99 research outputs found
What makes us human
Science needs a new model for testing how cells react, both to things that can cure us and things that can kill us. With her half-million-dollar grant, assistant professor Kristen Comfort ’02 is developing a human model with dynamic potential
Exploring the Limits of the Dipole Approximation with Angle-Resolved Electron Time-of-Flight Spectrometry
Understanding the electronic structure of atoms and molecules is fundamental in determining their basic properties as well as the interactions that occur with different particles such as light. One such interaction is single photoionization; a process in which a photon collides with an atom or molecule and an electron with a certain kinetic energy is emitted, leaving behind a residual ion. Theoretical models of electronic structures use the dipole approximation to simplify x-ray interactions by assuming that the electromagnetic field of the radiation, expressed as a Taylor-series expansion, can be simplified by using only the first term. It has been known for some time that the dipole approximation becomes inaccurate at high photon energies, but the threshold at which this discrepancy begins is ambiguous. In order to enhance our understanding of these limitations, we measured the electron emissions of nitrogen. Beamline 8.0.1 at the Advanced Light Source was used with an electron Time-of-Flight (TOF) end station, which measures the time required for electrons emitted to travel a fixed distance. Data were collected over a broad range of photon energies (413 - 664 eV) using five analyzers rotated to 15 chamber angles. Preliminary analysis indicates that these results confirm the breakdown of the dipole approximation at photon energies well below 1 keV and that this breakdown is greatly enhanced in molecules just above the core-level ionization threshold. As a result, new theoretical models must be made that use higher order terms that were previously truncated
Electrostatic Effects in the Folding of the SH3 Domain of the c-Src Tyrosine Kinase: pH-Dependence in 3D-Domain Swapping and Amyloid Formation
The SH3 domain of the c-Src tyrosine kinase (c-Src-SH3) aggregates to form intertwined dimers and amyloid fibrils at mild acid pHs. In this work, we show that a single mutation of residue Gln128 of this SH3 domain has a significant effect on: (i) its thermal stability; and (ii) its propensity to form amyloid fibrils. The Gln128Glu mutant forms amyloid fibrils at neutral pH but not at mild acid pH, while Gln128Lys and Gln128Arg mutants do not form these aggregates under any of the conditions assayed. We have also solved the crystallographic structures of the wild-type (WT) and Gln128Glu, Gln128Lys and Gln128Arg mutants from crystals obtained at different pHs. At pH 5.0, crystals belong to the hexagonal space group P6522 and the asymmetric unit is formed by one chain of the protomer of the c-Src-SH3 domain in an open conformation. At pH 7.0, crystals belong to the orthorhombic space group P212121, with two molecules at the asymmetric unit showing the characteristic fold of the SH3 domain. Analysis of these crystallographic structures shows that the residue at position 128 is connected to Glu106 at the diverging β-turn through a cluster of water molecules. Changes in this hydrogen-bond network lead to the displacement of the c-Src-SH3 distal loop, resulting also in conformational changes of Leu100 that might be related to the binding of proline rich motifs. Our findings show that electrostatic interactions and solvation of residues close to the folding nucleation site of the c-Src-SH3 domain might play an important role during the folding reaction and the amyloid fibril formation.This research was funded by the Spanish Ministry of Science and Innovation and Ministry of Economy and Competitiveness and FEDER (EU): BIO2009-13261-C02-01/02 (ACA); BIO2012-39922-C02-01/02 (ACA); CTQ2013-4493 (JLN) and CSD2008-00005 (JLN); Andalusian Regional Government (Spain) and FEDER (EU): P09-CVI-5063 (ACA); and Valentian Regional Government (Spain) and FEDER (EU): Prometeo 2013/018 (JLN). Data collection was supported by European Synchrotron Radiation Facility (ESRF), Grenoble, France: BAG proposals MX-1406 (ACA) and MX-1541 (ACA); and ALBA (Barcelona, Spain) proposals 2012010072 (ACA) and 2012100378 (ACA)
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When the Slander is the Story:The Neutral Reportage Privilege in Theory and Practice
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Conformational Change and Assembly Through Edge β Strands in Transthyretin an Other Amyloid Proteins
When the Slander is the Story:The Neutral Reportage Privilege in Theory and Practice
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Premature withdrawal from treatment in a child guidance clinic : an exploratory study of the factors which underlie clients' decisions to withdraw from social work treatment at the Provincial Child Guidance Clinic, North Burnaby, B.C.
This is an exploratory study of the problem of clients' discontinuation in a child guidance clinic. The problem is considered first in terms of its therapeutic and administrative implications for clients and social workers. Reference is made to the professional literature which suggests the multi-causative factors which operate in a client's decision to withdraw from social work services. The problem is also related to social work prinicples and concepts. This is done to demonstrate that, by their continued efforts to understand the meaning of behaviour, to study the client in as much of his total life situation as possible, and to refine and enrich methods of family diagnosis, social workers can sharpen their diagnostic skills and their ability to select effective treatment goals. A brief discussion of the history of child guidance together with a more detailed account of the Provincial Child Guidance Clinic in North Burnaby gives a broad perspective to the problem of discontinuation. The problem is illustrated in five selected cases in which clients withdrew themselves and their children from Clinic services. The case records are examined, highlighting both dynamic patterns within the individual families and also their attitudes towards the child's problems and their Clinic experiences. These areas are thought to be significant factors relating to the parents' decisions to withdraw. Five follow-up interviews are conducted and recorded which indicate the clients' verbal reactions to the Clinic, including their conscious reasons for withdrawal. An assessment is made of the degree of Clinic help which the five families were able to employ. Common patterns are elucidated in the five cases and are designated as "withdrawal indicators". These indicators may, in the future, have prognostic value in determining which cases are likely to withdraw. The indicators are applied to six additional cases (tabulated in Appendix D). The results show that two-thirds of the indicators are present in each of the six cases. A further study is recommended in which the indicators would be applied to a larger number of discontinued cases, thus determining their reliability as predictive tools. The clients' reasons for withdrawal are discussed together with the recommendation that an additional study be done both to validate these reasons and to demonstrate new ones. In light of the findings various recommendations are made which the Clinic social work staff might implement in an attempt to decrease the rate of discontinuation. The withdrawal indicators should be recognized as forms of resistance and should be handled by the workers in early interviews. Increased skills in the areas of family diagnosis and a more discriminating system of recording will help to expedite the workers' recognition of the indicators. Also, greater skill by the workers in recognizing brief service cases, in handling reassignment, in their interpretation of the Clinic and its functions, and in their choice of words, will help to strengthen the clients' motivation to a continued Clinic contact. Recommendations are also made whereby the waiting-period, which emerges as the strongest reason for discontinuation, might be utilized as a therapeutic tool in treatment. Withdrawal must, in nearly all cases, reflect the clients' dissatisfactions with the services of the Clinic. To attain their goals for their clients, the agency, and themselves, the Clinic social workers must strive to understand and decrease the rate of discontinuation.Arts, Faculty ofSocial Work, School ofGraduat
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