Elastic, anelastic, and piezoelectric coefficients of langasite: resonance ultrasound spectroscopy with laser-Doppler interferometry

This paper presents advanced techniques to determine all independent elastic-stiffness coefficients C/sub ij/, the associated internal friction Q/sub ij//sup -1/, and piezoelectric coefficients e/sub ij/ of monocrystal langasite (La/sub 3/Ga/sub 5/SiO/sub 14/) using a single rectangular parallelepiped specimen. Langasite's crystal structure belongs to the trigonal system with point group 32, and thus possesses six independent C/sub ij/, two e/sub ij/, and two dielectric coefficients /spl epsiv//sub ij/. All of the elastic and piezoelectric coefficients affect the mechanical resonance frequencies of the solid specimen, and measuring them very accurately permits one to determine the C/sub ij/ and e/sub ij/ with known density, dimensions, and e/sub ij/. We developed a piezoelectric tripod to support the specimen upward and measured the free-vibration resonance frequencies with minimum load from its own weight. This weak and stable acoustic coupling ensures accuracy of the frequency measurement better than 10/sup -5/, enough to determine the coefficients reliably. Our C/sub ij/ fall in the range of results measured with previous (conventional) methods. Our e/sub 11/ is smaller than the reported values by 1.2-13%, and e/sub 14/ is larger by 44-97%. For the internal friction measurement, we used a solenoid coil to vibrate the specimen without any contact. The longitudinal-wave internal friction considerably exceeds the shear-wave internal friction, which can be explained by phonon-phonon interactions.     

Developing independence in a life transition: Investing the self in the concerns of the day.

Developing independence involves mastering the tasks of each life transition. Those more anxious about developing independence will become more invested in the normative tasks of each transition, and this anxiety will spread to the domain represented by these tasks. In Study 1, Honors College students expressed their anxiety about developing independence in academic performance at the beginning of college when this was the normative task and in social relationships after college when this was the normative task. This anxiety could be distinguished from other (e.g., academic) anxiety. In Study 2, sorority women expressed anxiety about developing independence in family and sorority relationships. Data demonstrate the social construction of anxiety and the dynamics of personality change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

X-ray Fluorescence Uptake Measurement of Functionalized Gold Nanoparticles in Tumor Cell Microsamples

Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demonstrate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells. A comparison with mass spectroscopy quantification is provided, experimental results are both supported and sensitivity limits of this XFI approach extrapolated by Monte-Carlo simulations, yielding a minimum detectable nanoparticle mass of just 5 pg. This study demonstrates the high sensitivity level of XFI, allowing non-destructive uptake measurements with very small microsamples within just seconds of irradiation time.     

Structural Investigation and Molecular Modeling Studies of Strobilurin-Based Fungicides Active against the Rice Blast Pathogen Pyricularia oryzae

The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen.     

Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholesterol, polyunsaturated phospholipids and diacylglycerol species were noted in non-tumorous HBV compared to HCV liver. Moreover, polyunsaturated phospholipids and diacylglycerols, and ceramides declined in tumors of HBV infected patients. All of these lipids remained unchanged in HCV-related HCC. In HCV tumors, polyunsaturated phosphatidylinositol levels were even induced. There were no associations of these lipid classes in non-tumor tissues with hepatic inflammation and fibrosis scores. Moreover, these lipids did not correlate with tumor grade or T-stage in HCC tissues. Lipid reprogramming of the three analysed HBV/HCV related tumors mostly resembled HBV-HCC. Indeed, lipid composition of non-tumorous HCV tissue, HCV tumors, HBV tumors and HBV/HCV tumors was highly similar. The tumor suppressor protein p53 regulates lipid metabolism. The p53 and p53S392 protein levels were induced in the tumors of HBV, HCV and double infected patients, and this was significant in HBV infection. Negative correlation of tumor p53 protein with free cholesterol indicates a role of p53 in cholesterol metabolism. In summary, the current study suggests that therapeutic strategies to target lipid metabolism in chronic viral hepatitis and associated cancers have to consider disease etiology.     

Characterization of Apo-Form Selective Inhibition of Indoleamine 2,3-Dioxygenase**

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.