the role of nephrin and its interaction partners in the formation of the SD. The purpose was to identify novel proteins that associate with nephrin in order to define the essential molecular complex required for the establishment of the SD. The aim was also to decipher the role of novel nephrin interacting proteins in podocytes. Nephrin binds to nephrin-like proteins Neph1 and Neph2, and to adherens junction protein P-cadherin. These interactions have been suggested to play a role in the formation of the SD. In this thesis work, we identified densin as a novel interaction partner for nephrin. Densin was localized to the SD and it was shown to bind to adherens junction protein beta-catenin. Furthermore, densin was shown to behave in a similar fashion as adherens junction proteins in cell-cell contacts. These results indicate that densin may play a role in cell adhesion and, therefore, may contribute to the formation of the SD together with nephrin and adherens junction proteins. Nephrin was also shown to bind to Neph3, which has been previously localized to the SD. Neph3 and Neph1 were shown to induce cell adhesion alone, whereas nephrin needed to trans-interact with Neph1 or Neph3 from the opposite cell surface in order to make cell-cell contacts. This was associated with the decreased tyrosine phosphorylation of nephrin. These data extend the current knowledge of the molecular composition of the nephrin protein complex at the SD and also provide novel insights of how the SD may be formed. This thesis work also showed that densin was up-regulated in the podocytes of CNF patients. Neph3 was up-regulated in nephrin deficient mouse kidneys, which share similar podocyte alterations and lack of the SD as observed in CNF patients podocytes. These data suggest that densin and Neph3 may have a role in the formation of morphological alterations in podocytes detected in CNF patients. Furthermore, this thesis work showed that deletion of beta-catenin specifically from adult mouse podocytes protected the mice from the development of adriamycin-induced podocyte injury and proteinuria compared to wild-type mice. These results show that beta-catenin play a role in the adriamycin induced podocyte injury. Podocyte injury is a hallmark in many kidney diseases and the changes observed in the podocytes of CNF patient share characteristics with injured podocytes observed in chronic kidney diseases. Therefore, the results obtained in this thesis work suggest that densin, Neph3 and beta-catenin participate in the molecular pathways which result in morphological alterations commonly detected in injured podocytes in kidney diseases.

Young people's perceptions of the wood products industry : a relational view

The basis for this study was in poor attractiveness of the wood products industry among young people as a field to study and work in. The purpose was to produce new information of how to improve the relationship between young people and the wood products industry in order to better attract young people with different relational orientation. A survey was conducted among students of comprehensive schools and students of wood industry at vocational schools selected by systematic cluster sampling. The final sample consisted of 613 students. The study combined the theories and concepts of relationships, communication and trust of several disciplines. In addition, it applied theories of relationship marketing, stakeholders, publics, involvement and concepts of reputation and values. It studied the central relational elements in the form of antecedents, relationship state and its consequences. The study examined, how young people with different background and level of interest perceive wood industry as a field to study and work in from relational point of view, what are the central deficiencies in perceived relational elements and what are the public relations activities enhancing the relationship between wood industry and young people with less and high interest in the sector. The results indicate poor visibility of the wood industry among young people: unfamiliarity with the industry and unawareness of the opportunities to study in the field. It appeared that instead of increasing only information sharing, interactive communication in different forms is needed. The study also suggests that behaviors of the industry sector advancing perceived trustworthiness are of crucial importance. Moreover, the wood industry needs to pay attention to its behaviors and communication also among other stakeholder groups, especially the media, as reputation plays an important role in building up trust and satisfaction between young people and the sector. Finally, the less and highly interested young people were found to assess the relationship partly through different relational elements. In order to develop the relationship with highly interested young people they should be regarded clearly as future employees of the wood industry through activities affirming that they are desired and valued employees in the sector. Further, openness of information disclosure, whether concerning current situation or future prospects, seems to increase credibility and attractiveness of the wood industry. Highly interested young people were also found to appreciate socially responsible activities. The less interested young people seem to be insecure about the reliability of the wood industry as an employer, as well as, its ability and interest to invest in young people s skills. In addition,involvement in issues relevant for young people was found crucial in enhancing the relationship with the less interested young people.The conclusions of the study provide tools for enhancing the attractiveness of the wood industry among young people not only to the industry itself, but also to its advocates, teachers and student counselors of comprehensive and vocational schools, authorities and policy makers.

The success of the diversified farm : resource-based view

Farms and rural areas have many specific valuable resources that can be used to create non-agricultural products and services. Most of the research regarding on-farm diversification has hitherto concentrated on business start-up or farm survival strategies. Resource allocation and also financial success have not been the primary focus of investigations as yet. In this study these specific topics were investigated i.e. resource allocation and also the financial success of diversified farms from a farm management perspective. The key question addressed in this dissertation, is how tangible and intangible resources of the diversified farm affect the financial success. This study’s theoretical background deals with resource-based theory, and also certain themes of the theory of learning organisation and other decision-making theories. Two datasets were utilised in this study. First, data were collected by postal survey in 2001 (n = 663). Second, data were collected in a follow-up survey in 2006 (n = 439). Data were analysed using multivariate data analyses and path analyses. The study results reveal that, diversified farms performed differently. Success and resources were linked. Professional and management skills affected other resources, and hence directly or indirectly influenced success per se. In the light of empirical analyses of this study, tangible and intangible resources owned by the diversified farm impacted on its financial success. The findings of this study underline the importance of skills and networks for entrepreneur(s). Practically speaking all respondents of this study used either agricultural resources for non-farm businesses or non-farm resources for agricultural enterprises. To share resources in this way was seen as a pragmatic opportunity recognised by farmers. One of the downsides of diversification might be the phenomenon of over-diversification, which can be defined as the situation in which a farm diversifies beyond its optimal limit. The empirical findings of this study reveal that capital and labour resource constrains did have adverse effects on financial success. The evidence indicates that farms that were capital and labour resource constrained in 2001 were still less profitable than their ‘no problems’ counterparts five years later.

A quantum chemical investigation of the metal centres in cytochrome c oxidase

Quantum effects are often of key importance for the function of biological systems at molecular level. Cellular respiration, where energy is extracted from the reduction of molecular oxygen to water, is no exception. In this work, the end station of the electron transport chain in mitochondria, cytochrome c oxidase, is investigated using quantum chemical methodology. Cytochrome c oxidase contains two haems, haem a and haem a3. Haem a3, with its copper companion, CuB, is involved in the final reduction of oxygen into water. This binuclear centre receives the necessary electrons from haem a. Haem a, in turn, receives its electrons from a copper ion pair in the vicinity, called CuA. Density functional theory (DFT) has been used to clarify the charge and spin distributions of haem a, as well as changes in these during redox activity. Upon reduction, the added electron is shown to be evenly distributed over the entire haem structure, important for the accommodation of the prosthetic group within the protein. At the same time, the spin distribution of the open-shell oxidised state is more localised to the central iron. The exact spin density distribution has been disputed in the literature, however, different experiments indicating different distributions of the unpaired electron. The apparent contradiction is shown to be due to the false assumption of a unit amount of unpaired electron density; in fact, the oxidised state has about 1.3 unpaired electrons. The validity of the DFT results have been corroborated by wave function based coupled cluster calculations. Point charges, for use in classical force field based simulations, have been parameterised for the four metal centres, using a newly developed methodology. In the procedure, the subsystem for which point charges are to be obtained, is surrounded by an outer region, with the purpose of stabilising the inner region, both electronically and structurally. Finally, the possibility of vibrational promotion of the electron transfer step between haem a and a3 has been investigated. Calculating the full vibrational spectra, at DFT level, of a combined model of the two haems, revealed several normal modes that do shift electron density between the haems. The magnitude of the shift was found to be moderate, at most. The proposed mechanism could have an assisting role in the electron transfer, which still seems to be dominated by electron tunnelling.

The Interplays of Histories, Economies and Cultures in Human Adaptation and Settlement Patterns : The Cases of the Faroe Islands and Greenland

The Arctic peoples are currently faced with the challenge of adapting to climate change. Adaptive strategies have been central for the survival of the Northern communities also in the past. This doctoral dissertation is a comparative study of how two Northern societies, the Faroe Islands and Greenland, have responded to challenges caused by the interplay of environmental, political and socio-economic changes. Its main objective is to describe the characteristics of respective adaptive strategies developed in the two societies and to show which connections exist between adaptation and the development of the settlement patterns. This study is based on document analysis, supported by an analysis of demographic and economic statistics. For the field work, the empirical method of landscape-reading was applied. A narrative approach was used to explain interrelations between adaptive strategies and societal developments in the Faroe Islands and Greenland. Maps illustrating development and changes in settlement patterns in different time periods are central for this study because they illustrate the impacts of adaptation on settlement development. The results of this dissertation show that people in the Faroe Islands and Greenland have consciously developed their settlements and used this as an adaptive strategy: different types of settlements were established depending on which kind of resource base was available. Strong dependency on a single resource is likely to increase the probability that settlement development was impacted by it. The interrelation of natural resource use and settlement pattern development has weakened in the Faroe Islands and Greenland from the mid-1900s. Since then, the importance of the government settlement policies has become pronounced and the existing settlement pattern, including settlements without prospects for genuine economic viability, has been preserved. Currently, the Northern communities are increasingly dependent on worldwide developments. In the light of this study, the communities can respond to challenges of globalization and climate change and develop new kind of adaptive strategies, such as diversification of their economic activities. This dissertation shows that it is important to extend studies about community adaptation in the High North to consider the overall development of the Northern settlement patterns.

4QMMT - The Problem of the Epilogue

The main focus of this study is the epilogue of 4QMMT (4QMiqsat Ma aseh ha-Torah), a text of obscure genre containing a halakhic section found in cave 4 at Qumran. In the official edition published in the series Discoveries of the Judaean Desert (DJD X), the extant document was divided by its editors, Elisha Qimron and John Strugnell, into three literary divisions: Section A) the calendar section representing a 364-day solar calendar, Section B) the halakhot, and Section C) an epilogue. The work begins with text critical inspection of the manuscripts containing text from the epilogue (mss 4Q397, 4Q398, and 4Q399). However, since the relationship of the epilogue to the other sections of the whole document 4QMMT is under investigation, the calendrical fragments (4Q327 and 4Q394 3-7, lines 1-3) and the halakhic section also receive some attention, albeit more limited and purpose oriented. In Ch. 2, after a transcription of the fragments of the epilogue, a synopsis is presented in order to evaluate the composite text of the DJD X edition in light of the evidence provided by the individual manuscripts. As a result, several critical comments are offered, and finally, an alternative arrangement of the fragments of the epilogue with an English translation. In the following chapter (Ch. 3), the diversity of the two main literary divisions, the halakhic section and the epilogue, is discussed, and it is demonstrated that the author(s) of 4QMMT adopted and adjusted the covenantal pattern known from biblical law collections, more specifically Deuteronomy. The question of the genre of 4QMMT is investigated in Ch. 4. The final chapter (Ch. 5) contains an analysis of the use of Scripture in the epilogue. In a close reading, both the explicit citations and the more subtle allusions are investigated in an attempt to trace the theology of the epilogue. The main emphases of the epilogue are covenantal faithfulness, repentance and return. The contents of the document reflect a grave concern for the purity of the cult in Jerusalem, and in the epilogue Deuteronomic language and expressions are used to convince the readers of the necessity of a reformation. The large number of late copies found in cave 4 at Qumran witness the significance of 4QMMT and the continuous importance of the Jerusalem Temple for the Qumran community.