Activation of rat parotid low Km cyclic AMP phosphodiesterase by isoproterenol

Approximately 94% of rat parotid cyclic AMP phosphodiesterase activity measured at a substrate concentration of 0.1 microM cyclic AMP was found in the 100,000 X g supernatant while the remaining enzyme activity was in the particulate fraction. Incubation of parotid slices with 10 microM isoproterenol resulted in approximately 40% activation of the cyclic AMP phosphodiesterase activity of the 100,000 X g supernatant. The enzyme activity in the particulate fraction was unaffected. The activation resulted from an increase in the value of the Vmax while the apparent Km (0.51 microM) was unaffected. The concentration of isoproterenol required to give half-maximal activation was 0.34 microM. The activation was rapid, became significant after 2 min and reached maximum after 30 min incubation of the parotid slices with isoproterenol. The activation of the enzyme activity by isoproterenol could be blocked by propanolol but was unaffected by cycloheximide. Dibutyryl-cyclic AMP was also effective while phenylephrine and carbamylcholine were ineffective in increasing the activity of the enzyme.     

A Novel Measure of Chromosome Instability Can Account for Prognostic Difference in Multiple Myeloma

Multiple myeloma (MM) is characterized by complex genetic abnormalities whose complexity signifies varying degree of chromosomal instability (CIN). In this study, we introduced a novel CIN measure, chromosome instability genome event count (CINGEC), which considered both copy number aberrations and interstitial breakpoints from high-resolution genome-wide assays. When assessed in two aCGH MM datasets, higher CINGEC was associated with poor survival. We then derived a CINGEC-associated gene expression profile (GEP) signature, CINGECS, using a dataset that has both aCGH and GEP. Genes in CINGECS were mainly involved in DNA damage responses besides in aneuploidy and other generic oncogenic processes contrary to other CIN associated GEP signatures. Finally, we confirmed its survival association in three GEP datasets that encompassed newly diagnosed patients treated with transplant-based protocol with or without novel agents for induction as well as relapsed patients treated with bortezomib. Furthermore, CINGECS was independent of many GEP-based prognostic signatures. In conclusion, our novel CIN measure has definite biological and clinical significance in myeloma.     

MRI-Based Intelligence Quotient (IQ) Estimation with Sparse Learning

In this paper, we propose a novel framework for IQ estimation using Magnetic Resonance Imaging (MRI) data. In particular, we devise a new feature selection method based on an extended dirty model for jointly considering both element-wise sparsity and group-wise sparsity. Meanwhile, due to the absence of large dataset with consistent scanning protocols for the IQ estimation, we integrate multiple datasets scanned from different sites with different scanning parameters and protocols. In this way, there is large variability in these different datasets. To address this issue, we design a two-step procedure for 1) first identifying the possible scanning site for each testing subject and 2) then estimating the testing subject’s IQ by using a specific estimator designed for that scanning site. We perform two experiments to test the performance of our method by using the MRI data collected from 164 typically developing children between 6 and 15 years old. In the first experiment, we use a multi-kernel Support Vector Regression (SVR) for estimating IQ values, and obtain an average correlation coefficient of 0.718 and also an average root mean square error of 8.695 between the true IQs and the estimated ones. In the second experiment, we use a single-kernel SVR for IQ estimation, and achieve an average correlation coefficient of 0.684 and an average root mean square error of 9.166. All these results show the effectiveness of using imaging data for IQ prediction, which is rarely done in the field according to our knowledge.     

Continuous versus intraoperative expansion in the pig model.

Continuous tissue expansion utilizing a continuous infusion device that maintains a constant expander pressure was previously demonstrated to be feasible and successful in obtaining rapid tissue expansion in a canine model. Intraoperative tissue expansion has been described and has gained some clinical acceptance as a method to gain rapid expansion. We compared the efficacy of continuous tissue expansion versus intraoperative tissue expansion in a piglet model. After completing a pilot study, continuous tissue expansion was performed in six pigs (14.5 to 20 kg) on one flank over a 3-day period utilizing an improved prototype device; at the termination of continuous tissue expansion, intraoperative tissue expansion was performed on the opposite flank. There were no complications or continuous tissue expansion device malfunctions. Intraoperative tissue expansion gave a true gain in area of 7.4 percent, while continuous tissue expansion produced a 22 percent gain (p < 0.02). When the effects of both recruitment and expansion were added, continuous tissue expansion gave a dividend of 286 percent versus 192 percent for intraoperative tissue expansion (p < 0.01). Biomechanically, intraoperative tissue expansion skin showed few differences from unexpanded skin, while continuous tissue expansion skin showed a significant increase in stress relaxation (47.78 versus 38.74) and decrease in breaking strength. Histologic analysis revealed some epidermal hyperplasia and inflammation surrounding the continuous tissue expansion expander and some vascular congestion over the intraoperative tissue expansion expander. We conclude that continuous tissue expansion is superior to intraoperative tissue expansion and that the prototype device may be useful clinically.     

Enhanced nitrogen removal in bio-electrochemical systems by pH control

Microbial fuel cells can be designed to remove nitrogenous compounds out of wastewater, but their performance is at present limited to 0.33 kg NO₃ ⁻-Nm⁻³ net cathode compartment (NCC) d⁻¹. By maintaining the pH in the cathode at 7.2, nitrogen removal was increased from 0.22 to 0.50 kg NO₃ ⁻-Nm⁻³ NCC d⁻¹. Bio-electrochemical active microorganisms seem to struggle with the deterioration of their own environment due to slow proton fluxes. Therefore, the results suggest that an appropriate pH adjustment strategy is necessary to allow a sustained and enhanced biological activity in bio-electrochemical systems.     

Characteristics of false-negative smears tested in the normal screening situation.

It is common practice to rescreen false-negative (FN) smears. However, it is inevitable that this is done with some foreknowledge; at least it is known that the test smears contain one or more special cases. Therefore, we decided to test smears in the normal screening situation, when cytotechnologists are completely unaware of being tested. This experiment was done with five FNs and five true-positive (TP) smears. In a third experiment the FNs were tested with the cytotechnologists aware of their presence. Finally, 10 qualities of FNs and TPs were analyzed. In the normal screening situation, only in 1 of 25 tests was the FN recognized as malignant, while all the TPs were detected at the first testing. However, when the cytotechnologists were aware of being tested, the FN was detected in seven of eight tests. The FNs differed from the TPs in 5 of the 10 analyzed characteristics. FNs contained few (if any) large neoplastic epithelial fragments. Detached malignant cells were nearly lacking. The cancer cells had small nuclei that presented little anisokaryosis. The FNs possessed generally hypochromatic nuclei. These features explain why the malignant cells were almost never identified in the normal screening situation. We conclude that FNs and TPs differ and that it seems virtually impossible to avoid all false-negative diagnoses.     

Simulation of the regulation of EGFR endocytosis and EGFR-ERK signaling by endophilin-mediated RhoA-EGFR crosstalk

Deregulations of EGFR endocytosis in EGFR-ERK signaling are known to cause cancers and developmental disorders. Mutations that impaired c-Cbl-EGFR association delay EGFR endocytosis and produce higher mitogenic signals in lung cancer. ROCK, an effector of small GTPase RhoA was shown to negatively regulate EGFR endocytosis via endophilin A1. A mathematical model was developed to study how RhoA and ROCK regulate EGFR endocytosis. Our study suggested that over-expressing RhoA as well as ROCK prolonged ERK activation partly by reducing EGFR endocytosis. Overall, our study hypothesized an alternative role of RhoA in tumorigenesis in addition to its regulation of cytoskeleton and cell motility.