Diversity of structure and function of alpha1alpha6beta3delta GABAA receptors: comparison with alpha1beta3delta and alpha6beta3delta receptors

delta subunit-containing gamma-aminobutyric acid, type A (GABA(A))receptors are expressed extrasynaptically and mediate tonic inhibition. In cerebellar granule cells, they often form receptors together with alpha(1) and/or alpha(6) subunits. We were interested in determining the architecture of receptors containing both subunits. We predefined the subunit arrangement of several different GABA(A) receptor pentamers by concatenation. These receptors composed of alpha(1), alpha(6), beta(3), and delta subunits were expressed in Xenopus oocytes. Currents elicited in response to GABA were determined in the presence and absence of 3alpha,21-dihydroxy-5alpha-pregnan-20-one (THDOC) or ethanol, or currents were elicited by 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP). Several subunit configurations formed active channels. We therefore conclude that delta can assume multiple positions in a receptor pentamer made up of alpha(1), alpha(6), beta(3), and delta subunits. The different receptors differ in their functional properties. Functional expression of one receptor type was only evident in the combined presence of the neurosteroid THDOC with the channel agonist GABA. Most, but not all, receptors active with GABA/THDOC responded to THIP. None of the receptors was modulated by ethanol concentrations up to 30 mm. Several observations point to a preferred position of delta subunits between two alpha subunits in alpha(1)alpha(6)beta(3)delta receptors. This property is shared by alpha(1)beta(3)delta and alpha(6)beta(3)delta receptors, but there are differences in the additionally expressed isoforms.

Influence of cristalline structure of two minerals clays of type 1/1 on their pozzolanic power

Two clayey materials, one provided by a patner in mineral sector and the other coming from Balengou (West Region Cameroon) were subject of a comparative study in order to evaluate the influence of their crystalline structure on their pozzolanic property. These two natural materials were preliminary enriched in clay minerals by wet sieving and the fractions obtained are denoted K and H respectively. K and H were calcinated at 700 °C, with a heating rate of 5 °C/min and 10 hours dwell at the peak temperature, the products obtained were named MK and MH. Samples K, H, MK and MH were physicochemically characterized by the chemical (ICP), thermal(TGA/DTA) and mineralogical (DRX and Spectrometry IR) analyses together with the measurement of specific surface (BET), crystallinity and the pouzzolanicity test. The results confirmed K as a kaolinitic and H halloysic clay. The kaolinite and the halloysite respectively presented in these clayey materials exhibited a poor crystallinity, but the degree of disorder is higher in K than in H. These results were largely affected by the significant fraction of gibbsite in kaolinitic clay K. At the crude state, the pozzolanic activity of the material H is weak compared with that of K, but the heat treatment makes largely improve this property for both samples.

A Sociological Study of the Political Subsystem in Yugoslavia

In this critical analysis of sociological studies of the political subsystem in Yugoslavia since the fall of communism Mr. Ilic examined the work of the majority of leading researchers of politics in the country between 1990 and 1996. Where the question of continuity was important, he also looked at previous research by the writers in question. His aim was to demonstrate the overall extent of existing research and at the same time to identify its limits and the social conditions which defined it. Particular areas examined included the problems of defining basic concepts and selecting the theoretically most relevant indicators; the sources of data including the types of authentic materials exploited; problems of research work (contacts, field control, etc.); problems of analysisl and finally the problems arising from different relations with the people who commission the research. In the first stage of the research, looking at methods of defining key terms, special attention was paid to the analysis of the most frequently used terms such as democracy, totalitarianism, the political left and right, and populism. Numerous weaknesses were noted in the analytic application of these terms. In studies of the possibilities of creating a democratic political system in Serbia and its possible forms (democracy of the majority or consensual democracy), the profound social division of Serbian society was neglected. The left-right distinction tends to be identified with the government-opposition relation, in the way of practical politics. The idea of populism was used to pass responsibility for the policy of war from the manipulator to the manipulated, while the concept of totalitarianism is used in a rather old-fashioned way, with echoes of the cold war. In general, the terminology used in the majority of recent research on the political subsystem in Yugoslavia is characterised by a special ideological style and by practical political material, rather than by developed theoretical effort. The second section of analysis considered the wider theoretical background of the research and focused on studies of the processes of transformation and transition in Yugoslav society, particularly the work of Mladen Lazic and Silvano Bolcic, who he sees as representing the most important and influential contemporary Yugoslav sociologists. Here Mr. Ilic showed that the meaning of empirical data is closely connected with the stratification schemes towards which they are oriented, so that the same data can have different meanings in shown through different schemes. He went on to show the observed theoretical frames in the context of wider ideological understanding of the authors' ideas and research. Here the emphasis was on the formalistic character of such notions as command economy and command work which were used in analysing the functioning and the collapse of communist society, although Mr. Ilic passed favourable judgement on the Lazic's critique of political over-determination in its various attempts to explain the disintegration of the communist political (sub)system. The next stage of the analysis was devoted to the problem of empirical identification of the observed phenomena. Here again the notions of the political left and right were of key importance. He sees two specific problems in using these notion in talking about Yugoslavia, the first being that the process of transition in the FR Yugoslavia has hardly begun. The communist government has in effect remained in power continuously since 1945, despite the introduction of a multi-party system in 1990. The process of privatisation of public property was interrupted at a very early stage and the results of this are evident on the structural level in the continuous weakening of the social status of the middle class and on the political level because the social structure and dominant form of property direct the majority of votes towards to communists in power. This has been combined with strong chauvinist confusion associated with the wars in Croatia and Bosnia, and these ideas were incorporated by all the relevant Yugoslav political parties, making it more difficult to differentiate between them empirically. In this context he quotes the situation of the stream of political scientists who emerged in the Faculty of Political Science in Belgrade. During the time of the one-party regime, this faculty functioned as ideological support for official communist policy and its teachers were unable to develop views which differed from the official line, but rather treated all contrasting ideas in the same way, neglecting their differences. Following the introduction of a multi-party system, these authors changed their idea of a public enemy, but still retained an undifferentiated and theoretically undeveloped approach to the issue of the identification of political ideas. The fourth section of the work looked at problems of explanation in studying the political subsystem and the attempts at an adequate causal explanation of the triumph of Slobodan Milosevic's communists at four subsequent elections was identified as the key methodological problem. The main problem Mr. Ilic isolated here was the neglect of structural factors in explaining the voters' choice. He then went on to look at the way empirical evidence is collected and studied, pointing out many mistakes in planning and determining the samples used in surveys as well as in the scientifically incorrect use of results. He found these weaknesses particularly noticeable in the works of representatives of the so-called nationalistic orientation in Yugoslav sociology of politics, and he pointed out the practical political abuses which these methodological weaknesses made possible. He also identified similar types of mistakes in research by Serbian political parties made on the basis of party documentation and using methods of content analysis. He found various none-sided applications of survey data and looked at attempts to apply other sources of data (statistics, official party documents, various research results). Mr. Ilic concluded that there are two main sets of characteristics in modern Yugoslav sociological studies of political subsystems. There are a considerable number of surveys with ambitious aspirations to explain political phenomena, but at the same time there is a clear lack of a developed sociological theory of political (sub)systems. He feels that, in the absence of such theory, most researcher are over-ready to accept the theoretical solutions found for interpretation of political phenomena in other countries. He sees a need for a stronger methodological bases for future research, either 1) in complementary usage of different sources and ways of collecting data, or 2) in including more of a historical dimension in different attempts to explain the political subsystem in Yugoslavia.

Understanding Research Fatigue in the Context of Community-University Relations

Community research fatigue has been understudied within the context of community-university relationships and knowledge production. Community-based research (CBR), often occurring within a limited geography and population, increases the possibility that community members feel exhausted or over-whelmed by university research —particularly when they do not see tangible results from research activities. Prompted by informal stories of research fatigue from community members, a small graduate student team sought to understand the extent to which community members experienced research fatigue, and what factors contributed to or relieved feelings of research fatigue. In order to explore these dimensions of research fatigue, semi-structured, face-to-face interviews were conducted with 21 participants, including community members (n = 9), staff and faculty (n = 10), and students (n = 2). The objective of the research was to identify university practices that contribute to research fatigue and how to address the issue at the university level. Qualitative data analysis revealed several important actionable findings: the structure and conduct of community-based research, structured reciprocity and impact, and the role of trust in research. This study’s findings are used to assess the quality of Clark University’s research relationship with its adjacent community. Recommendations are offered; such as to improve partnerships, the impact of CBR, and to develop clear principles of practice.

Structural and surface property characterization of titanium dioxide nanotubes for orthopedic implants

This research focused on the to modification of the surface structure of titanium implants with nanostructured morphology of TiO2 nanotubes and studied the interaction of nanotubes with osteoblast cells to understand the parameters that affect the cell growth. The electrical, mechanical, and structural properties of TiO2 nanotubes were characterized to establish a better understanding on the properties of such nanoscale morphological structures. To achieve the objectives of this research work I transformed the titanium and its alloys, either in bulk sheet form, bulk machined form, or thin film deposited on another substrate into a surface of titania nanotubes using a low cost and environmentally friendly process. The process requires only a simple electrolyte, low cost electrode, and a DC power supply. With this simple approach of scalable nanofabrication, a typical result is nanotubes that are each approximately 100nm in diameter and have a wall thickness of about 20nm. By changing the fabrication parameters, independent nanotubes can be fabricated with open volume between them. Titanium in this form is termed onedimensional since electron transport is narrowly confined along the length of the nanotube. My Ph.D. accomplishments have successfully shown that osteoblast cells, the cells that are the precursors to bone, have a strong tendency to attach to the inside and outside of the titanium nanotubes onto which they are grown using their filopodia – cell’s foot used for locomotion – anchored to titanium nanotubes. In fact it was shown that the cell prefers to find many anchoring sites. These sites are critical for cell locomotion during the first several weeks of maturity and upon calcification as a strongly anchored bone cell. In addition I have shown that such a surface has a greater cell density than a smooth titanium surface. My work also developed a process that uses a focused and controllably rastered ion beam as a nano-scalpel to cut away sections of the osteoblast cells to probe the attachment beneath the main cell body. Ultimately the more rapid growth of osteoblasts, coupled with a stronger cell-surface interface, could provide cost reduction, shorter rehabilitation, and fewer follow-on surgeries due to implant loosening.

Experimental and theoretical study of microstructure effect on piezoelectric property of one dimensional ZnO nanostructures

Emerging nanogenerators have attracted the attention of the research community, focusing on energy generation using piezoelectric nanomaterials. Nanogenerators can be utilized for powering NEMS/MEMS devices. Understanding the piezoelectric properties of ZnO one-dimensional materials such as ZnO nanobelts (NBs) and Nanowires (NWs) can have a significant impact on the design of new devices. The goal of this dissertation is to study the piezoelectric properties of one-dimensional ZnO nanostructures both experimentally and theoretically. First, the experimental procedure for producing the ZnO nanostructures is discussed. The produced ZnO nanostructures were characterized using an in-situ atomic force microscope and a piezoelectric force microscope. It is shown that the electrical conductivity of ZnO NBs is a function of applied mechanical force and its crystalline structure. This phenomenon was described in the context of formation of an electric field due to the piezoelectric property of ZnO NBs. In the PFM studies, it was shown that the piezoelectric response of the ZnO NBs depends on their production method and presence of defects in the NB. Second, a model was proposed for making nanocomposite electrical generators based on ZnO nanowires. The proposed model has advantages over the original configuration of nanogenerators which uses an AFM tip for bending the ZnO NWs. Higher stability of the electric source, capability for producing larger electric fields, and lower production costs are advantages of this configuration. Finally, piezoelectric properties of ZnO NBs were simulated using the molecular dynamics (MD) technique. The size-scale effect on piezoelectric properties of ZnO NBs was captured, and it is shown that the piezoelectric coefficient of ZnO NBs decreases by increasing their lateral dimensions. This phenomenon is attributed to the surface charge redistribution and compression of unit cells that are placed on the outer shell of ZnO NBs.

Monopsony Power, Pay Structure and Training

Although interest in monopsonistic influences on labor market outcomes has revived in recent years, only a few empirical studies provide direct evidence on this topic. In this article, the authors analyze the effect of monopsony power on pay structure, using a direct measure of labor market thinness. The authors find evidence of monopsony power, as firms facing fewer local competitors offer lower wages to skilled labor and trainees, but not to unskilled labor. The findings have important implications for the economic theory of training, as most recent models assume monopsonistic pay-setting for skilled labor, but not for trainees.

Multi-scale micro-structure generation strategy for up-scaling transport in clays

Clays and claystones are used as backfill and barrier materials in the design of waste repositories, because they act as hydraulic barriers and retain contaminants. Transport through such barriers occurs mainly by molecular diffusion. There is thus an interest to relate the diffusion properties of clays to their structural properties. In previous work, we have developed a concept for up-scaling pore-scale molecular diffusion coefficients using a grid-based model for the sample pore structure. Here we present an operational algorithm which can generate such model pore structures of polymineral materials. The obtained pore maps match the rock’s mineralogical components and its macroscopic properties such as porosity, grain and pore size distributions. Representative ensembles of grains in 2D or 3D are created by a lattice Monte Carlo (MC) method, which minimizes the interfacial energy of grains starting from an initial grain distribution. Pores are generated at grain boundaries and/or within grains. The method is general and allows to generate anisotropic structures with grains of approximately predetermined shapes, or with mixtures of different grain types. A specific focus of this study was on the simulation of clay-like materials. The generated clay pore maps were then used to derive upscaled effective diffusion coefficients for non-sorbing tracers using a homogenization technique. The large number of generated maps allowed to check the relations between micro-structural features of clays and their effective transport parameters, as is required to explain and extrapolate experimental diffusion results. As examples, we present a set of 2D and 3D simulations and investigated the effects of nanopores within particles (interlayer pores) and micropores between particles. Archie’s simple power law is followed in systems with only micropores. When nanopores are present, additional parameters are required; the data reveal that effective diffusion coefficients could be described by a sum of two power functions, related to the micro- and nanoporosity. We further used the model to investigate the relationships between particle orientation and effective transport properties of the sample.

Why do individuals behave differently in commons dilemmas?: The case of alpine farmers using common property pastures in Grindelwald, Switzerland

The sustainable use of common-pool resources depends on users’ behaviour with regards to appropriation and provision. Most knowledge about behaviour in such situations comes from experimental research. As experiments take place in confined environments, motivational drivers and actions in the field might differ. This paper analyses farmers’ use of common property pastures in Grindelwald, Switzerland. Binary logistic regression is applied to survey data to explore the effect of farmers’ attributes on livestock endowment, appropriation and provision behaviour. Furthermore, Q methodology is used to assess the impact of broader contextual variables on the sustainability of common property pastures. It is shown that the strongest associations exist between (a) socio-economic attributes and change in livestock endowment; (b) norms and appropriation behaviour; and (c) area and pay-off and provision behaviour. Relevant contextual variables are the economic value of the resource units, off-farm income opportunities, and the subsidy structure. We conclude that with increasing farm size farmers reduce the use and maintenance of common property. Additionally, we postulate that readiness to maintain a resource increases with appropriation activities and the net returns generated from appropriation.

Structural, metamorphic and geochronological relations between the Zanskar Shear Zone and the Miyar Shear Zone (NW Indian Himalaya): Evidence for two distinct tectonic structures and implications for the evolution of the High Himalayan Crystalline of Zanskar

The geologic structures and metamorphic zonation of the northwestern Indian Himalaya contrast significantly with those in the central and eastern parts of the range, where the high-grade metamorphic rocks of the High Himalayan Crystalline (HHC) thrust southward over the weakly metamorphosed sediments of the Lesser Himalaya along the Main Central Thrust (MCT). Indeed, the hanging wall of the MCT in the NW Himalaya mainly consists of the greenschist facies metasediments of the Chamba zone, whereas HHC high-grade rocks are exposed more internally in the range as a large-scale dome called the Gianbul dome. This Gianbul dome is bounded by two oppositely directed shear zones, the NE-dipping Zanskar Shear Zone (ZSZ) on the northern flank and the SW-dipping Miyar Shear Zone (MSZ) on the southern limb. Current models for the emplacement of the HHC in NW India as a dome structure differ mainly in terms of the roles played by both the ZSZ and the MSZ during the tectonothermal evolution of the HHC. In both the channel flow model and wedge extrusion model, the ZSZ acts as a backstop normal fault along which the high-grade metamorphic rocks of the HHC of Zanskar are exhumed. In contrast, the recently proposed tectonic wedging model argues that the ZSZ and the MSZ correspond to one single detachment system that operates as a subhorizontal backthrust off of the MCT. Thus, the kinematic evolution of the two shear zones, the ZSZ and the MSZ, and their structural, metamorphic and chronological relations appear to be diagnostic features for discriminating the different models. In this paper, structural, metamorphic and geochronological data demonstrate that the MSZ and the ZSZ experienced two distinct kinematic evolutions. As such, the data presented in this paper rule out the hypothesis that the MSZ and the ZSZ constitute one single detachment system, as postulated by the tectonic wedging model. Structural, metamorphic and geochronological data are used to present an alternative tectonic model for the large-scale doming in the NW Indian Himalaya involving early NE-directed tectonics, weakness in the upper crust, reduced erosion at the orogenic front and rapid exhumation along both the ZSZ and the MSZ.

Property Condition Disclosure Law: Why Did States Mandate 'Seller Tell All'?

Thirty-six US states have already enacted some form of seller's property condition disclosure law. At a time when there is a movement in this direction nationally, this paper attempts to ascertain the factors that lead states to adopt disclosure law. Motivation for the study stems from the fact that not all states have yet adopted the law, and states that have enacted the law have done so in different years. The analytical structure employs hazard models, using a unique set of economic and institutional attributes for a panel of 50 US States spanning 21 years, from 1984 to 2004. The proportional hazard analysis of law adoption reveals that greater number of disciplinary actions tends to favor passage of the law. Greater broker supervision, implying generally higher awareness among real estate agents, seems to have a negative impact on the likelihood of a state adopting a property condition disclosure law.

Property Condition Disclosure Law: Does 'Seller Tell All' Matter in Property Values?

At the time when at least two-thirds of the US states have already mandated some form of seller's property condition disclosure statement and there is a movement in this direction nationally, this paper examines the impact of seller's property condition disclosure law on the residential real estate values, the information asymmetry in housing transactions and shift of risk from buyers and brokers to the sellers, and attempts to ascertain the factors that lead to adoption of the disclosur law. The analytical structure employs parametric panel data models, semi-parametric propensity score matching models, and an event study framework using a unique set of economic and institutional attributes for a quarterly panel of 291 US Metropolitan Statistical Areas (MSAs) and 50 US States spanning 21 years from 1984 to 2004. Exploiting the MSA level variation in house prices, the study finds that the average seller may be able to fetch a higher price (about three to four percent) for the house if she furnishes a state-mandated seller's property condition disclosure statement to the buyer.

Structure-function analysis of human Integrator subunit-4

Structure-function analysis of human Integrator subunit 4 Anupama Sataluri Advisor: Eric. J. Wagner, Ph.D. Uridine-rich small nuclear RNAs (U snRNA) are RNA Polymerase-II (RNAPII) transcripts that are ubiquitously expressed and are known to be essential for gene expression. snRNAs play a key role in mRNA splicing and in histone mRNA expression. Inaccurate snRNA biosynthesis can lead to diseases related to defective splicing and histone mRNA expression. Although the 3′ end formation mechanism and processing machinery of other RNAPII transcripts such as mRNA has been well studied, the mechanism of snRNA 3′ end processing has remained a mystery until the recent discovery of the machinery that mediates this process. In 2005, a complex of 14 subunits (the Integrator complex) associated with RNA Polymerase-II was discovered. The 14subunits were annotated Integrator 1-14 based on their size. The subunits of this complex together were found to facilitate 3′ end processing of snRNA. Identification of the Integrator complex propelled research in the direction of understanding the events of snRNA 3’end processing. Recent studies from our lab confirmed that Integrator subunit (IntS) 9 and 11 together perform the endonucleolytic cleavage of the nascent snRNA 3′ end to generate mature snRNA. However, the role of other members of the Integrator complex remains elusive. Current research in our lab is focused on deciphering the role of each subunit within the Integrator complex This work specifically focuses on elucidating the role of human Integrator subunit 4 (IntS4) and understanding how it facilitates the overall function of the complex. IntS4 has structural similarity with a protein called “Symplekin”, which is part of the mRNA 3’end processing machinery. Symplekin has been thoroughly researched in recent years and structure-function correlation studies in the context of mRNA 3’end processing have reported a scaffold function for Symplekin due to the presence of HEAT repeat motifs in its N-terminus. Based upon the structural similarity between IntS4 and Symplekin, we hypothesized that Integrator subunit 4 may be behaving as a Symplekin-like scaffold molecule that facilitates the interaction between other members of the Integrator Complex. To answer this question, the two important goals of this study were to: 1) identify the region of IntS4, which is important for snRNA 3′ end processing and 2) determine binding partners of IntS4 which promote its function as a scaffold. IntS4 structurally consists of a highly conserved N-terminus with 8 HEAT repeats, followed by a nonconserved C- terminus. A series of siRNA resistant N and C-terminus deletion constructs as well as specific point mutants within its N-terminal HEAT repeats were generated for human IntS4 and, utilizing a snRNA transcriptional readthrough GFP-reporter assay, we tested their ability to rescue misprocessing. This assay revealed a possible scaffold like property of IntS4. To probe IntS4 for interaction partners, we performed co-immunoprecipitation on nuclear extracts of IntS4 expressing stable cell lines and identified IntS3 and IntS5 among other Integrator subunits to be binding partners which facilitate the scaffold like function of hIntS4. These findings have established a critical role for IntS4 in snRNA 3′ end processing, identified that both its N and C termini are essential for its function, and mapped putative interaction domains with other Integrator subunits.

On the fine structure of oxygen distribution in surface water layers in the area between Iceland and Faroe Islands

During the international "Overflow-Expedition'' 1973 on R.V. "Meteor" oxygen concentrations in surface layers were measured in order to determine the oxygen gradients within the first two meters and to add some informations to the mechanisms of oxygen exchange at the air-sea interface. These investigations may be interesting also with regard to longterm- observations of the oxygen distribution in the Atlantic, especially the problem of the A.O.U. (apparent oxygen utilization) determination. To measure oxygen gradients a special sampler was built which is able to take water samples each 20 cm of the first 2 meters. These data were supplemented by further samples down to 150 m, taken by conventional water samplers, from which samples were also taken to measure N2/O2-relations. By comparing these relations with theoretical relations in air-saturated water the influence of biological production and consumption on the oxygen contents in water could be estimated. A simple glass apparatus was built to extract gas from the water samples, and hereafter the N2/O2-relations were determined by mass spectrometry. Most distributions of the oxygen anomaly show a negative oxygen balance which varies largely, probably due to strong mixing processes in the Iceland-Faroe ridge area. The distribution of surface oxygen saturation values are of two different types. The values of the stations 260, 262 and 270 stem from mixed water and show homogeneous supersaturations, as can be found instantly when whitecaps appear. The values of 9 other stations are from water, sampled during calm periods which has been mixed and supersaturated before. They show a decreasing oxygen saturation towards the sea surface and often undersaturation in the upper decimeters up to 98 % and even 91 %. So at the air-sea interface even less initial oxygen saturation than 100 % can be found after supersaturation during heavy weather periods.