| 1. |
- Bäck, Per, 1987-
(författare)
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On Hom-associative Ore Extensions
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, we introduce and study hom-associative Ore extensions. These are non-unital, non-associative, non-commutative polynomial rings in which the associativity condition is “twisted” by an additive group homomorphism. In particular, they are examples of hom-associative algebras, and they generalize the classical non-commutative polynomial rings introduced by Ore known as Ore extensions to the non-unital, hom-associative setting. At the same time, when the twisted associativity condition is null, they also generalize to the general non-unital, non-associative setting. We deduce necessary and sufficient conditions for hom-associative Ore extensions to exist, and construct concrete examples thereof. These include hom-associative generalizations of the quantum plane, the universal enveloping algebra of the two-dimensional non-abelian Lie algebra, and the first Weyl algebra, to name a few. The aforementioned algebras turn out to be formal hom-associative deformations of their associative counterparts, the latter two which cannot be formally deformed in the associative setting. Moreover, these are all weakly unital algebras, and we provide a way of embedding any multiplicative, non-unital hom-associative algebra into a multiplicative, weakly unital hom-associative algebra. This generalizes the classical unitalization of non-unital, associative algebras. We then study the hom-associative Weyl algebras in arbitrary characteristic, classify them up to isomorphism, and in the zero characteristic case, we prove that an analogue of the Dixmier conjecture is true. We also study hom-modules over hom-associative rings, and by doing so, we are able to prove a Hilbert's basis theorem for hom-associative Ore extensions. Our theorem includes as special cases both the classical Hilbert's basis theorem for Ore extensions and a Hilbert's basis theorem for unital, non-associative Ore extensions. Last, we construct examples of both hom-associative and non-associative Ore extensions which are all Noetherian by our theorem.
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| 2. |
- Capriata, Corrado Carlo Maria
(författare)
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Dynamics and Intrinsic Variability of Spintronic Devices
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Spintronics is a scientific domain focusing on utilizing electron spin for information processing. This is the element that distinguishes it from electronics, which only utilizes the charge of electrons. A common purpose of spintronic devices is to implement additional functionalities to state-of-the-art Complementary Metal-Oxide Semiconductor (CMOS) technology. The aim of this work was to assess the intrinsic variabilities of Nano-Constriction Spin Hall Nano-Oscillators (NC-SHNOs) and the dynamics of Perpendicular Magnetic Tunnel Junctions (pMTJs). The first part of the thesis focuses on NC-SHNO and two-dimensional arrays. They are nanometer-sized microwave oscillators, allowing for a wide frequency tuning range, and are compatible with CMOS Back End Of Line (BEOL). These devices are based on a heavy metal/ferromagnetic bilayer. Environmental conditions during processing, fabrication techniques, and temperature of operation can all create variabilities in the device's functioning. Crystallization grains naturally form during the sputtering of the metals. Atomic Force Microscope (AFM) characterization showed the grains being of different shapes, about 30 nm in size. Here, the aim was to develop a simulation technique based on importing the measured grain structure into micromagnetic simulations. Their results match the device-to-device variability and multi-modal behavior found in microwave measurements. Moreover, the presence of grains influences the synchronization of the arrays.The second part of this work focuses on pMTJ. These non-volatile memory elements have two metastable states, parallel (P) and antiparallel (AP), separated by an energy barrier Eb. Here, the aim was to show their potential as True Random Number Generators (TRNGs). A pulse-activated measurement set-up was used to realize random bitstreams. The randomness was confirmed by the National Institute of Standards and Technology Statistical Testing Suite (NIST-STS). After one whitening Exclusive OR (XOR) stage, all tests were successfully passed.The assessment was completed with the development of a model describing both macrospin and domain wall-mediated magnetization reversals, i.e. switching between P and AP. The analysis of the reversal dynamics was carried out with micromagnetic simulations and String Method calculations. As expected, Eb is lowered by the field and by decreasing the device size. This allows for faster fluctuations, marking the device as a potential TRNG. Both the switching attempt frequency and the energy barrier were explored by finite-temperature micromagnetic simulations.This thesis shows the potential of realistic simulations combined with measurements to assess oscillators. It also shows the efficacy of spintronic devices as 10s-MHz TRNG.
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| 3. |
- Löwenmark, Thyra, 1995-
(författare)
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Gut microbiota in colorectal cancer : The importance of Parvimonas micra
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is a heterogenous disease consisting of multiple molecular subtypes, each of which has diverse treatment responses and prognoses. The importance of the gut microbiota in CRC development and progression has undergone increasing recognition in recent years, with a structural segregation in terms of microbial composition between CRC patients and healthy controls. However, many questions remain before a full understanding of the impact of the gut microbiota on CRC is reached. The overall aim of this thesis was to explore the role of gut microbes in CRC, including their potential as CRC biomarkers and associations with clinicopathological, immunological, and molecular traits of CRC. A particular focus was the CRC-associated oral pathogen Parvimonas micra.To investigate faecal microbiota as a potential biomarker for CRC, we studied the presence of specific bacteria in faeces from CRC patients and controls using qPCR. We found higher levels of P. micra in faecal samples from CRC patients than from control patients. A test for high levels of P. micra was able to identify CRC with a specificity of 87.3% and a sensitivity of 60.5%. Adding the oral pathogen Fusobacterium nucleatum, colibactin-producing bacteria, and faecal haemoglobin to the test enhanced its sensitivity.We further aimed to explore the associations of P. micra and F. nucleatum with molecular subtypes of CRC and the tumour immune response. The levels of P. micra and F. nucleatum, as analysed by qPCR in both faeces and tumour tissue from CRC patients, were found to be positively correlated. High levels of intratumoural P. micra and F. nucleatum were associated with tumours of the microsatellite instable subtype and BRAF-mutated tumours. For F. nucleatum, an additional association with right-sided tumours was found. Moreover, both P. micra and F. nucleatum in tumour tissue were associated with the immune-activated consensus molecular subtype (CMS) 1 subtype of CRC. In line with this finding, we found novel associations between intratumoural P. micra and specific immune traits, which were evaluated by flow cytometry, indicating an active immune response in CRC. These results were further confirmed using transcriptomics. However, no associations with specific immune traits were found for F. nucleatum.We also investigated associations between faecal and intratumoural levels of P. micra and F. nucleatum and survival in CRC patients. CRC patients with high levels of intratumoural P. micra and F. nucleatum showed reduced five-year cancer-specific survival. This association remained significant for P. micra in multivariable analysis. No associations with cancer-specific survival were found for levels of P. micra and F. nucleatum in faeces.To investigate the faecal microbial landscape of CRC patients on a larger scale, we used 16S rRNA sequencing. Network analysis revealed a cluster of associated bacteria, including P. micra and F. nucleatum, as well as other CRC-related pathogens such as Bacteroides fragilis, Peptostreptococcus stomatitis, and Porphyromonas spp. Furthermore, beta-diversity analysis indicated a significantly different gut microbial composition depending on tumour location and microsatellite instability status. Interestingly, three of the six annotated species most strongly associated with microsatellite instable tumours were also present in the cluster: P. micra, F. nucleatum, and P. stomatis.In conclusion, our results suggest P. micra as a putative candidate for a future non-invasive microbial test panel for detection of CRC. Moreover, our results indicate that intratumoural P. micra and F. nucleatum are associated with immune-active subtypes of CRC, including microsatellite instable tumours and tumours of the CMS1 subtype, as well as decreased patient survival. Furthermore, P. micra and F. nucleatum were found to be associated with a cluster of other CRC-related oral pathogens. An improved understanding of the role of the gut microbiota in tumour progression may lead to the identification of important biomarkers for CRC disease and outcome, as well as potential targets for future therapy.
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| 4. |
- Ramos Santesmases, David
(författare)
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Process development of III-V-based infrared detectors
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type-II Superlattice (T2SL) detectors have revolutionized the field of infraredimaging, establishing themselves as the forefront technology in defense, space,and industrial applications. These detectors enable larger formats and higheroperating temperatures (HOT) that minimize the need for bulky and energyconsumingcryogenic cooling, paving the way for imaging systems with reducedSize, Weight, and Power (SWaP).Their versatility across various IR wavebands—long-wavelength, midwavelength,and extended short-wavelength—combined with the intrinsicscalability characteristic of III-V detectors, positions T2SL technology as the idealchoice for next-generation HOT and high-resolution (HD) detectors.This thesis focuses on improving the manufacturing process for T2SL arrays toreduce surface leakage currents induced during pixel etching. This challengebecomes more pronounced with smaller pixels and directly affects the maximumoperating temperature.The investigation into T2SL detector performance provides comprehensiveinsights into the detectors' electrical characteristics. This includes 1/f noiseanalysis and a detailed experimental and quantitative modeling of surface leakagecurrents, proposing strategies for their reduction. Furthermore, the study delvesinto light-matter interactions within focal plane arrays (FPAs) to describe opticalconcentration effects to increase the sensitivity and provides Modulation transferfunction measurements and simulations to discuss the resolution of T2SL arrays.Employing diverse Sb-based T2SL detector photodiode structures, this thesisreports significant progress in the fabrication process, leading to remarkableachievements. These include the demonstration and industrial production of a640 × 512 – 15 μm format FPA operating at 150 K; the production of 10, 7.5,and 5 μm pitch arrays, all capable of functioning at 150 K; and the demonstrationof small-pitch HD FPAs, with the capability of operating at 150K.
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| 5. |
- Zurauskaite, Laura
(författare)
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Ge/high-k Gates for Monolithic 3D Integration
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Continuous scaling of transistor dimensions has been in the heart of semiconductorindustry for many years. Recently the scaling has been enabled by various performance boosters which resulted in increased processing complexity and cost, forcing the chip manufacturers to look for some alternative solutions. Monolithic 3D integration has been identified as a promising candidate for future CMOS technology nodes, as it could enable a further increasein device density through stacking tiers of older and cheaper generation transistorson top of each other. One of the major challenges faced by monolithic 3D integration is the thermal budget during upper tier fabrication since high temperature steps used in conventional CMOS processing can damage the bottom tier devices. To this respect, Ge has an advantage over Si due to its intrinsically low processing temperature. However, realizing Ge devices that provide performance and reliability comparable to Si devices is not straight forward. Gate stack formation in Ge devices is particularly challenging, as Ge lacks a stable oxide for surface passivation.In this work, gate stack solutions for Ge-based devices for monolithic 3D integration applications have been extensively studied. Low temperature Ge surface passivation with GeOx and Si-cap process has been investigated and characterized in terms of interface state density, oxide trap density and fixed charge density. GeOx has been integrated with other high-k dielectrics, suchas Al2O3, Tm2O3 and HfO2, and with the help of post deposition and forming gas treatments provided sufficient surface passivation with low interface state density. However, devices with GeOx passivation suffered from poor reliability stemming from the lack of thermal stability and high oxide trap density in GeOx layer. On the other hand, Si-cap integrated with TmSiO interfacial layer has been shown to provide both low interface trap density and oxide trap density, albeit within a narrow process window for Si-cap growth conditions. Selected gate stacks with GeOx and Si-cap passivation have been integrated in Ge pFET process on in-house fabricated germanium on insulator substrates. Subthreshold slope values inline with previous reports have been achieved, as well as 60 % higher hole mobility than in reference silicon on insulator pFETs. Moreover, initial results of Si-cap and TmSiO interfacial layer integration ingermanium on insulator nFETs have been demonstrated.This work presents both advantages and limitations of each gate stacksolution on Ge platform. The processes employed in this work are monolithic 3D integration compatible, and demonstrate that with some process optimization Ge transistors could be integrated on Si platform in monolithic3D integration fashion.
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| 6. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 7. |
- Almdalal, T., et al.
(författare)
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Clinical T1a Renal Cell Carcinoma, Not Always a Harmless Disease-A National Register Study
- 2022
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 39, s. 22-28
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Tidskriftsartikel (refereegranskat)abstract
- Background: T1a renal cell carcinoma (RCC) is typically considered a curable dis-ease, irrespective of the choice of local treatment modality.& nbsp;Objective: To identify factors associated with the risk of local and distant recur-rence, and overall survival (OS) in patients with primary nonmetastatic clinical T1a RCC.& nbsp;Design, setting, and participants: A population-based nationwide register study of all 1935 patients with cT1a RCC, diagnosed during 2005-2012, identified through The National Swedish Kidney Cancer Register, was conducted.& nbsp;Outcome measurements and statistical analysis: Outcome variables were recur-rence (local or distant) and OS. Possible explanatory variables included tumor size, RCC type, T stage, surgical technique, age, and gender. Associations with disease recurrence and OS were evaluated by multivariable regression and Cox multivari-ate analyses, respectively.& nbsp;& nbsp;Results and limitations: Among 1935 patients, 938 were treated with radical nephrectomy, 738 with partial nephrectomy, and 169 with ablative treatments, while 90 patients had no surgery. Seventy-eight (4%) patients were upstaged to pT3. Local or metastatic recurrences occurred in 145 (7.5%) patients, significantly more often after ablation (17.8%). The risk of recurrence was associated with tumor size, upstaging, and ablation. Larger tumor size, disease recurrence, and older age adversely affected OS, whereas partial nephrectomy and chromophobe RCC (chRCC) were associated with improved survival. Limitations include register design and a lack of comorbidity or performance status data.& nbsp;Conclusions: Upstaging and recurrence occurred, respectively, in 4.0% and 7.5% of patients with nonmetastatic RCCs <= 4 cm. Tumor size upstaging and ablation were associated with the risk for recurrence, while tumor size and recurrence were associated with decreased OS. Patients with chRCC and partial nephrectomy had prolonged OS in a real-world setting.& nbsp;Patient summary: We studied factors that may influence the risk of disease recurrence and overall survival, in a large nationwide patient cohort having non metastatic renal cell carcinoma < 4 cm. Tumor size, tumor type, and treatment were associated with the risk of recurrence and overall death. Partial nephrectomy prolonged overall survival. (C)2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.
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| 8. |
- Almdalal, Tarik, et al.
(författare)
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Predictive characteristics for disease recurrence and overall survival in non-metastatic clinical T1 renal cell carcinoma : results from the National Swedish Kidney Cancer Register
- 2023
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 57:1-6, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivePatients with clinical T1 renal cell carcinoma (cT1RCC) have risks for recurrence and reduced overall survival despite being in the best prognostic group. This study aimed to evaluate the association of different treatments on disease recurrence and overall survival using clinical and pathological characteristics in a nation-wide cT1RCC cohort.Materials and methodsA total of 4,965 patients, registered in the National Swedish Kidney Cancer Register (NSKCR) between 2005 and 2014, with ≥ 5-years follow-up were identified: 3,040 males and 1,925 females, mean age 65 years. Times to recurrence and overall survival were analyzed with Kaplan-Meier curves, log-rank test, and Cox regression models.ResultsAge, TNM-stage, tumor size, RCC-type, and performed treatment were all associated with disease recurrence. Patients selected for ablative treatments had increased risk for recurrent disease: hazard ratio (HR) = 3.79 [95% confidence interval (CI) = 2.69–5.32]. In multivariate analyses, age, gender, tumor size, RCC-type, N-stage, recurrence and performed treatment were all independently associated with overall survival. Patients with chRCC had a 41% better overall survival (HR = 0.59, 95% CI = 0.44–0.78; p < 0.001) than ccRCC. Patients treated with partial nephrectomy (PN) had an 18% better overall survival (HR = 0.83, 95% CI = 0.71–0.95, p < 0.001) than patients treated with radical nephrectomy.ConclusionsAge, gender, T-stage, tumor size, RCC type and treatment modality are all associated with risk of recurrence. Furthermore, age, male gender, tumor size, N-stage and recurrence are associated with reduced overall survival. Patients with chRCC, compared with ccRCC and pRCC patients, and PN compared with RN treated patients, had an advantageous overall survival, indicating a possible survival advantage of nephron sparing treatment.
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| 9. |
- Björner, Kajsa, et al.
(författare)
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High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival
- 2023
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Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 128
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn's disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1β (IL-1β). How these biomarkers relate to CAC pathogenesis or survival is unknown.AIM: The primary aim of this study was to investigate iNOS and IL-1β immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC.METHODS: Immunohistochemistry was performed on tissue sections as follows: CAC (n = 59); sporadic CRC (sCRC) (n = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) (n = 22); paracancerous IBD (pIBD) (n = 12). The expression of iNOS and IL-1β was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases.RESULTS: Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS (P < 0.01) and IL-1β (P < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa (P < 0.001), whereas IL-1β was higher (P < 0.05). Immunoreactivity differences of iNOS or IL-1β among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases.CONCLUSION: Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1β in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward.
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| 10. |
- Healy, Katie, et al.
(författare)
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Salivary IgG to SARS-CoV-2 indicates seroconversion and correlates to serum neutralization in mRNA-vaccinated immunocompromised individuals
- 2022
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Ingår i: Med. - : Cell Press. - 2666-6359 .- 2666-6340. ; 3:2, s. 137-153.e3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immunocompromised individuals are highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Whether vaccine-induced immunity in these individuals involves oral cavity, a primary site of infection, is presently unknown.Methods: Immunocompromised patients (n = 404) and healthy controls (n = 82) participated in a prospective clinical trial (NCT04780659) encompassing two doses of the mRNA BNT162b2 vaccine. Primary immunodeficiency (PID), secondary immunodeficiencies caused by human immunodeficiency virus (HIV) infection, allogeneic hematopoietic stem cell transplantation (HSCT)/chimeric antigen receptor T cell therapy (CAR-T), solid organ transplantation (SOT), and chronic lymphocytic leukemia (CLL) patients were included. Salivary and serum immunoglobulin G (IgG) reactivities to SARS-CoV-2 spike were measured by multiplex bead-based assays and Elecsys anti-SARS-CoV-2 S assay.Findings: IgG responses to SARS-CoV-2 spike antigens in saliva in HIV and HSCT/CAR-T groups were comparable to those of healthy controls after vaccination. The PID, SOT, and CLL patients had weaker responses, influenced mainly by disease parameters or immunosuppressants. Salivary responses correlated remarkably well with specific IgG titers and the neutralizing capacity in serum. Receiver operating characteristic curve analysis for the predictive power of salivary IgG yielded area under the curve (AUC) = 0.95 and positive predictive value (PPV) = 90.7% for the entire cohort after vaccination.Conclusions: Saliva conveys vaccine responses induced by mRNA BNT162b2. The predictive power of salivary spike IgG makes it highly suitable for screening vulnerable groups for revaccination.
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