Intimacy and Desire Through the Lens of an Aro-Ace Woman of Color

Centering asexuality and aromanticism challenges romantic and sexual norms related to intimacy and desire. In my thesis, I use an autoethnographic approach to examine how my understandings of intimacy and desire shifted when I realized I was aromantic and asexual, or aro-ace for short. Drawing from written conversations, journal entries, and memories, I unravel the effects of amatonormativity and compulsory sexuality as normative structures that shaped my perceptions of intimacy and desire. I consider the ways romantic and sexual norms interact with the institutional power of schools, media, and marriage. I also explore the ways asexual and aromantic, feminist, queer, and anarchist communities challenge and resist these norms. I demonstrate the usefulness of asexuality and aromanticism as analytical lenses. I also argue that asexual and aromantic perspectives reveal the extensive, often oppressive, influences of normative structures and institutions on interpersonal relationships

Teaching for students\u27 confident transition from number to algebra

The adoption by all states and territories of the national curriculum by 2013 saw students in schools across the country taught introductory algebraic concepts from Year Five. In the twenty first century the need to be algebraically competent has become a necessity much as computation was in the previous centuries. The Researcher has found from experience that students who have struggled with number and number operations will then most probably make poor progress in their study of algebra. The transition from number to algebra requires a robust understanding of number and number operations This study investigated the balance of instructional strategies employed by teachers to support students transition from number to algebra. This research examined how teachers’ beliefs underpinned the way that they approached the teaching of algebra in Years Seven and Eight in Western Australian schools. This was a mixed methods study. The quantitative data from two questionnaires were used to analyse the teachers professed beliefs and also to contribute to the findings from the qualitative data to form the case study. The qualitative data was gathered from interviews, a focus group meeting, personal reflections by the teachers and video of four lessons taken of each teacher’s practice. The greatest variation in content planning and teaching evident in the teachers’ work was in the transitional material, namely moving students from working with number to algebraic variables. This research makes a contribution to our (and teachers’) knowledge about teaching algebra and it provides insights into understanding good practice in the teaching of beginning algebra

The World City of Gaming

There are many routes to world city status. Most places get there by being financial, trade, or manufacturing hubs, or as is the case with the biggest and most connected world cities, a concentration of all three. Las Vegas took a different path. It achieved world city status via one key sector—gaming

Parent assessment of medical student skills in ambulatory pediatrics

Background: Partnership with parents is a vital part of pediatric medical education, yet few studies have examined parent attitudes towards learners in pediatric settings. Methods: Questionnaires were used to determine parent and student assessment of professional and clinical skills (primary outcome) and parent attitudes towards 3rd year medical students (secondary outcome) at the University of Alberta. Chi Square, Kendall’s Tau and Kappa coefficients were calculated to compare parent and student responses in 8 areas: communication, respect, knowledge, listening, history taking, physical examination, supervision, and overall satisfaction. Results: Overall satisfaction with medical student involvement by parents was high: 56.7% of all parents ranked the encounter as ‘excellent’. Areas of lesser satisfaction included physician supervision of students. Compared to the parent assessment, students tended to underrate many of their skills, including communication, history taking and physical exam. There was no relationship between parent demographics and their attitude to rating any of the students’ skills. Conclusions: Parents were satisfied with medical student involvement in the care of their children. Areas identified for improvement included increased supervision of students in both history taking and physical examination. This is one of the largest studies examining parent attitudes towards pediatric students. The results may enhance undergraduate curriculum development and teaching in pediatric ambulatory clinics and strengthen the ongoing partnership between the community and teaching clinics

Transmembrane protein 106B, a risk factor in frontotemporal lobar degeneration, is a lysosomal type II transmembrane protein and affects autophagy

Frontotemporal lobar degeneration (FTLD) is a fatal neurodegenerative disease with presenile onset. Clinically, it mainly presents with language disorders or personality and behavioural changes whereas pathologically patients Show atrophy of the frontal and temporal lobes of the brain. Like in other neurodegenerative disorders, abnormal protein deposition can be detected in the affected areas of the brain nervous system. However, several different proteins have been identified to be the main component of These inclusions accordingly leading to the differentiation of so far five distinct types of FTLD, namely FTLD-tau, FTLD-TDP (TAR DNA-binding protein 43), FTLD-FUS (Fused in Sarcoma), FTLD-PR (dipeptide repeat protein) and FTLDUPS (ubiquitin-proteasome system). FTLD-TDP comprises 45 % of all FTLD cases and thus represents one of the two main pathological subtypes of FTLD. In the last few years, tremendous progress has been made in the identification of the genetic causes for FTLD-subtypes; among them, the identification of mutations in the progranulin (GRN) gene in FTLD-TDP. Interestingly, even though haploinsufficiency of progranulin was demonstrated to be causative for FTLD-TDP, the same GRN mutation could present with different ages of disease onset in different patients. This argued for additional factors that might modulate disease onset. In order to identify such genetic factors, a genome-wide association study was performed in genetically or pathologically confirmed FTLD-TDP cases. Thereby, twelve single-nucleotide polymorphisms mapped to a 68 kb interval located on chromosome 7p21.3 implicating that this might be a common genetic susceptibility locus for FTLD-TDP. This region only comprised one gene encoding for the transmembrane protein 106B (TMEM106B). Interestingly, the risk allele of TMEM106B was especially associated with FTLD risk in patients carrying a GRN mutation which suggested a functional relationship between those two proteins. However, TMEM106B was an uncharacterized protein of unknown function. Thus, the Motivation of my study was to investigate the biochemical features of TMEM106B, followed by examining the relationship between TMEM106B and GRN and finally, by investigating TMEM106B function. In the first part of this study, Membrane orientation, cellular localization and the glycosylation status of TMEM106B were determined and tools developed. By sequential inactivation of the five predicted N-glycosylation motifs, TMEM106B was demonstrated to be a type II transmembrane protein that is N-glycosylated at the amino acid positions 146 (N1), 152 (N2), 165 (N3), 184 (N4)and 257 (N5). Moreover, only N4 and N5 proved to be complex glycosylated whereas N1, N2 and N3 did not. By immunofluorescence, TMEM106B was determined to be a lysosomal protein. Interestingly, mutants where one of the two complex glycosylation motifs was deleted showed a different intracellular localization whereas deleting the non-complex glycosylation motifs did not change TMEM106B localization. This indicated that complex glycosylation was essential for correct TMEM106B positioning in the cell. In the second part of this study, the influence of TMEM106B expression on GRN levels was analysed in various cell lines. However, neither overexpression nor knockdown of TMEM106B changed intracellular or secreted GRN levels indicating that both proteins probably do not influence each other directly. However, interestingly, bafilomycin A1 (BafA1) treatment which inhibits lysosomal acidification and thus lysosomal function increased both GRN and TMEM106B protein levels suggesting that both proteins might act in a common pathway or might be located in the same compartment. Since treatment with proteasomal inhibitors did not increase TMEM106B levels, this observation further indicated that TMEM106B is mainly degraded by the lysosome. In the third part of this study, the endogenous function of TMEM106B was investigated using siRNA-mediated TMEM106B knockdown in a cell culture model. Thereby, TMEM106B knockdown was shown to change lysosomal positioning as lysosomes clustered tightly at the microtubule-organizing center instead of being distributed throughout the cell. A rescue experiment, where endogenous TMEM106B was knocked down first and then, additionally, either a control vector or exogenous TMEM106B was transfected, proved that lysosomal clustering was the result of TMEM106B loss and not a side effect of siRNA transfection. Furthermore, lysosomal clustering upon TMEM106B knockdown was shown to be dependent on functional retrograde transport and an intact microtubule network. In addition, lysosomes were demonstrated to be still acidic and, in principle, functional upon TMEM106B knockdown. Interestingly, however, lysosomal and autophagosomal protein levels increased significantly upon TMEM106B knockdown, suggesting that the autophagic pathway might be affected by TMEM106B levels. Since GRN had been implicated in playing an important role for lysosomal function and thus in the autophagic pathway, the finding that TMEM106B also has an impact on this pathway might explain why TMEM106B polymorphisms are especially associated with GRN mutation carriers but also why TMEM106B is a general risk factor for FTLD. Changes in the autophagic pathway seem to be common in neurodegenerative disorders as for example in Alzheimer’s, Parkinson’s and Huntington’s disease, the autophagic pathway has been reported to be impaired in the course of disease. My findings would support the notion that also in FTLD, autophagy plays an essential part in disease progression.Frontotemporale lobäre Degeneration (FTLD) ist die zweithäufigste Ursache präseniler Demenz. Klinische Symptome beinhalten vor allem eine Veränderung der Persönlichkeit und des sozialen Verhaltens sowie Sprachstörungen. Auf pathologischer Ebene ist die Krankheit durch eine Atrophie der Frontal- und Temporallappen des Gehirns gekennzeichnet. Außerdem können, ähnlich wie bei anderen neurodegenerativen Erkrankungen, in den betroffenen Bereichen des Nervensystems unnatürliche Proteinablagerungen festgestellt werden. Interessanterweise wurden allerdings mehrere unterschiedliche Proteine als Hauptkomponente dieser Einschlusskörper identifiziert. Dies führte zur Unterscheidung von fünf verschiedenen FTLD-Untergruppen: FTLD-Tau, FTLD-TDP (TAR DNA-bindendes Protein 43), FTLD-FUS (“Fused in Sarcoma”), FTLD-DPR (“dipeptide repeat” Protein) und FTLD-UPS (Ubiquitin-Proteasom System). Mit 45 % stellt FTLD-TDP neben FTLD-Tau die größte pathologische FTLD-Untergruppe dar. In den letzten Jahren wurden große Fortschritte bei der Identifizierung der genetischen Ursachen dieser FTLD-Untergruppen gemacht. So wurden auch Mutationen im Progranulin-Gen (GRN) als Ursache für FTLD-TDP entdeckt, die zu einer Haploinsuffizienz führen. Jedoch ist immer noch unklar, weshalb Patienten mit der gleichen GRN-Mutation in unterschiedlichem Alter erkranken. Es ist allerdings sehr wahrscheinlich, dass dies auf weitere Faktoren, die sich auf das Erkrankungsalter auswirken, zurückzuführen ist. Deshalb wurde eine Genom-weite Assoziationsstudie mit pathologisch verifizierten FTLD-TDP-Fällen durchgeführt, um zusätzliche genetische Faktoren zu ermitteln. Dabei wurde ein 68 kb-großer Bereich auf Chromosom 7p21.3 als gemeinsamer genetischer Suszeptibilitätslokus identifiziert. Diese Region beinhaltet nur ein Gen, welches das bisher nicht charakterisierte Transmembranprotein 106B (TMEM106B) kodiert. Des weiteren zeigte das Risikoallel von TMEM106B (T/T) eine besonders starke Assoziation zum Erkrankungsrisiko bei FTLD-Patienten, die zusätzlich eine GRN-Mutation aufwiesen, was auf einen funktionalen Zusammenhang zwischen diesen beiden Proteinen schließen lässt. Allerdings war zu diesem Zeitpunkt noch nichts über die Eigenschaften des Proteins TMEM106B bekannt. Das Ziel dieser Studie bestand deshalb darin, die Rolle von TMEM106B in FTLDTDP zu untersuchen. Dafür wurden zunächst dessen biochemische Charakteristika untersucht, gefolgt von dem Einfluss von TMEM106B auf GRN und schließlich seine Funktion. Im ersten Teil dieser Arbeit wurden deshalb die Membranorientierung, die zelluläre Lokalisierung und der Glykosylierungsstatus von TMEM106B bestimmt sowie Methoden und Antikörper etabliert. Durch sequenzielle Inhibierung der durch Computeranalysen prognostizierten NGlykosylierungsmotive konnte gezeigt werden, dass es sich bei TMEM106B um ein Typ-II-Transmembranprotein handelt, das an den Aminosäurepositionen 146 (N1), 152 (N2), 165 (N3), 184 (N4) and 257 (N5) N-glycosyliert ist. Dabei sind N4 und N5 komplex glykosyliert, während bei N1, N2 und N3 keine komplexen Glykosylierungen nachgewiesen werden konnten. Durch Immunfluoreszenzversuche wurde ersichtlich, dass es sich bei TMEM106B um ein lysosomales Protein handelt. Interessanterweise änderte sich die zelluläre Lokalisierung von TMEM106BMutanten, bei denen eines oder beide der komplex glykosylierten Arginine deletiert wurden, wohingegen die Mutantion der nicht-komplex glykosylierten Motive keinen Einfluss auf die Lokalisation von TMEM106B ausübte. Dies deutet darauf hin, dass die komplexe Glykosylierung von TMEM106B die Positionierung von TMEM106B in der Zelle maßgeblich beeinflusst. Im zweiten Teil der Studie wurde unter Verwendung verschiedener Zelllinien der Einfluss von TMEM106B auf GRN ermittelt. Allerdings veränderten sich nach Überexpression oder Herabregulation von TMEM106B durch RNA-Interferenz weder die intra- noch die extrazellulären GRN-Proteinmengen, was darauf hindeutet, dass sich TMEM106B und GRN auf Expressionsebene wahrscheinlich nicht gegenseitig beeinflussen. Interessanterweise aber führte die Behandlung mit Bafilomycin A1 (BafA1), einer Chemikalie, die die lysosomale Ansäuerung und damit die lysosomale Funktion inhibiert, sowohl zu einem Anstieg der GRN- als auch der TMEM106BProteinmenge. Dies könnte darauf hinweisen, dass beide Proteine in einem gemeinsamen Signalweg agieren oder sich im gleichen zellulären Kompartiment befinden. Da eine Behandlung mit proteasomalen Inhibitoren die TMEM106B-Mengen nicht erhöhte, deutet diese Beobachtung außerdem darauf hin, dass überschüssiges TMEM106B vor allem über den lysosomalen Abbauweg degradiert wird. Im dritten Teil dieser Arbeit wurde mit Hilfe eines Zellkulturmodells, bei welchem TMEM106B durch RNA-Interferenz herunterreguliert wurde, die endogene Funktion von TMEM106B untersucht. Interessanterweise führte dabei die Herabregulation von TMEM106B zu einer Veränderung der Lokalisierung von Lysosomen in der Zelle: Statt sich über das gesamte Zellvolumen zu verteilen, sammelten sich die Lysosomen hauptsächlich in Form eines engen “Clusters” am Zentrosom. Dieses Phänomen wurde durch ein “Rescue”-Experiment bestätigt. Hierbei konnte gezeigt werden, dass Zellen, in welchen endogenes TMEM106B durch RNA-Interferenz herab reguliert und in welche zusätzlich exogenes TMEM106B transfiziert worden war, eine normale Verteilung der Lysosomen aufwiesen. Außerdem wurde gezeigt, dass das Clustern der Lysosomen nach der Herabregulation von TMEM106B sowohl von einem intakten Mikrotubuli-Netzwerk also auch von einer funktionalen retrograden Transportmaschinerie abhängig ist. Darüber hinaus wurde nachgewiesen, dass nach TMEM106B-Herabregulation Lysosomen nach wie vor einen sauren pH-Wert aufweisen und prinzipiell funktionell sind. Allerdings waren nach TMEM106B-Herabregulation sowohl lysosomale als auch autophagosomale Proteinmengen signifikant erhöht, was darauf hindeutet, dass der lysosomale Abbauweg durch TMEM106B beeinflusst wird. Es wird vermutet, dass GRN eine wichtige Rolle für die Funktion von Lysosomen und damit für Autophagie spielt. Dass TMEM106B wahrscheinlich ebenfalls diesen Abbauweg beeinflusst, könnte erklären, warum TMEM106B-Polymorphismen in besonderer Weise mit GRN-Mutationsträgern assoziiert sind und warum TMEM106B einen allgemeinen Risikofaktor für FTLD darstellt. Veränderungen im lysosomalen Abbauweg sind ein häufiges Erscheinungsbild in neurodegenerativen Erkrankungen. So konnte beispielsweise ab einem bestimmten Zeitpunkt des Krankheitsverlaufs sowohl bei Alzheimer- als auch bei Parkinson- oder Huntington-Erkrankten eine Hemmung des Autophagie-Signalwegs festgestellt werden. Die Ergebnisse dieser Arbeit deuten darauf hin, dass auch bei der FTLD-TDP Autophagie eine wesentliche Rolle für das Fortschreiten der Krankheit spielen könnte

How To Introduce On-Line Agricultural Products Navigation System On Google Earth Success

In the agriculture industry many brokers exploit the benefits between farmers and customers and decrease farmers’ income. As technology has developed, the internet has become the best advertising medium for many industries. In light of this, this study based on Google Earth, has designed an on-line Agricultural Products Navigation System operated by mobile devices which can easily exclude brokers, and build the bridge between farmers and customers in order to increase farmers income and customer benefits. Moreover, based on the IS success model of DeLone and McLean, by using qualitative methodology we expect this model will be able to provide system developers with the knowledge to improve the success of their systems

Psychiatric and psychosocial outcome of orthotopic liver transplantation

Background. The study aimed to explore the prevalence of psychiatric disorders among orthotopic liver transplantation (OLT) recipients, and to investigate how psychiatric morbidity was linked to health-related quality of life (HRQOL). Methods: We recruited 75 patients who had undergone OLT a median of 3.8 years previously (range = 5-129 months). Psychiatric morbidity was assessed using the Structural Clinical Interview for the IDSM-III-R. Psychometric observer-rating and self-rating scales were administered to evaluate cognitive functioning (SKT), depressive symptomatology (HAMD(17)), Posttraumatic stress symptoms (PTSS-10), social support (SSS), and HRQOL (SF-36 Health Status Questionnaire). Treatment characteristics were obtained from medical records. Results: 22.7% (n = 17) of our sample had a current or probable psychiatric diagnosis according to DSM-III-R: 2.7% full posttraumatic stress disorder (PTSD) (n = 2), 2.7% major depressive disorder (MDD) comorbid to full PTSD (n = 2), 1.3% MDD comorbid to partial PTSD (n = 1), and 16% partial PTSD (n = 12). Patients with PTSD symptoms demonstrated lower cognitive performance, higher severity of depressive symptoms and more unfavorable perception of social support. OLT-related PTSD symptomatology was associated with maximal decrements in HRQOL. The duration of intensive care treatment, the number of medical complications, and the occurrence of acute rejection were positively correlated with the risk of PTSD symptoms subsequent to OLT. Conclusion: OLT-related PTSD symptomatology impairing HRQOL is a complication for a subgroup of OLT recipients. Health-care providers should be aware of the possible presence of PTSD in OLT survivors. Copyright (C) 2002 S. KargerAG, Basel

Developing Non‑Residential Building Stock Archetypes For LCI—A German Case Study Of Office And Administration Buildings

To accomplish the national and international climate goals, building renovation and optimisation of their energy and resource efficiency are essential. Thus, reliable information on the building stock (BS) is necessary. Most previous building typologies are focussing on residential buildings and the operational phase. This paper shows the development of a methodology for generating non-residential building (NRB) typologies for life cycle inventory analysis (LCI) of building constructions. Hereby, archetypes of office, administration and department (OAD) buildings are developed, exemplarily for the German NRB stock

Complex-valued Adaptive System Identification via Low-Rank Tensor Decomposition

Machine learning (ML) and tensor-based methods have been of significant interest for the scientific community for the last few decades. In a previous work we presented a novel tensor-based system identification framework to ease the computational burden of tensor-only architectures while still being able to achieve exceptionally good performance. However, the derived approach only allows to process real-valued problems and is therefore not directly applicable on a wide range of signal processing and communications problems, which often deal with complex-valued systems. In this work we therefore derive two new architectures to allow the processing of complex-valued signals, and show that these extensions are able to surpass the trivial, complex-valued extension of the original architecture in terms of performance, while only requiring a slight overhead in computational resources to allow for complex-valued operations