129 research outputs found
Spallation Neutron Production by 0.8, 1.2 and 1.6 GeV Protons on various Targets
Spallation neutron production in proton induced reactions on Al, Fe, Zr, W,
Pb and Th targets at 1.2 GeV and on Fe and Pb at 0.8, and 1.6 GeV measured at
the SATURNE accelerator in Saclay is reported. The experimental
double-differential cross-sections are compared with calculations performed
with different intra-nuclear cascade models implemented in high energy
transport codes. The broad angular coverage also allowed the determination of
average neutron multiplicities above 2 MeV. Deficiencies in some of the models
commonly used for applications are pointed out.Comment: 20 pages, 32 figures, revised version, accepted fpr publication in
Phys. Rev.
Calorimetric Investigation of Copper Binding in the N-Terminal Region of the Prion Protein at Low Copper Loading: Evidence for an Entropically Favorable First Binding Event
Although
the Cu<sup>2+</sup>-binding sites of the prion protein have been well
studied when the protein is fully saturated by Cu<sup>2+</sup>, the
Cu<sup>2+</sup>-loading mechanism is just beginning to come into view.
Because the Cu<sup>2+</sup>-binding modes at low and intermediate
Cu<sup>2+</sup> occupancy necessarily represent the highest-affinity
binding modes, these are very likely populated under physiological
conditions, and it is thus essential to characterize them in order
to understand better the biological function of copper–prion
interactions. Besides binding-affinity data, almost no other thermodynamic
parameters (e.g., Δ<i>H</i> and Δ<i>S</i>) have been measured, thus leaving undetermined the enthalpic and
entropic factors that govern the free energy of Cu<sup>2+</sup> binding
to the prion protein. In this study, isothermal titration calorimetry
(ITC) was used to quantify the thermodynamic parameters (<i>K</i>, Δ<i>G</i>, Δ<i>H</i>, and <i>T</i>Δ<i>S</i>) of Cu<sup>2+</sup> binding to
a peptide, PrPÂ(23–28, 57–98), that encompasses the majority
of the residues implicated in Cu<sup>2+</sup> binding by full-length
PrP. Use of the buffer <i>N</i>-(2-acetomido)-aminoethanesulfonic
acid (ACES), which is also a well-characterized Cu<sup>2+</sup> chelator,
allowed for the isolation of the two highest affinity binding events.
Circular dichroism spectroscopy was used to characterize the different
binding modes as a function of added Cu<sup>2+</sup>. The <i>K</i><sub>d</sub> values determined by ITC, 7 and 380 nM, are
well in line with those reported by others. The first binding event
benefits significantly from a positive entropy, whereas the second
binding event is enthalpically driven. The thermodynamic values associated
with Cu<sup>2+</sup> binding by the Aβ peptide, which is implicated
in Alzheimer’s disease, bear striking parallels to those found
here for the prion protein
Knowledge and competency standards for specialized cognitive behavior therapy for adult obsessive-compulsive disorder
Obsessive-Compulsive Disorder (OCD) is a leading cause of disability world-wide (World Health Organization, 2008). Treatment of OCD is a specialized field whose aim is recovery from illness for as many patients as possible. The evidence-based psychotherapeutic treatment for OCD is specialized cognitive behavior therapy (CBT, NICE, 2005, Koran and Simpson, 2013). However, these treatments are not accessible to many sufferers around the world. Currently available guidelines for care are deemed to be essential but insufficient because of highly variable clinician knowledge and competencies specific to OCD. The phase two mandate of the 14 nation International OCD Accreditation Task Force (ATF) created by the Canadian Institute for Obsessive Compulsive Disorders is development of knowledge and competency standards for specialized treatments for OCD through the lifespan deemed by experts to be foundational to transformative change in this field. This paper presents knowledge and competency standards for specialized CBT for adult OCD developed to inform, advance, and offer a model for clinical practice and training for OCD. During upcoming ATF phases three and four criteria and processes for training in specialized treatments for OCD through the lifespan for certification (individuals) and accreditation (sites) will be developed based on the ATF standards
An impulse-driven liquid-droplet deposition interface for combining LC with MALDI MS and MS/MS
Improving the signal intensity and sensitivity of MALDI mass spectrometry by using nanoliter spots deposited by induction-based fluidics
Electrospray mass spectrometry of neuac oligomers associated with the c fragment of the tetanus toxin
Methods for Analysis of Matrix Metalloproteinase Regulation of Neutrophil-Endothelial Cell Adhesion
Recent evidence indicates novel role for matrix metalloproteinases (MMPs), in particular gelatinase A (MMP-2), in the regulation of vascular biology that are unrelated to their well-known proteolytic breakdown of matrix proteins. We have previously reported that MMP-2 can modulate vascular reactivity by cleavage of the Gly32-Leu33 bound in big endothelin-1 (ET-1) yielding a novel vasoactive peptide ET-1[1-32]. These studies were conducted to investigate whether gelatinolytic MMPs could affect neutrophil-endothelial cell attachment. ET-1[1-32] produced by MMP-2 up-regulated CD11b/CD18 expression on human neutrophils, thereby promoted their adhesion to cultured endothelial cells. ET-1[1-32] evoked release of gelatinase B (MMP-9), which in turn cleaved big ET-1 to yield ET-1[1-32], thus revealing a self-amplifying loop for ET-1[1-32] generation. ET-1[1-32] was rather resistant to cleavage by neutrophil proteases and further metabolism of ET-1[1-32] was not a prerequisite for its biological actions on neutrophils. The neutrophil responses to ET-1[1-32] were mediated via activation of ET(A)receptors through activation of the Ras/Raf-1/MEK/ERK signaling pathway. These results suggest a novel role for gelatinase A and B in the regulation of neutrophil functions and their interactions with endothelial cells. Here we describe the methods in detail as they relate to our previously published work
Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues
<p>Abstract</p> <p>Background</p> <p>During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).</p> <p>Methods</p> <p>Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue.</p> <p>Results</p> <p>We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue.</p> <p>Conclusions</p> <p>Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.</p
Change in obsessive beliefs as predictor and mediator of symptom change during treatment of obsessive-compulsive disorder – a process-outcome study
- …