Behavioral Modeling and Simulation of Mixed-Signal System-on-a-Chip using SystemC

We describe an efficient software framework for rapid behavioral modeling and simulation of mixed-signalSystem-on-a-Chip (SoC). The framework is based on the SystemC C++ class libraries and has beenproven to be a very effective tool for exploring different system-level architectures in the early stages of thedesign process. We also present the results of three case studies where we have used the framework: a 10-bit, 60Mega-sample/s pipelined ADC, 14-bit, 100 Mega-sample/s pipelined ADC with background calibration, and aCMOS camera-on-a-chip.     

An area-and-power-efficient 8.4-bit ENOB 30 MS/s SAR ADC in 65 nm CMOS

Area and power consumption are two main concerns for the electronics towards the digitalization of in-probe 3D ultrasound imaging systems. This work presents a 10-bit 30 MS/s successive approximation register analog-to-digital converter, which achieves good area efficiency as well as power efficiency, by using a symmetrical MSB-capacitor-split capacitor array with customized small-value finger capacitors. Moreover, simplified dynamic digital logic and a dynamic comparator have been designed. Fabricated in a 65 nm CMOS technology, the core circuit only occupies 0.016 mm². The ADC achieves a signal-to-noise ratio of 52.2 dB, and consumes 61.3 μW at 30 MS/s from a 1 V supply voltage, resulting in a figure of merit (FoM) of 6.2 fJ/conversion-step. The FoM defined by including the area is 0.1 mm² fJ/conversion-step.     

Effect of a changed temperature regime on the benthos of a norwegian regulated river

The lowermost 20 km of the River Surna, north-western Norway receives cool water during summer from a hypolimnetic release mountain reservoir. The benthic fauna is completely dominated by insects. Benthic densities immediately below the power station are much lower than at all other localities. Although benthic densities increase downstream of the power station, they never exceed the densities above. The dominant insect group, chironomids, can be divided into four categories according to their abundance and distribution above and below the power station: (1) rare or absent above, but common or abundant below; (2) abundant or common above but rare or absent below; (3) slightly less abundant below; (4) unchanged abundance. No major differences in the species composition were recorded for stonefilies, mayflies and caddisflies.     

Metabolic Effects of Krill Oil are Essentially Similar to Those of Fish Oil but at Lower Dose of EPA and DHA,in Healthy Volunteers

The purpose of the present study is to investigate the effects of krill oil and fish oil on serum lipids and markers of oxidative stress and inflammation and to evaluate if different molecular forms, triacylglycerol and phospholipids, of omega-3 polyunsaturated fatty acids (PUFAs) influence the plasma level of EPA and DHA differently. One hundred thirteen subjects with normal or slightly elevated total blood cholesterol and/or triglyceride levels were randomized into three groups and given either six capsules of krill oil (N = 36; 3.0 g/day, EPA + DHA = 543 mg) or three capsules of fish oil (N = 40; 1.8 g/day, EPA + DHA = 864 mg) daily for 7 weeks. A third group did not receive any supplementation and served as controls (N = 37). A significant increase in plasma EPA, DHA, and DPA was observed in the subjects supplemented with n-3 PUFAs as compared with the controls, but there were no significant differences in the changes in any of the n-3 PUFAs between the fish oil and the krill oil groups. No statistically significant differences in changes in any of the serum lipids or the markers of oxidative stress and inflammation between the study groups were observed. Krill oil and fish oil thus represent comparable dietary sources of n-3 PUFAs, even if the EPA + DHA dose in the krill oil was 62.8% of that in the fish oil.     

Increased Postprandial Triglyceride-Rich Lipoprotein Levels in Elderly Survivors of Myocardial Infarction

Postprandial triglyceride-rich lipoproteins (TRL) levels are a predictor for coronary atherosclerosis. The aim of the study was to compare fasting high density lipoprotein (HDL) cholesterol, plasma lipoprotein lipase (LPL) activity, and postprandial TRL between elderly survivors of myocardial infarction (MI) and healthy controls. A case-control study was performed in 44 elderly patients 65-85 years of age with a previous history of MI and 43 age- and sex-matched healthy controls. Each participant underwent physical examination and was given a standard oral fat load with subsequent blood sampling over the next 8 h. Total and chylomicron triglycerides were assessed by area under the curve (AUC), incremental are under the curve (AUCi) and triglyceride response (TGR). Elderly MI patients had significantly lower postheparin LPL activity (87.4 +/- 36.9 mU/ml) (mean +/- 1 SD) than healthy controls (106.0 +/- 29.0 mU/ml) (P = 0.014). Decreased postheparin LPL activity was accompanied by significant increased and delayed clearance of postprandial TRL. Fasting HDL cholesterol was significantly lower in elderly MI patients than controls (1.45 +/- 0.32 and 1.66 +/- 0.47 mmol/l, respectively, P = 0.048). Multiple regression analysis revealed postheparin LPL activity as an independent predictor for postprandial TRL and fasting HDL cholesterol. Logistic regressions analysis revealed HDL cholesterol, triglycerides measured 2 h after the oral fat load, and postheparin LPL activity as independent predictors for MI. Our findings indicate that decreased fasting HDL cholesterol is associated with increased postprandial triglyceridemia which could be a target for life-style and therapeutic interventions in patients at risk for cardiovascular disease.     

Discovery of GPR183 Agonists Based on an Antagonist Scaffold

The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca²⁺ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch.     

Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Minnesota Multiphasic Personality Inventory correlates of dysphasic language disturbances.

Compared the MMPI performances of 15 male dysphasic brain-damaged adults with the performances of 15 matched control brain-damaged Ss without specific language impairment. A significant overall difference on the 9 clinical scales combined was shown by multivariate analysis, with higher scores obtained by dysphasic Ss. Further univariate analysis showed significantly higher scores on the Pd and Sc scales. Results are discussed in terms of (a) evidence for a closer relation between MMPI variables and behavioral measures than between MMPI variables and neurological measures of lesion laterality, and (b) the interpretive limitations implied by uncritical transference of MMPI findings based on psychiatric patients and normals to patients with central nervous system lesions. The need for validation studies investigating social behavior correlates of MMPI results in brain-damaged samples is emphasized. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous Cell Detachment and Reattachment in Cancer Cell Lines: An In Vitro Model of Metastasis and Malignancy

There is an unmet need for simplified in vitro models of malignancy and metastasis that facilitate fast, affordable and scalable gene and compound analysis. “Adherent” cancer cell lines frequently release “free-floating” cells into suspension that are viable and can reattach. This, in a simplistic way, mimics the metastatic process. We compared the gene expression profiles of naturally co-existing populations of floating and adherent cells in SW620 (colon), C33a (cervix) and HeLa (cervix) cancer cells. We found that 1227, 1367 and 1333 genes were at least 2-fold differentially expressed in the respective cell lines, of which 122 were shared among the three cell lines. As proof of principle, we focused on the anti-metastatic gene NM23-H1, which was downregulated both at the RNA and protein level in the floating cell populations of all three cell lines. Knockdown of NM23-H1 significantly increased the number of floating (and viable) cells, whereas overexpression of NM23-H1 significantly reduced the proportion of floating cells. Other potential regulators of these cellular states were identified through pathway analysis, including hypoxia, mTOR (mechanistic target of rapamycin), cell adhesion and cell polarity signal transduction pathways. Hypoxia, a condition linked to malignancy and metastasis, reduced NM23-H1 expression and significantly increased the number of free-floating cells. Inhibition of mTOR or Rho-associated protein kinase (ROCK) significantly increased cell death specifically in the floating and not the adherent cell population. In conclusion, our study suggests that dynamic subpopulations of free-floating and adherent cells is a useful model to screen and identify genes, drugs and pathways that regulate the process of cancer metastasis, such as cell detachment and anoikis.     

Microfluidic pump based on the phenomenon of electroosmosis of the second kind

A micropump based on strong polarization of ion-exchange beads and corresponding actuation by electroosmosis of the second kind was designed and fabricated. Experimental results from operation with AC and DC voltage showed a close to second order relationship between flow and voltage, in good agreement with theory. The difference between experimental and theoretical flow rates and pressures is attributed to the hydrodynamic resistance of the channel network. A modified pump design which should yield higher flow rates and pressures was suggested.