35 resultados para critical phenomena

em Helda - Digital Repository of University of Helsinki


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Fluid bed granulation is a key pharmaceutical process which improves many of the powder properties for tablet compression. Dry mixing, wetting and drying phases are included in the fluid bed granulation process. Granules of high quality can be obtained by understanding and controlling the critical process parameters by timely measurements. Physical process measurements and particle size data of a fluid bed granulator that are analysed in an integrated manner are included in process analytical technologies (PAT). Recent regulatory guidelines strongly encourage the pharmaceutical industry to apply scientific and risk management approaches to the development of a product and its manufacturing process. The aim of this study was to utilise PAT tools to increase the process understanding of fluid bed granulation and drying. Inlet air humidity levels and granulation liquid feed affect powder moisture during fluid bed granulation. Moisture influences on many process, granule and tablet qualities. The approach in this thesis was to identify sources of variation that are mainly related to moisture. The aim was to determine correlations and relationships, and utilise the PAT and design space concepts for the fluid bed granulation and drying. Monitoring the material behaviour in a fluidised bed has traditionally relied on the observational ability and experience of an operator. There has been a lack of good criteria for characterising material behaviour during spraying and drying phases, even though the entire performance of a process and end product quality are dependent on it. The granules were produced in an instrumented bench-scale Glatt WSG5 fluid bed granulator. The effect of inlet air humidity and granulation liquid feed on the temperature measurements at different locations of a fluid bed granulator system were determined. This revealed dynamic changes in the measurements and enabled finding the most optimal sites for process control. The moisture originating from the granulation liquid and inlet air affected the temperature of the mass and pressure difference over granules. Moreover, the effects of inlet air humidity and granulation liquid feed rate on granule size were evaluated and compensatory techniques used to optimize particle size. Various end-point indication techniques of drying were compared. The ∆T method, which is based on thermodynamic principles, eliminated the effects of humidity variations and resulted in the most precise estimation of the drying end-point. The influence of fluidisation behaviour on drying end-point detection was determined. The feasibility of the ∆T method and thus the similarities of end-point moisture contents were found to be dependent on the variation in fluidisation between manufacturing batches. A novel parameter that describes behaviour of material in a fluid bed was developed. Flow rate of the process air and turbine fan speed were used to calculate this parameter and it was compared to the fluidisation behaviour and the particle size results. The design space process trajectories for smooth fluidisation based on the fluidisation parameters were determined. With this design space it is possible to avoid excessive fluidisation and improper fluidisation and bed collapse. Furthermore, various process phenomena and failure modes were observed with the in-line particle size analyser. Both rapid increase and a decrease in granule size could be monitored in a timely manner. The fluidisation parameter and the pressure difference over filters were also discovered to express particle size when the granules had been formed. The various physical parameters evaluated in this thesis give valuable information of fluid bed process performance and increase the process understanding.

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The ability to deliver the drug to the patient in a safe, efficacious and cost-effective manner depends largely on the physicochemical properties of the active pharmaceutical ingredient (API) in the solid state. In this context, crystallization is of critical importance in pharmaceutical industry, as it defines physical and powder properties of crystalline APIs. An improved knowledge of the various aspects of crystallization process is therefore needed. The overall goal of this thesis was to gain better understanding of the relationships between crystallization, solid-state form and properties of pharmaceutical solids with a focus on a crystal engineering approach to design technological properties of APIs. Specifically, solid-state properties of the crystalline forms of the model APIs, erythromycin A and baclofen, and the influence of solvent on their crystallization behavior were investigated. In addition, the physical phenomena associated with wet granulation and hot-melting processing of the model APIs were examined at the molecular level. Finally, the effect of crystal habit modification of a model API on its tabletting properties was evaluated. The thesis enabled the understanding of the relationship between the crystalline forms of the model APIs, which is of practical importance for solid-state control during processing and storage. Moreover, a new crystalline form, baclofen monohydrate, was discovered and characterized. Upon polymorph screening, erythromycin A demonstrated high solvate-forming propensity thus emphasizing the need for careful control of the solvent effects during formulation. The solvent compositions that yield the desirable crystalline form of erythromycin A were defined. Furthermore, new examples on solvent-mediated phase transformations taking place during wet granulation of baclofen and hot-melt processing of erythromycin A dihydrate with PEG 6000 are reported. Since solvent-mediated phase transformations involve the crystallization of a stable phase and hence affect the dissolution kinetics and possibly absorption of the API these transformations must be well documented. Finally, a controlled-crystallization method utilizing HPMC as a crystal habit modifier was developed for erythromycin A dihydrate. The crystals with modified habit were shown to posses improved compaction properties as compared with those of unmodified crystals. This result supports the idea of morphological crystal engineering as a tool for designing technological properties of APIs and is of utmost practical interest.

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There is a need for better understanding of the processes and new ideas to develop traditional pharmaceutical powder manufacturing procedures. Process analytical technology (PAT) has been developed to improve understanding of the processes and establish methods to monitor and control processes. The interest is in maintaining and even improving the whole manufacturing process and the final products at real-time. Process understanding can be a foundation for innovation and continuous improvement in pharmaceutical development and manufacturing. New methods are craved for to increase the quality and safety of the final products faster and more efficiently than ever before. The real-time process monitoring demands tools, which enable fast and noninvasive measurements with sufficient accuracy. Traditional quality control methods have been laborious and time consuming and they are performed off line i.e. the analysis has been removed from process area. Vibrational spectroscopic methods are responding this challenge and their utilisation have increased a lot during the past few years. In addition, other methods such as colour analysis can be utilised in noninvasive real-time process monitoring. In this study three pharmaceutical processes were investigated: drying, mixing and tabletting. In addition tablet properties were evaluated. Real-time monitoring was performed with NIR and Raman spectroscopies, colour analysis, particle size analysis and compression data during tabletting was evaluated using mathematical modelling. These methods were suitable for real-time monitoring of pharmaceutical unit operations and increase the knowledge of the critical parameters in the processes and the phenomena occurring during operations. They can improve our process understanding and therefore, finally, enhance the quality of final products.

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This dissertation studies the language of Latin letters that were written in Egypt and Vindolanda (in northern Britain) during the period 1st century BC 3rd century AD on papyri, ostraca, and wooden tablets. The majority of the texts is, in one way or another, connected with the Roman army. The focus of the study is on syntax and pragmatics. Besides traditional philological methods, modern syntactic theory is used as well, especially in the pragmatic analysis. The study begins with a critical survey of certain concepts that are current in the research on the Latin language, most importantly the concept of vulgar Latin , which, it is argued, seems to be used as an abstract noun for variation and change in Latin . Further, it is necessary to treat even the non-literary material primarily as written texts and not as straightforward reflections of spoken language. An examination of letter phraseology shows that there is considerable variation between the two major geographical areas of provenance. Latin letter writing in Egypt was influenced by Greek. The study highlights the importance of seeing the letters as a text type, with recurring phraseological elements appearing in the body text as well. It is argued that recognising these elements is essential for the correct analysis of the syntax. Three areas of syntax are discussed in detail: sentence connection (mainly parataxis), syntactically incoherent structures and word order (the order of the object and the verb). For certain types of sentence connection we may plausibly posit an origin in spoken Latin, but for many other linguistic phenomena attested in this material the issue of spoken Latin is anything but simple. Concerning the study of historical syntax, the letters offer information about the changing status of the accusative case. Incoherent structures may reflect contaminations in spoken language but usually the reason for them is the inability of the writer to put his thoughts into writing, especially when there is something more complicated to be expressed. Many incoherent expressions reflect the need to start the predication with a thematic constituent. Latin word order is seen as resulting from an interaction of syntactic and pragmatic factors. The preference for an order where the topic is placed sentence-initially can be seen in word order more generally as well. Furthermore, there appears a difference between Egypt and Vindolanda. The letters from Vindolanda show the order O(bject) V(erb) clearly more often than the letters from Egypt. Interestingly, this difference correlates with another, namely the use of the anaphoric pronoun is. This is an interesting observation in view of the fact that both of these are traditional Latin features, as opposed to those that foreshadow the Romance development (VO order and use of the anaphoric ille). However, it is difficult to say whether this is an indication of social or regional variation.

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Music as the Art of Anxiety: A Philosophical Approach to the Existential-Ontological Meaning of Music. The present research studies music as an art of anxiety from the points of view of both Martin Heidegger s thought and phenomenological philosophy in general. In the Heideggerian perspective, anxiety is understood as a fundamental mode of being (Grundbefindlichkeit) in human existence. Taken as an existential-ontological concept, anxiety is conceived philosophically and not psychologically. The central research questions are: what is the relationship between music and existential-ontological anxiety? In what way can music be considered as an art of anxiety? In thinking of music as a channel and manifestation of anxiety, what makes it a special case? What are the possible applications of phenomenology and Heideggerian thought in musicology? The main aim of the research is to develop a theory of music as an art of existential-ontological anxiety and to apply this theory to musicologically relevant phenomena. Furthermore, the research will contribute to contemporary musicological debates and research as it aims to outline the phenomenological study of music as a field of its own; the development of a specific methodology is implicit in these aims. The main subject of the study, a theory of music as an art of anxiety, integrates Heideggerian and phenomenological philosophies with critical and cultural theories concerning violence, social sacrifice, and mimetic desire (René Girard), music, noise and society (Jacques Attali), and the affect-based charme of music (Vladimir Jankélévitch). Thus, in addition to the subjective mood (Stimmung) of emptiness and meaninglessness, the philosophical concept of anxiety also refers to a state of disorder and chaos in general; for instance, to noise in the realm of sound and total (social) violence at the level of society. In this study, music is approached as conveying the existentially crucial human compulsion for signifying i.e., organizing chaos. In music, this happens primarily at the immediate level of experience, i.e. in affectivity, and also in relation to all of the aforementioned dimensions (sound, society, consciousness, and so on). Thus, music s existential-ontological meaning in human existence, Dasein, is in its ability to reveal different orders of existence as such. Indeed, this makes music the art of anxiety: more precisely, music can be existentially significant at the level of moods. The study proceeds from outlining the relevance of phenomenology and Heidegger s philosophy in musicology to the philosophical development of a theory of music as the art of anxiety. The theory is developed further through the study of three selected specific musical phenomena: the concept of a musical work, guitar smashing in the performance tradition of rock music, and Erik Bergman s orchestral work Colori ed improvvisazioni. The first example illustrates the level of individual human-subject in music as the art of anxiety, as a means of signifying chaos, while the second example focuses on the collective need to socio-culturally channel violence. The third example, being music-analytical, studies contemporary music s ability to mirror the structures of anxiety at the level of a specific musical text. The selected examples illustrate that, in addition to the philosophical orientation, the research also contributes to music analysis, popular music studies, and the cultural-critical study of music. Key words: music, anxiety, phenomenology, Martin Heidegger, ontology, guitar smashing, Erik Bergman, musical work, affectivity, Stimmung, René Girard

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This is an ethnographic case study of the creation and emergence of a playworld – a pedagogical approach aimed at promoting children’s development and learning in early education settings through the use of play and drama. The data was collected in a Finnish experimental mixed-age elementary school classroom in the school year 2003-2004. In the playworld students and teachers explore different social and cultural phenomena through taking on the roles of characters from a story or a piece of literature and acting inside the frames of an improvised plot. The thesis takes under scrutiny the notion of agency in education. It produces theoretically grounded empirical knowledge of the ways in which children struggle to become recognized and agentive actors in early education settings and how their agency develops in their interaction with adults. The study builds on the activity theoretical and sociocultural tradition and develops a methodological framework called video-based narrative interaction analysis for studying student agency as developing over time but manifesting through the situational material and discursive local interactions. The research questions are: 1. What are the children’s ways of enacting their agency in the playworld? 2. How do the children’s agentive actions change and develop over the spring? 3. What are the potentials and challenges of the playworld for promoting student agency? 4. How do the teachers and the children deal with the contradiction between control and agency in the playworld? The study consists of a summary part and four empirical articles which each have a particular viewpoint. Articles I and II deal with individual students’ paths to agency. In Article I the focus is on the role of resistance and questioning in enabling important spaces for agency. Article II takes a critical gender perspective and analyzes how two girls struggled towards recognition in the playworld. It also illuminates the role of imagination in developing a sense of agency. Article III examines how the open-ended and improvisational nature of the playworld interaction provided experiences and a sense of ‘shared agency’ for the students and teachers in the class. Article IV turns the focus on the teachers and analyzes how their role actions in the playworld helped the children to enact agency. It also discusses the challenges that the teachers faced in this work and asks what makes the playworld activity sustainable in the class. The summary part provides a critical literature review on the concept of agency and argues that the inherently contradictory nature of the phenomenon of agency has not been sufficiently theorized. The summary part also locates the playworld intervention in a historical frame by discussing the changing conceptions of adulthood and childhood in the West. By focusing on the changing role of play and art in both adults’ and children’s contemporary lives, the thesis opens up an important but often neglected perspective on the problem of promoting student agency in education. The results illustrate how engaging in a collectively imagined and dramatized pretend play space together with the children enabled the teachers to momentarily put aside their “knower” positions in the classroom. The fictive roles and the narrative plot helped them to create a necessary incompleteness and open-endedness in the activity that stimulated the children’s initiatives. This meant that the children too could momentarily step out of their traditional classroom positions as pupils and initiate action to further the collective play. Engaging in this kind of unconventional activity and taking up and enacting agency was, however, very challenging for the participating children and teachers. It often contradicted the need to sustain control and order in the classroom. The study concludes that play- and drama-based pedagogies offer a unique but undeveloped potential for developing educational spaces that help teachers and children deal with the often contradictory requirements of schooling.

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The study of social phenomena in the World Wide Web has been rather fragmentary, andthere is no coherent, reseach-based theory about sense of community in Web environment. Sense of community means part of one's self-concept that has to do with perceiving oneself belonging to, and feeling affinity to a certain social grouping. The present study aimed to find evidence for sense of community in Web environment, and specifically find out what the most critical psychological factors of sense of community would be. Based on known characteristics of real life communities and sense of community, and few occational studies of Web-communities, it was hypothesized that the following factors would be the most critical ones and that they could be grouped as prerequisites, facilitators and consequences of sense of community: awareness and social presence (prerequisites), criteria for membership and borders, common purpose, social interaction and reciprocity, norms and conformity, common history (facilitators), trust and accountability (consequences). In addition to critical factors, the present study aimed to find out if this kind of grouping would be valid. Furthermore, the effect of Web-community members' background variables to sense of community was of interest. In order to answer the questions, an online-questionnaire was created and tested. It included propositions that reflect factors that precede, facilitate and follow the sense of community in Web environment. A factor analysis was calculated to find out the critical factors and analyses of variance were calculated to see if the grouping to prerequisites, facilitators and consequences was right and how the background variables would affect the sense of community in Web environment. The results indicated that the psychological structure of sense of community in Web environment could not be presented with critical variables grouped as prerequisites, facilitators and consequences. Most factors did facilitate the sense of community, but based on this data it could not be argued that some of the factors chronologically precedesense of community and some follow it. Instead, the factor analysis revealed that the most critical factors in sense of community in Web environment are 1) reciprocal involvement, 2) basic trust for others, 3) similarity and common purpose of members, and 4) shared history of members. The most influencing background variables were the member's own participation activity (indicated with reading and writing messages) and the phase in membership lifecycle (from visitor to leader). The more the member participated and the further in membership life cycle he was, the more he felt sense of community. There are many descreptions of sense of community, but the present study was one of the first to actually measure the phenomenon in Web environment, and that gained well documented, valid results based on large data, proving that sense of community in Web environment is possible, and clarifying its psychological structure, thus enhancing the understanding of sense of community in Web environment. Keywords: sense of community, Web-community, psychology of the Internet

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The aim of this work was the assessment about the structure and use of the conceptual model of occlusion in operational weather forecasting. In the beginning a survey has been made about the conceptual model of occlusion as introduced to operational forecasters in the Finnish Meteorological Institute (FMI). In the same context an overview has been performed about the use of the conceptual model in modern operational weather forecasting, especially in connection with the widespread use of numerical forecasts. In order to evaluate the features of the occlusions in operational weather forecasting, all the occlusion processes occurring during year 2003 over Europe and Northern Atlantic area have been investigated using the conceptual model of occlusion and the methods suggested in the FMI. The investigation has yielded a classification of the occluded cyclones on the basis of the extent the conceptual model has fitted the description of the observed thermal structure. The seasonal and geographical distribution of the classes has been inspected. Some relevant cases belonging to different classes have been collected and analyzed in detail: in this deeper investigation tools and techniques, which are not routinely used in operational weather forecasting, have been adopted. Both the statistical investigation of the occluded cyclones during year 2003 and the case studies have revealed that the traditional classification of the types of the occlusion on the basis of the thermal structure doesn t take into account the bigger variety of occlusion structures which can be observed. Moreover the conceptual model of occlusion has turned out to be often inadequate in describing well developed cyclones. A deep and constructive revision of the conceptual model of occlusion is therefore suggested in light of the result obtained in this work. The revision should take into account both the progresses which are being made in building a theoretical footing for the occlusion process and the recent tools and meteorological quantities which are nowadays available.

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Long-term monitoring data collected from wild smolts of Atlantic salmon (Salmo salar) in the Simojoki river, northern Finland, were used in studying the relationships between the smolt size and age, smolt and postsmolt migration, environmental conditions and postsmolt survival. The onset of the smolt run was significantly dependent on the rising water temperature and decreasing discharge of the river in the spring. The mean length of smolts migrating early in the season was commonly higher and the mean age always older than among smolts migrating later. Many of the smolts migrating early in the season and almost all smolts migrating later had started their new growth in spring in the river before their sea entry. Among postsmolts, the time required for emigration from the estuary was dependent on the sea surface temperature (SST) off the river, being significantly shorter in years with warm than cold sea temperatures. After leaving the estuary, the postsmolts migrated southwards along the eastern coast of the northern Gulf of Bothnia, the geographical distribution of the tag recoveries coinciding with the warm thermal zone in spring in the coastal area. After arriving in the southern Gulf of Bothnia in late summer the postsmolts mostly migrated near the western coast, reaching the Baltic Main Basin in late autumn. Until the early 1990s there was only a weak positive association between smolt length and postsmolt survival. However, following a subsequent decrease in the mean smolt size, a significant positive dependence was observed between smolt size and the reported recapture rate of tagged salmon. The differences in recapture rates between smolts tagged during the first and second half of the annual migration season were insignificant, indicating that the seasonal variation in smolt size and age seem to be too small to affect survival. Among the climatic factors examined, the summer SST in the Gulf of Bothnia was most clearly related to the survival of the wild postsmolts. Postsmolt survival appeared to be highest in years when the SST in June in the Bothnian Bay varied between 9 and 12 ºC. In addition, the survival of wild postsmolts showed a significant positive dependence on the SST in July in the Bothnian Sea, but not on the abundance of the prey fish (0+ herring, Clupea harengus and sprat, Sprattus sprattus) in the Bothnian Sea and in the Baltic Main Basin. The results suggest, that if the incidence of extreme weather conditions were to increase due to climatic changes, it would probably reduce the postsmolt survival of wild salmon populations. For improving the performance of hatchery-reared smolts, it could be useful to examine opportunities to produce smolts that are in their smolt traits and abilities more similar to the wild smolts described in this thesis.

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The Molecular Adsorbent Recirculating System (MARS) is an extracorporeal albumin dialysis device which is used in the treatment of liver failure patients. This treatment was first utilized in Finland in 2001, and since then, over 200 patients have been treated. The aim of this thesis was to evaluate the impact of the MARS treatment on patient outcome, the clinical and biochemical variables, as well as on the psychological and economic aspects of the treatment in Finland. This thesis encompasses 195 MARS-treated patients (including patients with acute liver failure (ALF), acute-on-chronic liver failure (AOCLF) and graft failure), and a historical control group of 46 ALF patients who did not undergo MARS. All patients received a similar standard medical therapy at the same intensive care unit. The baseline data (demographics, laboratory and clinical variables) and MARS treatment-related and health-related quality-of-life data were recorded before and after treatment. The direct medical costs were determined for a period of 3.5 years.Additionally, the outcome of patients (survival, native liver recovery and need for liver transplantation) and survival predicting factors were investigated. In the outcome analysis, for the MARS-treated ALF patients, their 6-month survival (75% vs. 61%, P=0.07) and their native liver recovery rate (49% vs. 17%, P<0.001) were higher, and their need for transplantations was lower (29% vs. 57%, P= 0.001) than for the historical controls. However, the etiological distribution of the ALF patients referred to our unit has changed considerably over the past decade and the percentage of patients with a more favorable prognosis has increased. The etiology of liver failure was the most important predictor of the outcome. Other survival predicting factors in ALF included hepatic encephalopathy, the coagulation factors and the liver enzyme levels prior to MARS treatment. In terms of prognosis, the MARS treatment of the cirrhotic AOCLF patient seems meaningful only when the patient is eligible for transplantation. The MARS treatment appears to halt the progression of encephalopathy and reduce the blood concentration of neuroactive amino acids, albumin-bound and water-soluble toxins. In general, the effects of the MARS treatment seem to stabilize the patients, thus allowing additional time either for the native liver to recover, or for the patients to endure the prolonged waiting for transplantation. Furthermore, for the ALF patients, the MARS treatment appeared to be less costly and more cost-efficient than the standard medical therapy alone. In conclusion, the MARS treatment appears to have a beneficial effect on the patient outcome in ALF and in those AOCLF patients who can be bridged to transplantation.

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The Antarctic system comprises of the continent itself, Antarctica, and the ocean surrounding it, the Southern Ocean. The system has an important part in the global climate due to its size, its high latitude location and the negative radiation balance of its large ice sheets. Antarctica has also been in focus for several decades due to increased ultraviolet (UV) levels caused by stratospheric ozone depletion, and the disintegration of its ice shelves. In this study, measurements were made during three Austral summers to study the optical properties of the Antarctic system and to produce radiation information for additional modeling studies. These are related to specific phenomena found in the system. During the summer of 1997-1998, measurements of beam absorption and beam attenuation coefficients, and downwelling and upwelling irradiance were made in the Southern Ocean along a S-N transect at 6°E. The attenuation of photosynthetically active radiation (PAR) was calculated and used together with hydrographic measurements to judge whether the phytoplankton in the investigated areas of the Southern Ocean are light limited. By using the Kirk formula the diffuse attenuation coefficient was linked to the absorption and scattering coefficients. The diffuse attenuation coefficients (Kpar) for PAR were found to vary between 0.03 and 0.09 1/m. Using the values for KPAR and the definition of the Sverdrup critical depth, the studied Southern Ocean plankton systems were found not to be light limited. Variabilities in the spectral and total albedo of snow were studied in the Queen Maud Land region of Antarctica during the summers of 1999-2000 and 2000-2001. The measurement areas were the vicinity of the South African Antarctic research station SANAE 4, and a traverse near the Finnish Antarctic research station Aboa. The midday mean total albedos for snow were between 0.83, for clear skies, and 0.86, for overcast skies, at Aboa and between 0.81 and 0.83 for SANAE 4. The mean spectral albedo levels at Aboa and SANAE 4 were very close to each other. The variations in the spectral albedos were due more to differences in ambient conditions than variations in snow properties. A Monte-Carlo model was developed to study the spectral albedo and to develop a novel nondestructive method to measure the diffuse attenuation coefficient of snow. The method was based on the decay of upwelling radiation moving horizontally away from a source of downwelling light. This was assumed to have a relation to the diffuse attenuation coefficient. In the model, the attenuation coefficient obtained from the upwelling irradiance was higher than that obtained using vertical profiles of downwelling irradiance. The model results were compared to field measurements made on dry snow in Finnish Lapland and they correlated reasonably well. Low-elevation (below 1000 m) blue-ice areas may experience substantial melt-freeze cycles due to absorbed solar radiation and the small heat conductivity in the ice. A two-dimensional (x-z) model has been developed to simulate the formation and water circulation in the subsurface ponds. The model results show that for a physically reasonable parameter set the formation of liquid water within the ice can be reproduced. The results however are sensitive to the chosen parameter values, and their exact values are not well known. Vertical convection and a weak overturning circulation is generated stratifying the fluid and transporting warmer water downward, thereby causing additional melting at the base of the pond. In a 50-year integration, a global warming scenario mimicked by a decadal scale increase of 3 degrees per 100 years in air temperature, leads to a general increase in subsurface water volume. The ice did not disintegrate due to the air temperature increase after the 50 year integration.