A search for new particles in proton‐nucleus collisions at 400 GeV/c

We report preliminary results from a search for new particles produced in proton‐nucleus collisions at 400 GeV/c. A double‐arm spectrometer is used to detect two‐body final states where each spectrometer arm has the capability of uniquely identifying Π±, K±, p, ?, μ±, and ϕ. The Jψ is measured in the μ+μ− mode.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87398/2/30_1.pd

The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains

We have investigated the contribution to ionic selectivity of residues in the selectivity filter and pore helices of the P1 and P2 domains in the acid sensitive potassium channel TASK-1. We used site directed mutagenesis and electrophysiological studies, assisted by structural models built through computational methods. We have measured selectivity in channels expressed in Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and current amplitudes when Rb+ or Na+ replaced extracellular K+. Both P1 and P2 contribute to selectivity, and most mutations, including mutation of residues in the triplets GYG and GFG in P1 and P2, made channels nonselective. We interpret the effects of these—and of other mutations—in terms of the way the pore is likely to be stabilised structurally. We show also that residues in the outer pore mouth contribute to selectivity in TASK-1. Mutations resulting in loss of selectivity (e.g. I94S, G95A) were associated with slowing of the response of channels to depolarisation. More important physiologically, pH sensitivity is also lost or altered by such mutations. Mutations that retained selectivity (e.g. I94L, I94V) also retained their response to acidification. It is likely that responses both to voltage and pH changes involve gating at the selectivity filter

Motivations, expectations, and experiences of expatriate academic staff on an international branch campus in China

This article explores the experiences of non-Chinese academic staff working on an international branch campus in China. The article presents findings from an interview study that explored the expectations of expatriate staff and what motivated them to want to work abroad. The second part of the article reports on whether and how these expectations and motivations were fulfilled. The findings suggest that, although staff found many benefits from working on the international branch campus, they were insufficiently prepared for the structural and cultural differences inherent in working as an academic in China. The authors argue that more of the academics’ initial expectations and motivations could have been realized if better staff induction and ongoing collective professional development had been in place. In particular, university-level discourse communicated through policy and marketing texts, which promoted the vision of one inclusive and diverse international university community, militated against attention being paid to the structural, political, and cultural differences inherent in working as an academic in China. The authors argue that professional development that acknowledges the differences, difficulties, and disjunctions that staff are likely to encounter in their work is important in building successful international branch campuses both at the level of the organization and of the individual

Structures of the CCR5 N Terminus and of a Tyrosine-Sulfated Antibody with HIV-1 gp120 and CD4

The CCR5 co-receptor binds to the HIV-l gp120 envelope glycoprotein and facilitates HIV-l entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (α-helix) and 412d (extendedloop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-l interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system

Structures of the CCR5 N Terminus and of a Tyrosine-Sulfated Antibody with HIV-1 gp120 and CD4

The CCR5 co-receptor binds to the HIV-l gp120 envelope glycoprotein and facilitates HIV-l entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (α-helix) and 412d (extendedloop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-l interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system

The role of Comprehension in Requirements and Implications for Use Case Descriptions

Within requirements engineering it is generally accepted that in writing specifications (or indeed any requirements phase document), one attempts to produce an artefact which will be simple to comprehend for the user. That is, whether the document is intended for customers to validate requirements, or engineers to understand what the design must deliver, comprehension is an important goal for the author. Indeed, advice on producing ‘readable’ or ‘understandable’ documents is often included in courses on requirements engineering. However, few researchers, particularly within the software engineering domain, have attempted either to define or to understand the nature of comprehension and it’s implications for guidance on the production of quality requirements. Therefore, this paper examines thoroughly the nature of textual comprehension, drawing heavily from research in discourse process, and suggests some implications for requirements (and other) software documentation. In essence, we find that the guidance on writing requirements, often prevalent within software engineering, may be based upon assumptions which are an oversimplification of the nature of comprehension. Hence, the paper examines guidelines which have been proposed, in this case for use case descriptions, and the extent to which they agree with discourse process theory; before suggesting refinements to the guidelines which attempt to utilise lessons learned from our richer understanding of the underlying discourse process theory. For example, we suggest subtly different sets of writing guidelines for the different tasks of requirements, specification and design

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Sialylation of campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice

<p>Background: Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucially determines the structural homology between LOS and gangliosides, explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C. jejuni are recognised by TLR4 and sialoadhesin; however, the functional implications of these interactions in vivo are unknown.</p> <p>Methodology/Principal Findings: In this study we investigated the effects of bacterial sialylation on phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo. Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MΦ, but not by BM-DC. In addition, LOS sialylation increased the production of IL-10, IL-6 and IFN-β by both BM-MΦ and BM-DC. Subsequent in vivo experiments revealed that sialylation augmented the deposition of fluorescent bacteria in splenic DC, but not macrophages. In addition, sialylation significantly amplified the production of type I interferons, which was independent of pDC.</p> <p>Conclusions/Significance: These results identify novel immune stimulatory effects of C. jejuni sialylation, which may be important in inducing cross-reactive humoral responses that cause GBS</p&gt

Experimental Facilities Development

This research was sponsored by the National Science Foundation Grant NSF PHy 87-1440