| 1. |
- Hedegaard, Jakob, et al.
(författare)
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Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
- 2016
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
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Tidskriftsartikel (refereegranskat)abstract
- Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
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| 2. |
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| 3. |
- Aine, Mattias, et al.
(författare)
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Molecular analyses of triple-negative breast cancer in the young and elderly
- 2021
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breast cancer in young adults has been implicated with a worse outcome. Analyses of genomic traits associated with age have been heterogenous, likely because of an incomplete accounting for underlying molecular subtypes. We aimed to resolve whether triple-negative breast cancer (TNBC) in younger versus older patients represent similar or different molecular diseases in the context of genetic and transcriptional subtypes and immune cell infiltration.PATIENTS AND METHODS: In total, 237 patients from a reported population-based south Swedish TNBC cohort profiled by RNA sequencing and whole-genome sequencing (WGS) were included. Patients were binned in 10-year intervals. Complimentary PD-L1 and CD20 immunohistochemistry and estimation of tumor-infiltrating lymphocytes (TILs) were performed. Cases were analyzed for differences in patient outcome, genomic, transcriptional, and immune landscape features versus age at diagnosis. Additionally, 560 public WGS breast cancer profiles were used for validation.RESULTS: Median age at diagnosis was 62 years (range 26-91). Age was not associated with invasive disease-free survival or overall survival after adjuvant chemotherapy. Among the BRCA1-deficient cases (82/237), 90% were diagnosed before the age of 70 and were predominantly of the basal-like subtype. In the full TNBC cohort, reported associations of patient age with changes in Ki67 expression, PIK3CA mutations, and a luminal androgen receptor subtype were confirmed. Within DNA repair deficiency or gene expression defined molecular subgroups, age-related alterations in, e.g., overall gene expression, immune cell marker gene expression, genetic mutational and rearrangement signatures, amount of copy number alterations, and tumor mutational burden did, however, not appear distinct. Similar non-significant associations for genetic alterations with age were obtained for other breast cancer subgroups in public WGS data. Consistent with age-related immunosenescence, TIL counts decreased linearly with patient age across different genetic TNBC subtypes.CONCLUSIONS: Age-related alterations in TNBC, as well as breast cancer in general, need to be viewed in the context of underlying genomic phenotypes. Based on this notion, age at diagnosis alone does not appear to provide an additional layer of biological complexity above that of proposed genetic and transcriptional phenotypes of TNBC. Consequently, treatment decisions should be less influenced by age and more driven by tumor biology.
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| 4. |
- Almazidou, Maria, et al.
(författare)
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Maria-mottagningarna i Stockholm, Göteborg och Malmö - Ungdomar i öppenvård år 2013
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Trestad2 är en nationell satsning där de tre städerna Stockholm, Göteborg och Malmö samarbetar för att minska användandet av cannabis bland ungdomar. Inom ramen för projektet har det skapats en modell för att identifiera och följa trender i de tre storstäderna vad gäller droganvändning och psykosocial situation för ungdomar som påbörjar behandling för missbruksproblem. Framtagandet av relevanta indikatorer har skett i nära samarbete mellan praktiker och forskare utifrån en sammanvägning av forskningsmässiga, metodologiska och kliniskt betydelsefulla utgångspunkter. Underlaget utgörs av uppgifter om 788 ungdomar som inledde öppenvårdsbehandling vid någon av städernas Maria-mottagningar under år 2013 och har inhämtats med intervjumetoden UngDOK.Sammanställningen av indikatorer visar att flickor utgör cirka en fjärdedel av det totala antalet ungdomar som påbörjar öppenvård för problem med alkohol eller narkotika. Ungdomarnas medianålder när vårdkontakten inleds är 17 år och mer än hälften av ungdomarna har kommit i kontakt med Maria-mottagningarna via eget eller nätverkets initiativ. Nästan två tredjedelar av ungdomarna uppger att de har eller har haft omfattande problem under sin skolgång och cirka en tiondel av ungdomarna varken studerar, arbetar eller praktiserar. Drygt tre fjärdedelar av ungdomarna anger cannabis som sin primära drog, men nästan hälften av dem har även en riskfylld alkoholkonsumtion. Den genomsnittliga debutåldern för den primära drogen är 15 år. Ungefär en fjärdedel av ungdomarna har tidigare fått vård och behandling för alkohol- eller narkotikaproblem. Förekomsten av besvärliga uppväxtvillkor är hög hos ungdomarna och över hälften av dem har erfarenheter av att ha växt upp med våld, psykiska problem och/eller missbruk i familjen. Drygt en tredjedel av samtliga ungdomar har eller har haft kontakt med den psykiatriska vården.Vissa skillnader mellan de tre städernas Maria-mottagningar kan identifieras. Ungdomarna som påbörjar kontakt med mottagningen i Stockholm verkar ha problem av något lindrigare art jämfört med Göteborg och Malmö och utgör mindre andelar både när det gäller komplicerande bakgrundsfaktorer och nuvarande problembeteenden. Det finns även mindre skillnader i åldersstrukturen i de tre städerna, där Stockholm har fler ungdomar under 18 år medan både Göteborg och Malmö har fler som är över 18 år. Det finns även vissa könsskillnader genom att flickorna i samtliga tre städer tycks ha en tyngre problematik i jämförelse med pojkarna. Flickorna saknar i högre grad sysselsättning, anger oftare problem i skolan, har haft svårare uppväxtvillkor och har i större utsträckning haft kontakt med psykiatrin i jämförelse med pojkarna.Att sammanställa och rapportera deskriptiva indikatorer om individer som påbörjar behandling för alkohol- och narkotikaproblem kan ha flera fördelar. En sådan är att informationen kan ligga till grund för en ökad förståelse av ungdomars alkohol- och narkotikaanvändning och dess omfattning. Även om rapportens uppgifter inte är heltäckande, beskriver den en större population av svenska ungdomar med en problematisk användning av alkohol och droger. Föreliggande rapport är således en första ansats till att ge en sammanfattande bild av de ungdomar som påbörjar behandling vid Maria-mottagningarnas öppenvård i Stockholm, Göteborg och Malmö.
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| 5. |
- Andersson, Anna, et al.
(författare)
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Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations
- 2005
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 19:6, s. 1042-1050
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Tidskriftsartikel (refereegranskat)abstract
- Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14) [IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11) [PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias cosegregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design.
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| 6. |
- Astromskas, Gvidas, et al.
(författare)
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Temperature dependence of GaSb overgrowth of tungsten on GaSb (001) substrates using MOVPE
- 2008
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Ingår i: 20th International Conference on Indium Phosphide and Related Materials, 2008. IPRM 2008. - 1092-8669. ; , s. 354-356
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Konferensbidrag (refereegranskat)abstract
- We demonstrate GaSb overgrowth over tungsten patterns and that selective area epitaxy is achievable in the W/GaSb system. By controlling the facet growth at low temperatures, it is possible to embed a metal grating in a thin layer.
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| 7. |
- Astromskas, Gvidas, et al.
(författare)
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Thin InAs membranes and GaSb buffer layers on GaAs(001) substrates
- 2012
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Ingår i: Journal of Vacuum Science and Technology B. - : American Vacuum Society. - 1520-8567. ; 30:5
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Tidskriftsartikel (refereegranskat)abstract
- Thin InAs layers and membranes are fabricated on GaAs substrates using GaSb buffer layers grown by MOVPE. The quality of the GaSb buffer layers is optimized and epitaxial InAs layers are grown on GaSb layers of various thickness. The best GaSb buffer layers are obtained for a nucleation temperature of 450 degrees C and a subsequent growth temperature of 570 degrees C with a V/III ratio of 3, as confirmed by both the structural (high-resolution XRD, AFM) and electrical (Hall) measurements. Furthermore, a clear relationship between the structural quality of the GaSb and InAs layers is established. Finally, free-standing InAs structures are fabricated where Hall measurements reveal a mobility that depends on the film thickness.
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| 8. |
- Athle, Robin, et al.
(författare)
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Effects of TiN Top Electrode Texturing on Ferroelectricity in Hf1-xZrxO2
- 2021
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Ingår i: ACS applied materials & interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:9, s. 11089-11095
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Tidskriftsartikel (refereegranskat)abstract
- Ferroelectric memories based on hafnium oxide are an attractive alternative to conventional memory technologies due to their scalability and energy efficiency. However, there are still many open questions regarding the optimal material stack and processing conditions for reliable device performance. Here, we report on the impact of the sputtering process conditions of the commonly used TiN top electrode on the ferroelectric properties of Hf1-xZrxO2. By manipulating the deposition pressure and chemistry, we control the preferential orientation of the TiN grains between (111) and (002). We observe that (111) textured TiN is superior to (002) texturing for achieving high remanent polarization (Pr). Furthermore, we find that additional nitrogen supply during TiN deposition leads to >5× greater endurance, possibly by limiting the scavenging of oxygen from the Hf1-xZrxO2 film. These results help explain the large Pr variation reported in the literature for Hf1-xZrxO2/TiN and highlights the necessity of tuning the top electrode of the ferroelectric stack for successful device implementation.
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| 9. |
- Athle, Robin, et al.
(författare)
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Ferroelectric Tunnel Junction Memristors for In-Memory Computing Accelerators
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Ingår i: Advanced Intelligent Systems. - 2640-4567.
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Tidskriftsartikel (refereegranskat)abstract
- Neuromorphic computing has seen great interest as leaps in artificial intelligence (AI) applications have exposed limitations due to heavy memory access, with the von Neumann computing architecture. The parallel in-memory computing provided by neuromorphic computing has the potential to significantly improve latency and power consumption. Key to analog neuromorphic computing hardware are memristors, providing non-volatile multistate conductance levels, high switching speed, and energy efficiency. Ferroelectric tunnel junction (FTJ) memristors are prime candidates for this purpose, but the impact of the particular characteristics for their performance upon integration into large crossbar arrays, the core compute element for both inference and training in deep neural networks, requires close investigation. In this work, a W/HfxZr1−xO2/TiN FTJ with 60 programmable conductance states, a dynamic range (DR) up to 10, current density >3 A m−2 at V read = 0.3 V and highly nonlinear current–voltage (I–V) characteristics (>1100) is experimentally demonstrated. Using a circuit macro-model, the system level performance of a true crossbar array is evaluated and a 92% classification accuracy of the modified nation institute of science and technology (MNIST) dataset is achieved. Finally, the low on conductance in combination with the highly nonlinear I–V characteristics enable the realization of large selector-free crossbar arrays for neuromorphic hardware accelerators.
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| 10. |
- Athle, Robin, et al.
(författare)
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Impact of Temperature-Induced Oxide Defects on HfxZr1−xO2 Ferroelectric Tunnel Junction Memristor Performance
- 2023
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Ingår i: IEEE Transactions on Electron Devices. - 0018-9383. ; 70:3, s. 1412-1416
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we evaluate the importance of the postmetallization annealing (PMA) temperature on the performance of HfxZr1−xO2-based ferroelectric tunnel junctions (FTJs). Our results indicate a significant difference in tunneling electroresistance (TER) ratio and endurance, depending on the PMA temperature despite negligible variations in remanent polarization. We conclude that the minimization of conductive oxide defect states is central to achieve high performance. Through carefully optimized PMA conditions, we demonstrate FTJs with a TER = 3 and low mean cycle-to-cycle variation of < 1.5% combined with at least 16 separable conductance states providing a 4-bit resolution analog FTJ.
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