Internet Protocol multimedia subsystem (IMS) is an architecture for services such as voice over Internet Protocol (VoIP) in IP based communication systems. IMS is standardized by the 3GPP standardization forum, and was first released in 2002. Since then IMS has not had the wide adoption by operators as first anticipated. As 3G already supported voice and video, the operators could not justify the expense of IMS. The current emergence of the fourth generation mobile communication system named Long Term Evolution (LTE) has, however, increased the need for knowledge of IMS and of creating services for it. LTE networks are IP only networks that provide low latency. In order to use LTE for making phone calls, VoIP technologies are needed. IMS is the architecture intended to be used for Voice over LTE (VoLTE). The need for tools for education within IMS was seen in 2006 by Enea Experts in Linköping, Sweden. The author of this thesis designed an IMS for educational purposes, but the project was never fully completed. This thesis will reexamine the design decisions previously made by the author. The requirements stated by the customer remain: that an IMS with basic signaling and logging should be easy to install, maintain, and evolve at a low cost. A literature study of IMS and VoLTE is presented to contribute with knowledge in these areas. The previous design and implementation made by the author is presented and analyzed. The third-party software that the previous implementation was based on is reexamined. Existing open source components are analyzed in order to identify how they can be used to solve the problem and to identify what remains to be developed in order to fulfill the requirements. New design suggestions, presented in today´s context, are proposed and verified using analytical reasoning and experiments. The outcome of the final work is new verified design decisions for the customer to use when implementing a new IMS for educational purposes. The thesis should also provide useful insights which instructors and students can use to teach and learn more about IMS. / Internet Protocol multimedia subsystem (IMS) är en arkitektur för tjänster, som IP-telefoni (Voice over Internet Protocol, VoIP), i IP baserade kommunikationssystem. IMS standardi¬seras av standardiseringsforumet 3GPP och första utgåvan släpptes år 2002. IMS fick dock inte det breda genomslag bland operatörer som förväntats. Eftersom 3G redan hade stöd för tal och video kunde operatörerna inte se skäl till ytterligare utgifter för IMS. Den fjärde generationens mobila kommunikationssystem, Long Term Evolution (LTE) är helt IP-baserat och ger lägre fördröjningar i nätet. För att kunna ringa telefonsamtal via LTE krävs VoIP-teknik. IMS är en arkitektur avsedd för att användas för Voice over LTE (VoLTE). Den nuvarande utvecklingen av LTE har därför ökat behovet av kunskap om IMS och av utveckling av IMS-tjänster. Enea Experts i Linköping insåg behovet av verktyg för utbildning inom IMS år 2006. Författaren av det här examensarbetet designade därför ett IMS för utbildningssyfte. Projektet slutfördes dock aldrig. Syftet med examensarbetet är att ompröva de tidigare designbesluten. Kundens krav kvarstår: att ett IMS med grundläggande signalering och loggning bör vara enkelt att installera, enkelt att underhålla och möjligt att utveckla till en låg kostnad. Arbetet innehåller en litteraturstudie av IMS och VoLTE för att ge en inblick i dessa områden. Den tidigare designen och implementationen presenteras och analyseras. Tredjeparts mjukvara, som den tidigare implementationen baserades på, omprövas. Befintliga programvaror med öppen källkod analyseras i syfte att kartlägga hur de kan användas för att lösa uppgiften, samt att identifiera vad som återstår att utveckla för att uppfylla kraven. Nya beslut kring design presenteras och besluten verifieras med experiment och analytiskt resonemang. Resultatet av detta examensarbete innefattar nya verifierade beslut kring design som kunden kan använda vid utveckling av ett nytt IMS för utbildningssyfte. Arbetet erbjuder också värdefulla insikter som instruktörer och elever kan använda för att undervisa samt för att lära sig mer om IMS.

The environmental politics in Sweden are portrayed in the Swedish environmental discourse to be both ambiguous and a pioneer state internationally. Sweden has an established aim to solve the sixteen identified grand environmental issues in Sweden until the next generation (2025). For example, Tracy Skillington, mentioned in the field of research, argues of an absence of climate justice for future generations. This paper will therefore examine the way Sweden relates to future generations in the Swedish environmental politics through a lens of climate justice. I will approach this subject through a discourse analysis of three Swedish propositions which can be used to understand the background meaning of legislations, and therefore also can be regarded as authoritarian in the Swedish environmental discourse. The analysis will be based on the logic of signs in the discourse and structured according to the analysis tool, problem – reason – solution. The main problem in Swedish environmental discourse can relate to the ambiguous formulation of the generational aim. Sweden expresses, in their environmental discourse (proposition 1997/98:145), a confidence to solve the environmental issues until the next generation, meanwhile maintaining other political priorities such as economic growth. Sweden describes an overall change of society to sustainable development. In the Swedish environmental discourse terms such as justice and crisis are excluded, which forms and characterizes the Swedish discourse. The problems in Swedish environmental discourse are being visible though the environmental aims seem unreachable on the set timeline. There are three identified reasons in the Swedish environmental discourse, nature as an economic human resource, the environmental quality issues in Sweden depends on other states environmental actions due to the transnational problem and the initial environmental goals are portrayed as impossible to fulfill. Sweden legitimize their environmental discourse through the solutions found in the three propositions. The choice to use generation to describe the Swedish aim, could be understood to unify the Swedish environmental discourse. In the propositions, a change in the meaning of the generational aim will be shown, which makes a prominent difference for future generations. In proposition 2016/17:146, a transition to climate is made which means less focus on future generation in the Swedish discourse. The next generation has a prominent role in the environmental discourse of Sweden, but it turns out unclear what exact meaning the generation of today include in the term next generation. The promises made in the first proposition, are emptied of the initial meaning, why it is questionable if climate justice towards the next generation can be reached in the Swedish environmental discourse.

Rare diseases (RD) are a heterogeneous group of diseases that affect about 5% of the world population. RDs represent more than 7.000 different phenotypes and many of them are genetically determined. RDs provide unique biological models for understanding the basic principles of molecular and cellular organization and function of human tissues and organs. Results of studies focused at pathogenesis of RDs are often used to diagnose and treat the affected patients. Significant progress in molecular genetic techniques, specifically the use of the next generation sequencing (NGS) in clinical practice, substantially facilitated and improved efficiency of RD laboratory diagnostics. Moreover, these novel testing algorithms identified the previously unknown molecular causes of many RDs. This thesis demonstrates the utility of NGS techniques and bioinformatics processing of obtained data in studies aimed at understanding molecular basis of selected RDs. These methods led to identification and characterization of causative pathogenic variants in the NDUFAF6 and PLD1 genes among patients affected by the Acadian variant of Fanconi disease and patients with a rare congenital heart defect, respectively. This approach was further used to analyze exomes of a large cohort of patients with different types of...

Advances in DNA sequencing revolutionized the field of genomics over the last 5 years. New sequencing instruments make it possible to rapidly generate large amounts of sequence data at substantially lower cost. These high-throughput sequencing technologies (e.g. Roche 454 FLX, Life Technology SOLiD, Dover Polonator, Helicos HeliScope and Illumina Genome Analyzer) make whole genome sequencing and resequencing, transcript sequencing as well as quantification of gene expression, DNA-protein interactions and DNA methylation feasible at an unanticipated scale. In the field of evolutionary genomics, high-throughput sequencing permitted studies of whole genomes from ancient specimens of different hominin groups. Further, it allowed large-scale population genetics studies of present-day humans as well as different types of sequence-based comparative genomics studies in primates. Such comparisons of humans with closely related apes and hominins are important not only to better understand human origins and the biological background of what sets humans apart from other organisms, but also for understanding the molecular basis for diseases and disorders, particularly those that affect uniquely human traits, such as speech disorders, autism or schizophrenia. However, while the cost and time required to create comparative data sets have been greatly reduced, the error profiles and limitations of the new platforms differ significantly from those of previous approaches. This requires a specific experimental design in order to circumvent these issues, or to handle them during data analysis. During the course of my PhD, I analyzed and improved current protocols and algorithms for next generation sequencing data, taking into account the specific characteristics of these new sequencing technologies. The presented approaches and algorithms were applied in different projects and are widely used within the department of Evolutionary Genetics at the Max Planck Institute of Evolutionary Anthropology. In this thesis, I will present selected analyses from the whole genome shotgun sequencing of two ancient hominins and the quantification of gene expression from short-sequence tags in five tissues from three primates.

>Magister Scientiae - MSc / Aims DNA metabarcoding has recently emerged as a valuable supplementary tool to ensure food authenticity within the global food market. However, it is widely known that highly processed food samples are one of DNA metabarcoding’s greatest shortfalls due to high DNA degradation, presence of PCR inhibitors and the incomplete removal of several undesirable compounds (such as polysaccharides) that makes the amplification of desired DNA challenging. This project has two main aims, the first of which was to determine and develop a cost and time effective DNA metabarcoding system that could successfully describe to species level the ingredient composition of highly processed vegetarian food products. The DNA metabarcoding system was thoroughly evaluated and tested by combining well-researched primers with varying concentrations into a multiplex reaction. The combination of plant and animal primers selected that yielded the best results were used to determine the species composition in the samples. The second aim is to determine the possible presence of meat contaminants within the highly processed vegetarian food samples. Numerous studies have shown that food adulteration is a wide-spread phenomenon throughout the world due to the economic gains it can provide. Animal primers were introduced into the multiplex reaction to aid in the identification of any meat products that could have been inserted into the vegetarian products to lower the overall cost to company. Methodology Thirty-two highly processed vegetarian food samples were collected in the Cape Town area from local and franchised supermarkets. DNA was extracted using the Chloroform/Isoamyl alcohol method best suited for plant-based samples followed by amplification of the following mini-barcoding regions: the mitochondrial 16S ribosomal rRNA, cytochrome B, tRNALeu – trnL – UAA intron and the ribosomal internal transcribed spacer region – ITS2 for plant and fungi identification. The PCR products were purified using the Qiaquick kit and library preparation and building was conducted using the TruSeq DNA PCR-free Library kit. Final purification was completed using AMPure XP kit and the pooled libraries were sequenced on an Illumina Miseq using 300bp paired-end run. Statistical and bioinformatic analysis on the NGS raw sequence reads was performed in R version 3.6.3. Results The results of the data analysis showed that the cytochrome B primer couldn’t detect any animal DNA in the vegetarian samples, however animal-derived sequences were detected in the positives present, validating the efficacy of the multiplex reaction. Mitochondrial 16S ribosomal rRNA was only able to detect plant-based DNA due to the structural homology between chloroplast and mitochondrial DNA. The fungal ribosomal internal transcribed spacer region – ITS2 detected sequences deriving from “Viridiplantae”. This result could have been due to the fungal and plant ribosomal internal transcribed spacer region – ITS2 sharing a reverse primer during amplification. The trnL region was able to detect the presence of undeclared coriander, mustard and wheat in 8 (29%), 6 (21%) and 5 (18%) samples respectively. Additionally, trnL was able to detect the presence of tobacco in 11 (35%) samples. This could have been due to cross-contamination between samples being co-extracted and amplified at the same time for separate studies. The PITS2 region was able to detect the presence of undeclared barley, mustard and wheat in 8 (25%), 4 (14%) and 4 (14%) samples respectively. Our results show the possibility of DNA metabarcoding for the authentication of a wide range of species present in highly processed vegetarian samples using a single assay. However, further optimization of the technique for the identification of both plant and animal species within vegetarian samples needs to be performed before the wide-spread implementation of this technology would be both feasible and viable. Eliminating primer biases, decreasing the risk of homology between different primers in the same assay as well as preventing the amplification of sequencing of undesirable DNA need to be further explored and ultimately mitigated before DNA metabarcoding can be widely seen as an effective and cost-effective method for authentication and food control.

Implementation of the Next Generation Science Standards requires developing elementary teacher content and pedagogical content knowledge of science and engineering concepts. Teacher preparation for this undertaking appears inadequate with little known about how in-service Mid-Atlantic urban elementary science teachers approach this task. The purpose of this basic qualitative interview study was to explore the research questions related to perceived learning needs of 8 elementary science teachers and 5 of their administrators serving as instructional leaders. Strategies needed for professional growth to support learning and barriers that hamper it at both building and district levels were included. These questions were considered through the lens of Schön's reflective learning and Weick's sensemaking theories. Analysis with provisional and open coding strategies identified informal and formal supports and barriers to teachers' learning. Results indicated that informal supports, primarily internet usage, emerged as most valuable to the teachers' learning. Formal structures, including professional learning communities and grade level meetings, arose as both supportive and restrictive at the building and district levels. Existing formal supports emerged as the least useful because of the dominance of other priorities competing for time and resources. Addressing weaknesses within formal supports through more effective planning in professional development can promote positive change. Improvement to professional development approaches using the internet and increased hands on activities can be integrated into formal supports. Explicit attention to these strategies can strengthen teacher effectiveness bringing positive social change.

Indiana University-Purdue University Indianapolis (IUPUI) / Disturbances in membrane composition and protein folding in the endoplasmic reticulum (ER) trigger the unfolded protein response (UPR). Three UPR sensory proteins, PERK (PEK/EIF2AK3), IRE1, and ATF6 are each activated by ER stress. PERK phosphorylation of the alpha subunit of eIF2 represses global protein synthesis, lowering influx of nascent polypeptides into the stressed ER, coincident with the preferential translation of ATF4 (CREB2). Results from cultured cells demonstrate that ATF4 induces transcriptional expression of genes directed by the PERK arm of the UPR, including genes involved in amino acid metabolism, resistance to oxidative stress, and the proapoptotic transcription factor CHOP (GADD153/DDIT3). In this study, we characterized two ATF4 knockout mouse models and show in liver exposed to ER stress that ATF4 is not required for CHOP expression, but rather ATF6 is a primary inducer. RNA-sequence analysis indicated that ATF4 was responsible for a small portion of the PERK-dependent genes in the UPR. This smaller than expected subset of gene expression lends itself to the relevance of UPR crosstalk, with ATF6, XBP1, and CHOP being capable of upregulating UPR genes in the absence of ATF4. RNA-sequence analysis also revealed a requirement for expression of ATF4 for expression of a comparable number of genes basally, including those involved in oxidative stress response and cholesterol metabolism. Consistent with this pattern of gene expression, loss of ATF4 in our mouse model resulted in enhanced oxidative damage and increased free cholesterol in liver under stress accompanied by lowered cholesterol in sera. Taken together, this study highlights both an expansion of the role of ATF4 in transcriptional regulation of genes involved in metabolism in the basal state and a more specialized role during ER stress. These findings are important for understanding the variances of the UPR signaling between cell culture and in vivo and for a greater understanding of all the roles ATF4 plays within the cell.

La leucémie myéloïde aigüe (LMA) est la forme de leucémie la plus fréquente chez l’adulte au Canada. Bien que de nombreux réarrangements chromosomiques récurrents aient été identifiés chez les patients LMA, près de la moitié des cas présentent un caryotype normal (LMA-CN). L’étude de la LMA-CN in vitro est rendue difficile par le fait que la survie des cellules primaires de patients est défectueuse sur le long terme et que les lignées cellulaires leucémiques ont un caryotype hautement anormal. En 2009, Munker et son équipe ont établi une nouvelle lignée cellulaire, CG-SH, ayant la particularité d’avoir un caryotype normal. L’objectif principal de ce projet d’étude est de caractériser plus en détail ce nouveau modèle d’étude. Nous avons identifié l’ensemble des variants génétiques présents dans CG-SH grâce au séquençage du génome entier. Les variants susceptibles de participer à la leucémogénèse ont été isolés, tels que des insertions détectées dans EZH2 et GATA2, et de nombreux variants faux-sens détectés dans des gènes pertinents pour la LMA. Nous avons montré que les cellules CG-SH sont sensibles à l’effet prolifératif d’une combinaison de cytokines, qui agissent sur le comportement des cellules en modifiant l’expression des gènes associés à la régulation de la prolifération, de l’apoptose et de la différentiation. De plus, les cytokines diminuent le taux de nécrose des cellules en culture sur le court terme. La présente étude a permis d’approfondir notre connaissance sur les caractéristiques moléculaires de la lignée cellulaire CG-SH, un nouveau modèle d’étude in vitro de la LMA-CN. / Acute myeloid leukemia (AML) is the most frequent form of leukemia in the adult population in Canada. Although many recurrent chromosomal rearrangements have been identified in AML, almost half of all adult patients will present with a normal karyotype (NK-AML). The in vitro study of NK-AML is difficult because the long-term survival of primary patient samples is deficient and AML cell lines have a highly abnormal karyotype. In 2009, Munker and collegues established a new cell line, CG-SH, with the advantage of having a normal karyotype. The main goal of this research project is to further characterize this new model system. We identified all the genetic variants present in the CG-SH cells using whole genome sequencing. We also isolated the variants that are susceptible to participate to leukemogenesis, including the insertions detected in EZH2 and GATA2, and several missense mutations occurring in relevant genes for AML. We found that a combination of cytokines promotes the proliferation of CG-SH cells, and that cytokines act on the cells behavior through expression changes of the genes involved in the regulation of proliferation, apoptosis and differentiation. Moreover, cytokines trigger a decrease of the necrotic rate of CG-SH on the short-term. The current study allowed us to better appreciate molecular characteristics of the CG-SH cell line, a new model to study NK-AML in vitro.

Background: Rare genetic mutations cause familial early-onset stroke disorders, known as “Mendelian strokes”. The broader relevance of rare mutations in unrelated young stroke patients is uncertain. We hypothesize that rare mutations in known and novel genes are important risk factors for stroke. Methods: Exome sequencing was used to characterize rare disruptive protein-altering mutations in 185 young cases and 185 matched controls from INTERSTROKE, a large and globally representative stroke study. The major objectives were: 1) to precisely define the role of known Mendelian stroke genes and 2) to discover novel gene and pathway associations. Results: A focused assessment of known Mendelian stroke genes revealed a significant contribution from NOTCH3, the causal gene for Cerebral Autosomal Dominant Arteriopathies with Subcortical Infarcts and Leucoencephalopathies (CADASIL). CADASIL mutations were identified in six cases and no controls (P=0.03). The clinical presentation of CADASIL mutation carriers deviated from known symptomatology, consisting of small-vessel ischemic strokes (SVIS) accompanied by secondary features including migraine and depression. A novel role for non-CADASIL NOTCH3 mutations in ICH was also elucidated (OR=2.86; 95% CI, 1.13 to 7.93, P=0.02). Such mutations were present in 22% of ICH cases and 8% of matching controls. An agnostic evaluation of all genes did not reveal any genome-wide significant associations. However, NOTCH3 was among the top ICH genes out of 13,706 tested, and many others were also biologically relevant, notably, AARS2 and NBEAL2. A protective association was identified for the renin angiotensin system (P=8.1x10-4), whereas type II diabetes mellitus was associated with increased risk (P=1.9x10-2). Conclusion: Rare mutations influence risk of early-onset stroke. CADASIL mutations play an important role in unrelated stroke patients. Beyond CADASIL, a novel role was uncovered for other NOTCH3 mutations as common and significant risk factors for ICH. Novel biologically relevant genes and pathways may also affect stroke susceptibility. / Thesis / Master of Science in Medical Sciences (MSMS)

D. Tech. (Department of Process Control and Computer Systems, Faculty of Engineering and Technology), Vaal University of Technology. / In this research study, a scheme to minimise interference in converged mobile cellular networks (MCNs) and wireless sensor networks (WSNs) was designed and implemented. The focus was the mitigation of interference that arises when proximity service (ProSe)-enabled sensors engage in a device-to device (D2D) communication to alert smartphone users upon the detection of explosives at highly crowded areas like shopping malls. D2D is a technology that academia and industry experts believe will play a prominent role in the implementation of the next generation of mobile networks, specifically, the fifth generation (5G). However, the full roll out of D2D is being impeded by the interference that the technology introduces to the cellular network. D2D devices cause a significant amount of interference to the primary cellular network especially when radio resources are shared. In the downlink phase, primary user equipment is likely to suffer from interference emanating from a D2D transmitter. On the other hand, the immobile base station is affected by interference caused by the D2D transmitter in the uplink phase. This type of interference can be avoided or reduced if radio resources are allocated intelligently under strict coordination of the base station. An NP-hard optimisation problem was formulated and finding a solution to this problem in 1 ms is not possible. 5G has a frame structure duration of 10 ms with 10 subframes of 1 ms each. Heuristic algorithms were then developed to mitigate the interference affecting the primary network that could carry out resource allocation within the fast-scheduling period of 1 ms. Smartphones have progressed into devices capable of generating massive volumes of data. The challenge is that battery technology is not keeping up with the pace of smartphone technology, so any additional feature that designers want to add, is met with a lot of contempt from customers who are concerned about their smartphone batteries depleting rapidly. In this context, the strategy must be energy-efficient for smartphone users to embrace it. A system level simulator was developed using MATLAB to evaluate the efficacy of the proposed design. Extensive simulation results showed that ProSe-enabled sensors can safely be integrated into cellular networks participating in D2D communication with smart phones, without introducing significant harm to the primary cellular network. The results showed that after implementing the proposed strategy, overall user throughput decreased by 3.63 %. In cellular networks, this is a modest figure since a reduction of up to 5% is acceptable to both users and network providers. The figure generally capped in service level agreements signed between network providers and users is 5%. The proposed technique also resulted in a 0 % reduction in SINR of CUEs in a cellular network, according to the findings. In terms of D2D link throughput for different D2D transmit levels, the method proposed in this research work surpassed a similar scheme proposed in literature by an average of 18.3%.