Haemonchus contortus is a parasitic nematode that is controlled by several nematocides which target ion channels. We have identified two H. contortus ion channel genes, Hcounc- 49B and C that encode two GABA-gated chloride channel subunits. Electrophysiological analysis shows that the Hco-UNC-49B subunit forms a functional homomeric channel in Xenopus laevis oocytes that produces a robust response to GABA and is highly sensitive to picrotoxin. In contrast, Hco-UNC-49C alone does not respond to GABA but can assemble with Hco-UNC-49B to form a heteromeric channel with an increased sensitivity to GABA and a lower sensitivity to picrotoxin. To investigate the subunit requirements for high agonist sensitivity, we generated cross-assembled channels by co-expressing the H. contortus subunits with UNC-49 subunits from the nematode Caenorhabditis elegans (Cel-UNC-49). Co-expressing the Cel-UNC-49B with Hco- UNC-49C produced a heteromeric channel with a low sensitivity to GABA. In contrast, co-expressing Hco-UNC-49B with Cel-UNC-49C produced a heteromeric channel that was highly sensitive to GABA. These results suggest that the Hco-UNC-49B subunit is the key determinant for the high agonist sensitivity of heteromeric channels.

Das rasant voranschreitende Wirtschaftswachstum Chiles in Zusammenhang mit einer sehr liberalen Wirtschafts- und Stadtentwicklungspolitik ist Ursache für eine tiefgreifende gesellschaftliche und urbane Umstrukturierung der chilenischen Hauptstadt. Die Nutznießer dieser Entwicklung sind in jüngster Zeit besonders auch Angehörige der unteren Mittelschicht, für die eigens preiswerte bewachte und umzäunte Wohnprojekte ins Leben gerufen werden. Schwerpunkt der vorliegenden Untersuchung war es, diese sich neu formierende Gesellschaftsschicht genauer zu betrachten und zu untersuchen, mit welchen Anpassungshandlungen diese auf die veränderten Lebens- und Wohnbedingungen innerhalb dieser sogenannten condominios reagieren. Das Konzept condominio scheint zunächst die ideale Antwort auf zahlreiche Handlungsprobleme zu sein; das Wohnen im abgeschlossenen Wohnviertel gibt das Gefühl der Sicherheit und Kontrolle der unmittelbaren Umgebung und ist durch seine Exklusivität gleichzeitig ein willkommenes Statussymbol. Erst auf den zweiten Blick wird sichtbar, was das condominio nicht leisten kann und welche weiteren Probleme mit dem Wohnen im abgeschlossenen Viertel entstehen. Im Laufe der Analyse wurde jedoch die trotz aller Problemlagen essentielle Bedeutung des condominios für ihre Bewohner erkennbar. Die neue Wohnform der unteren Mittelschicht ist nicht nur ein Produkt der sich in ihren Potentialen, Ansprüchen und Werten verändernden Anwohner. Sie wird auch aktiv für die Konstruktion von sozialen Identitäten genutzt und ist damit also zentrales Element in der Formation und Identifikation dieser Gesellschafts-schicht.

Vår uppsats kommer beröra Zombies på film och fokusera på filmen Land of the Dead. Många människor upplever zombies som inget mer än monster, en fara för karaktärerna att klara sig undan. Vi vill uppmärksamma att all populärkultur i varierande utsträckning gestaltar verklighet, och analysera hur Zombies används för att gestalta aspekter av vårt samhälle.

A novel CMOS inverter has been proposed. We utilize gated N-I-P transistor to replace the conventional PMOSFET for solving the problem of width compensation. Also, we carefully investigate and analyze the non-conventional CMOS characteristics with NTFET and/or UTB JL MOSFET as driver and gated N-I-P transistor as a load. According to the results, our proposed novel CMOS inverter has correct logic behavior and its delay time is reduced about 87.2 % when compared with the CTFET. Also, our proposed CMOS still can get a 43.2 % reduction in delay time when compared with JL CMOS. In addition, because of the N-type output drain node and the SOI structure, our proposed CMOS does not need any physical isolation technique, thereby improving the packing density. Our proposed CMOS indeed obtain a 54.1 % reduction of the total area compared with the conventional CMOS. Our proposed CMOS also can achieve a 40.1 % reduction in the total area when compared with the SOI-based CMOS. More importantly, due to the reduced process steps, the cost reduction can be achieved. We therefore believe that a high packing density novel CMOS inverter with reduced process steps can become one of the contenders for future CMOS scaling.

Since the fall of communism, some crucial political, economic and social changes have been taking place in the former communist societies. The objective of the thesis is to examine the processes of residential differentiation taking place in the urban landscape of the Polish city of Gdańsk after the introduction of the capitalist system. The focus is on different forms of residential differentiation and the social, economic and historical factors behind these forms. The empirical material that forms the basis of the thesis consists of interviews, newspaper articles, a questionnaire, official (national and local) reports and documents. Study I examines the way in which different social, economic, historical and physical conditions coincide in the formation of space and the processes of decline in the period of transformation in Poland. The focus lies on a specific residential area in the center of Gdańsk and the lack of improvements in this particular area, which would stop its successive decline. Study II explains the emergence of gated communities in the post-communist urban context and discusses the reasons for their increasing numbers and popularity. The main argument is that the popularity of gated communities is tightly intertwined with the communist past, emerging in reaction to the housing conditions that prevailed under communism. Study III investigates how social class markers are constructed in the discourse on gated communities in post-socialist Poland. The “new” capitalistic system, with its inherent social divisions, is described in the discourse as creating demands for “new” forms of housing, where gates function as separators, protectors and class identifiers. Study IV concentrates on the support for the formation of gated communities in the legal and regulatory framework in Poland since 1989. The paper asserts that the outcome of liberal politics and legal regulation in the country is the neglect of spatial planning and imprecise urban policies. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Submitted.</p>

Understanding the impact of changes made daily by development teams working on large-scale software products is a challenge faced by many organizations nowadays. Development efficiency can be severely affected by the increase in fragility that can creep in as products evolve and become more complex. Processes, such as gated check-in mechanisms, can be put in place to detect problematic changes before submission, but are usually limited in effectiveness due to their reliance on statically-defined sets of tests. Traditional change-impact analysis techniques can be combined with information gathered at run-time in order to create a system that can select tests for change verification. This report provides the high-level architecture of a system, named Ratchet, that combines static analysis of C++ programs, enabled by the reuse of the Clang compiler frontend, and code-coverage information gathered from automated test runs, in order to automatically select and schedule tests that exercise functions and methods possibly affected by the change. Prototype implementations of the static-analysis components of the system are provided, along with a basic evaluation of their capabilities through synthetic examples. / text

No description available.

The Arabidopsis thaliana genome encodes twenty putative cyclic nucleotide-gated channel (CNGC) genes. Studies on A. thaliana CNGCs so far have revealed their ability to selectively transport cations that play a role in various stress responses and development, however, the regulation of plant CNGCs is not yet fully understood. Thus, in this study I have attempted to analyze the structure-function relationship of AtCNGCs, mainly by using suppressor mutants of the rare gain-of function mutant, cpr22. The A. thaliana mutant cpr22 resulted from an approximately 3kb deletion that fused the 5’ half and the 3’ half of two CNGC-encoding genes, AtCNGC11 and AtCNGC12, respectively. The expression of this chimeric CNGC, the AtCNGC11/12 gene confers easily detectable characteristics such as stunted morphology with curly leaves and hypersensitive response-like spontaneous lesion formation. Through a suppressor screen, twenty nine new alleles were identified in AtCNGC11/12. Since the cytosolic C-terminal region contains important regulatory domains, such as a cyclic-nucleotide binding domain, eleven cytosolic C-terminal mutants, S17, S35, S81, S83, S84, S100, S135, S136, S137, S140 and S144, were analyzed. A detailed analysis of two mutants, S100 (AtCNGC11/12:G459R) and S137 (AtCNGC11/12:R381H), suggested that G459 and R381 are important for basic channel function rather than channel regulation. Site-directed mutagenesis and fast protein liquid chromatography (FPLC) showed that these two amino acids influence both intra- and inter-subunit interactions that are involved in stabilizing the tertiary structure of the channel. In addition, calmodulin binding domain(s) (CaMBD) and cyclic nucleotide binding domain(s) (CNBD) of some of AtCNGCs were studied using computational modeling and biophysical analyses. The data indicated that AtCNGC12 has two CaMBDs in both N- and C- cytosolic termini, whereas AtCNGC11 has only one CaMBD located in the N-terminal region of the channel. In addition, a thermal shift assay suggested that AtCNGC12 has higher affinity to bind cAMP over cGMP. Taken together, the current study contributes to identify key residues for channel function and provides new insights into CaMBD and CNBD in plant CNGCs.

Inflammatory bowel disease (IBD) alters neuronal regulation of the gastrointestinal (GI) tract. The superior mesenteric ganglia (SMG) contain sympathetic neurons that modulate GI functions such, as motility and blood flow. IBD reduces the release of noradrenaline, a sympathetic neurotransmitter. We hypothesized that the reduction in NA release is due to inhibition of voltage-gated calcium current (ICa), as calcium influx is a regulator of neurotransmitter release. We also hypothesized that tumor necrosis factor α (TNFα), a proinflammatory cytokine elevated during IBD, can also inhibit the ICa of SMG neurons. Therefore, we compared ICa amplitude in neurons from normal mice and mice with dextran sulphate sodium (DSS; 5% w/v)-induced colitis. Neurons dissociated from the SMG were cultured overnight and changes to ICa were investigated using electrophysiological, Ca2+ imaging, PCR and neurotransmitter release techniques. Colitis significantly reduced ICa of SMG neurons by selectively inhibiting N-type Ca2+ channels. This was accompanied by a reduction in mRNA encoding the N-type channel alpha subunit (CaV 2.2) and a rightward shift in the voltage dependence of activation of ICa. Colitis reduced the NA release from the colon and jejunum. Depolarization-induced release of tritiated-NA was inhibited by ω-Conotoxin GVIA (300 nM). These results suggest that the changes in VGCC observed at the cell bodies of SMG neurons were also occurring at the nerve terminals during colitis. Similar experimental techniques were performed using SMG neurons incubated overnight in TNFα (1nM). TNFα decreased ICa and depolarization-induced Ca2+ influx in SMG neurons. Similar to DSS-induced colitis, the reduction in ICa was limited to N-type Ca2+ channels. Preincubation of neurons with SC 514 (20μM) and Bay 11 7082 (1µM), inhibitors of nuclear factor kappa B signaling, prevented the reduction in ICa. Preincubation with the p38 MAPK inhibitor, PD 169316 (30µM), recovered a smaller portion of the reduction in Ca2+ influx. These data suggest that DSS colitis and TNFα inhibit N-type VGCC ICa in sympathetic neurons and identify a novel role for NF-κB and p38 MAPK in the regulation of neurotransmitter release. These findings also suggest that DSS colitis inhibits NA release by altering sympathetic N-type VGCC in the colon and jejunum. / Thesis (Master, Physiology) -- Queen's University, 2008-09-02 12:06:20.438

The Arabidopsis thaliana genome encodes twenty putative cyclic nucleotide-gated channel (CNGC) genes. Studies on A. thaliana CNGCs so far have revealed their ability to selectively transport cations that play a role in various stress responses and development, however, the regulation of plant CNGCs is not yet fully understood. Thus, in this study I have attempted to analyze the structure-function relationship of AtCNGCs, mainly by using suppressor mutants of the rare gain-of function mutant, cpr22. The A. thaliana mutant cpr22 resulted from an approximately 3kb deletion that fused the 5’ half and the 3’ half of two CNGC-encoding genes, AtCNGC11 and AtCNGC12, respectively. The expression of this chimeric CNGC, the AtCNGC11/12 gene confers easily detectable characteristics such as stunted morphology with curly leaves and hypersensitive response-like spontaneous lesion formation. Through a suppressor screen, twenty nine new alleles were identified in AtCNGC11/12. Since the cytosolic C-terminal region contains important regulatory domains, such as a cyclic-nucleotide binding domain, eleven cytosolic C-terminal mutants, S17, S35, S81, S83, S84, S100, S135, S136, S137, S140 and S144, were analyzed. A detailed analysis of two mutants, S100 (AtCNGC11/12:G459R) and S137 (AtCNGC11/12:R381H), suggested that G459 and R381 are important for basic channel function rather than channel regulation. Site-directed mutagenesis and fast protein liquid chromatography (FPLC) showed that these two amino acids influence both intra- and inter-subunit interactions that are involved in stabilizing the tertiary structure of the channel. In addition, calmodulin binding domain(s) (CaMBD) and cyclic nucleotide binding domain(s) (CNBD) of some of AtCNGCs were studied using computational modeling and biophysical analyses. The data indicated that AtCNGC12 has two CaMBDs in both N- and C- cytosolic termini, whereas AtCNGC11 has only one CaMBD located in the N-terminal region of the channel. In addition, a thermal shift assay suggested that AtCNGC12 has higher affinity to bind cAMP over cGMP. Taken together, the current study contributes to identify key residues for channel function and provides new insights into CaMBD and CNBD in plant CNGCs.