Development of the normalization method for the Jagiellonian PET scanner

This work aims at applying the theory of the component-based normalization for the Jagiellonian PET scanner, currently under development at the Jagiellonian University. In any Positron Emission Tomography acquisition, efficiency along a line-of-response can vary due to several physical and geometrical effects, leading to severe artifacts in the reconstructed image. To mitigate these effects, a normalization coefficient is applied to each line-of-response, defined as the product of several components. Specificity of the Jagiellonian PET scanner geometry is taken into account. Results obtained from GATE simulations are compared with preliminary results obtained from experimental data.Comment: 8 pages, 6 figures, submitted to Acta Physica Polonica

Changes Over Time in Masters Level School Counselor Education Programs

A national survey regarding the preparation of entry-level school counseling students was conducted to assess changes over time that may have occurred in the credit hours, screening methods, faculty experiences, course content, fieldwork requirements, and importance of The Education Trust concepts. Key findings include increases in the number of faculty with school counseling experience and the number of programs requiring practicum and internship to be completed in a school setting, and decreases in the number of courses designed specifically for school counseling students and the importance of supervision

Changes Over Time in Masters Level School Counselor Education Programs

A national survey regarding the preparation of entry-level school counseling students was conducted to assess changes over time that may have occurred in the credit hours, screening methods, faculty experiences, course content, fieldwork requirements, and importance of The Education Trust concepts. Key findings include increases in the number of faculty with school counseling experience and the number of programs requiring practicum and internship to be completed in a school setting, and decreases in the number of courses designed specifically for school counseling students and the importance of supervision

The Importance and Implementation of Eight Components of College and Career Readiness Counseling in School Counselor Education Programs

School counselor education program administrators (N = 131) responded to an online questionnaire where the importance and extent of implementation of The College Board’s National Office of School Counselor Advocacy (NOSCA) Eight Components of College and Career Readiness in their school counselor education program were assessed. The mean importance of the components was rated between ‘moderately important’ and ‘very important’ by participants, and the components were ‘usually’ implemented in the curriculum of their programs. Implications of this study include the need for increased attention in graduate-level school counselor training programs on equity-focused college and career readiness counseling and knowledge of current national initiatives

Effect of Airfoil Parametrization on the Optimization of Counter Rotating Open Rotors

The present study compares two optimizations performed on Counter Rotating Open Rotors (CRORs) running at the same operating condition. The main difference between the two optimizations is the airfoil profile used to construct the blades. The first, uses the NACA 16 family of airfoils, whereas the second one, uses a parametrized airfoil type, CST. Two independent multi-objective optimizations are carried out using approximately the same computational resources. All the design variables except those concerning the airfoil profile, are kept with the same design freedom so that a fair comparison can be made. Both sets of configurations are aerodynamically optimized for maximum thrust coefficient and efficiency at top of climb conditions. The optimization is performed using multi-objective Differential Evolution (DE) coupled with 3D RANS simulations and Radial Basis Function (RBF) meta-modeling

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Regulation of proteasome assembly and activity in health and disease

The proteasome degrades most cellular proteins in a controlled and tightly regulated manner and thereby controls many processes, including cell cycle, transcription, signalling, trafficking and protein quality control. Proteasomal degradation is vital in all cells and organisms, and dysfunction or failure of proteasomal degradation is associated with diverse human diseases, including cancer and neurodegeneration. Target selection is an important and well-established way to control protein degradation. In addition, mounting evidence indicates that cells adjust proteasome-mediated degradation to their needs by regulating proteasome abundance through the coordinated expression of proteasome subunits and assembly chaperones. Central to the regulation of proteasome assembly is TOR complex 1 (TORC1), which is the master regulator of cell growth and stress. This Review discusses how proteasome assembly and the regulation of proteasomal degradation are integrated with cellular physiology, including the interplay between the proteasome and autophagy pathways. Understanding these mechanisms has potential implications for disease therapy, as the misregulation of proteasome function contributes to human diseases such as cancer and neurodegeneration.</p

An engineered, quantifiable<i> in vitro </i>model for analysing the effect of proteostasis-targeting drugs on tissue physical properties

Cellular function depends on the maintenance of protein homeostasis (proteostasis) by regulated protein degradation. Chronic dysregulation of proteostasis is associated with neurodegenerative and age-related diseases, and drugs targeting components of the protein degradation apparatus are increasingly used in cancer therapies. However, as chronic imbalances rather than loss of function mediate their pathogenesis, research models that allow for the study of the complex effects of drugs on tissue properties in proteostasis-associated diseases are almost completely lacking. Here, to determine the functional effects of impaired proteostatic fine-tuning, we applied a combination of materials science characterisation techniques to a cell-derived, in vitro model of bone-like tissue formation in which we pharmacologically perturbed protein degradation. We show that low-level inhibition of VCP/p97 and the proteasome, two major components of the degradation machinery, have remarkably different effects on the bone-like material that human bone-marrow derived mesenchymal stromal cells (hMSC) form in vitro. Specifically, whilst proteasome inhibition mildly enhances tissue formation, Raman spectroscopic, atomic force microscopy-based indentation, and electron microscopy imaging reveal that VCP/p97 inhibition induces the formation of bone-like tissue that is softer, contains less protein, appears to have more crystalline mineral, and may involve aberrant micro- and ultra-structural tissue organisation. These observations contrast with findings from conventional osteogenic assays that failed to identify any effect on mineralisation. Taken together, these data suggest that mild proteostatic impairment in hMSC alters the bone-like material they form in ways that could explain some pathologies associated with VCP/p97-related diseases. They also demonstrate the utility of quantitative materials science approaches for tackling long-standing questions in biology and medicine, and could form the basis for preclinical drug testing platforms to develop therapies for diseases stemming from perturbed proteostasis or for cancer therapies targeting protein degradation. Our findings may also have important implications for the field of tissue engineering, as the manufacture of cell-derived biomaterial scaffolds may need to consider proteostasis to effectively replicate native tissues

Caspase involvement in autophagy

Caspases are a family of cysteine proteases widely known as the principal mediators of the apoptotic cell death response, but considerably less so as the contributors to the regulation of pathways outside cellular demise. In regards to autophagy, the modulatory roles of caspases have only recently begun to be adequately described. In contrast to apoptosis, autophagy promotes cell survival by providing energy and nutrients through the lysosomal degradation of cytoplasmic constituents. Under basal conditions autophagy and apoptosis cross-regulate each other through an elaborate network of interconnections which also includes the interplay between autophagyrelated proteins (ATGs) and caspases. In this review we focus on the effects of this crosstalk at the cellular level, as we aim to concentrate the main observations from research conducted so far on the fine-tuning of autophagy by caspases. Several members of this protease-family have been found to directly interact with key ATGs involved in different tiers across the autophagic cascade. Therefore, we firstly outline the core mechanism of macroautophagy in brief. In an effort to emphasize the importance of the intricate cross-regulation of ATGs and caspases, we also present examples drawn from Drosophila and plant models regarding the contribution of autophagy to apoptotic cell death during normal development

The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation

VCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. Its key role in governing protein homoeostasis has made VCP/p97 an appealing anticancer drug target. Here, we provide evidence that VCP/p97 acts as a regulator of cellular metabolism. We found that VCP/p97 was tied to multiple metabolic processes on the gene expression level in a diverse range of cancer cell lines and in patient-derived multiple myeloma cells. Cellular VCP/p97 dependency to maintain proteostasis was increased under conditions of glucose and glutamine limitation in a range of cancer cell lines from different tissues. Moreover, glutamine depletion led to increased VCP/p97 expression, whereas VCP/p97 inhibition perturbed metabolic processes and intracellular amino acid turnover. GCN2, an amino acid-sensing kinase, attenuated stress signalling and cell death triggered by VCP/p97 inhibition and nutrient shortages and modulated ERK activation, autophagy, and glycolytic metabolite turnover. Together, our data point to an interconnected role of VCP/p97 and GCN2 in maintaining cancer cell metabolic and protein homoeostasis