Browsing by Subject "stability"

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  • Segercrantz, Beata (Svenska handelshögskolan, 2011)
    226
    Many Finnish IT companies have gone through numerous organizational changes over the past decades. This book draws attention to how stability may be central to software product development experts and IT workers more generally, who continuously have to cope with such change in their workplaces. It does so by analyzing and theorizing change and stability as intertwined and co-existent, thus throwing light on how it is possible that, for example, even if ‘the walls fall down the blokes just code’ and maintain a sense of stability in their daily work. Rather than reproducing the picture of software product development as exciting cutting edge activities and organizational change as dramatic episodes, the study takes the reader beyond the myths surrounding these phenomena to the mundane practices, routines and organizings in product development during organizational change. An analysis of these ordinary practices offers insights into how software product development experts actively engage in constructing stability during organizational change through a variety of practices, including solidarity, homosociality, close relations to products, instrumental or functional views on products, preoccupations with certain tasks and humble obedience. Consequently, the study shows that it may be more appropriate to talk about varieties of stability, characterized by a multitude of practices of stabilizing rather than states of stagnation. Looking at different practices of stability in depth shows the creation of software as an arena for micro-politics, power relations and increasing pressures for order and formalization. The thesis gives particular attention to power relations and processes of positioning following organizational change: how social actors come to understand themselves in the context of ongoing organizational change, how they comply with and/or contest dominant meanings, how they identify and dis-identify with formalization, and how power relations often are reproduced despite dis-identification. Related to processes of positioning, the reader is also given a glimpse into what being at work in a male-dominated and relatively homogeneous work environment looks like. It shows how the strong presence of men or “blokes” of a particular age and education seems to become invisible in workplace talk that appears ‘non-conscious’ of gender.
  • Ottka, Claudia; Vapalahti, Katariina; Puurunen, Jenni; Vahtera, Laura; Lohi, Hannes (2021)
    Background Metabolomics has been proven to be an invaluable research tool by providing comprehensive insight into systemic metabolism. However, the lack of scalable and quantitative methods with known reference intervals (RIs) and documented reproducibility has prevented the use of metabolomics in the clinical setting. Objective The objective of this study was to validate the developed quantitative nuclear magnetic resonance (NMR) spectroscopy-based metabolomics platform for canine serum and plasma samples and determine optimal sample handling conditions for its use. Methods Altogether, 8247 canine samples were analyzed using a Bruker's 500 MHz NMR spectrometer. Using statistical approaches derived from international guidelines, we studied method precision, measurand stability in various long- and short-term storage conditions, as well as the effect of prolonged contact with red blood cells (RBCs), and differences among blood collection tubes. We also screened interferences with lipemia, hemolysis, and bilirubinemia. The results were compared against routine clinical chemistry methods, and RIs were defined for all measurands. Results We determined RIs for 123 measurands, most of which were previously unpublished. The reproducibility of the results of the NMR platform appeared generally outstanding, and the integrity of the results can be ensured by following standard blood drawing and processing guidelines. Conclusions Owing to the advantages of quantitative results, high reproducibility, and scalability, this canine metabolomics platform holds great potential for numerous clinical and research applications to improve canine health and well-being.
  • Tuominen-Soini, Heta; Salmela-Aro, Katariina; Niemivirta, Markku (2010)
    Tässä tutkimuksessa tarkastellaan ajallista pysyvyyttä ja sukupuolieroja yhdeksäsluokkalaisten ja lukiolaisten tavoiteorientaatioissa. Kahdessa pitkittäistutkimuksessa hyödynnettiin henkilösuuntautunutta lähestymistapaa ja tutkittiin nuorten tavoiteorientaatioiden pysyvyyttä ja muutosta lukuvuoden sisällä (9. luokan aikana, N = 530) ja lukuvuosien välillä (siirryttäessä lukion 2. luokalta 3. luokalle, N = 519). Nuoret voitiin jakaa neljään ryhmään heidän motivationaalisen orientaationsa mukaan (sitoutumattomat, menestysorientoituneet, oppimisorientoituneet ja välttämisorientoituneet) ja samankaltaiset ryhmät löydettiin molemmista opiskelukonteksteista. Ryhmät olivat hyvin pysyviä sekä 9. luokalla että lukiossa. Yleisesti ottaen pojat korostivat tyttöjä enemmän suhteellista menestymistä, mutta pyrkivät samalla selviämään koulutöistä mahdollisimman vähällä. Tytöt sen sijaan näyttäytyivät poikia oppimishakuisempina ja he korostivat koulussa menestymistä. Sukupuolierot tavoiteorientaatioissa olivat johdonmukaiset, mutta pienet ja ne korostuivat lukiolaisten otoksessa enemmän kuin yhdeksäsluokkalaisten otoksessa. Suurin ero liittyi poikien tyttöjä voimakkaampaan välttämisorientaatioon.
  • Korpilahti, Riikka (Helsingfors universitet, 2010)
    The purpose of this study was to develop articaine gargling water for local anesthesia in mouth and throat. Articaine is an amide type local anesthetic. Articaine has quick onset and it is short-acting. Articaine is safe and effective and it has rarely any adverse events. Allergic reactions are also uncommon. It has been planned to be done clinical trials with this gargling water. Xylitol and apple flavour were chosen as sweeteners to the gargling water and sodium carboxymethylcellulose was chosen as a viscosity enhancer. The purpose was also to increase preformulation knowledge of articaine in solution and in solid state. Articaine hydrochloride powder was investigated for shelf-life and for properties which are important in tableting in case it will be developed to a tablet formulation later. Compatibility of articaine hydrochloride and excipients of gargling water as powders was investigated by storing powders in temperature of 25 °C and relative humidity of 60 % up to three months. The shelf-life of articaine gargling water was investigated by storing the formulation in temperature of 25 °C and relative humidity of 60 % up to three months. Articaine concentration of solutions was determined by UV/VIS-spectrophotometry and high performance liquid chromatography (HPLC). Powders were investigated by HPLC and differential scanning calorimetry. Solid state of articaine hydrochloride powder was also investigated by X-ray powder diffractometry. In addition tablets were compressed from articaine hydrochloride. Compatibility of articaine with preservatives was also investigated in case it is necessary to add preservative to gargling water later. Methylparaben, propylparaben and potassium sorbate were chosen to this study. This study was done in solutions by storing solutions in temperature of 40 °C up to one and half months and determining articaine concentrations with HPLC. Articaine gargling water which is stabile for at least three months in room temperature was successfully developed. There were not any incompatibilities with articaine and excipients except with potassium sorbate. Articaine gargling water can be taken to the clinical trials. In compression study it was found that it is possible to make tablets from articaine hydrochloride. Breaking strengths of these tablets of pure articaine hydrochloride were not high but with suitable excipients it will be possible to create tablets hard enough.
  • Oduor, Joseph M. Ochieng; Kadija, Ermir; Nyachieo, Atunga; Mureithi, Marianne W.; Skurnik, Mikael (2020)
    Emergence of antibiotic-resistant bacteria is a serious threat to the public health. This is also true for Staphylococcus aureus and other staphylococci. Staphylococcus phages Stab20, Stab21, Stab22, and Stab23, were isolated in Albania. Based on genomic and phylogenetic analysis, they were classified to genus Kayvirus of the subfamily Twortvirinae. In this work, we describe the in-depth characterization of the phages that electron microscopy confirmed to be myoviruses. These phages showed tolerance to pH range of 5.4 to 9.4, to maximum UV radiation energy of 25 mu J/cm(2), to temperatures up to 45 degrees C, and to ethanol concentrations up to 25%, and complete resistance to chloroform. The adsorption rate constants of the phages ranged between 1.0 x 10(-9) mL/min and 4.7 x 10(-9) mL/min, and the burst size was from 42 to 130 plaque-forming units. The phages Stab20, 21, 22, and 23, originally isolated using Staphylococcus xylosus as a host, demonstrated varied host ranges among different Staphylococcus strains suggesting that they could be included in cocktail formulations for therapeutic or bio-control purpose. Phage particle proteomes, consisting on average of ca 60-70 gene products, revealed, in addition to straight-forward structural proteins, also the presence of enzymes such DNA polymerase, helicases, recombinases, exonucleases, and RNA ligase polymer. They are likely to be injected into the bacteria along with the genomic DNA to take over the host metabolism as soon as possible after infection.
  • Itkonen, Jaakko; Annala, Ada; Tavakoli, Shirin; Arango-Gonzalez, Blanca; Ueffing, Marius; Toropainen, Elisa; Ruponen, Marika; Casteleijn, Marco G.; Urtti, Arto (2020)
    Ciliary neurotrophic factor (CNTF) is one of the most studied neuroprotective agents with acknowledged potential in treating diseases of the posterior eye segment. Although its efficacy and mechanisms of action in the retina have been studied extensively, it is still not comprehensively understood which retinal cells mediate the therapeutic effects of CNTF. As with therapeutic proteins in general, it is poorly elucidated whether exogenous CNTF administered into the vitreous can enter and distribute into the retina and hence reach potentially responsive target cells. Here, we have characterized our purified recombinant human CNTF (rhCNTF), studied the protein's in vitro bioactivity in a cell-based assay, and evaluated the thermodynamic and oligomeric status of the protein during storage. Biological activity of rhCNTF was further evaluated in vivo in an animal model of retinal degeneration. The retinal penetration and distribution of rhCNTF after 24 h was studied utilizing two ex vivo retina models. Based on our characterization findings, our rhCNTF is correctly folded and biologically active. Moreover, based on initial screening and subsequent follow-up, we identified two buffers in which rhCNTF retains its stability during storage. Whereas rhCNTF did not show photoreceptor preservative effect or improve the function of photoreceptors in vivo, this could possibly be due to the used disease model or the short duration of action with a single intravitreal injection of rhCNTF. On the other hand, the lack of in vivo efficacy was shown to not be due to distribution limitations; permeation into the retina was observed in both retinal explant models as in 24 h rhCNTF penetrated the inner limiting membrane, and being mostly observed in the ganglion cell layer, distributed to different layers of the neural retina. As rhCNTF can reach deeper retinal layers, in general, having direct effects on resident CNTF-responsive target cells is plausible.
  • Segercrantz, Beata (Svenska handelshögskolan, 2007)
    Working Papers
    We all have fresh in our memory what happened to the IT sector only a few years ago when the IT-bubble burst. The upswing of productivity in this sector slowed down, investors lost large investments, many found themselves looking for a new job, and countless dreams fell apart. Product developers in the IT sector have experienced a large number of organizational restructurings since the IT boom, including rapid growth, downsizing processes, and structural reforms. Organizational restructurings seem to be a complex and continuous phenomenon people in this sector have to deal with. How do software product developers retrospectively construct their work in relation to organizational restructurings? How do organizational restructurings bring about specific social processes in product development? This working paper focuses on these questions. The overall aim is to develop an understanding of how software product developers construct their work during organizational restructurings. The theoretical frame of reference is based on a social constructionist approach and discourse analysis. This approach offers more or less radical and critical alternatives to mainstream organizational theory. Writings from this perspective attempt to investigate and understand sociocultural processes by which various realities are created. Therefore these studies aim at showing how people participate in constituting the social world (Gergen & Thatchenkery, 1996); knowledge of the world is seen to be constructed between people in daily interaction, in which language plays a central role. This means that interaction, especially the ways of talking and writing about product development during organizational restructurings, become the target of concern. This study consists of 25 in-depth interviews following a pilot study based on 57 semi-structured interviews. In this working paper I analyze 9 in-depth interviews. The interviews were conducted in eight IT firms. The analysis explores how discourses are constructed and function, as well as the consequences that follow from different discourses. The analysis shows that even though the product developers have experienced many organizational restructurings, some of which have been far-reaching, their accounts build strongly on a stability discourse. According to this discourse product development is, perhaps surprisingly, not influenced to a great extent by organizational restructurings. This does not mean that product development is static. According to the social constructionist approach, product development is constantly being reproduced and maintained in ongoing processes. In other words stable effects are also ongoing achievements and these are of particular interest in this study. The product developers maintain rather than change the product development through ongoing processes of construction, even when they experience continuous extensive organizational restructurings. The discourse of stability exists alongside other discourses, some which contradict each other. Together they direct product development and generate meanings. The product developers consequently take an active role in the construction of their work during organizational restructurings. When doing this they also negotiate credible positions for themselves
  • Antao, Laura H.; Pöyry, Juha; Leinonen, Reima; Roslin, Tomas (2020)
    Aim Biodiversity is currently undergoing rapid restructuring across the globe. However, the nature of biodiversity change is not well understood, as community-level changes may hide differential responses in individual population trajectories. Here, we quantify spatio-temporal community and stability dynamics using a long-term high-quality moth monitoring dataset. Location Finland, Northern Europe. Time period 1993-2012. Major taxa studied Nocturnal moths (Lepidoptera). Methods We quantified patterns of change in species richness, total abundance, dominance and temporal variability at different organizational levels over a 20 year period and along a latitudinal gradient of 1,100 km. We used mixed-effects and linear models to quantify temporal trends for the different community and stability metrics and to test for latitudinal (or longitudinal) effects. Results We found contrasting patterns for different community metrics, and strong latitudinal patterns. While total moth abundance has declined, species richness has simultaneously increased over the study period, but with rates accelerating with latitude. In addition, we revealed a latitudinal pattern in temporal variability-the northernmost locations exhibited higher variability over time, as quantified by both metrics of richness and aggregated species population trends. Main conclusions When combined, our findings likely reflect an influx of species expanding their ranges poleward in response to warming. The overall decline in abundance and the latitudinal effect on temporal variability highlight potentially severe consequences of global change for community structure and integrity across high-latitude regions. Importantly, our results underscore that increases in species richness may be paralleled by a loss of individuals, which in turn might affect higher trophic levels. Our findings suggest that the ongoing global species redistribution is affecting both community structure and stability over time, leading to compounded and partly opposing effects of global change depending on which biodiversity dimension we focus on.
  • Chen, Zhijie; Zhang, Feng; Zhang, Hongbo; Cheng, Liang; Chen, Kaizhe; Shen, Jieliang; Qi, Jin; Deng, Lianfu; He, Chuan; Santos, Helder A.; Cui, Wenguo (2021)
    Gene therapy is identified as a powerful strategy to overcome the limitations of traditional therapeutics to achieve satisfactory effects. However, various challenges related to the dosage form, delivery method, and, especially, application value, hampered the clinical transition of gene therapy. Here, aiming to regulate the cartilage inflammation and degeneration related abnormal IL-1 beta mRNA expression in osteoarthritis (OA), the interference oligonucleotides is integrated with the Au nanorods to fabricate the spherical nucleic acids (SNAs), to promote the stability and cell internalization efficiency. Furthermore, the complementary oligonucleotides are grafted onto hyaluronic acid (HA) to obtained DNA-grafted HA ((DNA)HA) for SNAs delivery by base pairing, resulting in significantly improved injectability and bio-stability of the system. After loading SNAs, the constructed (DNA)HA-SNAs system (HA-SNAs) performs a reversible NIR-triggered on-demand release of SNAs by photo-thermal induced DNA dehybridization and followed by post-NIR in situ hybridization. The in vitro and in vivo experiments showed that this system down-regulated catabolic proteases and up-regulated anabolic components in cartilage over extended periods of time, to safeguard the chondrocytes against degenerative changes and impede the continual advancement of OA.
  • Kinnunen, Eveliina (Helsingin yliopisto, 2020)
    Infant formulas are breast milk substitutes for 0 to 12-month-old infants. Addition of milk fat to infant formulas leads to an increase in solid fat content. Infant formulas are oil-in- water emulsions in which oil is dispersed into a continuous aqueous phase. Milk fat crystallization leads to partial coalescence and creaming which are types of instability in emulsions. Partial coalescence occurs when two droplets containing crystals collide and they partially coalesce by making contact between their oil phases. The aim of this thesis was to study if milk fat crystallization leads to partial coalescence which leads to a higher rate of creaming or the increasing density of crystallizing droplets leads to a lower rate of creaming. Also, the aim was to study the effect of interfacial layer on partial coalescence. Milk fat crystallization and emulsion stability were investigated from four series of oil-in- water emulsions containing different oils in different concentrations and either whey protein or lecithin as stabilizer. The samples were stored at 5, 20 and 40 °C and measured after 0, 7 and 28 days of storage. The crystallization of bulk fat and oil in emulsions were studied with melting enthalpies measured with differential scanning calorimetry. Emulsion stability was examined with particle size distribution, instability index and creaming velocity measurements. According to the results combining vegetable oil and butter oil, and emulsifying the fat decreases the total enthalpy change and crystallization onset temperature of oils. Mixing vegetable oil and butter oil before homogenization decreased crystallization onset temperature and total enthalpy change because the oils were in same droplet, and made the emulsions behave more like vegetable oil emulsions. Mixing the oils after homogenization made the emulsions behave similarly to butter oil emulsions. Whey protein was found to be a better stabilizer of emulsions than lecithin at 5 and 20 °C, but at 40 °C some Maillard reaction was noticed. It was suspected that the concentration of lecithin in emulsions was insufficient. Based on the results it could be stated that the increasing density due to crystallizing droplets made the emulsions more stable against creaming. Best stability of emulsions containing oil mixtures would be achieved if butter oil and vegetable oil were mixed after homogenization and whey protein used as emulsifier.
  • Pousi, Pipsa (Helsingin yliopisto, 2020)
    Avopurennassa vastakkaisten hammaskaarten hampaat eivät ole kontaktissa toisiinsa yhteen purtaessa vaan niiden väliin jää vertikaalinen aukko. Etualueen avopurennan esiintyvyys suomalaisessa aikuisväestössä on 1-2%, maitohampaistossa kuitenkin jopa 6-7%. Tämän kirjallisuuskatsauksen tavoitteena on esittää olemassa olevan tiedon ja tutkimusnäytön perusteella, mitkä ovat etualueen avopurennan hoitomuodot sen etiologia huomioiden, sekä arvioida hoidon pysyvyyttä. Tutkimusaineistona käytettiin tutkielman aiheesta laadittuja tieteellisiä julkaisuja. Julkaisujen hakemiseen käytettiin Medline-tietokannan Pubmed-käyttöliittymää. Etualueen avopurenta voidaan luokitella hampaistolliseksi ja luustolliseksi purentavirheeksi. Hampaistollinen avopurenta kehittyy varhaislapsuudessa aiheutuen tyypillisesti pitkittyneestä tutin tai peukalon imemisestä, suuhengityksestä tai kielen ja huulten virheellisistä funktioista. Tutista tulisi luopua 2-3 vuoden iässä. Avopurennan varhaishoidossa käytettäviä oikomiskojeita ovat mm. quad-helix, kiinteä kielieste, sekä myofunktionaaliset kojeet. Myös suurten risakudosten poisto on indikoitu. Haitalliset tavat yhdistettynä perinnöllisiin tekijöihin aiheuttavat usein luustollista etualueen avopurentaa. Myös leukanivelen kasvuhäiriöt ja sairaudet, kuten reuma, voivat olla avopurennan taustalla. Luustollisen avopurennan erityispiirteet ovat suuri goniaalikulma ja etukasvokorkeus, pieni takakasvokorkeus ja taaksepäin kallistunut kondyyli. Luustollisen avopurennan hoitoperiaatteita ovat molaarien puhkeamisen esto ekstraoraalivedolla tai luustoankkuroidulla palatinaalikaarella. Molaareita voidaan myös aktiivisesti intrudoida luustoankkureiden avulla tai posteriorisilla purentaesteillä. Alaleuan kasvusuuntaan pyritään vaikuttamaan vertikaalisella leukakapalla. Avopurennan palautumisluvut ovat suuria. Useiden tutkimusten mukaan hoitotuloksen pysyvyys on parhaimmillaan silloin, kun hoito on aloitettu varhain, ennen avopurennan kehittymistä luustolliseksi. Lukuisilla eri hoitomenetelmillä on saatu hyviäkin tuloksia avopurennan hoidossa, mutta pitkäaikaistutkimuksia on vähän. Tarvitaan pidempiä seurantajaksoja, jotta voidaan arvioida hoitotuloksien palautuvuutta tarkemmin. Jokaiselle potilaalle tulee tehdä yksilöllinen hoitosuunnitelma, jossa huomioidaan avopurennan etiologiset syyt. (228 sanaa)
  • Savelainen, Timo (Helsingfors universitet, 2013)
    Some problems in dry powder inhaler formulation include low dose efficiency and changes in dispersibility during storage. For lung deposition particles should have aerodynamic size of 1 - 5µm. Poor dispersion of drug particles from carriers' surface is thought to be the main reason for low dose efficacy. A tertiary component of small particles has been generally added to formulation to improve fine particle dose. Small particles are usually manufactured by micronization. This may induce crystal defects and amorphous sites on the surface of crystals. Amorphous sites are metastable and they may crystallize during storing. Changes in particles crystallinity may have an action on efficiency and stability of dry powder inhalers. Conditioning is designated as stabilisation of particles surface by mixture of solvent vapour and inert gas. Vapour may also dissolve surface roughness. This is called deliquescence. Ostwald ripening is phenomenon whereby small particles dissolves and recrystallizes onto larger crystals. This can be extended for surface asperities. Amorphous materials have also better solubility than crystalline materials so amorphous sites may also dissolve and recrystallize onto crystalline surface. Amorphous sites may crystallize spontaneously by absorbing plasticizing agents from vapour phase or by influence of temperature. The purpose of this work was to study process variables in conditioning and their effect on modification of surface roughness and stabilization of micronized α-lactose monohydrate and test drug substance. The purpose was also to study how surface modification and stabilization effects on powders flowability and stability of dry powder inhaler. The dry powder inhaler contained two different vicinity of lactose and two different drug substances. Conditioning was based on evaporation of liquid from open surface. Studied process variables were temperature of powder, temperature of bath of liquid phase and flow rate of nitrogen gas. The aim of this study was to form a process design for conditioning of new substances, to improve powders flowability and to remove changes in fine particle dose during storage. Surface roughness was studied by laser diffraction analysis and specific surface area measurements and also by electron microscopy. Specific surface area was measured by nitrogen adsorption method. Stabilization of amorphous sites ware studied by dynamic vapour sorption. Flowability was measured by angle of repose and with FlowPro device. Fine particle dose was measured with next generator impactor device. The study showed that increasing the amount of solvent in vapour increases surface smoothness and stabilization. Also increase of temperature of sample increased stabilization. Influence of temperature on surface smoothness was not as clear. Changes in temperature may have altered adsorption and kinetic of crystallization of dissolved molecules. Flowability of lactose was significantly improved. Condition did not improve dry powder inhalers fine particle dose, but there was significant difference between different process conditions. This was concluded to be caused of surface modification. It was also shown that different process conditions affected on formulations stability.
  • Tarmi, Siina (Helsingfors universitet, 2017)
    The scope of the literature review was to define the process for oil-in-water emulsion formation and the important properties of the emulsions which are suitable for microencapsulation. The aim of this study was to determine how whey protein isolate together with maltodextrin affects the properties of the emulsion. Camelina oil and black currant seed oil were used as core materials. The wall materials used were: maltodextrin (MD) and whey protein isolate (WPI). Six different wall systems consisting WPI in combination with MD at various ratios (1:1, 1:3 and 1:9) were used. In premilinary tests the emulsions were characterized for temperature, creaming index, apparent viscosity, flow behavior index, flow consistency index, droplet size (D4,3 zetasize,), droplet size distribution (PDI, span) and zetapotential. Droplet size and droplet size distributions were measured by a laser light scattering using a Zetasizer and by laser light diffraction instrument, Mastersizer 2000/3000. Oil droplet size was also measured with light blockade using a PAMAS. Rheological properties were characterized with rheometer. In actual test the emulsions were characterized for time (foam removal), temperature, droplet size (D10, D50, D90 ja D4,3), apparent viscosity, flow behavior index and flow consistency index. First degree polynomial was fitted with PLSR to the results. Statistical significances of regression coefficients were analyzed with t-test. In premilinary tests all the emulsions were stable during storage at 25 °C after 24 h. pH and zetapotentials which were all lower than -35 mV refer to good stability of emulsions. Change in droplet size and droplet size distribution was observed. Increasing maltodextrin concentration decreased droplet size (D4,3) and droplet size distribution width (PDI) when measuring by Mastersizer and Zetasizer. Apparent viscosity of the emulsions decreased by increasing maltodextrin concentration. PLS-regression showed that there were statistically differences between wall materials and temperatures, droplet size, size distribution and apparent viscosity. There were also statistically differences between oil and droplet size measured by PAMAS. In actual tests apparent viscosity of the emulsions decreased by increasing maltodextrin concentration. Increasing maltodextrin concentration also decreased the time of foam removal. PLS-regression showed that there were statistically differences between wall materials and temperatures after homogenization, time (foam removal), flow consistency index and apparent viscosity. There were also statistically differences between oil and temperatures, flow behavior index and droplet size distribution width. Whey protein isolate together with maltodextrin affect mostly to apparent viscosity of emulsions.
  • Janér, Henrik (2005)
    This thesis deals with the development of John Rawls's thought from A Theory of Justice to Political Liberalism. It does not deal with the early development of Rawls's thought: neither does it take issue with the application of his thought to the realm of international relations as developed in The Law of Peoples. In this thesis I rely on the work of Samuel Freeman. Therefore the thesis centers on a specific aspect of Rawls's argument for stability, the finality argument. It is primarily the finality argument that Rawls becomes dissatisfied with and thus recasts in Political Liberalism. I look at how Rawls begins to shift his view in the important transitional essay Kantian Constructivism in Moral Theory. Nevertheless, my interest in this essay does not hinge on the topic of constructivism. Instead, I have found that the most important aspect of this essay, if one is interested in studying the shift from A Theory of Justice to Political Liberalism, is the emphasis that Rawls puts on the practical role of philosophy. A conception of justice has to fill this role. It has to be able to order conflicts in society, by specifying how interests and wants are to be ordered. It is this role that the argument from finality in A Theory of Justice is unfit to fill. While there are significant shifts of emphasis in Rawls's work from A Theory of Justice to Political Liberalism I have found that there is a thin red line running through his work. The role of reconciliation in political philosophy accounts for the unity to which I refer. Following Samuel Freeman's terminology this role of reconciliation in political philosophy shows the possibility of just democratic constitution. Finally, I argue that one has to take this underlying unity into account if one wants to fashion a coherent criticism of Rawls. I raise doubts about whether Rawls's theory is fit to deal with pluralism in the political sphere and suggest where the problem in his theory lies. I base this criticism on the picture underlying the development of Rawls's thought.
  • Toppari, Antti (Helsingfors universitet, 2011)
    Nowadays growing number of new active pharmaceutical ingredients (API) have large molecular weight and are hydrophobic. The energy of their crystal lattice is bigger and polarity has decreased. This leads to weakened solubility and dissolution rate of the drug. These properties can be enhanced for example by amorphization. Amorphous form has the best dissolution rate in the solid state. In the amorphous form drug molecules are randomly arranged, so the energy required to dissolve molecules is lower compared to the crystalline counterpart. The disadvantage of amorphous form is that it is unstable. Amorphous form tends to crystallize. Stability of amorphous form can be enhanced by adding an adjuvant to drug product. Adjuvant is usually a polymer. Polymers prevent crystallization both by forming bonds with API molecules and by steric hindrance. The key thing in stabilizing amorphous form is good miscibility between API and polymer. They have to be mixed in a molecular level so that the polymer is able to prevent crystallization. The aim of this work was to study miscibility of drug and polymer and stability of their dispersion with different analytical methods. Amorphous dispersions were made by rotary evaporator and freeze dryer. Amorphicity was confirmed with X-ray powder diffraction (XRPD) right after preparation. Itraconazole and theophylline were the chosen molecules to be stabilized. Itraconazole was expected to be easier and theophylline more difficult to stabilize. Itraconazole was stabilized with HPMC and theophylline was stabilized with PVP. Miscibility was studied with XRPD and differential scanning calorimetry (DSC). In addition it was studied with polarized light microscope if miscibility was possible to see visually. Dispersions were kept in stressed conditions and the crystallization was analyzed with XRPD. Stability was also examined with isothermal microcalorimetry (IMC). The dispersion of itraconazole and theophylline 40/60 (w/w) was completely miscible. It was proved by linear combination of XRPD results and single glass transition temperature in DSC. Homogenic well mixed film was observed with light microscope. Phase separation was observed with other compositions. Dispersions of theophylline and PVP mixed only partly. Stability of itraconazole dispersions were better than theophylline dispersions which were mixed poorer. So miscibility was important thing considering stability. The results from isothermal microcalorimetry were similar to results from conventional stability studies. Complementary analytical methods should be used when studying miscibility so that the results are more reliable. Light microscope is one method in addition to mostly used XRPD and DSC. Analyzing light microscope photos is quite subjective but it gives an idea of miscibility. Isothermal microcalorimetry can be one option for conventional stability studies. If right conditions can be made where the crystallization is not too fast, it may be possible to predict stability with isothermal microcalorimetry.
  • Taivainen, Sanna (Helsingfors universitet, 2016)
    Suspension is nowadays the most commonly used dosage form in preclinical animal studies. However, suspension can be physically unstable and changes in particle size or crystal form of an active pharmaceutical ingredient (API) can occur during storage. Conventionally suspensions are also prepared in a mortar, and hence the quality of suspensions is operator-dependent. One of the aims in this study was to prepare suspensions using a mortar and pestle and an Ultra-turrax homogenizer to find out how the preparation method affects the particle size of suspension. A solution containing methylcellulose and Tween 80 was used as a vehicle, and five active APIs with different physico-chemical properties as model drugs. Moreover, an aim of the study was to evaluate the stability of the suspensions stored at room temperature and in the refrigerator and freezer by physical (laser diffraction, optical microscopy, X-ray powder diffraction) and chemical (high-performance liquid chromatography) methods of analysis. The aim of the study was also to assess and compare the suitability of laser diffraction and optical microscopy for the determination of partice size during preclinical studies. The suspensions prepared using a mortar and pestle and Ultra-turrax had a similar particle size in almost all cases. The particle size of API that was difficult to grind decreased significantly, also when using Ultra-turrax although the capacity used was minimum. Both prepation methods had the best repeatability of particle size when the API was easy to grind. However, Ultra-turrax could provide better homogeneity of quality than a mortar and pestle if the settings were optimized. The effect of different operators was not studied in this study. The stability of suspensions in different storage conditions was dependent on the properties of API. The particle size of all frozen suspensions decreased after two days based on laser diffraction results. Although the reason was not found from literature or supplementary tests (particle size analysis of the vehicle and pH-measurements), freezing of suspensions should be treated with caution based on this study. The crystal structures of APIs remained stabile with the exception of typical disproportionation of the API salt. Suspensions were mainly chemically stabile in all conditions, but water-solubility of API seemed to decrease stability. The micellar solubilization of drugs was also observed. The best way to determine the particle size of preclinical suspensions proved to be the combination of laser diffraction and optical microscopy images. The microscopy images confirmed the validity of the size distributions measured by laser diffraction and provided information about e.g. particle aggregation. On the other hand, optical microscopy image analysis was not suitable method for particle sizing.
  • Itkonen, Jaakko (Helsingfors universitet, 2014)
    Proteins are endogenous molecules that carry out most biological functions in vivo. They are called as the biological workhorses. Proteins are made up of polypeptide chains that usually fold in the three dimensional space to adopt a native stable conformation. Stability of proteins is dependent on the interplay of environmental factors (pH, temperature, ionic strength). For most proteins, the biological function closely relates to the structural attributes of the protein. Misfolding or unfolding of proteins often result in aggregation. Protein aggregation in vivo is known to cause debilitating and fatal diseases such as Alzheimer's, Huntington's, Parkinson's and age related macular degeneration (AMD). Instability (physical and chemical) of proteins in vitro is believed to result in aggregation. This is a huge concern for the biopharmaceutical industry as it not only limits the effectiveness of the manufacturing process but also poses a great risk of fatality in vivo due to the immunogenic nature of the aggregates. Mechanisms of protein aggregation are complex and not well understood. Regulatory requirements for patient safety in biopharmaceutical products require characterization and analysis of aggregates in protein drug formulations. This review provides an overview of protein aggregation in general and highlights the different analytical methods used to characterize protein aggregates in biopharmaceuticals. Neurotrophic factors influence survival, differentiation, proliferation and death of neuronal cells within the central nervous system. Human ciliary neurotrophic factor (hCNTF) has neuroprotective properties and is also known to influence energy balance. Consequently, hCNTF has potential therapeutic applications in neurodegenerative, obesity and diabetes related disorders. Clinical and biological applications of CNTF necessitate a recombinant expression system to produce large amounts of functional protein. Previous studies have reported that recombinant expression of CNTF in Escherichia coli (E. coli) was limited by low yields and the need to refold the protein from inclusion bodies. In this report, we describe a strategy to effectively screen fusion constructs and expression conditions for soluble hCNTF production in E. coli. Most conditions tested with the codon optimized hCNTF sequence in fusion with soluble tags resulted in soluble expression of the protein. The construct 6-His-CNTF showed soluble expression in all the conditions tested. Our results suggest that codon optimization of the hCNTF sequence is sufficient for soluble expression in E. coli. The recombinant hCNTF was found to bind to CNTFRα with an EC50 = 36 nM.
  • Zhou, Xiao (Helsingin yliopisto, 2014)
    Divicine and isouramil are the causative agents of favism. The stability of divicine is of vital importance in faba bean detoxification. The literature review of this thesis focused on the hydrolysis of vicine to divicine, the oxidation processes of divicine and its stability studies. The main aims of this thesis were to produce divicine using the hydrolysis of vicine with ?-glucosidase, and study the effects of nitrogen/air atmosphere, reducing agent, pH and temperature on the stability of divicine. The identities of other compounds observed in vicine hydrolysis were also to be investigated. In addition, convicine was also hydrolyzed in the extracts and pure convicine fractions. Vicine and convicine were co-extracted from dehulled faba bean flour and were separated with preparative HPLC-MS. The extracts and the pure vicine and convicine fractions were hydrolyzed with ?-glucosidase to yield divicine and isouramil. The identities of the compounds formed during vicine fraction hydrolysis were studied by MS. In the following stability studies, the pure vicine fractions were hydrolyzed with ?-glucosidase under nitrogen and in the presence of (+)-sodium L-ascorbate. Moreover, the fractions were firstly hydrolyzed under air, next, the formed divicine was incubated at pH 3.0 or 5.0 at 20 or 37 ºC. An analytical HPLC method was used to study the changes during hydrolysis and stability tests. It was found that higher ?-glucosidase concentration and longer incubation period resulted in higher hydrolysis degrees of vicine and convicine. Further, vicine was hydrolyzed more rapidly at pH 3.0 than 5.0. Vicine was hydrolyzed to divicine. Divicine further generated two compounds, named compound 1 and compound 2 in this thesis. Their corresponding retention times and absorption maxima were: 2.15 min, 282 nm; 1.79 min, 262 nm; and 1.94 min, 210 nm. Compound 1 was directly generated from divicine. It was possibly oxidized divicine, but its characterization with MS failed in this study. Compound 1 decomposed to compound 2 at pH 5.0 at 20 ºC, but at pH 3.0 at 20 ºC, divicine might directly decompose to compound 2. Only one compound (named compound 3) was formed during convicine hydrolysis, and its retention time and absorption maximum were 2.50 min and 280 nm. Divicine and compounds 1, 2, and 3 were not stable, they finally decomposed to non-UV absorbing substances. Divicine was more stable under nitrogen than under air, and in the presence of (+)-sodium L-ascorbate than without its presence. Divicine decomposed similarly at pH 3.0 and 5.0 at 37 ºC, but at 20 ºC, divicine was more stable at pH 5.0. At both pH values, the stability of divicine was increased at 20 ºC compared with 37 ºC.
  • Solansuu, Kati (Helsingfors universitet, 2018)
    Formulation development for protein drugs should base on the knowledge of the mechanism of protein degradation. Excipients and formulation can be chosen to stabilize the protein and prevent decomposition. Stability testing is important to identify the likely degradation routes and provide information for formulation development and stability-indicating analytical method development. Gonadotropin-releasing hormone (GnRH) is a neuropeptide hormone that regulates the synthesis and release of gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FHS). Analogs of the endogenous GnRH have been developed to achieve more potent and longer-acting agonists or antagonists. GnRH agonists degrade in several pathways. The primary degradation routes are hydrolysis/backbone cleavage, oxidation, isomerization and aggregation. The stability of GnRH agonists in solid dosage forms has not been studied as excessively as in solutions. The objective of this study was to evaluate the stability of a GnRH agonist (API) at different storage conditions in powder form and in tablet formulations with maize starch or hydroxypropyl methylcellulose (HPMC). The samples were stored for three months at 5 °C (common refrigerator conditions) 25 °C/58 %RH (long-term conditions), and 40 °C/75 %RH (accelerated storage conditions). The samples were analyzed using high performance liquid chromatography. Additionally, the mechanical properties of the formulations and tablets were studied. The stability of API was confirmed in tablet dosage form, when maize starch or HPMC were used as excipients. No degradation products of API were found. As a pure powder API did not degrade either, but it did not stay physically stable at 40 °C/75 %RH. Stressed conditions could be used to find out degradation products in solid state that were not found in this study. Further, the formulations were not ideal, because neither of the studied excipient produced tablets with desirable properties.
  • Stockwell, Jason D.; Doubek, Jonathan P.; Adrian, Rita; Anneville, Orlane; Carey, Cayelan C.; Carvalho, Laurence; Domis, Lisette de Senerpont; Dur, Gaël; Frassl, Marieke A.; Grossart, Hans-Peter; Ibelings, Bas W.; Lajeunesse, Marc J.; Lewandowska, Aleksandra; Llames, María E.; Matsuzaki, Shin-Ichiro S.; Nodine, Emily R.; Noges, Peeter; Patil, Vijay P.; Pomati, Francesco; Rinke, Karsten; Rudstam, Lars G.; Rusak, James A.; Salmaso, Nico; Seltmann, Christian T.; Straile, Dietmar; Thackeray, Stephen J.; Thiery, Wim; Urrutia-Cordero, Pablo; Venail, Patrick; Verburg, Piet; Woolway, R. Iestyn; Zohary, Tamar; Andersen, Mikkel R.; Bhattacharya, Ruchi; Hejzlar, Josef; Janatian, Nasime; Kpodonu, Alfred T. N. K.; Williamson, Tanner J.; Wilson, Harriet L. (2020)
    In many regions across the globe, extreme weather events such as storms have increased in frequency, intensity, and duration due to climate change. Ecological theory predicts that such extreme events should have large impacts on ecosystem structure and function. High winds and precipitation associated with storms can affect lakes via short-term runoff events from watersheds and physical mixing of the water column. In addition, lakes connected to rivers and streams will also experience flushing due to high flow rates. Although we have a well-developed understanding of how wind and precipitation events can alter lake physical processes and some aspects of biogeochemical cycling, our mechanistic understanding of the emergent responses of phytoplankton communities is poor. Here we provide a comprehensive synthesis that identifies how storms interact with lake and watershed attributes and their antecedent conditions to generate changes in lake physical and chemical environments. Such changes can restructure phytoplankton communities and their dynamics, as well as result in altered ecological function (e.g., carbon, nutrient and energy cycling) in the short- and long-term. We summarize the current understanding of storm-induced phytoplankton dynamics, identify knowledge gaps with a systematic review of the literature, and suggest future research directions across a gradient of lake types and environmental conditions.