| 1. |
- Jiang, Yiwen, et al.
(författare)
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Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin
- 2017
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 18:4, s. 977-990
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Tidskriftsartikel (refereegranskat)abstract
- The identity of the glioblastoma (GBM) cell of origin and its contributions to disease progression and treatment response remain largely unknown. We have analyzed how the phenotypic state of the initially transformed cell affects mouse GBM development and essential GBM cell (GC) properties. We find that GBM induced in neural stem-cell-like glial fibrillary acidic protein (GFAP)-expressing cells in the subventricular zone of adult mice shows accelerated tumor development and produces more malignant GCs (mGC1GFAP) that are less resistant to cancer drugs, compared with those originating from more differentiated nestin- (mGC2NES) or 2,'3'-cyclic nucleotide 3'-phosphodiesterase (mGC3CNP)-expressing cells. Transcriptome analysis of mouse GCs identified a 196 mouse cell origin (MCO) gene signature that was used to partition 61 patient-derived GC lines. Human GC lines that clustered with the mGC1GFAP cells were also significantly more self-renewing, tumorigenic, and sensitive to cancer drugs compared with those that clustered with mouse GCs of more differentiated origin.
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| 2. |
- Gustafsson, Ola, et al.
(författare)
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Heat exchanger design aspects related to noise in heat pump applications
- 2016
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Ingår i: Applied Thermal Engineering. - : Elsevier. - 1359-4311 .- 1873-5606. ; 93, s. 742-749
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Tidskriftsartikel (refereegranskat)abstract
- An increased use of heat pumps is one of the measures that can be taken to reduce energy consumption on a large scale. For a wider acceptance, and major heat pump market expansion, it is crucial to develop heat pumps that cause minimal disturbance. Results from field measurements made by SP Technical Research Institute of Sweden indicate that the use of indirect heat pumps has potential to significantly reduce the outdoor noise level of ambient air heat pumps. The noise level caused by such heat pumps has been shown to be highly influenced by the design of the air-to-fluid heat exchanger. The overall purpose of this study is to propose a design of an air-to-fluid heat exchanger that allows for a well performing system as well as a low level of noise and cost. Two different types of heat exchangers, with flat tubes and round tubes, are compared theoretically. According to the modelling results, a heat exchanger with flat tubes and plain fins is the most suitable out of the studied designs due to its low heat transfer resistance on the tube side. The round tube heat exchangers showed to be significantly less suitable, displacing more than twice the volume.
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| 3. |
- Haglund, Lena, 1953-, et al.
(författare)
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The use of MOHO intervention methods for enabling occupational change in mental health.
- 2019
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Konferensbidrag (refereegranskat)abstract
- The presented MOHO intervention methods; strategies and interventions, for facilitating change has not been investigated in practice in Sweden. MOHO is often seen as an assessment model. Many assessments have been translated and tested for scientific standard in Sweden but the intervention part has not been noticed in the same way. The aim of the presented survey was to investigate the use of the methods for facilitating change with MOHO in a Swedish context. Ten OT in the area of mental health were invited to partaken in the survey. In their daily work they reported on a questionnaire which methods they used if they were applying MOHO in the treatment sessions together with the client. Regarding therapeutic strategies in total 78 treatment sessions were reported. After following a treatment planning process including different MOHO assessments depending on the client ́s needs, it was stated that the main areas of concern for the clients were volition or habit or performance capacity to almost the same extent for all three elements. The result show that two of the strategies; “Validation” and “Identifying” was use most frequently. “Providing Physical Support” and “Negotiating” was used very sparingly. The most surprising result was that ”Structuring” was rated as number 6of the 9 strategies. When OT describe what they are doing, structuring daily occupations very often is mention as a regular intervention. The interventions are currently being tested, the results will be presented in September.
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| 4. |
- Haglund Stignor, Caroline, et al.
(författare)
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New type of energy efficient heat exchanger for indirectly cooled display cabinets - Laboratory and field tests
- 2018
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Ingår i: Refrigeration Science and Technology. - 9782362150241 ; , s. 206-214
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Konferensbidrag (refereegranskat)abstract
- In this study, a completely new type of air-to-liquid heat exchanger, adapted for obtaining good heat transfer performance even at a laminar flow regime on the liquid side has been evaluated in a display cabinet application. The heat exchanger consists of parallel plates, with liquid in every second passage and air in the other passages. Tests were performed with a traditional open vertical display cabinet, first with a traditional finned-tube coil and thereafter with the new type of heat exchanger, both in a climate chamber and thereafter in the field. The results from both tests showed that the liquid inlet temperature could be increased by around 6°C, from the range -8°C - -7°C with the traditional coil to the range -2°C -1°C with the new type of heat exchanger, which can lead to considerable energy savings and operation without the need for defrosting of the heat exchanger.
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| 5. |
- Li, Joaquim, et al.
(författare)
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Equation of state of PEG/PEO in good solvent. Comparison between a one-parameter EOS and experiments
- 2015
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Ingår i: Polymer. - : Elsevier BV. - 0032-3861. ; 80, s. 205-213
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Tidskriftsartikel (refereegranskat)abstract
- We investigate, through osmotic pressure measurements, the validity of the single-parameter equation of state (EOS) for solutions of polyethylene glycols in water, by Cohen et al. 1,2 We show that it is physically meaningful and that a reasonable good correspondence between the osmotic pressures for PEG35 in large range of concentrations is obtained. We also take the chain length dependence into account in our analysis, as suggested by Cohen et al. By recalculating the experimental pressures in the paper by Jönsson et al. 3 applying the new calibration curve, which is based on the experimental results obtained in this study and the EOS obtained by Cohen et al., there is almost a perfect correspondence between the simulations and the experiments. These results have implications for correctly probing macromolecular interactions in wide range of systems when applying the osmotic stress method.
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| 6. |
- Mashayekhy Rad, Farshid, 1973-
(författare)
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Analytical methods for biomolecules involved in atmospheric aerosol formation in the Arctic
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the Arctic, increasing ice-free conditions and nutrients freed from the melting ice must strongly influence the marine life. Aerosol emissions from microbiological marine processes may affect the low clouds and fogs over the summer Arctic, which in turn have effects on the melting of sea ice. The radiative properties of the high Arctic low clouds are strongly dependent on the number concentration of airborne water-soluble particles, known as cloud condensation nuclei (CCN). If the effects of CCN on cloud optical properties is to be fully understood it is important to be able to specify the source and concentrations of the Arctic aerosol particles.Previous studies in the Arctic have indicated that organic material formed in the uppermost ocean surface is transferred to the atmosphere and plays a potentially very important role in the aerosol-fog/cloud cycle. However, many aspects of this process remain unverified and chemical characterisation of targeted groups of biomolecules is still notably fragmentary or non-existing. Investigation of biomolecules, particularly amino acids, peptides and proteins together with mono- and polysaccharides and fatty acids in the airborne aerosol, and their relative contributions to fog/cloud water, requires development of an array of “cutting edge” analytical techniques and methods.In this thesis, electrospray ionization mass spectrometry was used for all applications and target biomolecules. The measurements in the Arctic turned out to be challenging due to the highly complex, salty matrices, combined with very low concentration and high diversity of the target biomolecules, and each step of the analytical chain needed careful consideration. To increase the detectability of the very low levels of polysaccharides and proteins in aerosols, these compounds were hydrolyzed to their subunits, monosaccharides and amino acids. Monosaccharides were separated using hydrophilic interaction chromatography, which was beneficial for their detection in electrospray ionization mass spectrometry. Amino acids were derivatized, yielding improvement in reversed-phase chromatographic separation, ionization efficiency as well as selectivity. For fatty acids in a sea surface sample, a novel fast screening method was developed, utilizing travelling-wave ion mobility separation as an orthogonal technique connected to mass spectrometry. In addition, a method for the detection of wood burning as an anthropogenic source of aerosols was developed, utilizing anhydrous monosaccharides as markers. This method can be used in the upcoming expeditions for source apportionment studies.The results from the analyses of the aerosol and fog water samples, collected over the summer pack ice north of 80 °N, show that both total polysaccharides and total proteinaceous compounds (sum of proteins, peptides and amino acids) occurred at the pmol m-3 to nmol m-3 level. Interestingly, the levels were found higher between different years, suggested to be coupled to less ice coverage and thus to a higher biological activity in the ocean surface. The highest concentrations of polysaccharides, as an indication of marine polymer gels, were found during the summer over the pack ice area. In addition, a pilot source apportionment study was carried out combining the measurement of different molecular tracers, used as source markers. This study indicates the seasonality and abundance of marine polymer gels as an important feature of the Arctic Ocean connected to the melting and freezing of sea ice. It should be further studied how the abundance of these gels, which have a high potential for cloud droplet activation, affect the melting and freezing of the perennial sea ice.Given the successful development of analytical methods for targeted groups of biomolecules, this thesis has supported the importance of biomolecules as CCN and for cloud formation in the Arctic. Less ice coverage may further increase the number of biomolecular CCN which could change the radiative balance, by the formation of more low-level clouds. Overall, more studies are required to further unravel the complex relationship of biogenic sources, atmospheric chemistry and meteorology to assess the impact of climate change on the Arctic.
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| 7. |
- Niklasson, Mia, et al.
(författare)
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Mesenchymal transition and increased therapy resistance of glioblastoma cells is related to astrocyte reactivity
- 2019
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Ingår i: Journal of Pathology. - : WILEY. - 0022-3417 .- 1096-9896. ; 249:3, s. 295-307
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Tidskriftsartikel (refereegranskat)abstract
- Grade IV astrocytoma/glioblastoma multiforme (GBM) is essentially incurable, partly due to its heterogenous nature, demonstrated even within the glioma-initiating cell (GIC) population. Increased therapy resistance of GICs is coupled to transition into a mesenchymal (MES) cell state. The GBM MES molecular signature displays a pronounced inflammatory character and its expression vary within and between tumors. Herein, we investigate how MES transition of GBM cells relates to inflammatory responses of normal astroglia. In response to CNS insults astrocytes enter a reactive cell state and participate in directing neuroinflammation and subsequent healing processes. We found that the MES signature show strong resemblance to gene programs induced in reactive astrocytes. Likewise, astrocyte reactivity gene signatures were enriched in therapy-resistant MES-like GIC clones. Variable expression of astrocyte reactivity related genes also largely defined intratumoral GBM cell heterogeneity at the single-cell level and strongly correlated with our previously defined therapy-resistance signature (based on linked molecular and functional characterization of GIC clones). In line with this, therapy-resistant MES-like GIC secreted immunoregulatory and tissue repair related proteins characteristic of astrocyte reactivity. Moreover, sensitive GIC clones could be made reactive through long-term exposure to the proinflammatory cytokine interleukin 1 beta (IL1 beta). IL1 beta induced a slow MES transition, increased therapy resistance, and a shift in DNA methylation profile towards that of resistant clones, which confirmed a slow reprogramming process. In summary, GICs enter through MES transition a reactive-astrocyte-like cell state, connected to therapy resistance. Thus, from a biological point of view, MES GICs would preferably be called 'reactive GICs'. The ability of GBM cells to mimic astroglial reactivity contextualizes the immunomodulatory and microenvironment reshaping abilities of GBM cells that generate a tumor-promoting milieu. This insight will be important to guide the development of future sensitizing therapies targeting treatment-resistant relapse-driving cell populations as well as enhancing the efficiency of immunotherapies in GBM. (c) 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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| 8. |
- Schillén, Karin, et al.
(författare)
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Interaction between Bile Salt Sodium Glycodeoxycholate and PEO-PPO-PEO Triblock Copolymers in Aqueous Solution
- 2016
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Ingår i: RSC Advances. - 2046-2069. ; 6, s. 69313-69325
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Tidskriftsartikel (refereegranskat)abstract
- The interactions of the anionic bile salt NaGDC with three triblock copolymers based on poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), denoted P65, P123 and F127, were investigated using high-sensitive differential scanning calorimetry (DSC), turbidimetry, dynamic and static light scattering and small angle X-ray scattering (SAXS). P65 and P123 had the same hydrophilic PEO block lengths, whereas F127 and P123 had the same hydrophobic PPO block length. In water, the block copolymers self-assembled and formed spherical micelles at a critical micelle temperature, which depended on both the PPO/PEO composition ratio and the molecular weight of the copolymer. The mixed systems were studied at a constant P65, P123 or F127 concentration (i.e., 1.0 wt% or 5.0 wt%) with varying nNaGDC/npolymer molar ratio (MR) from 0 to 12. The DSC measurements presented endothermic enthalpy values (correlated to the amount of PPO that dehydrates in the aggregation process) that were suppressed at high MR. At 50 °C, the NaGDC molecules associated to the PPO core – PEO corona interface of the copolymer micelle forming a negatively charged block copolymer micelle–NaGDC complex. The complexes began to disintegrate upon NaGDC addition. Their resistance to disruption followed the stability order as inferred from the CMT values. At 20 °C, the unassociated block copolymer chains interacted with the NaGDC micelles and formed small NaGDC-rich complexes with a radius of ∼2 nm as determined by SAXS.
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| 9. |
- Segerman, Anna, et al.
(författare)
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Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 17:11, s. 2994-3009
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Tidskriftsartikel (refereegranskat)abstract
- Intratumoral heterogeneity is a hallmark of glioblastoma multiforme and thought to negatively affect treatment efficacy. Here, we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability among clones, including a range of responses to radiation and drugs. This widespread variability was observed as a continuumof multitherapy resistance phenotypes linked to a proneural-mesenchymal shift in the transcriptome. Multitherapy resistance was associated with a semi-stable cell state that was characterized by an altered DNA methylation pattern at promoter regions of mesenchymal master regulators and enhancers. The gradient of cell states within the GIC compartment constitutes a distinct form of heterogeneity. Our findings may open an avenue toward the development of new therapeutic rationales designed to reverse resistant cell states.
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| 10. |
- Strese, Sara, et al.
(författare)
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In vitro and in vivo anti-leukemic activity of the peptidase-potentiated alkylator melflufen in acute myeloid leukemia
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:4, s. 6341-6352
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Tidskriftsartikel (refereegranskat)abstract
- The novel aminopeptidase potentiated alkylating agent melflufen, was evaluated for activity in acute myeloid leukemia in a range of in vitro models, as well as in a patient derived xenograft study. All tested AML cell lines were highly sensitive to melflufen while melphalan was considerably less potent. In the HL-60 cell line model, synergy was observed for the combination of melflufen and cytarabine, an interaction that appeared sequence dependent with increased synergy when melflufen was added before cytarabine. Also, in primary cultures of AML cells from patients melflufen was highly active, while normal PBMC cultures appeared less sensitive, indicating a 7-fold in vitro therapeutic index. Melphalan, on the other hand, was only 2-fold more potent in the AML patient samples compared with PBMCs. Melflufen was equally active against non-malignant, immature CD34(+) progenitor cells and a more differentiated CD34(+) derived cell population (GM14), whereas the stem cell like cells were less sensitive to melphalan. Finally, melflufen treatment showed significant anti-leukemia activity and increased survival in a patient derived xenograft of AML in mice. In conclusion, melflufen demonstrates high and significant preclinical activity in AML and further clinical evaluation seem warranted in this disease.
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