| 1. |
- Gawlik, Kinga, et al.
(författare)
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Loss of Dystrophin and β-Sarcoglycan, Respectively, Significantly Exacerbates the Phenotype of Laminin α2 Chain-Deficient Animals.
- 2014
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 184:3, s. 740-752
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Tidskriftsartikel (refereegranskat)abstract
- The adhesion molecule laminin α2 chain interacts with the dystrophin-glycoprotein complex, contributes to normal muscle function, and protects skeletal muscles from damage. Complete loss of the laminin α2 chain in mice results in a severe muscular dystrophy phenotype and death at approximately 3 weeks of age. However, it is not clear if the remaining members of the dystrophin-glycoprotein complex further protect laminin α2 chain-deficient skeletal muscle fibers from degeneration. Hence, we generated mice deficient in laminin α2 chain and dystrophin (dy(3K)/mdx) and mice devoid of laminin α2 chain and β-sarcoglycan (dy(3K)/Sgcb). Severe muscular dystrophy and a lack of nourishment inevitably led to massive muscle wasting and death in double-knockout animals. The dy(3K)/Sgcb mice were generally more severely affected than dy(3K)/mdx mice. However, both double-knockout strains displayed exacerbated muscle degeneration, inflammation, fibrosis, and reduced life span (5 to 13 days) compared with single-knockout animals. However, neither extraocular nor cardiac muscle was affected in double-knockout animals. Our results suggest that, although laminin α2 chain, dystrophin, and β-sarcoglycan are all part of the same adhesion complex, they have complementary, but nonredundant, roles in maintaining sarcolemmal integrity and protecting skeletal muscle fibers from damage. Moreover, the double-knockout mice could potentially serve as models in which to study extremely aggressive muscle-wasting conditions.
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| 2. |
- Werntoft, Elisabet, et al.
(författare)
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Older people's views of prioritization in health care
- 2005
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Ingår i: Aging Clinical and Experimental Research. - : Kurtis. - 1594-0667 .- 1720-8319. ; 17:5, s. 402-411
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The aim of this study was to investigate and compare older people's views of prioritization in health care with specific regard to age, gender and HRQoL. METHODS: The sample was collected from a prospective longitudinal cohort study, the GAS project (Good Ageing in Skane) that is in progress in Sweden. For this study, 902 persons, 424 men and 478 women, aged between 60 and 93 years, were invited consecutively over a period of 17 months to participate in an additional structured interview based on an interview manual. Socio-demographic and HRQoL data were collected from the GAS project. For the analysis, the sample was divided into age groups: young-old, old-old, and oldest-old. RESULTS: Older people in general did not want age as a criterion for prioritization in health care. When pain was added as a criterion, age became even less important than when it was the sole criterion. The oldest-old, to a higher degree than the other age groups, prioritized younger patients, as did men, while women, more than men, preferred "old age" as an indicator for prioritization. The respondents' views on prioritization were also more associated with age and gender than HRQoL. CONCLUSIONS: Older people's views of priorities seem to differ from previous population-based studies, in that age per se as a criterion for selection between patients was not favored; health and wellbeing were more important. Differences were, however, found within the group of older people, as regards both age and gender.
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| 3. |
- Di Baldassarre, Giuliano, et al.
(författare)
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Multiple hazards and risk perceptions over time : the availability heuristic in Italy and Sweden under COVID-19
- 2021
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Ingår i: Natural hazards and earth system sciences. - : Copernicus Publications. - 1561-8633 .- 1684-9981. ; 21:11, s. 3439-3447
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Tidskriftsartikel (refereegranskat)abstract
- The severe impact of global crises, such as COVID-19 and climate change, is plausibly reshaping the way in which people perceive risks. In this paper, we examine and compare how global crises and local disasters influence public perceptions of multiple hazards in Italy and Sweden. To this end, we integrate information about the occurrence of hazardous events with the results of two nationwide surveys. These included more than 4000 participants and were conducted in two different phases of the COVID-19 pandemic corresponding to low (August 2020) and high (November 2020) levels of infection rates. We found that, in both countries, people are more worried about risks related to experienced events. This is in line with the cognitive process known as the availability heuristic: individuals assess the risk associated with a given hazard based on how easily it comes to their mind. Epidemics, for example, are perceived as less likely and more impactful in Italy compared to Sweden. This outcome can be explained by cross-country differences in the impact of, as well as governmental responses to, COVID-19. Notwithstanding the ongoing pandemic, people in both Italy and Sweden are highly concerned about climate change, and they rank it as the most likely threat.
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| 4. |
- Zamani, Leila, et al.
(författare)
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High cell density perfusion culture has a maintained exoproteome and metabolome
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Chinese hamster ovary (CHO) cells are the workhorse to produce recombinant proteins in the biopharmaceutical industry using mammalian cells and are commonly cultured in either fed-batch or perfusion mode. The optimization of the complex biological systems used in such processes is extremely challenging. Multi-omics approaches can reveal otherwise unknown characteristics of these systems and identify culture parameters that can be manipulated to optimize the cultivation process. Here we have ap- plied both metabolomic and proteomic profiling to a monoclonal antibody (mAb) production operated in perfusion mode to explore how cell biology and reactor environment change as the cell density reaches ≥ 200 x 106 cells/mL. The extracellular metabolic composition obtained in perfusion mode was also com- pared to fed-batch, which showed a more stable profile for perfusion despite a far larger range of viable cell densities. The proteomics data showed an increase of structural proteins as the cell density increased, and both the proteomic and metabolic results showed signs of oxidative stress and changes in glutathione metabolism at very high cell densities. The methodology presented herein could be a powerful tool for optimizing cultivation processes and recombinant protein production.
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| 5. |
- Ananthakrishnan, Gopal, 1982-
(författare)
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From Acoustics to Articulation : Study of the acoustic-articulatory relationship along with methods to normalize and adapt to variations in production across different speakers
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The focus of this thesis is the relationship between the articulation ofspeech and the acoustics of produced speech. There are several problems thatare encountered in understanding this relationship, given the non-linearity,variance and non-uniqueness in the mapping, as well as the differences thatexist in the size and shape of the articulators, and consequently the acoustics,for different speakers. The thesis covers mainly four topics pertaining to thearticulation and acoustics of speech.The first part of the thesis deals with variations among different speakersin the articulation of phonemes. While the speakers differ physically in theshape of their articulators and vocal tracts, the study tries to extract articula-tion strategies that are common to different speakers. Using multi-way linearanalysis methods, the study extracts articulatory parameters which can beused to estimate unknown articulations of phonemes made by one speaker;knowing other articulations made by the same speaker and those unknown ar-ticulations made by other speakers of the language. At the same time, a novelmethod to select the number of articulatory model parameters, as well as thearticulations that are representative of a speaker’s articulatory repertoire, issuggested.The second part is devoted to the study of uncertainty in the acoustic-to-articulatory mapping, specifically non-uniqueness in the mapping. Severalstudies in the past have shown that human beings are capable of producing agiven phoneme using non-unique articulatory configurations, when the artic-ulators are constrained. This was also demonstrated by synthesizing soundsusing theoretical articulatory models. The studies in this part of the the-sis investigate the existence of non-uniqueness in unconstrained read speech.This is carried out using a database of acoustic signals recorded synchronouslyalong with the positions of electromagnetic coils placed on selected points onthe lips, jaws, tongue and velum. This part, thus, largely devotes itself todescribing techniques that can be used to study non-uniqueness in the sta-tistical sense, using such a database. The results indicate that the acousticvectors corresponding to some frames in all the phonemes in the databasecan be mapped onto non-unique articulatory distributions. The predictabil-ity of these non-unique frames is investigated, along with verifying whetherapplying continuity constraints can resolve this non-uniqueness.The third part proposes several novel methods of looking at acoustic-articulatory relationships in the context of acoustic-to-articulatory inversion.The proposed methods include explicit modeling of non-uniqueness usingcross-modal Gaussian mixture modeling, as well as modeling the mappingas local regressions. Another innovative approach towards the mapping prob-lem has also been described in the form of relating articulatory and acousticgestures. Definitions and methods to obtain such gestures are presented alongwith an analysis of the gestures for different phoneme types. The relationshipbetween the acoustic and articulatory gestures is also outlined. A method toconduct acoustic-to-articulatory inverse mapping is also suggested, along withva method to evaluate it. An application of acoustic-to-articulatory inversionto improve speech recognition is also described in this part of the thesis.The final part of the thesis deals with problems related to modeling infantsacquiring the ability to speak; the model utilizing an articulatory synthesizeradapted to infant vocal tract sizes. The main problem addressed is related tomodeling how infants acquire acoustic correlates that are normalized betweeninfants and adults. A second problem of how infants decipher the number ofdegrees of articulatory freedom is also partially addressed. The main contri-bution is a realistic model which shows how an infant can learn the mappingbetween the acoustics produced during the babbling phase and the acous-tics heard from the adults. The knowledge required to map correspondingadult-infant speech sounds is shown to be learnt without the total numberof categories or one-one correspondences being specified explicitly. Instead,the model learns these features indirectly based on an overall approval rating,provided by a simulation of adult perception, on the basis of the imitation ofadult utterances by the infant model.Thus, the thesis tries to cover different aspects of the relationship betweenarticulation and acoustics of speech in the context of variations for differentspeakers and ages. Although not providing complete solutions, the thesis pro-poses novel directions for approaching the problem, with pointers to solutionsin some contexts.
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| 6. |
- Kravtsova, VV, et al.
(författare)
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Isoform-specific Na,K-ATPase and membrane cholesterol remodeling in motor endplates in distinct mouse models of myodystrophy
- 2020
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 318:5, s. C1030-C1041
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Tidskriftsartikel (refereegranskat)abstract
- Na,K-ATPase is a membrane transporter that is critically important for skeletal muscle function. Mdx and Bla/J mice are the experimental models of Duchenne muscular dystrophy and dysferlinopathy that are known to differ in the molecular mechanism of the pathology. This study examines the function of α1- and α2-Na,K-ATPase isozymes in respiratory diaphragm and postural soleus muscles from mdx and Bla/J mice compared with control С57Bl/6 mice. In diaphragm muscles, the motor endplate structure was severely disturbed (manifested by defragmentation) in mdx mice only. The endplate membrane of both Bla/J and mdx mice was depolarized due to specific loss of the α2-Na,K-ATPase electrogenic activity and its decreased membrane abundance. Total FXYD1 subunit (modulates Na,K-ATPase activity) abundance was decreased in both mouse models. However, the α2-Na,K-ATPase protein content as well as mRNA expression were specifically and significantly reduced only in mdx mice. The endplate membrane cholesterol redistribution was most pronounced in mdx mice. Soleus muscles from Bla/J and mdx mice demonstrated reduction of the α2-Na,K-ATPase membrane abundance and mRNA expression similar to the diaphragm muscles. In contrast to diaphragm, the α2-Na,K-ATPase protein content was altered in both Bla/J and mdx mice; membrane cholesterol re-distribution was not observed. Thus, the α2-Na,K-ATPase is altered in both Bla/J and mdx mouse models of chronic muscle pathology. However, despite some similarities, the α2-Na,K-ATPase and cholesterol abnormalities are more pronounced in mdx mice.
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| 7. |
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| 8. |
- Zamani, Leila, et al.
(författare)
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Conformational studies of a monoclonal antibody, IgG1, by chemical oxidation: Structural analysis by ultrahigh-pressure LC-electrospray ionization time-of-flight MS and multivariate data analysis
- 2008
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 380:2, s. 155-163
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Tidskriftsartikel (refereegranskat)abstract
- We describe the development of a method in which protein oxidation by H2O2 followed by ultrahigh-pressure liquid chromatography (UHPLC) coupled with electrospray ionization time-of-flight mass spectrometry (ESI-ToFMS) and multivariate analysis are used to detect alterations in conformational states of proteins. In the study reported here, an IgG1 monoclonal antibody in native and denatured conformational states was oxidized by treatment with hydrogen peroxide. Peptide fragments generated by tryptic digestion were then analyzed by UHPLC-ESI-ToFMS. After reducing noise and extracting peaks from the LC-MS data using MzExplorer, software developed in-house and based on Matlab, we were able to distinguish peptides arising from the native and denatured states of the oxidized protein by principal component analysis. Peptides containing residues, which are inclined to undergo oxidation, such as methionine, are founded to be particularly important in this approach. We believe that the methodology could facilitate attempts to characterize the conformational states of recombinant monoclonal antibodies and other proteins.
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| 9. |
- Aleksandrov, E, et al.
(författare)
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Emerging streams of intitutional theory in accounting research : current status and future directions
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- More than 30 years have passed since first calls to see accounting as social and institutional practice (Burchell et al., 1980; Hopwood, 1987; Hopwood & Miller, 1994). During these years, a significant number of theories have been striving to extend and challenge the hegemony of particular ways of seeing accounting (Jacobs, 2012) with acknowledging the need for inter-disciplinary approach and theoretical pluralism in contemporary studies. Within this theoretical pluralism, the institutional theory was recognized as one of the dominating theories in accounting research during last decades (Jacobs, 2012; Lounsbury, 2008; Modell, 2015).However, despite acknowledging the paradigmatic developments of institutional theory into several streams in organisational science (DiMaggio, 1988; Lawrence et al., 2009, 2011; Oliver, 1991; Thornton et al., 2012), few attempts were done to make a separate review of these streams and their value for accounting literature (Modell, 2009). Here, influential work of Lounsbury (2008) rather reflected organizational science literature with seeing accounting as a context which can give crucial insights into institutional and practice theories rather than vice versa. Jacobs (2012) in his study of theoretical pluralism in accounting research during 1992-2008 acknowledged the institutional theory domination but made few reflections on its progressions and implications for seeing accounting as social and institutional practice. And finally, more recent studies of Modell and his colleagues (Modell, 2015; Modell et al., 2017) made overviews of two streams of institutional theory (e.g. logic and work) and institutional theory combination possibility with other theories. While giving the valuable insights into understanding of issues related to theories combinations in accounting, these studies hardly review the accounting literature related to institutional theory streams which were criticised for apolitical nature but at the same time acknowledged as self-sufficient.Therefore, it seems that current studies rather ignore or criticize specific institutional theory streams, jumping into possible theory combinations agenda without revealing the value of these streams for accounting research. Such tendency may potentially lead to marginalization of accounting knowledge (Jacobs, 2016; Jacobs & Cuganesan, 2014) with the use of these streams under the quest for contribution to the interdisciplinary literature.In this regard, this paper aims to reflect upon the emerging streams of institutional theory, their application and influence on the accounting research of the last decade. Specifically, the paper’s ambition is to review and understand the role of institutional logics (IL), institutional entrepreneurship (IE) and institutional work (IW) in accounting research. These streams of institutional theory become increasingly valuable in accounting research for their explanatory capacities. But at the same time, but their application, especially in a combined form, can also raise criticalities within theoretical pluralism agenda. Therefore, we construct our research questions as:How have the emerging stream of institutional theory (IL, IE and IW) been used by accounting scholars?How have these streams influenced accounting research? What could be done in the future accounting research using emerging streams of institutional theory?In order to answer these research questions, we compile a structured literature review (Massaro et al., 2016) of articles published in scientific journals in the accounting field (levels 4 and 3 in ABS list). As a frame for analysis of the paper, we use conceptual clarification and analytical framework proposed by Lukka and Vinnari (2014) who made a distinction between domain theory and method theory in order to capture the relations between common knowledge about accounting as a social practice and the theories used to extend this knowledge. Applying to our paper, domain theory refers particularly to a set of knowledge about accounting as social and institutional practice. Method theory (i.e. IL, IE, IW) is a meta-level conceptual system, which can offer alternative perspectives and add new understanding/insights into domain theory. Following this analytical distinction, we examine the way how current accounting literature utilizes the selected institutional streams in domain-method dimension, how the theory or their combination (if any) are justified and used in a flow of argument for understanding of accounting practice.
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| 10. |
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