Anti-proliferative effect of metformin on a feline injection site sarcoma cell line independent of Mtor inhibition.

Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8.0mM. Using flow cytometry, the mechanism of cell death was determined to be apoptosis or necrosis. To evaluate the role of mTOR inhibition in metformin-induced cell death, Western blot was performed. No inhibition of mTOR or phosphorylated mTOR was found. Although metformin treatment leads to apoptotic or necrotic cell death in feline injection site sarcoma cells, the mechanism does not appear to be mediated by mTOR inhibition.

Avoiding Tokamak Disruptions by Applying Static Magnetic Fields That Align Locked Modes with Stabilizing Wave-Driven Currents.

Nonrotating ("locked") magnetic islands often lead to complete losses of confinement in tokamak plasmas, called major disruptions. Here locked islands were suppressed for the first time, by a combination of applied three-dimensional magnetic fields and injected millimeter waves. The applied fields were used to control the phase of locking and so align the island O point with the region where the injected waves generated noninductive currents. This resulted in stabilization of the locked island, disruption avoidance, recovery of high confinement, and high pressure, in accordance with the expected dependencies upon wave power and relative phase between the O point and driven current.

Evaluation and quantitative microbial risk assessment of a unique antimicrobial agent for hospital surface treatment.

BACKGROUND: It is generally agreed that contaminated hospital surfaces play a role in the transmission of hospital-acquired infections (HAIs). The ability of an antimicrobial agent, engineered at Emory University, to reduce bacterial bioburden on hospital surfaces was examined. A quantitative microbial risk assessment was also conducted to quantify the potential reduction of human health risks associated with application of this antimicrobial product. METHODS: A 1-arm, prospective observational study was conducted. High-frequency contact surfaces within 18 hospital patient rooms were sampled in between patient use. Negative binomial regression with repeated measures was used to examine log CFU/100 cm(2) reductions in total, gram-negative, and Staphylococcus aureus microorganisms. Standard risk assessment methods were used. RESULTS: Multivariate regression demonstrated significant reductions in gram-negative (P < .0001) and S aureus (P = .009) bacteria with increasing patient turnover. No reduction was observed in total bacteria (P = .93). Infection risks were reduced by 4 and 3 logs for gram-positive and gram-negative bacteria, respectively. These risk reductions, along with HAI survey studies, suggest that application of this antimicrobial product could prevent as many as 5%-10% of HAIs. CONCLUSIONS: This study was the first evaluation of a distinctive antimicrobial agent for hospital surface treatment. The findings provide support for the utility of an antimicrobial product in potentially reducing HAI transmission from contaminated environment surfaces.

Effects of surface-bound and intravenously administered heparin on cell-surface interactions: inflammation and coagulation.

Intravenous administration of heparin and heparin-bonded extracorporeal circuits are frequently used to mitigate the deleterious effects of blood contact with synthetic materials. The work described here utilized human blood in a micro-perfusion circuit to experimentally examine the effects of intravenous and surface-bound heparin on cellular activation. Activation markers of coagulation and of the inflammatory response were examined using flow cytometry; specifically, markers of platelet, monocyte, polymorphonuclear leukocyte (PMN), and lymphocyte activation were quantified. The results indicate that surface-bound heparin reduces the inflammatory response whereas systemically administered heparin does not. This finding has important implications for blood-contacting devices, particularly within the context of recently elucidated connections between inflammation pathways and coagulation disorders. Data presented indicate that surface-bound heparin and intravenously administered heparin play distinct, but vital roles in rendering biomaterial surfaces compatible with blood.

A correlation electron cyclotron emission diagnostic and the importance of multifield fluctuation measurements for testing nonlinear gyrokinetic turbulence simulations.

A correlation electron cyclotron emission (CECE) diagnostic has been used to measure local, turbulent fluctuations of the electron temperature in the core of DIII-D plasmas. This paper describes the hardware and testing of the CECE diagnostic and highlights the importance of measurements of multifield fluctuation profiles for the testing and validation of nonlinear gyrokinetic codes. The process of testing and validating such codes is critical for extrapolation to next-step fusion devices. For the first time, the radial profiles of electron temperature and density fluctuations are compared to nonlinear gyrokinetic simulations. The CECE diagnostic at DIII-D uses correlation radiometry to measure the rms amplitude and spectrum of the electron temperature fluctuations. Gaussian optics are used to produce a poloidal spot size with w(o) approximately 1.75 cm in the plasma. The intermediate frequency filters and the natural linewidth of the EC emission determine the radial resolution of the CECE diagnostic, which can be less than 1 cm. Wavenumbers resolved by the CECE diagnostic are k(theta) < or = 1.8 cm(-1) and k(r) < or = 4 cm(-1), relevant for studies of long-wavelength turbulence associated with the trapped electron mode and the ion temperature gradient mode. In neutral beam heated L-mode plasmas, core electron temperature fluctuations in the region 0.5 < r/a < 0.9, increase with radius from approximately 0.5% to approximately 2%, similar to density fluctuations that are measured simultaneously with beam emission spectroscopy. After incorporating "synthetic diagnostics" to effectively filter the code output, the simulations reproduce the characteristics of the turbulence and transport at one radial location r/a = 0.5, but not at a second location, r/a = 0.75. These results illustrate that measurements of the profiles of multiple fluctuating fields can provide a significant constraint on the turbulence models employed by the code.

Modification of the current profile in high-performance plasmas using off-axis electron-cyclotron-current drive in DIII-D.

Recent DIII-D experiments using off-axis electron cyclotron current drive (ECCD) have demonstrated the ability to modify the current profile in a plasma with toroidal beta near 3%. The resulting plasma simultaneously sustains the key elements required for Advanced Tokamak operation: high bootstrap current fraction, high beta, and good confinement. More than 85% of the plasma current is driven by noninductive means. ECCD is observed to produce strong negative central magnetic shear, which in turn acts to trigger confinement improvements in all transport channels in the plasma core.

Radial transport and electron-cyclotron-current drive in the TCV and DIII-D tokamaks.

Calculation of electron-cyclotron-current drive (ECCD) with the comprehensive CQL3D Fokker-Planck code for a TCV tokamak shot gives 550 kA of driven toroidal current, in marked disagreement with the 100-kA experimental value. Published ECCD efficiencies calculated with CQL3D in the much larger, higher-confinement DIII-D tokamak are in excellent agreement with experiment. The disagreement is resolved by including in the calculations electrostatic-type radial transport at levels given by global energy confinement in tokamaks. The radial transport of energy and toroidal current are in agreement.

Topical permethrin exposure inhibits antibody production and macrophage function in C57Bl/6N mice.

Permethrin was applied to the shaved dorsal interscapular region of C57Bl/6N mice at doses of 0.5, 1.5 or 5.0 microl/day. These doses corresponded to approximately 22-220 mg/kg/day topical insecticide. Mice were exposed to permethrin in this manner daily for 10 or 30 consecutive days, or every other day for 7 or 14 exposures. The splenic macrophage chemiluminescent response was depressed in a dose-dependent manner at 2 and 10 days post-exposure to permethrin. Phagocytic ability of macrophages was not inhibited. Antibody production as shown by plaque-forming cell (PFC) assay decreased significantly after 10 consecutive days of exposure to permethrin. These data indicate that topical permethrin exposure may produce systemic immune effects.

Internal kink instability during off-axis electron cyclotron current drive in the DIII-D tokamak

Experimental evidence is reported of an internal kink instability driven by a new mechanism: barely trapped suprathermal electrons produced by off-axis electron cyclotron heating on the DIII-D tokamak. It occurs in plasmas with an evolving safety factor profile q(r) when q(min) approaches 1. This instability is most active when ECCD is applied on the high field side of the flux surface. It has a bursting behavior with poloidal/toroidal mode number = m/n = 1/1. In positive magnetic shear plasmas, this mode becomes the fishbone instability. This observation can be qualitatively explained by the drift reversal of the barely trapped suprathermal electrons.

Suspected citrus pulp toxicosis in dairy cattle.

Thirteen lactating dairy cows from a herd of 650 died over a 6-week period. Most animals were down in milk production at 1 milking and were found dead at the next milking. Two cows had elevated heart rate and enlarged mandibular lymph nodes. Two others had azotemia, elevated heart rate, hyperglycemia, and weight loss. Necropsy of 10 cows revealed hemorrhages on the intestinal serosa and epicardium, lymphadenopathy, interstitial nephritis, small intestinal hemorrhage, and interstitial pneumonia. Histopathology showed lymphocytic to lymphogranulomatous inflammation in the heart, spleen, kidney, lymph nodes, liver, lung, pancreas, and adrenal gland. Phlebitis was present in 2 livers. The lesions resembled those of hairy vetch toxicosis, but no vetch was being fed. Similar lesions have been reported with the feeding of citrus pulp. Citrus pulp was being fed to the lactating cows and had been added to the diet 6 weeks before the first death. The syndrome resolved with elimination of citrus pulp from the diet.

Voice therapy. Techniques and applications.

Voice therapy is the cornerstone of treatment for patients with voice disorders. The therapeutic role of the speech pathologist is important in patients with functional and organic voice disorders. Voice rest and various other treatment options, techniques, and applications for voices disorders are examined in this article.

Phonological process development with MLU-referenced guidelines.

Sixty subjects between the ages of 21 and 48 months were placed into groups based on mean length of utterance (MLU) and chronological age (CA) to test Stampe's hypothesis about the development of phonological processes. The subjects were given the Phonological Process Analysis (Weiner, 1979), and a proportion score for each of sixteen phonological processes was derived for each subject. The use of the various phonological processes across MLU groups and age groups was analyzed by multiple regression correlation, three-way ANOVA, and Tukey's HSD tests. MLU was found to be the best classification for the subjects for describing the phonological processes. The results and discussions present MLU-referenced guidelines regarding the emergence, duration, elimination, and universality of the sixteen phonological processes.

Functions of consonant assimilation and reduplication in early word productions of mentally retarded children.

Spontaneous speech samples were elicited from eight mentally retarded children. Examples of consonant assimilation and reduplication found in their speech samples were separately analyzed to examine how these phonological processes function in the phonologies of retarded children. Results showed wide individual variability in subjects' use of consonant assimilation. Reduplication functioned to provide a method by which the subjects whose word productions were primarily monosyllabic could produce multisyllabic targets and/or to provide a method by which the subjects could produce multisyllabic words that had one syllable containing target consonants of consonant clusters absent from their phonetic repertoires.