Conceptual design of storage ring magnets for a diffraction limited light source upgrade of ALS, ALS-U

Lawrence Berkeley National Laboratory (LBNL) has been engaged in an internal laboratory directed research and development project to define a suitable accelerator physics lattice to support the diffraction limited upgrade of the Advanced Light Source (ALS). [1] Diffraction limited lattices require strong focusing elements throughout. Magnetics design is challenging in that the high gradient magnetic structures are required to operate in close proximity. Lattice development requires a coordinated engineering design effort to ensure the lattice design feasibility. We will present a review of the results of our magnet scoping studies as well as conceptual design specifications for the ALS-U lattice dipole, quadrupole, and sextupole magnet systems

Calpain cleavage and subcellular characterisation of the ferlin family.

The ferlins are a family of C2-domain containing proteins. C2 domains regulate vesicle fusion in synaptotagmins, and animal models of ferlin deficiency display pathologies related to Ca2+-dependent vesicle fusion. Dysferlin mutations cause limb-girdle muscular dystrophy due to defective membrane repair. Our group has previously shown that Ca2+-dependent proteases, calpains, cleave dysferlin following membrane injury, releasing mini-dysferlinC72, that we hypothesise mediates membrane repair. Otoferlin mutations cause non-syndromic deafness, while no pathology causing mutations have been identified in other ferlins. My project establishes that dysferlin and myoferlin, type-I ferlins, are present at the plasma membrane and endo-lysosomal pathway while otoferlin and Fer1L6, type-II ferlins, are present at the plasma membrane and recycling trans-Golgi compartments. I also show that dysferlin is cleaved to mini-dysferlinC72 following injury in all cell types by the ubiquitous calpains-1 and -2 in the alternatively spliced exon 40a, indicating dysferlin cleavage is a fundamental response to membrane injury. Exon 40a-containing dysferlin recruits to sites of membrane injury in myotubes, indicating mini-dysferlinC72 may function directly at sites of injury. Finally, I have shown that calpains also cleave otoferlin and myoferlin. Cleavage of other ferlins indicates ferlin cleavage is an evolutionarily conserved event, predating the split between type-I and type-II ferlins

Sigma-2 receptors as a biomarker of proliferation in solid tumours

Over the past several years, our group has provided considerable evidence that the expression of sigma-2 (σ2) receptors may serve as a biomarker of tumour cell proliferation. In these in vitro studies, σ2receptors were expressed 8–10 times more in proliferative (P) tumour cells than in quiescent (Q) tumour cells, and the extent and kinetics of their expression were independent of a number of biological, physiological and environmental factors often found in solid tumours. Moreover, the expression of σ2receptors followed both the population growth kinetics when Q-cells were recruited into the P-cell compartment and the proliferative status of human breast tumour cells treated with cytostatic concentrations of tamoxifen. However, these in vitro studies may or may not be indicative of what might occur in solid tumours. In the present study, the σ2receptor P:Q ratio was determined for the cells from subcutaneous 66 (diploid) and 67 (aneuploid) tumours grown in female nude mice. The σ2receptor P:Q ratio of the 66 tumours was 10.6 compared to the σ2receptor P:Q ratio of 9.5 measured for the 66 tissue culture model. The σ2receptor P:Q ratio of the 67 tumours was 4.5 compared to the σ2receptor P:Q ratio of ≈ 8 measured for the 67 tissue culture model. The agreement between the solid tumour and tissue culture data indicates that: (1) the expression of σ2receptors may be a reliable biomarker of the proliferative status of solid tumours and (2) radioligands with both high affinity and high selectivity for σ2receptors may have the potential to non-invasively assess the proliferative status of human solid tumours using imaging techniques such as positron emission tomography or single-photon emission computerized tomography. © 2000 Cancer Research Campaig

Vibrational dynamics of a two-dimensional microgranular crystal

We study the dynamics of an ordered hexagonal monolayer of polystyrene microspheres adhered to a glass substrate coated with a thin aluminum layer. A laser-induced transient grating technique is employed to generate and detect three types of acoustic modes across the entire Brillouin zone in the Γ−K direction: low-frequency contact-based modes of the granular monolayer, high-frequency modes originating from spheroidal vibrations of the microspheres, and surface Rayleigh waves. The dispersion relation of contact-based and spheroidal modes indicates that they are collective modes of the microgranular crystal controlled by particle-particle contacts. We observe a spheroidal resonance splitting caused by the symmetry breaking due to the substrate, as well as an avoided crossing between the Rayleigh and spheroidal modes. The measurements are found to be in agreement with our analytical model.United States. Department of Energy (Grant DE-FG02-00ER15087)National Science Foundation (U.S.) (Grant CHE-1111557

Effect of ploidy, recruitment, environmental factors, and tamoxifen treatment on the expression of sigma-2 receptors in proliferating and quiescent tumour cells

Recently, we demonstrated that sigma-2 receptors may have the potential to be a biomarker of tumour cell proliferation (Mach et al (1997) Cancer Res57: 156–161). If sigma-2 receptors were a biomarker of tumour cell proliferation, they would be amenable to detection by non-invasive imaging procedures, thus eliminating many of the problems associated with the flow cytometric measures of tumour cell proliferation presently used in the clinic. To be a good biomarker of tumour cell proliferation, the expression of sigma-2 receptors must be essentially independent of many of the biological, physiological, and/or environmental properties that are found in solid tumours. In the investigation reported here, the mouse mammary adenocarcinoma lines, 66 (diploid) and 67 (aneuploid), 9L rat brain tumour cells, and MCF-7 human breast tumour cells were used to study the extent and kinetics of expression of sigma-2 receptors in proliferative (P) and quiescent (Q) tumour cells as a function of species, cell type, ploidy, pH, nutrient depletion, metabolic state, recruitment from the Q-cell compartment to the P-cell compartment, and treatment with tamoxifen. In these experiments, the expression of sigma-2 receptors solely reflected the proliferative status of the tumour cells. None of the biological, physiological, or environmental properties that were investigated had a measurable effect on the expression of sigma-2 receptors in these model systems. Consequently, these data suggest that the proliferative status of tumours and normal tissues can be non-invasively assessed using radiolabelled ligands that selectively bind sigma-2 receptors. © 1999 Cancer Research Campaig

Prevention and management of complications following robot-assisted radical cystectomy: lessons learned after >250 consecutive cases

An increasing number of case series of robot-assisted radical cystectomy describe complication rates comparable to open series. Conflicting reports describe various pre-operative factors as predictors of post-operative complications. Furthermore, learning curves complicate these predictors and should also be taken into account. Despite these variables, there are a number of considerations, including patient selection, peri-operative care pathway, intra-operative technique and equipment choice that we have found to decrease post-operative complications and improve patient outcomes. In this topic paper, we briefly review the literature surrounding complication rates following robot-assisted radical cystectomy as well as describe our experience after >250 cases, outlining our suggestions for avoidance of surgical complications when building a practice that incorporates this technique

Building Innovative Online Korean and Japanese Courses: A Pilot on Technology- Enhanced Curriculum Development

Our pilot project created blended/online courses to accommodate the growing needs of precollegiate and collegiate students interested in learning Korean and Japanese. In the initial phase, we conducted a survey of students’ experiences with and perceptions about blended/online Asian language learning. We found a general lack of familiarity with, and moderate resistance toward, online language learning modes. With learner attitudes in mind, we developed online modules for beginning Korean and Japanese courses. In this article, we report the survey results and the process of developing these innovative blended and online modalities of content delivery, focusing on the strengths of the modules and the unforeseen development challenges. The impacts that these technology-enhanced environments may have on student perceptions of transactional distance and tele-/copresence are explored. We suggest that transforming conventional East Asian language courses into blended/online modes is not only feasible but also beneficial for foreign language teaching and learning

Gender Differences in Compensation, Job Satisfaction and Other Practice Patterns in Urology

The proportion of women in urology has increased from <0.5% in 1981 to 10% today. Furthermore, 33% of students matching in urology are now female. This analysis sought to characterize the female workforce in urology in comparison to men with regard to income, workload, and job satisfaction