An Electron Microscopy Study into Vps1 and the role of its F-actin Binding Regions within Clathrin-mediated Endocytosis

Abstract: Clathrin-mediated endocytosis is a conserved process utilised by metazoans and fungi for the internalisation of cell surface receptors into vesicles upon ligand binding. This is a vital process by which cells are able to communicate with other cells and there external environment. Transmission electron microscopy of endocytic sites in F-actin binding mutants of S. cerevisiae suggest an absolute requirement for Vps1p to bind F-actin in order to generate directional propagation of an invaginations against the internal osmotic pressure of the cell. Structural observations of endocytic pits by electron tomography revealed a dynamin-like structure indicative of a mode of scission analogous to that carried out by dynamin-1. Following this observation similarity searches were conducted between dynamin-1 and Vps1p revealing conservation of primary and secondary structure between the two proteins within the GTPase domain, middle domain and GTPase effector domain. Supported by recent findings the observations recorded here favour a model of scission that incorporates Vps1p in a manner that is comparable with its mammalian homologue, dynamin-1

Exploring Mechanical Niches Identified by Hair Follicle Compression and How These Transduce Proliferation and Differentiation Cues in Epidermally Derived cells.

In this study the hair follicle structure and surrounding tissue was investigated before, during and after the shaving process in order to better characterise the hair follicle hysteresis (lag in response) observed during the shaving process. Individual hair shafts were loaded with weights designed to mimic the forces generated during the shaving process and deformations in nuclear morphology were used as an indicator of force transduction. Upon identifying distinct mechanical compartments corresponding to regions consistent with the infundibulum, isthmus and suprabulbar regions the study then focussed on elucidating how dermal collagen may facilitate this. Multiphoton microscopy was utilised to interrogate the extrafollicular collagen and the subsequent images were analysed to reveal distinct differences in collagen bundling at the infundibulum, isthmus and suprabulbar regions. To model how heterogeneities in collagen bundling could impact upon epidermal and follicle homeostasis collagen hydrogels were constructed and characterised. Assessment of involucrin and Ki67 levels in HaCaT cells by confocal microscopy revealed elevated proliferation rates in cells on high density (HD) matrices compared with those on low density (LD) matrices which also correlated with increased nuclear volume. HD matrices have smaller collagen bundles and therefor represent a less stiff matrix compared with the low density LD matrices. ERK1/2, JNK and p38 MAPKs have been well reported as effectors on keratinocyte proliferation and differentiation rates in response to mechanical cues and so inhibitors of each were used to identify if these MAPKs were also important in transducing matrix density/stiffness cues that impact upon proliferation and differentiation rates. P38, ERK1/2 and JNK were all found to be important in mediating the proliferation advantage derived from the HD matrices, with JNK being a potential candidate in linking nuclear dynamics with collagen density-mediated proliferation and differentiation rates. JNK was further demonstrated as being the dominant player in transducing the proliferation advantage conferred by the HD matrix

A platform for discovering and sharing confidential ballistic crime data.

Criminal investigations generate large volumes of complex data that detectives have to analyse and understand. This data tends to be "siloed" within individual jurisdictions and re-using it in other investigations can be difficult. Investigations into trans-national crimes are hampered by the problem of discovering relevant data held by agencies in other countries and of sharing those data. Gun-crimes are one major type of incident that showcases this: guns are easily moved across borders and used in multiple crimes but finding that a weapon was used elsewhere in Europe is difficult. In this paper we report on the Odyssey Project, an EU-funded initiative to mine, manipulate and share data about weapons and crimes. The project demonstrates the automatic combining of data from disparate repositories for cross-correlation and automated analysis. The data arrive from different cultural/domains with multiple reference models using real-time data feeds and historical databases

FEDERALISM, NATIONALISM AND REGIONALISM IN CANADA

This article analyses the capacity of Canadian federalism to articulate andaccommodate the dual and regionalist character defining Canada througha range of arguments and opinions both for and against that have been generatedboth within the Canadian Federation and abroad. From the standpointof the Quebec sovereignists, federalism is highly restrictive of the Quebecnation’s freedom to express itself, by itself, within the Canadian contextas well as within international ambits; for Quebec nationalists, the termQuebec “nation” implies—indeed, requires—a “Quebec state”. But, fromthe standpoint of the Quebec federalists (a good number of whom understandQuebec as a sociological and political nation), the future of Quebeclies with its membership of the Canadian Federation, however much this hasto recognise Quebec as a “differential society” within Canada, and howevermuch it has to ensure that Quebec will develop and promote its interests asa nation. For yet others, the decentralist character of Canadian federalism,and the extensive provisions for asymmetry built into the system, mean that Quebec is already perhaps the most powerful sub-national government inthe world, such that it already has the powers necessary to fulfil its nationaldestiny, within the federation. Opinion outside Quebec ranges from thosewho accept this view, and embrace asymmetry, to those who argue that Quebecis simply one of ten existing provinces, each of which is distinct, andwhich should all be treated as equals in accordance with the constitutionaland political framework

'Tagging' bills in Parliament: Section 75 or Section 76?

The Constitution provides two procedures for passing ordinary bills in Parliament. Under the s 76 procedure, the provinces have real influence through their participation the NCOP. Under the s 75 procedure, provincial influence is very limited. The Constitution stipulates that bills that fall within an area of concurrent provincial/national competence must follow the s 76 process, but does not set out criteria to determine whether a bill should be 'tagged' as a s 76 or s 75 matter. Currently Parliament uses a Canadian test to 'tag' Bills. However, that approach fails to recognize the constitutional role of the NCOP. It is also designed to decide whether or not laws fall within the jurisdiction of provinces, an issue irrelevant to the tagging decision. This article argues that tagging decisions should be guided by South Africa's constitutional principles establishing the relationship between provinces and the national government, and suggests some criteria to ensure that those bills that most affect provinces are properly considered in the NCOP

Design and Analysis of a Novel Fluorescent Cell Stain

Undergraduate Basi

Cosmology and Dark Matter at the LHC

We examine the question of whether neutralinos produced at the LHC can be shown to be the particles making up the astronomically observed dark matter. If the WIMP alllowed region lies in the SUGRA coannihilation region, then a strong signal for this would be the unexpected near degeneracy of the stau and neutralino i.e., a mass difference \Delta M\simeq (5-15) GeV. For the mSUGRA model we show such a small mass difference can be measured at the LHC using the signal 3\tau+jet+E_T^{\rm miss}. Two observables, opposite sign minus like sign pairs and the peak of the \tau\tau mass distribution allows the simultaneous determination of \Delta M to 15% and the gluino mass M_{\tilde g} to be 6% at the benchmark point of M_{\tilde g}=850 GeV, A_0=0, \mu>0 with 30 fb^{-1}. With 10 fb^{-1}, \Delta M can be determined to 22% and one can probe the parameter space up to m_{1/2}=700 GeV with 100 fb^{-1}.Comment: 11 pages, 7 figures, Talk at IDM 2006, 11th September to 16th September, Greec

Teleoperation in the Presence of Communication Delays

Modern industrial processes, public service needs, and research interests have established a clear need to perform work remotely [12][4]. Teleoperators were developed with the advent of nuclear industry in the mid 1940\u27s and have been since used extensively to perform work in hazardous environments (nuclear, chemical), undersea (resource exploration, waste management, pollution monitoring), and in the outer space (sample acquisition, satellite deployment/repair). Sophisticated systems have been designed and built to meet these needs, providing the human operator with high bandwidth and high fidelity visual and kinesthetic feedback information about the task in progress [22] [32] [16] [6]

From sayings to texts: the literary contextualisation of Jesus’s words in the writings of Tertullian and Origen

This thesis addresses the subject of the early Christian re-use and interpretation of the words of Jesus. Unlike previous studies, which focus predominantly on the text of, and sources for, citations of Jesus’s sayings in the first two centuries, I examine the neglected hermeneutical principles and methods that early Christian authors employ when reading Jesus’s words. I begin by demonstrating that the dominant paradigm for reading Jesus’s words in the first two centuries of the common era was the noncontextualized saying. This trend matches the broader use of the words of wise figures among contemporaneous Greco-Roman authors. To be sure, one finds evidence of literary contextualisation—the process of drawing on the literary context for interpretive purposes—in Roman-era commentaries on Homer and the Hebrew Bible. Early Christian authors like Irenaeus, Justin and Clement, however, rarely apply such practices to the words of Jesus and rarely reflect on the methods and principles they employ when reading his sayings. I argue that two significant early Christian authors—Tertullian of Carthage (ca. 155– 220 CE) and Origen of Alexandria (ca. 180–253 CE)—are the first to develop hermeneutical principles for the interpretation of Jesus’s words. They do so by elevating the immediate literary context of Jesus’s words to the level of a normative principle. By “literary” context, I refer to the immediate narrative in which Jesus’s sayings appear. I substantiate this case by focussing, in particular, on their re-use of climactic sayings of Jesus that reside within larger pronouncement stories in the Synoptic Gospels. A key example is Jesus’s command to “render to Caesar what is Caesar’s and to God what is God’s” which memorably concludes the tribute passage (Matt. 22.15-22 and parallels). Literary contextualisation therefore refers to the use of the immediate textual context of Jesus’s words for explicitly interpretive purposes. The crucial assumption that underlies Tertullian and Origen’s practice of literary contextualisation is that the significance of Jesus’s words is tied to, and mediated by, their immediate literary context. Tertullian and Origen’s use of the immediate literary context of Jesus’s words resulted in, and was a core component of, a disciplined effort to exegete his sayings. With Tertullian and Origen, the perception of Jesus’s sayings, and the principles used to interpret them change in significant ways. First, Tertullian and Origen understand Jesus’s climactic sayings not as non-contextualized, individual fragments of teaching but as pronouncements that belong within larger literary units. Furthermore, they conceive of his sayings as scriptural texts that require interpretation in light of a larger scriptural corpus that they connect with the immediate context of Jesus’s words. Second, and in so doing, they transform the standard methods used to interpret Jesus’s sayings. I argue that Tertullian and Origen’s “hermeneutic of literary contextualisation”—the practice of reading Jesus’s sayings in light of their literary contexts—consists of three reading strategies. First, and most significantly, both authors reproduce the entire biographical narrative in which Jesus’s sayings reside as a way of intentionally countering perceived “non-contextualisation” of Jesus’s pronouncements. Second, and relatedly, Tertullian and Origen employ fine, textual details from the anecdote as a way of interpreting and clarifying the significance of Jesus’s words. Third, both authors interpret Jesus’s sayings in light of intertexts drawn from the Christian scriptures more broadly, which they connect with the co-text of Jesus’s words. Taken together, these reading practices reflect a significant shift away from reading Jesus’s words as sayings, or literary fragments, to interpreting them as texts embedded within a literary context. To account for this development, I argue that the hermeneutic of literary contextualisation employed by Tertullian and Origen fundamentally emerges from a complex set of historical, ideological and literary factors. Most crucial of all, I suggest, are the shifting principles involved in early Christian debate. Whereas early Christian authors were naturally more focussed on debating the authority of Jesus’s sayings, and the textual sources in which they resided, such issues no longer remain as pertinent for Tertullian and Origen. Instead, they take up issues centred on the interpretation of Jesus’s words. I therefore argue that Tertullian and Origen are among the first early Christian authors to explicitly consider the hermeneutical implications of reading Jesus’s words in light of their literary contexts

Evaluation of Reliability of Prototype Tractor – Mounted Cocoyam (Xanthosoma spp.) Harvester

An elevator digger type harvester for cocoyam (Xanthosoma spp.) was designed and fabricated at the Federal University of Technology, Akure using locally available materials. The harvester prototype is tractor – mounted and powered from the tractor Power – take – off shaft (P.T.O).  Field tests were conducted to evaluate the effect of different levels of operational parameters on the reliability of the implement. The operational parameters were forward speed (v), rake angle (α) and web speed (n). The harvester was operated at the forward speeds of 2, 4 and 6 km/h, rake angles of 15˚, 20˚ and 25˚ and web speeds of 540, 1000 rpm. These combinations were tested on a factorial basis employing a split - split plot design with three replications. The indices of reliability of the implement investigated were material failure to machine parts, clogging and machine adjustment. Cocoyam cormels were harvested from 10m long rows of crops on clay loam soil with a spacing of 0.8m x 0.6m according to each treatment. The soil moisture content during field experimentation was 9.46 ± 1.02%, and bulk density was 1.18 ± 0.22 g/cm3.  The field tests revealed that machine performance was limited by delays due to clogging and machine adjustments and a high percentage of tuber damage (55%). The analysis of variance performed on the descriptive statistics for machine performance variables obtained showed that the results are significant for only Machine adjustments at P < 0.01.  Keywords: Reliability, Breakdown, Web, Clogging, Material failure, Failure rate, Mean time before failure, Nigeri