The Benefactor: Assessing the Financial Performance of Charitable Organizations

This project provides students with a simulation of the process used by many private foundations in distributing grants to charities. In particular, the project is based on a fictitious benefactor of a large private foundation who has decided to appoint accounting students to grant-making committees. The committees are responsible for using not-for-profit specific financial performance measures to evaluate local charities and determine which charities should be awarded grants. The charities determined to have the strongest financial performance are awarded operating grants from the private foundation. The project complements traditional lecturing methods by providing a realistic context for introducing students to the importance of the not-for-profit sector and the accounting and financial performance issues faced by charitable organizations

Changes in intracellular ion activities induced by adrenaline in human and rat skeletal muscle

To study the stimulating effect of adrenaline (ADR) on active Na+/K+ transport we used double-barrelled ion-sensitive micro-electrodes to measure the activities of extracellular K+ (aKe) and intracellular Na+ (aNai) in isolated preparations of rat soleus muscle, normal human intercostal muscle and one case of hyperkalemic periodic paralysis (h.p.p.). In these preparations bath-application of ADR (10−6 M) resulted in a membrane hyperpolarization and transient decreasesaKe andaNai which could be blocked by ouabain (3×10−4 M). In the h.p.p. muslce a continuous rise ofaNai induced by elevation ofaKe to 5.2 mM could be stopped by ADR. In addition, the intracellular K+ activity (aKi), the free intracellular Ca2+ concentration (pCai) and intracellular pH (pHi) were monitored in rat soleus muscle. During ADRaKi increased, pHi remained constant and intracellular Ca2+ apparently decreased. In conclusion, our data show that ADR primarily stimulates the Na+/K+ pump in mammalian skeletal muscle. This stimulating action is not impaired in the h.p.p. muscle

Spitzer-MIPS Observations of the eta Cha Young Association

We have mapped the eta Chamaeleontis young stellar association in the far-infrared with the Multiband Imaging Photometer for Spitzer (MIPS) on the Spitzer Space Telescope. All sixteen members within the map region were detected at 24 um, along with five members at 70 um and two at 160 um. Ten stars show far-infrared excess emission indicating the presence of circumstellar disks; six of these have central clearings as evidenced by the onset of excess emission at >5 um. No new infrared excess sources are identified among the 113 2MASS field stars with 24 um photometry but not seen as X-ray sources, indicating that membership lists derived from X-ray surveys are reasonably complete. Circumstellar disks in the eta Cha association span the range from 1e-1 to 1e-4 in their fractional infrared luminosity, with a median Ldust /Lstar of 0.04. The presence of optically thick, optically thin, and intermediate optical depth disks within the same stellar group, in combination with the large fraction of disks with inner holes, indicates that the Cha association represents a crucial stage in circumstellar disk evolution.Comment: To appear in The Astrophysical Journa

Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells

Immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. One recent example targeted the virus-encoded G protein-coupled receptor US28 as a strategy for specific and efficient treatment of human cytomegalovirus (HCMV) infections. US28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. The chemokine-based fusion-toxin protein (FTP) consisted of a variant (F49A) of CX3CL1 specifically targeting US28 linked to the catalytic domain of Pseudomonas exotoxin A (PE). Here, we systematically seek to improve F49A-FTP by modifications in its three structural domains; we generated variants with (1) altered chemokine sequence (K14A, F49L, and F49E), (2) shortened and elongated linker region, and (3) modified toxin domain. Only F49L-FTP displayed higher selectivity in its binding to US28 versus CX3CR1, the endogenous receptor for CX3CL1, but this was not matched by a more selective killing of US28-expressing cells. A longer linker and different toxin variants decreased US28 affinity and selective killing. Thereby, F49A-FTP represents the best candidate for HCMV treatment. Many viruses encode internalizing receptors suggesting that not only HCMV but also, for instance, Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus may be targeted by FTPs

Osteoidosis leads to altered differentiation and function of osteoclasts

In patients with osteomalacia, a defect in bone mineralization leads to changed characteristics of the bone surface. Considering that the properties of the surrounding matrix influence function and differentiation of cells, we aimed to investigate the effect of osteoidosis on differentiation and function of osteoclasts. Based on osteomalacic bone biopsies, a model for osteoidosis in vitro (OIV) was established. Peripheral blood mononuclear cells were differentiated to osteoclasts on mineralized surfaces (MS) as internal control and on OIV. We observed a significantly reduced number of osteoclasts and surface resorption on OIV. Atomic force microscopy revealed a significant effect of the altered degree of mineralization on surface mechanics and an unmasking of collagen fibres on the surface. Indeed, coating of MS with RGD peptides mimicked the resorption phenotype observed in OIV, suggesting that the altered differentiation of osteoclasts on OIV might be associated with an interaction of the cells with amino acid sequences of unmasked extracellular matrix proteins containing RGD sequences. Transcriptome analysis uncovered a strong significant up-regulation of transmembrane glycoprotein TROP2 in osteoclastic cultures on OIV. TROP2 expression on OIV was also confirmed on the protein level and found on the bone surface of patients with osteomalacia. Taken together, our results show a direct influence of the mineralization state of the extracellular matrix surface on differentiation and function of osteoclasts on this surface which may be important for the pathophysiology of osteomalacia and other bone disorders with changed ratio of osteoid to bone

Optical Cherenkov radiation by cascaded nonlinear interaction: an efficient source of few-cycle energetic near- to mid-IR pulses

When ultrafast noncritical cascaded second-harmonic generation of energetic femtosecond pulses occur in a bulk lithium niobate crystal optical Cherenkov waves are formed in the near- to mid-IR. Numerical simulations show that the few-cycle solitons radiate Cherenkov (dispersive) waves in the \lambda=2.2-4.5\mic range when pumping at \lambda_1=1.2-1.8\mic. The exact phase-matching point depends on the soliton wavelength, and we show that a simple longpass filter can separate the Cherenkov waves from the solitons. The Cherenkov waves are born few-cycle with an excellent Gaussian pulse shape, and the conversion efficiency is up to 25%. Thus, optical Cherenkov waves formed with cascaded nonlinearities could become an efficient source of energetic near- to mid-IR few-cycle pulses.Comment: Extended version of Nonlinear Optics 2011 contribution http://www.opticsinfobase.org/abstract.cfm?URI=NLO-2011-NTuA7. Submitted for Optics Express special issue for NLO conferenc