| 1. |
- Al-Saffar, Anas Kh. 1969-
(author)
-
Gastrointestinal Permeability and Motility in Inflammatory Bowel Disease
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- Synchronized motility, permeability and secretory (hormones and enzymes) events are integral to normal physiology. Smooth muscle syncytium operates with enteric nervous system (ENS) and endocrine signalling to accommodate, mix and control passage of ingested materials. The intestinal epithelial cells (IECs) drive digestion and absorption while repelling harmful compounds.This thesis investigated GI barrier function (permeability, mucosal integrity), motility and hormonal patterns in inflammatory bowel disease (IBD) by: 1) assessing GI motility using a wireless motility capsule (WMC, SmartPill®) and video capsule endoscopy (VCE, Pillcam®), 2) investigation of intestinal fatty acid binding protein (I-FABP) as a biomarker of Crohn’s disease (CD) disease activity, 3) evaluation of small intestinal permeability in IBD, 4) investigating meal-related WMC motility and simultaneous hormonal (e.g., Ghrelin, GLP-1, GIP, PYY) patterns in IBD. Reference WMC motility values for transit times for gastric emptying, small bowel, orocecal, small+large bowel, colon and whole gut were established. Software-generated estimates and visually determined values were nearly identical. Compared with VCE estimates (represents fasting conditions), the WMC records longer GET and SBTT. Variations in intra-subject reproducibility must be considered in clinical investigations. This data was then used to investigate IBD patients. I-FABP was primarily expressed in the epithelium of the small bowel and to lesser extent also in the colon and stomach. Circulating I-FABP was elevated in active CD with a magnitude comparable to TNFα. I-FABP lowers and rises again in parallel with TNFα and HBI during infliximab treatment. I-FABP can be used as a jejunum and ileum selective prognostic biomarker for monitoring disease activity. Increased small intestine mucosal barrier permeability to lactulose in both CD and UC was found. Sucralose can serve a dual purpose in quantifying small and large intestinal permeability. Small intestinal hyper-permeability was not revealed as a transporter dependent nutrient (riboflavin) malabsorption. Using the WMC, consistent motility disturbances in IBD were limited, as were differences in pH. However, disturbances within many individuals were found. As part of the investigation, defects in gut peptide and metabolic hormone meal responses were found, typically higher plasma levels. No clear associations between hormones and motility were found. Effects on hunger/satiety signaling in IBD are anticipated.The present thesis shows the utility of the WMC and gut barrier tests in monitoring IBD patients.
|
|
| 2. |
- Bäck, Per, 1987-
(author)
-
On Hom-associative Ore Extensions
- 2022
-
Doctoral thesis (other academic/artistic)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.
|
|
| 3. |
- Capriata, Corrado Carlo Maria
(author)
-
Dynamics and Intrinsic Variability of Spintronic Devices
- 2023
-
Doctoral thesis (other academic/artistic)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.
|
|
| 4. |
- Chaourani, Panagiotis, 1989-
(author)
-
Sequential 3D Integration - Design Methodologies and Circuit Techniques
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- Sequential 3D (S3D) integration has been identified as a potential candidate for area efficient ICs. It entails the sequential processing of tiers of devices, one on top the other. The sequential nature of this processing allows the inter-tier vias to be processed like any other inter-metal vias, resulting in an unprecedented increase in the density of vertical interconnects. A lot of scientific attention has been directed towards the processing aspects of this 3-D integration approach, and in particular producing high-performance top-tier transistors without damaging the bottom tier devices and interconnects.As far as the applications of S3D integration are concerned, a lot of focus has been placed on digital circuits. However, the advent of Internet-of-Things applications has motivated the investigation of other circuits as well.As a first step, two S3D design platforms for custom ICs have been developed, one to facilitate the development of the in-house S3D process and the other to enable the exploration of S3D applications. Both contain device models and physical verification scripts. A novel parasitic extraction flow for S3D ICs has been also developed for the study of tier-to-tier parasitic coupling.The potential of S3D RF/AMS circuits has been explored and identified using these design platforms. A frequency-based partition scheme has been proposed, with high frequency blocks placed in the top-tier and low-frequency ones in the bottom. As a proof of concept, a receiver front-end for the ZigBee standard has been designed and a 35% area reduction with no performance trade-offs has been demonstrated.To highlight the prospects of S3D RF/AMS circuits, a study of S3D inductors has been carried out. Planar coils have been identified as the most optimal configuration for S3D inductors and ways to improve their quality factors have been explored. Furthermore, a set of guidelines has been proposed to allow the placement of bottom tier blocks under top-tier inductors towards very compact S3D integration. These guidelines take into consideration the operating frequencies and type of components placed in the bottom tier.Lastly, the prospects of S3D heterogeneous integration for circuit design have been analyzed with the focus lying on a Ge-over-Si approach. Based on the results of this analysis, track-and-hold circuits and digital cells have been identified as potential circuits that could benefit the most from a Ge-over-Si S3D integration scheme, thanks to the low on-resistance of Ge transistors in the triode region. To improve the performance of top-tier Ge transistors, a processing flow that enables the control of their back-gates has been also proposed, which allows controlling the threshold voltage of top-tier transistors a truntime.
|
|
| 5. |
- Halim, Md. Abdul, 1983-
(author)
-
Gut peptides in gastrointestinal motility and mucosal permeability
- 2016
-
Doctoral thesis (other academic/artistic)abstract
- Gut regulatory peptides, such as neuropeptides and incretins, play important roles in hunger, satiety and gastrointestinal motility, and possibly mucosal permeability. Many peptides secreted by myenteric nerves that regulate motor control are also produced in mucosal epithelial cells. Derangements in motility and mucosal permeability occur in many diseases. Current knowledge is fragmentary regarding gut peptide actions and mechanisms in motility and permeability.This thesis aimed to 1) develop probes and methods for gut permeability testing, 2) elucidate the role of neuropeptide S (NPS) in motility and permeability, 3) characterize nitrergic muscle relaxation and 4) characterize mechanisms of glucagon-like peptide 1 (GLP-1) and the drug ROSE-010 (GLP-1 analog) in motility inhibition.A rapid fluorescent permeability test was developed using riboflavin as a transcellular transport probe and the bisboronic acid 4,4'oBBV coupled to the fluorophore HPTS as a sensor for lactulose, a paracellular permeability probe. This yielded a lactulose:riboflavin ratio test.NPS induced muscle relaxation and increased permeability through NO-dependent mechanisms. Organ bath studies revealed that NPS induced NO-dependent muscle relaxation that was tetrodotoxin (TTX) sensitive. In addition to the epithelium, NPS and its receptor NPSR1 localized at myenteric nerves. Circulating NPS was too low to activate NPSR1, indicating NPS uses local autocrine/paracrine mechanisms.Nitrergic signaling inhibition by nitric oxide synthase inhibitor L-NMMA elicited premature duodenojejunal phase III contractions in migrating motility complex (MMC) in humans. L-NMMA shortened MMC cycle length, suppressed phase I and shifted motility towards phase II. Pre-treatment with atropine extended phase II, while ondansetron had no effect. Intestinal contractions were stimulated by L-NMMA, but not TTX. NOS immunoreactivity was detected in the myenteric plexus but not smooth muscle.Food-intake increased motility of human antrum, duodenum and jejunum. GLP-1 and ROSE-010 relaxed bethanechol-induced contractions in muscle strips. Relaxation was blocked by GLP-1 receptor antagonist exendin(9-39) amide, L-NMMA, adenylate cyclase inhibitor 2´5´-dideoxyadenosine or TTX. GLP-1R and GLP-2R were expressed in myenteric neurons, but not muscle.In conclusion, rapid chemistries for permeability were developed while physiological mechanisms of NPS, nitrergic and GLP-1 and ROSE-010 signaling were revealed. In the case of NPS, a tight synchrony between motility and permeability was found.
|
|
| 6. |
- Hellström, Solbritt, 1954-
(author)
-
Att vänja sig till det svenska språket : studier av en individuell skriftspråklig förändring utifrån Olof Bertilssons kyrkobok 1636-1668
- 2008
-
Doctoral thesis (other academic/artistic)abstract
- On the annexation of Jämtland by Sweden in 1645, Danish clergymen were allowed to remain on condition that they officiated in the Swedish language.This dissertation investigates the changes in the written language of one of these Danish clergymen and is based on the parish register kept by the Rev. Olof Bertilsson between 1636 and 1668. The premise for this study is that individual variations and alterations in written language do not occur arbitrarily, but display systematisation and express social consensus. The analytical basis for this approach is derived from Alexander Zheltukhin’s work on orthographic code theory and employs concepts used in sociolinguistics, but also borrows ideas from theories of mixed languages and second-language learning.Between 1636 and 1646 Olof Bertilsson displays a highly stable orthographic code with few variations. Following his attendance at the Riksdag (the Swedish Parlament) in Stockholm in 1647, a distinct change is evident in his orthography. Changes occur quite early in the spelling of some place-names, personal names and important and frequent ecclesiastical terms.A decisive factor in determining when and how change occurs is his access to examples of Swedish texts. In the last decade of his life, an influx of Swedish clergy, increased contacts with Swedish officials and help from young clergymen with a Swedish education, contribute to a predominance of Swedish forms in Olof Bertilsson’s individual orthographic code.
|
|
| 7. |
- Löwenmark, Thyra, 1995-
(author)
-
Gut microbiota in colorectal cancer : The importance of Parvimonas micra
- 2024
-
Doctoral thesis (other academic/artistic)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.
|
|
| 8. |
- Hellström, Charlotta, 1973-
(author)
-
Adolescent Gaming and Gambling in Relation to Negative Social Consequences and Health
- 2015
-
Doctoral thesis (other academic/artistic)abstract
- The aims of the thesis were to study relationships between the effects of online gaming and gambling and negative social consequences and ill health among adolescents and to determine whether gaming and gambling activities occur together.The papers in this thesis used epidemiological methods to obtain self-report information from Swedish adolescents aged 13–18 years. Time spent in online gaming was associated with negative social consequences, and this relationship was explained by online gaming motives. Gaming for fun and social motives was associated with a reduced risk of negative social consequences, whereas gaming to escape problems, gain status, or meet demands from others was associated with an increased risk.Increased online gaming time on weekdays increased the probability of having depressive, musculoskeletal, or psychosomatic symptoms, and was related to online gaming motives. The probability of ill health was low in those who reported gaming for fun or social motives. Adolescents with symptoms of attention deficit hyperactivity disorder (ADHD) were more sensitive to gambling frequency and to developing a gambling problem. However, among those identified as susceptible, adolescents with ADHD were equally affected compared with other susceptible participants in terms of their gambling frequency.Boys had a higher probability than girls of participating in online gambling in association with online gaming. Having at least one parent born outside Scandinavia was associated with a higher probability of online gambling, especially among girls. The effect of alcohol use as a factor contributing to online gambling was greater among boys than among girls.The results of this thesis contribute new knowledge about sex differences in online gaming and gambling behaviours and add to the limited research on online gaming and online gambling behaviours among adolescent girls. Gaming motives may be helpful for identifying online gamers needing support to reduce their unhealthy gaming behaviour. Information about factors related to gaming and gambling problems may be of interest to clinicians in psychiatry, psychology and social work, as well as to policymakers, parents and teachers involved in adolescent health and development. Effect preventive strategies should consider the sex differences in gaming and gambling behaviour in adolescents.
|
|
| 9. |
- Holdstock, Camilla, 1975-
(author)
-
Gastric Bypass in Morbid Obesity : Postoperative Changes in Metabolic, Inflammatory and Gut Regulatory Peptides
- 2008
-
Doctoral thesis (other academic/artistic)abstract
- This thesis examines the effect of surgical weight loss on gut and adipose tissue peptides involved in appetite regulation and energy homeostasis in morbidly obese humans. Roux-en-Y gastric bypass (RYGBP) is the gold standard operation used for effective long-term weight loss and improved health. The exact mechanisms for this outcome are under investigation.We measured ghrelin, a recently discovered hunger hormone, insulin, adiponectin and leptin along with anthropometry measures in 66 morbidly obese patients prior to and 6 and 12 months after RYGBP. Impressive weight loss occurred postoperatively as did alterations in the peptides. Consistent correlations were found between weight, leptin, ghrelin and insulin. The main findings were low ghrelin concentrations in obesity and an increase after RYGBP.We explored inflammatory proteins C-reactive protein (CRP), serum amyloid A and interleukin-6 before and during massive weight loss 6 and 12 months after RYGBP in morbidly obese subjects. The studied proteins declined after surgery and a correlation between CRP and homeostatic model of assessment for insulin resistance, independent of BMI, strongly linked insulin resistance and inflammation. CRP declined most in insulin-sensitive subjects.We examined the excluded stomach mucosa and vagus nerve by measuring gastrin, pepsinogen I (PGI), pancreatic polypeptide (PP) and ghrelin levels during week 1 and year after RYGBP. Ghrelin levels rose with weight loss but declined 24-hours after surgery, like PP, indicating transient vagal nerve damage. Low levels of gastrin and PGI suggest a resting mucosa.We evaluated gut peptides: peptide YY (PYY), glucaogon like peptide-1 (GLP-1), pro-neurotensin (pro-NT) and PP, in lean (young and middle-aged), obese and postoperative RYGBP subjects pre- and postprandially. RYGBP subjects had exaggerated levels of PYY and GLP-1 postprandially and higher basal proNT levels, implying a ‘satiety peptide tone’ that may contribute to the maintenance of weight loss.In summary, RYGBP results in marked weight loss and alterations in gut and adipose tissue peptides involved in appetite regulation and energy homeostasis. These postoperative peptide changes may contribute to impressive weight loss observed after RYGBP.
|
|
| 10. |
- Hou, Shuoben
(author)
-
Silicon Carbide High Temperature Photodetectors and Image Sensor
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- Silicon Carbide (SiC) has the advantages of ultraviolet (UV) sensing and high temperature characteristics because of its wide band gap. Both merits make SiC photodetectors very attractive in astronomy, oil drilling, combustion detection, biology and medical applications. Driven by the objective of probing the high temperature surface of Venus (460 °C), this thesis develops SiC photodetectors and an image sensor for extremely high temperature functions. The devices and circuits are demonstrated through the procedure of layout design, in-house processing and characterizations on two batches.The process flow has been optimized to be suitable for large scale integration (LSI) of SiC bipolar integrated circuits (IC). The improved processing steps are SiC dry etching, ohmic contacts and two-level metal interconnect with chemical-mechanical polishing (CMP). The optimized process flow is applied in the fabrication of discrete devices, a transistor-transistor logic (TTL) process design kit (PDK) and LSI circuits.The photodetectors developed in this thesis, including photodiodes with various mesa areas, a phototransistor and a phototransistor Darlington pair have stable characteristics in a wide temperature range (25 °C ~ 500 °C). The maximum operational temperature of the p-i-n photodiode (550 °C) is the highest recorded temperature accomplished ever by a photodiode. The optical responsivity of the photodetectors covers the spectrum from 220 nm to 380 nm, which is UV-only.The SiC pixel sensor and image sensor developed in this thesis are pioneer works. The pixel sensor overcomes the challenge of monolithic integration of SiC photodiode and transistors by sharing the same epitaxial layers and topside contacts. The pixel sensor is characterized from 25 °C to 500 °C. The whole image sensor circuit has 256 (16 ×16) pixel sensors and one 8-bit counter together with two 4-to-16 decoders for row/column selection. The digital circuits are built by the standard logic gates selected from the TTL PDK. The image sensor has 1959 transistors in total. The function of the image sensor up to 400 °C is verified by taking basic photos of nonuniform UV illumination on the pixel sensor array.This thesis makes an important attempt on the demonstration of SiC opto-electronic on-chip integration. The results lay a foundation on the development of future high temperature high resolution UV image sensors.
|
|
