The internal audit function is evolving from its traditional oversight function to one that includes a wider spectrum of activities that add value to their organizations. In addition, economic pressures have forced many companies to consider outsourcing as an alternative. These ongoing changes have caused some concern regarding the potential lack of objectivity and independence for internal auditors. This exploratory study examines whether outsourcing of the internal audit function is susceptible to client advocacy vis-a`-vis in-house auditing, which itself may be sensitive to an employer advocacy Sixty-six practicing members of the Institute of Internal Auditors (IIA) completed a case study involving a corporate acquisition scenario. Of the 66 participants, 35 were from corporations (in-house), while the remaining 31 were from the Big 4 accounting firms (outsource). Advocacy was manipulated by asking participants to assume the role of internal auditor for either the buyer or the seller of a target division. Result s indicate that significant advocacy existed in the judgments of both in-house and outsource internal auditors. However, the extent of advocacy was less severe in the case of outsource auditors.

J. Neurochem. (2008) 104, 1494–1503. Abstract Reduced derivatives of folic acid (folates) play a critical role in the development, function and repair of the CNS. However, the molecular systems regulating folate uptake and homeostasis in the central nervous system remain incompletely defined. Choroid plexus epithelial cells express high levels of folate receptor α (FRα) suggesting that the choroid plays an important role in CNS folate trafficking and maintenance of CSF folate levels. We have characterized 5‐methyltetrahydrofolate (5‐MTHF) uptake and metabolism by primary rat choroid plexus epithelial cells in vitro. Two distinct processes are apparent; one that is FRα dependent and one that is independent of the receptor. FRα binds 5‐MTHF with high affinity and facilitates efficient uptake of 5‐MTHF at low extracellular folate concentrations; a lower affinity FRα independent system accounts for increased folate uptake at higher concentrations. Cellular metabolism of 5‐MTHF depends on the route of folate entry into the cell. 5‐MTHF taken up via a non‐FRα ‐mediated process is rapidly metabolized to folylpolyglutamates, whereas 5‐MTHF that accumulates via FRα remains non‐metabolized, supporting the hypothesis that FRα may be part of a pathway for transcellular movement of the vitamin. The proton‐coupled folate transporter, proton‐coupled folate transporter (PCFT), mRNA was also shown to be expressed in choroid plexus epithelial cells. This is consistent with the role we have proposed for proton‐coupled folate transporter in FRα‐mediated transport as the mechanism of export of folates from the endocytic compartment containing FRα.

Purpose: Brain metastases are a common preterminal event in patients with metastatic melanoma and require radiation therapy. Our group has previously shown that human GRM1 (hGRM1) expressing melanoma cells release excess extracellular glutamate and are growth inhibited by riluzole, an inhibitor of glutamate release. Riluzole-treated cells accumulate in G 2 /M phase of the cell cycle at 24 hours, and then undergo apoptotic cell death. We evaluated whether riluzole enhanced radiosensitivity in melanoma cells.Experimental Design: Clonogenic assays were performed to evaluate clonogenic survival after treatment in hGRM1 expressing and nonexpressing melanoma cells. Western immunoblots were performed to confirm apoptotic cell death. A xenograft mouse model was used to validate the in vitro experiments. Tumors harvested from the xenografts were fixed and stained for apoptosis and DNA damage markers.Results: In the hGRM1-positive cell lines C8161 and UACC903, riluzole enhanced the lethal effects of ionizing radiation; no difference was seen in the hGRM1-negative UACC930 cell line. C8161 cells treated with riluzole plus irradiation also showed the highest levels of the cleaved forms of PARP and caspase-3; excised C8161 xenografts showed the greatest number of apoptotic cells by immunohistochemistry (P < 0.001). On cell cycle analysis, a sequence-dependent enrichment in the G 2 /M phase was shown with the combination of riluzole and irradiation. Xenografts treated with riluzole and weekly radiation fractions showed significant growth inhibition and revealed markedly increased DNA damage.Conclusions: We have shown, in vitro and in vivo, that the combination of riluzole and ionizing radiation leads to greater cytotoxicity. These results have clinical implications for patients with brain metastases receiving whole brain radiation therapy.

Near-infrared laser (785-nm)-excited Raman spectra from a red blood cell, optically trapped using the same laser beam, show significant changes as a function of trapping duration even at trapping power level of a few milliwatts. These changes in the Raman spectra and the bright-field images of the trapped cell, which show a gradual accumulation of the cell mass at the trap focus, suggest photoinduced aggregation of intracellular heme. The possible role of photoinduced protein denaturation and hemichrome formation in the observed aggregation of heme is discussed.

We report the use of Laguerre-Gaussian (LG) modes for controlled orientation and rotation of optically trapped red blood cells (RBCs). For LG modes with increasing topological charge the resulting increase in size of the intensity annulas led to trapping of the cells at larger tilt angle with respect to the beam axis and thus provided additional control on the stable orientation of the cells under trap. Further, the RBCs could also be driven as micro-rotors by a transfer of orbital angular momentum from the LG trapping beam having large topological charge or by rotating the profile of LG mode having fractional topological charge.

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Raman spectroscopy was performed on optically trapped red blood cells (RBCs) from blood samples of healthy volunteers (h-RBCs) and from patients suffering from P. vivax infection (m-RBCs). A significant fraction of m-RBCs produced Raman spectra with altered characteristics relative to h-RBCs. The observed spectral changes suggest a reduced oxygen-affinity or right shifting of the oxygen-dissociation curve for the intracellular hemoglobin in a significant fraction of m-RBCs with respect to its normal functional state.