| 1. |
- Roxhed, Niclas, et al.
(författare)
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Low-cost uncooled microbolometers for thermal imaging
- 2010
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Ingår i: OPTICAL SENSING AND DETECTION. - : SPIE. - 9780819481993 ; , s. 772611-
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Konferensbidrag (refereegranskat)abstract
- Cost efficient integration technologies and materials for manufacturing of uncooled infrared bolometer focal plane arrays (FPA) are presented. The technology platform enables 320x240 pixel resolution with a pitch down to 20 mu m and very low NETD. A heterogeneous 3D MEMS integration technology called SOIC (Silicon-On-Integrated-Circuit) is used to combine high performance Si/SiGe bolometers with state-of-the-art electronic read-out-integrated-circuits. The SOIC integration process consists of: (a) Separate fabrication of the CMOS wafer and the MEMS wafer. (b) Adhesive wafer bonding. (c) Sacrificial removal of the MEMS handle wafer. (d) Via-hole etching. (e) Via formation and MEMS device definition. (f) Sacrificial etching of the polymer adhesive. We will present an optimized process flow that only contains dry etch processes for the critical process steps. Thus, extremely small, sub-micrometer feature sizes and vias can be implemented for the infrared bolometer arrays. The Si/SiGe thermistor is grown epitaxially, forming a mono-crystalline multi layer structure. The temperature coefficient of resistance (TCR) is primarily controlled by the concentration of Ge present in the strained SiGe layers. TCR values of more than 3%/K can be achieved with a low signal-to-noise ratio due to the mono-crystalline nature of the material. In addition to its excellent electrical properties, the thermistor material is thermally stable up to temperatures above 600 degrees C, thus enabling the novel integration and packaging techniques described in this paper. Vacuum sealing at the wafer level reduces the overall costs compared to encapsulation after die singulation. Wafer bonding is performed using a Cu-Sn based metallic bonding process followed by getter activation at >= 350 degrees C achieving a pressure in the 0.001 mbar range. After assembling, the final metal phases are stable and fully compatible with high-temperature processes. Hermeticity over the product lifetime is accomplished by well-controlled electro-deposition of metal layers, optimized bonding parameters and a suitable bond frame design.
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| 2. |
- Alexandersson, Jenny, et al.
(författare)
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HR-strategier för regional tillväxt och samverkan? En studie av två arbetsmarknadsintermediärer
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med denna rapport är att bidra till en ökad förståelse för hur två regionala intermediära organisationer, inom HR-området, arbetar med förändrings- och kompetensrelaterade frågor.En interaktiv forskningsansats har tillämpats vilket innebär att planering och genomförande av forskningsarbetet har skett i dialog med berörda praktiker. Det empiriska materialet utgörs främst av 12 intervjuer med personer som arbetar inom de studerade intermediära organisationerna.Resultaten i denna studie visar att det finns många likheter mellan de två studerade intermediära organisationerna. Båda erbjuder ett brett spektra av HR-tjänster, ägs av sina kundföretag och har en samverkande roll mellan kundföretagen. Resultaten visar också att de båda intermediärerna har utvecklat en relativt speciell roll som intermediärer som innebär att de, i vissa avseenden, arbetar både som en extern och en intern HR-resurs till sina kundföretag. Även när det gäller arbetets organisering visar resultaten på flera likheter mellan de studerade intermediära organisationerna. Personalen i båda intermediärorganisationerna arbetar mycket flexibelt och anpassar sitt arbetssätt efter kundernas behov och önskemål. Få standardiserade modeller eller arbetsverktyg används i arbetet och det finns inte något utvecklat system för dokumentation och kunskapsöverföring som används aktivt inom intermediärorganisationerna. Samtidigt tyder resultaten på att ena av de två organisationerna har en något mer fast struktur med tydligt definierade arbetsområden och roller. Det finns också vissa skillnader mellan organisationerna vad gäller hur man önskar att inrikta och organisera sitt arbete i framtiden. Vidare visar resultaten från denna studie att personalen, inom de båda studerade organisationerna, upplever att deras arbete kan bidra till att kundföretagen får nya perspektiv och synsätt. I bästa fall kan även arbetet bidra till att företagen kan arbeta mer strategiskt och att de lär sig hantera olika problematiska situationer på egen hand och får en ökad beredskap att hantera förändring och problem i framtiden. Samtidigt är många uppdrag av mer akut och kortsiktig karaktär vilket innebär att det kan vara svårt att bidra till mer långsiktiga resultat i kundföretagen.
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| 3. |
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| 4. |
- Blomberg, Jeanette, et al.
(författare)
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Inhibition of cellular FLICE-like inhibitory protein abolishes insensitivity to interferon-α in a resistant variant of the human U937 cell line
- 2011
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Ingår i: Apoptosis (London). - : Springer Science and Business Media LLC. - 1360-8185 .- 1573-675X. ; 16:8, s. 783-794
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Tidskriftsartikel (refereegranskat)abstract
- Type I interferons constitute a family of pleiotropic cytokines that have a key role in both adaptive and innate immunity. The interferon signalling pathways mediate transcriptional regulation of hundreds of genes, which result in mRNA degradation, decreased protein synthesis, cell cycle inhibition and induction of apoptosis. To elucidate regulatory networks important for interferon induced cell death, we generated interferon resistant U937 cells by selection in progressively increasing concentrations of interferon-α (IFN-α). The results show that IFN-α activates the death receptor signalling pathway and that IFN resistance was associated with cross-resistance to several death receptor ligands in a manner similar to previously described Fas resistant U937 cell lines. Increased expression of the long splice variant of the cellular FLICE-like inhibitor protein (cFLIP-L) was associated with the resistance to death receptor and IFN-α stimulation. Accordingly, inhibition of cFLIP-L expression with cycloheximide or through cFLIP short harpin RNA interference restored sensitivity to Fas and/or IFN-α. Thus, we now show that selection for interferon resistance can generate cells with increased expression of cFLIP, which protects the cells from both IFN-α and death receptor mediated apoptosis.
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| 5. |
- Blomberg, Jeanette, 1977-, et al.
(författare)
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Reduced FAS transcription in clones of U937 cells that have acquired resistance to Fas-induced apoptosis
- 2009
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 276:2, s. 497-508
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Tidskriftsartikel (refereegranskat)abstract
- Susceptibility to cell death is a prerequisite for the elimination of tumour cells by cytotoxic immune cells, chemotherapy or irradiation. Activation of the death receptor Fas is critical for the regulation of immune cell homeostasis and efficient killing of tumour cells by apoptosis. To define the molecular changes that occur during selection for insensitivity to Fas-induced apoptosis, a resistant variant of the U937 cell line was established. Individual resistant clones were isolated and characterized. The most frequently observed defect in the resistant cells was reduced Fas expression, which correlated with decreased FAS transcription. Clones with such reduced Fas expression also displayed partial cross-resistance to tumour necrosis factor-alpha stimulation, but the mRNA expression of tumour necrosis factor receptors was not decreased. Reintroduction of Fas conferred susceptibility to Fas but not to tumour necrosis factor-alpha stimulation, suggesting that several alterations could be present in the clones. The reduced Fas expression could not be explained by mutations in the FAS coding sequence or promoter region, or by silencing through methylations. Protein kinase B and extracellular signal-regulated kinase, components of signalling pathways downstream of Ras, were shown to be activated in some of the resistant clones, but none of the three RAS genes was mutated, and experiments using chemical inhibitors could not establish that the activation of these proteins was the cause of Fas resistance as described in other systems. Taken together, the data illustrate that Fas resistance can be caused by reduced Fas expression, which is a result of an unidentified mode of regulation.
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| 6. |
- Bonlokke, Jakob H., et al.
(författare)
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Exposures and Health Effects of Bioaerosols in Seafood Processing Workers - a Position Statement
- 2019
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Ingår i: Journal of Agromedicine. - 1059-924X .- 1545-0813. ; 24:4, s. 441-448
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Tidskriftsartikel (refereegranskat)abstract
- © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Occupational hazards exist in the processing of seafood both in land-based facilities as well as on board vessels. Recent findings on occupational injury and respiratory health risks among seafood processing workers were presented and discussed at the IFISH5 conference. Particular emphasis was put on the challenges that im/migrant workers encounter, the greater risks onboard factory vessels, especially where processing machinery are retrofitted to older vessels not primarily designed for this purpose, and the difficulties in assessing and preventing bioaerosol exposures and associated respiratory health risks despite recent advances in characterising agents responsible for allergic and non-allergic reactions. Based on appraisal of existing knowledge in the published literature and new findings presented at the conference, recommendations for immediate actions as well as for future research have been proposed. Among these include the importance of improving extraction ventilation systems, optimising machinery performance, enclosure of bioaerosol sources, improved work organization, and making special efforts to identify and support the needs of im/migrant workers to ensure they also benefit from such improvements. There is a need for studies that incorporate longitudinal study designs, have improved exposure and diagnostic methods, and that address seafood processing in countries with high seafood processing activities such as Asia and those that involve im/migrant workers worldwide. The medical and scientific community has an important role to play in prevention but cannot do this in isolation and should cooperate closely with hygienists, engineers, and national and international agencies to obtain better health outcomes for workers in the seafood industry.
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| 7. |
- Castleton, Christopher, 1969-, et al.
(författare)
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Managing the supercell approximation for charged defects in semiconductors : Finite-size scaling, charge correction factors, the band-gap problem, and the ab initio dielectric constant
- 2006
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 73:035215, s. 11-
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Tidskriftsartikel (refereegranskat)abstract
- The errors arising in ab initio density functional theory studies of semiconductor point defects using the supercell approximation are analyzed. It is demonstrated that (a) the leading finite size errors are inverse linear and inverse cubic in the supercell size and (b) finite size scaling over a series of supercells gives reliable isolated charged defect formation energies to around +-0.05 eV. The scaled results are used to test three correction methods. The Makov-Payne method is insufficient, but combined with the scaling parameters yields an ab initio dielectric constant of 11.6+-4.1 for InP. Gamma point corrections for defect level dispersion are completely incorrect, even for shallow levels, but realigning the total potential in real-space between defect and bulk cells actually corrects the electrostatic defect-defect interaction errors as well. Isolated defect energies to +-0.1 eV are then obtained using a 64 atom supercell, though this does not improve for larger cells. Finally, finite size scaling of known dopant levels shows how to treat the band gap problem: in < or = 200 atom supercells with no corrections, continuing to consider levels into the theoretical conductin band (extended gap) comes closest to experiment. However, for larger cells or when supercell approximation errors are removed, a scissors scheme stretching the theoretical band gap onto the experimental one is in fact correct.
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| 8. |
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| 9. |
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| 10. |
- Deneberg, Stefan, et al.
(författare)
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Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:20, s. 5573-5582
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetically normal acute myeloid leukemia (CN-AML) comprise between forty and fifty percent of all adult acute myeloid leukemia (AML) cases. In this clinically diverse group molecular aberrations such as FLT3ITD, NPM1 and CEBPA mutations recently have added to the prognostic accuracy. Aberrant DNA methylation is a hallmark of cancer including AML. We investigated in total 118 CN-AML samples in a test and a validation cohort for genome-wide promoter DNA methylation with Illumina Methylation Bead arrays and compared them to normal myeloid precursors and global gene expression. IDH and NPM1 mutations were associated with different methylation patterns (p=0.0004 and 0.04, respectively). Genome-wide methylation levels were elevated in IDH mutated samples (p=0.006). We observed a negative impact of DNA methylation on transcription. Genes targeted by Polycomb group (PcG) proteins and genes associated with bivalent histone marks in stem cells showed increased aberrant methylation in AML (p<0.0001). Furthermore, high methylation levels of PcG target genes were independently associated with better progression free (OR 0.47, p=0.01) and overall survival (OR 0.36, p=0.001). In summary, genome wide methylation patterns show preferential methylation of PcG targets with prognostic impact in CN-AML.
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| 11. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 12. |
- Haroun-Izquierdo, Alvaro, et al.
(författare)
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Adaptive single-KIR(+)NKG2C(+) NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia
- 2022
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Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 10:11, s. e005577-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNatural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML). Current treatments are hampered by variability in NK cell subset responses, a limitation which could be circumvented by specific expansion of highly potent single killer immunoglobulin-like receptor (KIR)(+)NKG2C(+) adaptive NK cells to maximize missing-self reactivity.MethodsWe developed a GMP-compliant protocol to expand adaptive NK cells from cryopreserved cells derived from select third-party superdonors, that is, donors harboring large adaptive NK cell subsets with desired KIR specificities at baseline. We studied the adaptive state of the cell product (ADAPT-NK) by flow cytometry and mass cytometry as well as cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq). We investigated the functional responses of ADAPT-NK cells against a wide range of tumor target cell lines and primary AML samples using flow cytometry and IncuCyte as well as in a mouse model of AML.ResultsADAPT-NK cells were >90% pure with a homogeneous expression of a single self-HLA specific KIR and expanded a median of 470-fold. The ADAPT-NK cells largely retained their adaptive transcriptional signature with activation of effector programs without signs of exhaustion. ADAPT-NK cells showed high degranulation capacity and efficient killing of HLA-C/KIR mismatched tumor cell lines as well as primary leukemic blasts from AML patients. Finally, the expanded adaptive NK cells had preserved robust antibody-dependent cellular cytotoxicity potential and combination of ADAPT-NK cells with an anti-CD16/IL-15/anti-CD33 tri-specific engager led to near-complete killing of resistant CD45(dim) blast subtypes.ConclusionsThese preclinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population with full missing-self recognition capability.
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| 13. |
- Herold, Nikolas, et al.
(författare)
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Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies
- 2017
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 23:2, s. 256-263
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Tidskriftsartikel (refereegranskat)abstract
- The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults'. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP)(2-5), which causes DNA damage through perturbation of DNA synthesis(6). Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment(7-9). Here we demonstrate that the deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) promotes the detoxification of intracellular ara-CTP pools. Recombinant SAMHD1 exhibited ara-CTPase activity in vitro, and cells in which SAMHD1 expression was transiently reduced by treatment with the simian immunodeficiency virus (SIV) protein Vpx were dramatically more sensitive to ara-C-induced cytotoxicity. CRISPR-Cas9-mediated disruption of the gene encoding SAMHD1 sensitized cells to ara-C, and this sensitivity could be abrogated by ectopic expression of wild-type (WT), but not dNTPase-deficient, SAMHD1. Mouse models of AML lacking SAMHD1 were hypersensitive to ara-C, and treatment ex vivo with Vpx sensitized primary patient derived AML blasts to ara-C. Finally, we identified SAMHD1 as a risk factor in cohorts of both pediatric and adult patients with de novo AML who received ara-C treatment. Thus, SAMHD1 expression levels dictate patient sensitivity to ara-C, providing proof-of-concept that the targeting of SAMHD1 by Vpx could be an attractive therapeutic strategy for potentiating ara-C efficacy in hematological malignancies.
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| 14. |
- Hossain, Mohammad Istiak
(författare)
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Designing Efficient Access Control to Comply Massive-Multiservice IoT over Cellular Networks
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Internet of Things (IoT) has come in reality to improve our living quality. Automation is embraced in all the possible business verticals that have diverse communication needs ranged from static devices’ sporadic transmission to mobile devices’ every minute transmission. Despite, there are many technologies available today to support IoT services; cellular systems can play a vital role for IoT services, like wearables, vehicular, and industrial IoT, rollout which have either mobility or security concern. IoT services generated traffic are foreseen as a sporadic-bursty traffic. As the cellular networks are designed to serve continuous data traffic, the existing system’s access control mechanism cannot efficiently conform to the burstiness of traffic. This limits the scope of the network scalability in terms of simultaneous serving devices’ capacity. Also, this bursty pattern can extensively increase the rate of network’s congestion incident. In this thesis, we focus on these underlying challenges to support a large number of heterogeneous IoT services with existing services over the same radio network. An important question for supporting IoT services over cellular networks is how detrimental are the effects of IoT services on other services of cellular networks. This dissertation seeks to answer this with quantitative results to indicate the real constraints of existing networks.An important conclusion is that existing cellular system is incompetent to support the bursty arrival of massive IoT devices in terms of radio networks’ access control plane’s scalability. Therefore, this dissertation presents solutions to overcome the identified limitations of access control planes. To improve the performance of the access control plane, we incorporate a vertical core network controlled group management scheme that can assure the operator’s granular control over capillary gateways. Besides, this introduces a unique handover opportunity between cellular and capillary network vertices. Then, we present a simple but efficient initial access mechanism to overcome the initial access collision at the very early stage. Finally, we show the impact of access collision and retransmission on the initial access resource dimensioning.We present a practical traffic model that is realistic for the traffic scenario for mixed-traffic. Our presented results and analysis depict the trade-offs between access rate, retransmission and resource allocation over time and frequency.Our results reveal that with proposed schemes of the cellular system’s access control plane can be scalable and resilient to accommodate a large number of IoT devices without incurring extra delay or need of resources to the system.
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| 15. |
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| 16. |
- Höglund, Andreas, 1980-, et al.
(författare)
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Chk2 deficiency in Myc overexpressing lymphoma cells elicits a synergistic lethal response in combination with PARP inhibition.
- 2011
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Ingår i: Cell Cycle. - Georgetown, TX : Landes Bioscience. - 1538-4101 .- 1551-4005. ; 10:20, s. 3598-3607
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Tidskriftsartikel (refereegranskat)abstract
- Myc is a transcription factor frequently found deregulated in human cancer. The Myc- mediated cellular transformation process is associated with fast proliferative cells and inherent genomic instability, giving rise to malignant, invasive neoplasms with poor prognosis for survival. Transcription-independent functions of Myc include stimulation of replication. Excessive Myc expression stimulates a replication-associated DNA damage response that signal via the phosphoinositide 3-kinase (PI3K) related protein kinases (PIKKs) ATM and ATR. These in turn activate the DNA damage transducers Chk1 and Chk2. Here, we show that Myc can stimulate Chek2 transcript indirectly in vitro, as well as in B cells of !-Myc transgenic mice or in the intestine of ApcMin mice. However, Chk2 is dispensable for Myc’s ability to transform cells in vitro and for the survival of established lymphoma cells from !-Myc transgenic mice. Chk2 deficiency induces polyploidy and slow growth but the cells are viable and protected against DNA damage. However, inhibition of both Chk1/Chk2 with AZD7762 induces cell death and significantly delays disease progression of transplanted lymphoma cells in vivo. DNA damage recruits PARP family members to sites of DNA breaks that in turn facilitate the induction of DNA repair. Strikingly, combining Chk2 and PARP inhibition elicits a synergistic lethal response in the context of Myc overexpression. Our data indicates that only certain types of chemotherapy would give rise to a synergistic lethal response in combination with specific Chk2 inhibitors, which will be important if Chk2 inhibitors enter the clinic.
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| 17. |
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| 18. |
- Höglund, Andreas, et al.
(författare)
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Diffusion mechanism of Zn in InP and GaP from first principles
- 2008
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 77:11, s. 113201-
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Tidskriftsartikel (refereegranskat)abstract
- The diffusion mechanism of Zn in GaP and InP has been investigated using first-principles computational methods. It is found that the kickout mechanism is the favored diffusion process under all doping conditions for InP, and under all except n-type conditions for GaP. In n-type GaP the dissociative mechanism is probable. In both p-type GaP and InP, the diffusing species is found to be Zn. The activation energy for the kickout process is 2.49 eV in GaP and 1.60 eV in InP, and therefore unintentional diffusion of Zn should be a larger concern in InP than in GaP. The dependence of the activation energy both on the doping conditions of the material and on the stoichiometry is explained, and found to be in qualitative agreement with the experimentally observed dependencies. The calculated activation energies agree reasonably with experimental data, assuming that the region from which Zn diffuses is p type. Explanations are also found as to why Zn tends to accumulate at pn junctions in InP and to why a relatively low fraction of Zn is found on substitutional sites in InP.
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| 19. |
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| 20. |
- Höglund, Andreas, 1977-
(författare)
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Electronic Structure Calculations of Point Defects in Semiconductors
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis point defects in semiconductors are studied by electronic structure calculations. Results are presented for the stability and equilibrium concentrations of native defects in GaP, InP, InAs, and InSb, for the entire range of doping conditions and stoichiometry. The native defects are also studied on the (110) surfaces of InP, InAs, and InSb. Comparing the relative stability at the surface and in the bulk, it is concluded that the defects have a tendency to migrate to the surface. It is found that the cation vacancy is not stable, but decomposes into an anion antisite-anion vacancy complex. The surface charge accumulation in InAs is explained by complementary intrinsic doping by native defects and extrinsic doping by residual hydrogen. A technical investigation of the supercell treatment of defects is performed, testing existing correction schemes and suggesting a more reliable alternative. It is shown that the defect level of [2VCu-IIICu] in the solarcell-material CuIn1-xGaxSe2 leads to a smaller band gap of the ordered defect γ-phase, which possibly explains why the maximal efficiency for CuIn1-xGaxSe2 has been found for x=0.3 and not for x=0.6, as expected from the band gap of the α-phase. It is found that Zn diffuses via the kick-out mechanism in InP and GaP with activation energies of 1.60 eV and 2.49 eV, respectively. Explanations are found for the tendency of Zn to accumulate at pn-junctions in InP and to why a relatively low fraction of Zn is found on substitutional sites in InP. Finally, it is shown that the equilibrium solubility of dopants in semiconductors can be increased significantly by strategic alloying. This is shown to be due to the local stress in the material, and the solubility in an alloy can in fact be much higher than in either of the constituting elements. The equilibrium solubility of Zn in Ga0.9In0.1P is for example five orders of magnitude larger than in GaP or InP.
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| 21. |
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| 22. |
- Höglund, Andreas, et al.
(författare)
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Increasing the equilibrium solubility of dopants in semiconductor multilayers and alloys
- 2008
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 100:10, s. 105501-
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Tidskriftsartikel (refereegranskat)abstract
- We have theoretically studied the possibility to control the equilibrium solubility of dopants in semiconductor alloys, by strategic tuning of the alloy concentration. From the modeled cases of C-0 in SixGe1-x, Zn- and Cd- in GaxIn1-xP it is seen that under certain conditions the dopant solubility can be orders of magnitude higher in an alloy or multilayer than in either of the elements of the alloy. This is found to be due to the solubility's strong dependence on the lattice constant for size mismatched dopants. The equilibrium doping concentration in alloys or multilayers could therefore be increased significantly. More specifically, Zn- in a GaxIn1-xP multilayer is found to have a maximum solubility for x=0.9, which is 5 orders of magnitude larger than that of pure InP.
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| 23. |
- Höglund, Andreas, 1980-, et al.
(författare)
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Myc sensitizes p53-deficient cancer cells to the DNA-damaging effects of the DNA methyltransferase inhibitor decitabine
- 2009
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Ingår i: Blood. - : The American Society of Hematology. - 0006-4971 .- 1528-0020. ; 113:18, s. 4281-4288
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Tidskriftsartikel (refereegranskat)abstract
- Decitabine (also referred to as 5-aza-2'-deoxycytidine) is a drug that has recently been approved by the Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome (MDS). The mechanism of action is believed to be the blocking of DNA methylation and thereby reactivating silenced genes involved in harnessing MDS. When analyzing reactivation of genes involved in Burkitt lymphoma (BL), we discovered that decitabine also sensitizes tumor cells by inducing DNA damage. This sensitization is grossly augmented by the MYC oncogene, which is overexpressed in BL, and occurs in cells lacking a functional p53 tumor suppressor pathway. In p53-deficient BL cells and p53(-/-) mouse embryo fibroblasts, Myc overrides a transient G2-block exerted by decitabine via activation of Chk1. This triggers aneuploidy and cell death that correlates with, but can occur in the absence of, Epstein-Barr virus (EBV) reactivation, caspase activation, and/or expression of the BH3-only protein Puma. In vivo modeling of Myc-induced lymphoma suggests that decitabine constitutes a potential new drug against lymphoma that would selectively sensitize tumor cells but spare normal tissue.
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| 24. |
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| 25. |
- Höglund, Andreas, et al.
(författare)
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Point defects on the (110) surfaces of InP, InAs, and InSb : A comparison with bulk
- 2006
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 74:7
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Tidskriftsartikel (refereegranskat)abstract
- The basic properties of point defects, such as local geometries, positions of charge-transfer levels, and formation energies, have been calculated using density-functional theory, both in the bulk and on the (110) surface of InP, InAs, and InSb. Based on these results we discuss the electronic properties of bulk and surface defects, defect segregation, and compensation. In comparing the relative stability of the surface and bulk defects, it is found that the native defects generally have higher formation energies in the bulk. From this it can be concluded that at equilibrium there is a considerably larger fraction of defects at the surface and under nonequilibrium conditions defects are expected to segregate to the surface, given sufficient time. In most cases the charge state of a defect changes upon segregation, altering the charge-carrier concentrations. The photothresholds are also calculated for the three semiconductors and are found to be in good agreement with experimental data.
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| 26. |
- Höglund, Andreas, 1980-
(författare)
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Regulation of DNA damage responses by the Myc oncogene : implications for future anti-cancer therapies
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Myc is a transcription factor frequently found deregulated in human cancer. Cells with deregulated expression of Myc carry a selective advantage against its neighbours due to the fact that Myc-mediated transcription governs crucial cellular events such as proliferation and growth. In addition, Myc has been implicated in several other aspects of tumour biology like cellular immortality, the formation of new blood vessels and the colonization of distant tissues through the process of metastasis. Therapy aimed at disrupting essential pathways regulated by Myc is important because of the many different types of cancers that depend on continued signalling along these pathways. This thesis describes new treatment opportunities for cancers with a high Myc signature. In Paper Ι, we describe a new role for the DNA methyltransferase inhibitor Decitabine in the treatment of Myc transformed tumours cells. We show that the therapeutic potential of Decitabine in the treatment of Burkitt Lymphoma relies not only on its ability to cause reactivation of silenced genes such as pro-apoptotic PUMA, but also on the DNA damage that this drug induces. In vivo, Decitabine delays disease progression of transplanted lymphoma cells. In Paper ΙΙ, we identify the DNA damage checkpoint kinase Chk1 as a therapeutic target in Myc overexpressing cancers. We show that targeting Chk1 with shRNA or with a novel small molecule inhibitor cause a delay in disease progression of transplanted lymphoma cells in vivo. In Paper ΙΙΙ, the Chk1-related kinase Chk2 is evaluated as a therapeutic target in Myc overexpressing cancers. Myc overexpressing cells are not dependent on Chk2 but we show that Chk2 abrogation using shRNA causes polyploidization and protection against DNA damage. However, Chk2-targeted therapy elicits a synergistic lethal response in combination with inhibition of the DNA repair associated protein PARP. In conclusion, this thesis shows the potential of targeting the DNA damage machinery and the functional hubs important for maintenance of genomic stability in tumours with a deregulated expression of Myc.
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| 27. |
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| 28. |
- Höglund, Andreas, et al.
(författare)
-
Relative concentration and structure of native defects in GaP
- 2005
-
Ingår i: Physical Review B. ; 72:19, s. 195213-
-
Tidskriftsartikel (refereegranskat)abstract
- The native defects in the compound semiconductor GaP have been studied using a pseudopotential Density Functional Theory method in order todetermine their relative concentrations and the most stable charge states. The electronic and atomic structures are presented and the defect concentrations are estimated using calculated formation energies. Relaxation effects are taken into account fully and produce negative-Ucharge transfer levels for V\sS{P}{} and P\sS{Ga}{}. The concentration of V\sS{Ga}{} is in good agreement with the results of positron annihilation experiments. The charge transfer levels presented compare qualitatively well with experiments where available. The effect of stoichiometry on the defect concentrations is also described and is shown to be considerable.The lowest formation energies are found for P\sS{Ga}{+2} in p-type and V\sS{Ga}{-3} in n-type GaP under P-rich conditions, and for Ga\sS{P}{-2} in n-type GaP under Ga-rich conditions.Finally, the finite size errors arising from the use of supercells with periodic boundary conditions are examined.
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| 29. |
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| 30. |
- Höglund, Andreas, 1980-, et al.
(författare)
-
Therapeutic implications for the induced levels of Chk1 in Myc- expressing cancer cells
- 2011
-
Ingår i: Clinical Cancer Research. - Philadelphia : Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 17:22, s. 7067-7079
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The transcription factor c-Myc (or "Myc") is a master regulator of pathways driving cell growth and proliferation. MYC is deregulated in many human cancers, making its downstream target genes attractive candidates for drug development. We report the unexpected finding that B-cell lymphomas from mice and patients exhibit a striking correlation between high levels of Myc and checkpoint kinase 1 (Chk1). Experimental Design: By in vitro cell biology studies as well as preclinical studies using a genetically engineered mouse model, we evaluated the role of Chk1 in Myc-overexpressing cells. Results: We show that Myc indirectly induces Chek1 transcript and protein expression, independently of DNA damage response proteins such as ATM and p53. Importantly, we show that inhibition of Chk1, by either RNA interference or a novel highly selective small molecule inhibitor, results in caspase-dependent apoptosis that affects Myc-overexpressing cells in both in vitro and in vivo mouse models of B-cell lymphoma. Conclusion: Our data suggest that Chk1 inhibitors should be further evaluated as potential drugs against Myc-driven malignancies such as certain B-cell lymphoma/leukemia, neuroblastoma, and some breast and lung cancers. Clin Cancer Res; 17(22); 7067-79. (C) 2011 AACR.
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| 31. |
- Höglund, Cecilia, et al.
(författare)
-
Effekter av ledarutveckling för individ och organisation
- 2009
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport är en delrapport inom ramen för ett longitudinellt forsknings- och utvecklingsprojekt vid HELIX VINN Excellence Centre vid Linköpings universitet. Det övergripande projektets syfte är att beskriva och analysera förutsättningar för en förbättrad koordination bland toppchefer i en växande och geografiskt expanderande organisation, samt hur koordinationen cheferna emellan kan förstås i termer av en kollektiv lärprocess. Som en del i detta större projekt har det även ingått att göra vissa fördjupningsstudier. Denna rapport är en sådan fördjupningsstudie där fokus varit på effekter av en ledarutvecklingssatsning som genomförts under ett antals års tid i en del av organisationen. Det empiriska underlaget samlades in under våren 2009.Rapporten har tagits fram i ett nära samarbete mellan forskarna i projektet. Cecilia Höglund och Lisa Östman, studenter vid PA-programmet i Linköping, har även samlat in och presenterat empirin inom ramen för sin kandidatuppsats ”Ledarutvecklingsprogram - användbart eller ej?”. Vi vill speciellt tacka de personer på fallföretaget som öppnat sina dörrar och tagit av sin tid för att möjliggöra vårt intervjuande.
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| 32. |
- Imam, Mewlude, et al.
(författare)
-
Gas phase chemical vapor deposition chemistry of triethylboron probed by boron-carbon thin film deposition and quantum chemical calculations
- 2015
-
Ingår i: Journal of Materials Chemistry C. - : ROYAL SOC CHEMISTRY. - 2050-7526 .- 2050-7534. ; 3:41, s. 10898-10906
-
Tidskriftsartikel (refereegranskat)abstract
- We present triethylboron (TEB) as a single-source precursor for chemical vapor deposition (CVD) of BxC thin films and study its gas phase chemistry under CVD conditions by quantum chemical calculations. A comprehensive thermochemical catalogue for the species of the gas phase chemistry of TEB is examined and found to be dominated by beta-hydride eliminations of C2H4 to yield BH3. A complementary bimolecular reaction path based on H-2 assisted C2H6 elimination to BH3 is also significant at lower temperatures in the presence of hydrogen. Furthermore, we find a temperature window of 600-1000 degrees C for the deposition of X-ray amorphous BxC films with 2.5 less than= x less than= 4.5 from TEB. Films grown at temperatures below 600 degrees C contain high amounts of H, while temperatures above 1000 degrees C result in C-rich films. The film density and hardness are determined to be in the range of 2.40-2.65 g cm(-3) and 29-39 GPa, respectively, within the determined temperature window.
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| 33. |
- Imam, Mewlude, et al.
(författare)
-
Gas Phase Chemistry of Trimethylboron in Thermal Chemical Vapor Deposition
- 2017
-
Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 121:47, s. 26465-26471
-
Tidskriftsartikel (refereegranskat)abstract
- Alkylboranes, such as trimethylboron (TMB) and triethylboron (TEB), are promising alternative precursors in low temperature chemical vapor deposition (CVD) of boron-containing thin films. In this study, CVD growth of B-C films using TMB and quantum-chemical calculations to elucidate a gas phase chemical mechanism were undertaken. Dense, amorphous, boron-rich (B/C 1.5-3) films were deposited at 1000 degrees C in both dihydrogen and argon ambients, while films with crystalline B4C and B25C inclusions were deposited at 1100 degrees C in dihydrogen. A script-based automatization scheme was implemented for the quantum-chemical computations to enable time efficient screening of thousands of possible gas phase CVD reactions. The quantum-chemical calculations suggest TMB is mainly decomposed by an unimolecular alpha-H elimination of methane, which is complemented by dihydrogen-assisted elimination of methane in dihydrogen.
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| 34. |
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| 35. |
- Jacobsson, Amanda, et al.
(författare)
-
”Ambulanssjukvården behöver genomgripande förändringar”
- 2021
-
Ingår i: Dagens Medicin. - : Dagens Medicin. - 1402-1943. ; :2021-06-23
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Debattörer från Ambulance health research network vill se en nationell ledningsstruktur, ökad evidens för vården, akademisk kompetens i ledningsfunktioner samt en nationell utbildnings- och kompetensstandard.
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| 36. |
- Jacobsson, Andreas, et al.
(författare)
-
Direct in-hospital admission via ambulance (DIVA) : A retrospective observational study
- 2020
-
Ingår i: International Emergency Nursing. - : Elsevier. - 1755-599X .- 1878-013X. ; 52
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prolonged stays in emergency departments increase the risk of adverse events in elderly patients. To optimize care for nonurgent patients who need in-hospital admission, a patient-focused improvement project named Direct In-hospital admission Via Ambulance (DIVA) was launched at Örebro University Hospital.PURPOSE: This study describes the effects of DIVA. The primary outcome was time to in-hospital admission. Secondary outcomes were the in-hospital admission rate, the in-hospital length of stay and patient characteristics.METHOD: This was a retrospective observational study. Descriptive and comparative statistics were used. All patients identified by the ambulance nurse as nonurgent but with an apparent need for in-hospital admission were candidates for direct in-hospital admission. The results were compared with those of a reference group.RESULT: In total, 127 patients were included, with 45 patients in the DIVA group and 82 patients in the reference group. In the DIVA group, 24 patients were directly admitted. The median time to in-hospital admisson was 49.5 min for direct admitted patients and 278.5 min for the reference group. There was a statistical significant difference between the groups (p < 0.01).CONCLUSION: The current study indicates that time to in-hospital admission could be reduced by DIVA.
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| 37. |
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| 38. |
- Kock, Henrik, et al.
(författare)
-
Outsourcing HR Services : The Role of Human Resource Intermediaries
- 2012
-
Ingår i: European Journal of Training and Development. - : Emerald Group Publishing Limited. - 2046-9012 .- 2046-9020. ; 36:8, s. 772-790
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose – In this article, the area of interest is an emerging type of organisation called human resource intermediaries (HRIs), which focus on delivering human resource (HR) services to public sector organisations and private companies. The purpose of this article is, thus, to explore HRIs as deliverers of HR services. More specifically, the article will seek to analyse and discuss how employees in HRIs understand their role as providers of HR services to their clients and what characterises the HRIs' work and the nature of their assignments.Design/methodology/approach – The empirical foundation of this article comprises a longitudinal case study of three Swedish HRI organisations. The data consist of interviews with 19 managers and consultants from the three HRIs.Findings – The results indicate that HRIs want to take on a broad, strategic and proactive role in relation to their customers. However, due to external and internal constraints, such as the HRIs' internal work processes, the nature of their assignments and the client's HR competence level, the roles that HRIs play in practice tend to be more specific, operational and reactive.Practical implications – An important challenge for HRIs is to avoid being overwhelmed by short‐term and reactive assignments that deliver value to their clients through the use of standard solutions. Long‐term relationships, the structures of ownership and membership, and the availability of unique networks can also prove to be valuable for clients.Originality/value – This study explores HRIs as an emerging type of organisation within the area of human resources. Compared with HR consultants who specialise in handling specific HR‐related problems, HRIs target the entire flow of human resources in, within, and out of client organisations.
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| 39. |
- Kronbichler, Andreas, et al.
(författare)
-
Clinical associations with venous thromboembolism in anti-neutrophil cytoplasm antibody-associated vasculitides
- 2017
-
Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 56:5, s. 704-708
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To assess potential associations for the development of venous thromboembolic events in patients with ANCA-associated vasculitides (AAV). Methods. Four hundred and seventeen patients enrolled to participate in randomized controlled trials conducted by the European Vasculitis Society were identified. Univariate and multivariate analyses were performed to validate previously proposed and identify novel risks associated with venous thromboembolism (VTE) in AAV. Results. VTE occurred in 41 of 417 (9.8%) patients. Uncorrected univariate analysis identified BVAS (odds ratio, OR= 1.05, 95% CI: 1.01, 1.10; P = 0.013), subsequent development of malignancy (OR = 2.6, 95% CI: 1.19, 5.71; P = 0.017), mucous membrane or eye involvement (OR = 2.13, 95% CI: 1.10, 4.11; P = 0.024) and baseline creatinine (OR = 1.08, 95% CI: 0.99, 1.18; P = 0.037) as being associated with the development of VTE. Multivariate analysis highlighted CRP (per 10 mg/l increase, OR= 1.05, 95% CI: 1.01, 1.09; P = 0.025), cutaneous involvement (OR = 4.83, 95% CI: 1.63, 14.38; P = 0.005) and gastrointestinal involvement (OR = 6.27, 95% CI: 1.34, 29.37; P = 0.02) among the BVAS items as well as baseline creatinine (per 100 mmol/l increase, OR= 1.17, 95% CI: 1.02, 1.35; P = 0.029) as being associated with VTEs. Conclusion. Our results highlight a role of CRP, baseline creatinine, and cutaneous and gastrointestinal involvement in the risk stratification as being associated with thromboembolic events. Moreover, there might be an association between VTEs and subsequent development of malignancy and disease activity in general.
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| 40. |
- Larsson, Johanna K, et al.
(författare)
-
Cancer Risk in Collagenous Colitis
- 2019
-
Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:11
-
Tidskriftsartikel (refereegranskat)abstract
- Data on malignancy in patients with collagenous colitis (CC) is scarce. We aimed to determine the incidence of cancers in patients with CC. In a two-stages, observational study, data on cancers in patients diagnosed with CC during 2000-2015, were collected from two cohorts. The risk was calculated according to the age-standardized rate for the first cohort and according to the standardized incidence ratio for the second cohort. The first cohort comprised 738 patients (394 from Scotland and 344 from Sweden; mean age 71 +/- 11 and 66 +/- 13 years, respectively). The incidence rates for lung cancer (RR 3.9, p = 0.001), bladder cancer (RR 9.2, p = 0.019), and non-melanoma skin cancer (NMSC) (RR 15, p = 0.001) were increased. As the majority of NMSC cases (15/16) came from Sweden, a second Swedish cohort, comprising 1141 patients (863 women, mean age 65 years, range 20-95 years) was collected. There were 93 cancer cases (besides NMSC). The risk for colon cancer was decreased (SIR 0.23, p= 0.0087). The risk for cutaneous squamous cell carcinoma was instead markedly increased (SIR 3.27, p = 0.001).
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| 41. |
- Ljungström, Viktor, et al.
(författare)
-
Whole-exome sequencing in relapsing chronic lymphocytic leukemia : clinical impact of recurrent RPS15 mutations
- 2016
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 127:8, s. 1007-1016
-
Tidskriftsartikel (refereegranskat)abstract
- Fludarabine, cyclophosphamide and rituximab (FCR) is first-line treatment for medically fit chronic lymphocytic leukemia (CLL) patients, however despite good response rates many patients eventually relapse. Whilst recent high-throughput studies have identified novel recurrent genetic lesions in adverse-prognostic CLL, the mechanisms leading to relapse after FCR therapy are not completely understood. To gain insight into this issue, we performed whole-exome sequencing of sequential samples from 41 CLL patients who were uniformly treated with FCR but relapsed after a median of 2 years. In addition to mutations with known adverse-prognostic impact (TP53, NOTCH1, ATM, SF3B1, NFKBIE, BIRC3) a large proportion of cases (19.5%) harbored mutations in RPS15, a gene encoding a component of the 40S ribosomal subunit. Extended screening, totaling 1119 patients, supported a role for RPS15 mutations in aggressive CLL, with one-third of RPS15-mutant cases also carrying TP53 aberrations. In most cases selection of dominant, relapse-specific subclones was observed over time. However, RPS15 mutations were clonal prior to treatment and remained stable at relapse. Notably, all RPS15 mutations represented somatic missense variants and resided within a 7 amino-acid evolutionarily conserved region. We confirmed the recently postulated direct interaction between RPS15 and MDM2/MDMX and transient expression of mutant RPS15 revealed defective regulation of endogenous p53 compared to wildtype RPS15. In summary, we provide novel insights into the heterogeneous genetic landscape of CLL relapsing after FCR treatment and highlight a novel mechanism underlying clinical aggressiveness involving a mutated ribosomal protein, potentially representing an early genetic lesion in CLL pathobiology.
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| 42. |
- Llona-Minguez, Sabin, et al.
(författare)
-
Discovery of the First Potent and Selective Inhibitors of Human dCTP Pyrophosphatase 1
- 2016
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 59:3, s. 1140-1148
-
Tidskriftsartikel (refereegranskat)abstract
- The dCTPase pyrophosphatase 1 (dCTPase) regulates the intracellular nucleotide pool through hydrolytic degradation of canonical and noncanonical nucleotide triphosphates (dNTPs). dCTPase is highly expressed in multiple carcinomas and is associated with cancer cell sternness. Here we report on the development of the first potent and selective dCTPase inhibitors that enhance the cytotoxic effect of cytidine analogues in leukemia cells. Boronate 30 displays a promising in vitro ADME profile, including plasma and mouse microsomal half-lives, aqueous solubility, cell permeability and CYP inhibition, deeming it a suitable compound for in vivo studies.
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| 43. |
- Llona-Minguez, Sabin, et al.
(författare)
-
Identification of Triazolothiadiazoles as Potent Inhibitors of the dCTP Pyrophosphatase 1
- 2017
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 60:5, s. 2148-2154
-
Tidskriftsartikel (refereegranskat)abstract
- The dCTP pyrophosphatase 1 (dCTPase) is involved in the regulation of the cellular dNTP pool and has been linked to cancer progression. Here we report on the discovery of a series of 3,6-disubstituted triazolothiadiazoles as potent dCTPase inhibitors. Compounds 16 and 18 display good correlation between enzymatic inhibition and target engagement, together with efficacy in a cellular synergy model, deeming them as a promising starting point for hit -to-lead development.
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| 44. |
- Mathsson, Linda, et al.
(författare)
-
Cryoglobulin-induced cytokine production via FcgammaRIIa: inverse effects of complement blockade on the production of TNF-alpha and IL-10. Implications for the growth of malignant B-cell clones.
- 2005
-
Ingår i: British Journal of Haematology. ; 129:6, s. 830-838
-
Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies produced by patients with lymphoproliferative diseases sometimes appear as cryoglobulins (CG), immunoglobulins (Ig) that reversibly agglutinate and form immune complexes (IC) when cooled below normal body temperature or through variation in pH and ionic strength. In accordance with our findings of IC-induced cytokine production from peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus, we investigated whether CG can also induce cytokine production. One IgG and one IgM type I CG from two patients with multiple myeloma and Waldenstrom's macroglobulinaemia were individually purified and added to PBMC cultures. In separate experiments temperature and ionic strength were varied, or FcgammaRIIa, FcgammaRIII and complement activation were blocked; supernatant cytokine levels were then determined by enzyme-linked immunosorbent assay. CG-induced cytokine production from monocytes varied with precipitation induced by changes in temperature and ionic strength and was mediated via FcRIIa- and complement-dependent mechanisms. Complement blockade resulted in increased IgG CG-induced interleukin (IL)-10 production that was inversely correlated with decreased production of tumour necrosis factor-alpha. CG-induced IL-10 might be a growth factor for malignant B-lymphocytes in CG-associated lymphoproliferative diseases with constant complement consumption. Knowledge of mechanisms underlying CG-induced cytokine production can be useful for designing treatments for type I CG-associated pathology in lymphoproliferative diseases.
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| 45. |
- Nordvall Lagerås, Andreas, 1981-
(författare)
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Markov Chains, Renewal, Branching and Coalescent Processes : Four Topics in Probability Theory
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of four papers.In paper 1, we prove central limit theorems for Markov chains under (local) contraction conditions. As a corollary we obtain a central limit theorem for Markov chains associated with iterated function systems with contractive maps and place-dependent Dini-continuous probabilities.In paper 2, properties of inverse subordinators are investigated, in particular similarities with renewal processes. The main tool is a theorem on processes that are both renewal and Cox processes.In paper 3, distributional properties of supercritical and especially immortal branching processes are derived. The marginal distributions of immortal branching processes are found to be compound geometric.In paper 4, a description of a dynamic population model is presented, such that samples from the population have genealogies as given by a Lambda-coalescent with mutations. Depending on whether the sample is grouped according to litters or families, the sampling distribution is either regenerative or non-regenerative.
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| 46. |
- Pettersson, Gunilla, et al.
(författare)
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Increased joint-forming ability of ductile kraft pulp fibres by polyelectrolyte multilayer treatment-Influence of refining and drying strategies
- 2007
-
Ingår i: Nordic Pulp & Paper Research Journal. - 0283-2631 .- 2000-0669. ; 22:2, s. 228-235
-
Tidskriftsartikel (refereegranskat)abstract
- In this study a sack paper furnish was used. It consisted of a high-consistency kraft pulp refined in either an atmospheric pressure or a pressurized system. The pulps were subsequently low-consistency refined in an Escher-Wyss laboratory refiner to 17.5-20.5 SR. Ordinary ISO sheets and freely dried sheets were manufactured from these pulp samples to serve as reference sheets. The laboratory sheets made of pulp from the pressurized system had a higher strain at break and tensile energy adsorption index but a lower tensile index than sheets made of pulp from a conventional atmospheric highconsistency refiner. These sheets were subject to a polyelectrolyte multilayer treatment to increase the interaction between the fibres, thus enhancing the paper strength properties. The polyelectrolyte multilayers (PEM) were applied by sequentially treating fibres from an unbleached kraft pulp for sack paper production with cationic starch and anionic carboxymethyl cellulose. The multilayer treatment was only applied to 50% of the stock and both ordinary ISO sheets and freely dried sheets were prepared with one and three layers of polyelectrolyte. Evaluation of the strength properties of the sheets showed that the addition of only one layer of starch increased strain at break, tensile index, tensile energy adsorption index, and out-of-plane properties measured as Scott-bond values. Using the multilayer technique created large increases in Scott-bond, a measure of the internal bonding of the sheets. The achieved effects were significantly larger than those usually achieved by applying starch alone to enhance the out-of plane strength properties. Also, the density increased considerably when the third layer was applied, for both ISO and freely dried sheets, though the tensile strength was enhanced significantly only in the freely dried sheets.
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| 47. |
- Pfirrmann, Markus, et al.
(författare)
-
The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia
- 2020
-
Ingår i: Leukemia. - : NATURE PUBLISHING GROUP. - 0887-6924 .- 1476-5551. ; 34:8, s. 2138-2149
-
Tidskriftsartikel (refereegranskat)abstract
- Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation. In 2949 patients not involved in any score development, higher hazard ratios and concordance indices in any comparison demonstrated the best discrimination of long-term survival with the ELTS score. In a second step, of 5154 patients analyzed to investigate risk group classification differences, 23% (n = 1197) were allocated to high-risk by the Sokal score. Of the 1197 Sokal high-risk patients, 56% were non-high-risk according to the ELTS score and had a significantly more favorable long-term survival prognosis than the 526 high-risk patients according to both scores. The Sokal score identified too many patients as high-risk and relatively few (40%) as low-risk (versus 60% with the ELTS score). Inappropriate risk classification jeopardizes optimal treatment selection. The ELTS score outperformed the Sokal score, the Euro, and the EUTOS score regarding risk group discrimination. The recent recommendation of the European LeukemiaNet for preferred use of the ELTS score was supported with significant statistical evidence.
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| 48. |
- Pudelko, Linda, et al.
(författare)
-
Glioblastoma and glioblastoma stem cells are dependent on functional MTH1
- 2017
-
Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 8:49, s. 84671-84684
-
Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is an aggressive form of brain cancer with poor prognosis. Cancer cells are characterized by a specific redox environment that adjusts metabolism to its specific needs and allows the tumor to grow and metastasize. As a consequence, cancer cells and especially GBM cells suffer from elevated oxidative pressure which requires antioxidant-defense and other sanitation enzymes to be upregulated. MTH1, which degrades oxidized nucleotides, is one of these defense enzymes and represents a promising cancer target. We found MTH1 expression levels elevated and correlated with GBM aggressiveness and discovered that siRNA knock-down or inhibition of MTH1 with small molecules efficiently reduced viability of patient-derived GBM cultures. The effect of MTH1 loss on GBM viability was likely mediated through incorporation of oxidized nucleotides and subsequent DNA damage. We revealed that MTH1 inhibition targets GBM independent of aggressiveness as well as potently kills putative GBM stem cells in vitro. We used an orthotopic zebrafish model to confirm our results in vivo and light-sheet microscopy to follow the effect of MTH1 inhibition in GBM in real time. In conclusion, MTH1 represents a promising target for GBM therapy and MTH1 inhibitors may also be effective in patients that suffer from recurring disease.
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| 49. |
- Qu, Ying, et al.
(författare)
-
Differential methylation in CN-AML preferentially targets non-CGI regions and is dictated by DNMT3A mutational status and associated with predominant hypomethylation of HOX genes
- 2014
-
Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 9:8, s. 1108-1119
-
Tidskriftsartikel (refereegranskat)abstract
- The extent and role of aberrant DNA methylation in promoter CpG islands (CGIs) have been extensively studied in leukemia and other malignancies. Still, CGIs represent only a small fraction of the methylome. We aimed to characterize genome-wide differential methylation of cytogenetically normal AML (CN-AML) cells compared with normal CD34(+) bone marrow cells using the Illumina (R) 450K methylation array. Differential methylation in CN-AML was most prominent in genomic areas far from CGIs, in so called open sea regions. Furthermore, differential methylation was specifically found in genes encoding transcription factors (TFs), with WT1 being the most differentially methylated TF. Among genetic mutations in AML, DNMT3A mutations showed the most prominent association with the DNA methylation pattern, characterized by hypomethylation of CGIs (as compared with DNMT3A wild type cases). The differential methylation in DNMT3A mutant cells vs. wild type cells was predominantly found in HOX genes, which were hypomethylated. These results were confirmed and validated in an independent CN-AML cohort. In conclusion, we show that, in CN-AML, the most pronounced changes in DNA methylation occur in non-CGI regions and that DNMT3A mutations confer a pattern of global hypomethylation that specifically targets HOX genes.
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| 50. |
- Rudh, Andreas
(författare)
-
Aposematism, Crypsis and Population Differentiation in the Strawberry Poison Frog
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Evolutionary transitions between the two major predator avoidance strategies aposematism and crypsis are expected to be associated with changes in many important traits of animals. However, empirical studies on populations experiencing ongoing or recent transitions between these strategies are rare. This thesis investigates the co-evolution of traits among populations of the Strawberry poison frog D.pumilio in Bocas del Toro, Panama. I found that all investigated populations were genetically distinct but that colour and pattern did not correlate with genetic or geographic distance, which suggests that selection needs to be invoked to explain the observed variation. Based on the chromatic contrast between frog dorsal colour and the natural habitat substrates used by the frogs, the populations were defined as bright or dull coloured. I found that frogs from bright coloured populations were larger. This is expected if aposematism is enhanced by large signals while crypsis is enhanced by small size. Further, individuals from bright coloured populations had a coarser black dorsal pattern, which is expected if crypsis is impaired by a bold pattern. The importance of pattern coarseness was confirmed by an avian detection experiment showing that coarse patterned dark green prey were more easily detected than dark green prey without pattern or with fine pattern. I put forward the hypothesis that enhanced protection, gained by aposematism, may affect behaviours that influence dispersal and pairing patterns. Indeed, males from bright coloured populations displayed at more exposed sites and showed a tendency to be more explorative and aggressive. In summary, my results show that the bright and dull coloured populations most likely represent an aposematic and a cryptic strategy, respectively. Furthermore, I show that evolutionary changes between aposematism and crypsis can be associated with coevolution of both morphology and behaviour. I argue that this coevolution may increase the likelihood of both pre- and post-zygotic reproductive isolation. This is because greater phenotypic differences between populations increase the likelihood of selection against badly adapted migrants and hybrids with intermediate traits.
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