Alternative techniques for beam halo measurements

In future high intensity, high energy accelerators it must be ensured that particle losses are minimized, as activation of the vacuum chambers or other components makes maintenance and upgrade work time consuming and costly. It is imperative to have a clear understanding of the mechanisms that can lead to halo formation and to have the possibility to test available theoretical models with an adequate experimental setup. Measurements based on optical transition radiation (OTR) are a well-established technique for measurements of the transverse beam profile. However, in order to be suitable for halo measurements as well, the dynamic range of the final image acquisition system needs to be high, being able to cover at least five orders of magnitude in intensity changes. Here, the performance of a standard acquisition system as it is used in the CLIC test facility (CTF3) is compared to a step-by-step measurement with a small movable photo multiplier tube and an innovative camera system based on charge injection device (CID) technology. Special emphasis is given on a description of the characteristics of the latter system

Measurement of beam losses at the australian synchrotron

The unprecedented requirements that new machines are setting on their diagnostic systems is leading to the development of new generation of devices with large dynamic range, sensitivity and time resolution. Beam loss detection is particularly challenging due to the large extension of new facilities that need to be covered with localized detector. Candidates to mitigate this problem consist of systems in which the sensitive part of the radiation detectors can be extended over long distance of beam lines. In this document we study the feasibility of a BLM system based on optical f ber as an active detector for an electron storage ring. The Australian Synchrotron (AS) comprises a 216 m ring that stores electrons up to 3 GeV. The Accelerator has recently claimed the world record ultra low transverse emittance (below pm rad) and its surroundings are rich in synchrotron radiation. Therefore, the AS provides beam conditions very similar to those expected in the CLIC/ILC damping rings. A qualitative benchmark of beam losses in a damping ring-like environment is presented here. A wide range of beam loss rates can be achieved by modifying three beam parameters strongly correlated to the beam lifetime: bunch charge (with a variation range between 1 uA and 10 mA), horizontal/vertical coupling and of dynamic aperture. The controlled beam losses are observed by means of the Cherenkov light produced in a 365 μ m core Silica f ber. The output light is coupled to different type of photo sensors namely: Metal Semiconductor Metal (MSM), Multi Pixel Photon Counters (MPPCs), standard PhotoMulTiplier (PMT) tubes, Avalanche Photo- Diodes (APD) and PIN diodes. A detailed comparison of the sensitivities and time resolution obtained with the different read-outs are discussed in this contribution

Game semantic analysis of equivalence in IMJ

Using game semantics, we investigate the problem of verifying contextual equivalences in Interface Middleweight Java (IMJ), an imperative object calculus in which program phrases are typed using interfaces. Working in the setting where data types are non-recursive and restricted to finite domains, we identify the frontier between decidability and undecidability by reference to the structure of interfaces present in typing judgments. In particular, we show how to determine the decidability status of problem instances (over a fixed type signature) by examining the position of methods inside the term type and the types of its free identifiers. Our results build upon the recent fully abstract game semantics of IMJ. Decidability is proved by translation into visibly pushdown register automata over infinite alphabets with fresh-input recognition

The endothelial glycocalyx prefers albumin for evoking shear stress-induced, nitric oxide-mediated coronary dilatation

Background: Shear stress induces coronary dilatation via production of nitric oxide ( NO). This should involve the endothelial glycocalyx ( EG). A greater effect was expected of albumin versus hydroxyethyl starch ( HES) perfusion, because albumin seals coronary leaks more effectively than HES in an EG-dependent way. Methods: Isolated hearts ( guinea pigs) were perfused at constant pressure with Krebs-Henseleit buffer augmented with 1/3 volume 5% human albumin or 6% HES ( 200/0.5 or 450/0.7). Coronary flow was also determined after EG digestion ( heparinase) and with nitro-L-arginine ( NO-L-Ag). Results: Coronary flow ( 9.50 +/- 1.09, 5.10 +/- 0.49, 4.87 +/- 1.19 and 4.15 +/- 0.09 ml/ min/ g for `albumin', `HES 200', `HES 450' and `control', respectively, n = 5-6) did not correlate with perfusate viscosity ( 0.83, 1.02, 1.24 and 0.77 cP, respectively). NO-L-Ag and heparinase diminished dilatation by albumin, but not additively. Alone NO-L-Ag suppressed coronary flow during infusion of HES 450. Electron microscopy revealed a coronary EG of 300 nm, reduced to 20 nm after heparinase. Cultured endothelial cells possessed an EG of 20 nm to begin with. Conclusions: Albumin induces greater endothelial shear stress than HES, despite lower viscosity, provided the EG contains negative groups. HES 450 causes some NO-mediated dilatation via even a rudimentary EG. Cultured endothelial cells express only a rudimentary glycocalyx, limiting their usefulness as a model system. Copyright (c) 2007 S. Karger AG, Basel

Diverse and Active Roles for Adipocytes During Mammary Gland Growth and Function

The mammary gland is unique in its requirement to develop in close association with a depot of adipose tissue that is commonly referred to as the mammary fat pad. As discussed throughout this issue, the mammary fat pad represents a complex stromal microenvironment that includes a variety of cell types. In this article we focus on adipocytes as local regulators of epithelial cell growth and their function during lactation. Several important considerations arise from such a discussion. There is a clear and close interrelationship between different stromal tissue types within the mammary fat pad and its adipocytes. Furthermore, these relationships are both stage- and species-dependent, although many questions remain unanswered regarding their roles in these different states. Several lines of evidence also suggest that adipocytes within the mammary fat pad may function differently from those in other fat depots. Finally, past and future technologies present a variety of opportunities to model these complexities in order to more precisely delineate the many potential functions of adipocytes within the mammary glands. A thorough understanding of the role for this cell type in the mammary glands could present numerous opportunities to modify both breast cancer risk and lactation performance

Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardization

BACKGROUND: In order to establish a consistent method for brachial artery reactivity assessment, we analyzed commonly used approaches to the test and their effects on the magnitude and time-course of flow mediated dilation (FMD), and on test variability and repeatability. As a popular and noninvasive assessment of endothelial function, several different approaches have been employed to measure brachial artery reactivity with B-mode ultrasound. Despite some efforts, there remains a lack of defined normal values and large variability in measurement technique. METHODS: Twenty-six healthy volunteers underwent repeated brachial artery diameter measurements by B-mode ultrasound. Following baseline diameter recordings we assessed endothelium-dependent flow mediated dilation by inflating a blood pressure cuff either on the upper arm (proximal) or on the forearm (distal). RESULTS: Thirty-seven measures were performed using proximal occlusion and 25 with distal occlusion. Following proximal occlusion relative to distal occlusion, FMD was larger (16.2 ± 1.2% vs. 7.3 ± 0.9%, p < 0.0001) and elongated (107.2 s vs. 67.8 s, p = 0.0001). Measurement of the test repeatability showed that differences between the repeated measures were greater on average when the measurements were done using the proximal method as compared to the distal method (2.4%; 95% CI 0.5–4.3; p = 0.013). CONCLUSION: These findings suggest that forearm compression holds statistical advantages over upper arm compression. Added to documented physiological and practical reasons, we propose that future studies should use forearm compression in the assessment of endothelial function

MCAM: Multiple Clustering Analysis Methodology for Deriving Hypotheses and Insights from High-Throughput Proteomic Datasets

Advances in proteomic technologies continue to substantially accelerate capability for generating experimental data on protein levels, states, and activities in biological samples. For example, studies on receptor tyrosine kinase signaling networks can now capture the phosphorylation state of hundreds to thousands of proteins across multiple conditions. However, little is known about the function of many of these protein modifications, or the enzymes responsible for modifying them. To address this challenge, we have developed an approach that enhances the power of clustering techniques to infer functional and regulatory meaning of protein states in cell signaling networks. We have created a new computational framework for applying clustering to biological data in order to overcome the typical dependence on specific a priori assumptions and expert knowledge concerning the technical aspects of clustering. Multiple clustering analysis methodology (‘MCAM’) employs an array of diverse data transformations, distance metrics, set sizes, and clustering algorithms, in a combinatorial fashion, to create a suite of clustering sets. These sets are then evaluated based on their ability to produce biological insights through statistical enrichment of metadata relating to knowledge concerning protein functions, kinase substrates, and sequence motifs. We applied MCAM to a set of dynamic phosphorylation measurements of the ERRB network to explore the relationships between algorithmic parameters and the biological meaning that could be inferred and report on interesting biological predictions. Further, we applied MCAM to multiple phosphoproteomic datasets for the ERBB network, which allowed us to compare independent and incomplete overlapping measurements of phosphorylation sites in the network. We report specific and global differences of the ERBB network stimulated with different ligands and with changes in HER2 expression. Overall, we offer MCAM as a broadly-applicable approach for analysis of proteomic data which may help increase the current understanding of molecular networks in a variety of biological problems.National Institutes of Health (U.S.) (NIH-U54-CA112967 )National Institutes of Health (U.S.) (NIH-R01-CA096504

Deficiency of FLCN in Mouse Kidney Led to Development of Polycystic Kidneys and Renal Neoplasia

The Birt–Hogg–Dubé (BHD) disease is a genetic cancer syndrome. The responsible gene, BHD, has been identified by positional cloning and thought to be a novel tumor suppressor gene. BHD mutations cause many types of diseases including renal cell carcinomas, fibrofolliculomas, spontaneous pneumothorax, lung cysts, and colonic polyps/cancers. By combining Gateway Technology with the Ksp-Cre gene knockout system, we have developed a kidney-specific BHD knockout mouse model. BHDflox/flox/Ksp-Cre mice developed enlarged kidneys characterized by polycystic kidneys, hyperplasia, and cystic renal cell carcinoma. The affected BHDflox/flox/Ksp-Cre mice died of renal failure at approximate three weeks of age, having blood urea nitrogen levels over tenfold higher than those of BHD flox/+/Ksp-Cre and wild-type littermate controls. We further demonstrated that these phenotypes were caused by inactivation of BHD and subsequent activation of the mTOR pathway. Application of rapamycin, which inhibits mTOR activity, to the affected mice led to extended survival and inhibited further progression of cystogenesis. These results provide a correlation of kidney-targeted gene inactivation with renal carcinoma, and they suggest that the BHD product FLCN, functioning as a cyst and tumor suppressor, like other hamartoma syndrome–related proteins such as PTEN, LKB1, and TSC1/2, is a component of the mTOR pathway, constituting a novel FLCN-mTOR signaling branch that regulates cell growth/proliferation