A MOMENT MATCHING APPROACH FOR MODELLING ATM CELL ARRIVAL PROCESSES

This paper presents a moment matching approach for constructing an equivalent model of an ATM cell arrival process based on inter-cell arrival time measurement. As compared to a renowned parameter-matching technique proposed by Heffes and Lucatoni, the advantage of this approach is that the matching parameters are more easily obtained in real traffic situation. This approach has been tested on an MMBP^[Poisson] process, and results show that only the first four moments are required to capture the key characteristics in this process.     

The microRNA-455 Null Mouse Has Memory Deficit and Increased Anxiety,Targeting Key Genes Involved in Alzheimer’s Disease

The complete molecular mechanisms underlying the pathophysiology of Alzheimer’s disease (AD) remain to be elucidated. Recently, microRNA-455-3p has been identified as a circulating biomarker of early AD, with increased expression in post-mortem brain tissue of AD patients. MicroRNA-455-3p also directly targets and down-regulates APP, with the overexpression of miR-455-3p suppressing its toxic effects. Here, we show that miR-455-3p expression decreases with age in the brains of wild-type mice. We generated a miR-455 null mouse utilising CRISPR-Cas9 to explore its function further. Loss of miR-455 resulted in increased weight gain, potentially indicative of metabolic disturbances. Furthermore, performance on the novel object recognition task diminished significantly in miR-455 null mice (p = 0.004), indicating deficits in recognition memory. A slight increase in anxiety was also captured on the open field test. BACE1 and TAU were identified as new direct targets for miR-455-3p, with overexpression of miR-455-3p leading to a reduction in the expression of APP, BACE1 and TAU in neuroblastoma cells. In the hippocampus of miR-455 null mice at 14 months of age, the levels of protein for APP, BACE1 and TAU were all increased. Such findings reinforce the involvement of miR-455 in AD progression and demonstrate its action on cognitive performance.     

Biophysical Modulation of Mesenchymal Stem Cell Differentiation in the Context of Skeletal Repair

A prominent feature of the skeleton is its ability to remodel in response to biophysical stimuli and to repair under varied biophysical conditions. This allows the skeleton considerable adaptation to meet its physiological roles of stability and movement. Skeletal cells and their mesenchymal precursors exist in a native environment rich with biophysical signals, and they sense and respond to those signals to meet organismal demands of the skeleton. While mechanical strain is the most recognized of the skeletal biophysical stimuli, signaling phenomena also include fluid flow, hydrostatic pressure, shear stress, and ion-movement-related electrokinetic phenomena including, prominently, streaming potentials. Because of the complex interactions of these electromechanical signals, it is difficult to isolate the significance of each. The application of external electrical and electromagnetic fields allows an exploration of the effects of these stimuli on cell differentiation and extra-cellular matrix formation in the absence of mechanical strain. This review takes a distinctly translational approach to mechanistic and preclinical studies of differentiation and skeletal lineage commitment of mesenchymal cells under biophysical stimulation. In vitro studies facilitate the examination of isolated cellular responses while in vivo studies permit the observation of cell differentiation and extracellular matrix synthesis.     

Frequency-Dependent Properties of the Hyperpolarization-Activated Cation Current,If, in Adult Mouse Heart Primary Pacemaker Myocytes

A number of distinct electrophysiological mechanisms that modulate the myogenic spontaneous pacemaker activity in the sinoatrial node (SAN) of the mammalian heart have been investigated extensively. There is agreement that several (3 or 4) different transmembrane ionic current changes (referred to as the voltage clock) are involved; and that the resulting net current interacts with direct and indirect effects of changes in intracellular Ca²⁺ (the calcium clock). However, significant uncertainties, and important knowledge gaps, remain concerning the functional roles in SAN spontaneous pacing of many of the individual ion channel- or exchanger-mediated transmembrane current changes. We report results from patch clamp studies and mathematical modeling of the hyperpolarization-activated current, I_f, in the generation/modulation of the diastolic depolarization, or pacemaker potential, produced by individual myocytes that were enzymatically isolated from the adult mouse sinoatrial node (SAN). Amphotericin-mediated patch microelectrode recordings at 35 °C were made under control conditions and in the presence of 5 or 10 nM isoproterenol (ISO). These sets of results were complemented and integrated with mathematical modeling of the current changes that take place in the range of membrane potentials (−70 to −50 mV), which corresponds to the ‘pacemaker depolarization’ in the adult mouse SAN. Our results reveal a very small, but functionally important, approximately steady-state or time-independent current generated by residual activation of I_f channels that are expressed in these pacemaker myocytes. Recordings of the pacemaker depolarization and action potential, combined with measurements of changes in I_f, and the well-known increases in the L-type Ca²⁺ current, I_CaL, demonstrated that I_CaL activation, is essential for myogenic pacing. Moreover, after being enhanced (approximately 3-fold) by 5 or 10 nM ISO, I_CaL contributes significantly to the positive chronotropic effect. Our mathematical model has been developed in an attempt to better understand the underlying mechanisms for the pacemaker depolarization and action potential in adult mouse SAN myocytes. After being updated with our new experimental data describing I_f, our simulations reveal a novel functional component of I_f in adult mouse SAN. Computational work carried out with this model also confirms that in the presence of ISO the residual activation of I_f and opening of I_CaL channels combine to generate a net current change during the slow diastolic depolarization phase that is essential for the observed accelerated pacemaking rate of these SAN myocytes.     

High hydrostatic pressure modification of whey protein concentrate for improved functional properties

Whey protein concentrate (WPC) has many applications in the food industry. Previous research demonstrated that treatment of whey proteins with high hydrostatic pressure (HHP) can enhance solubility and foaming properties of whey proteins. The objective of this study was to use HHP to improve functional properties of fresh WPC, compared with functional properties of reconstituted commercial whey protein concentrate 35 (WPC 35) powder. Fluid whey was ultrafiltered to concentrate proteins and reconstituted to equivalent total solids (8.23%) as reconstituted commercial WPC 35 powder. Solutions of WPC were treated with 300 and 400 MPa (0- and 15-min holding time) and 600 MPa (0-min holding time) pressure. After HHP, the solubility of the WPC was determined at both pH 4.6 and 7.0 using UDY and BioRad protein assay methods. Overrun and foam stability were determined after protein dispersions were whipped for 15 min. The protein solubility was greater at pH 7.0 than at pH 4.6, but there were no significant differences at different HHP treatment conditions. The maintenance of protein solubility after HHP indicates that HHP-treated WPC might be appropriate for applications to food systems. Untreated WPC exhibited the smallest overrun percentage, whereas the largest percentage for overrun and foam stability was obtained for WPC treated at 300 MPa for 15 min. Additionally, HHP-WPC treated at 300 MPa for 15 min acquired larger overrun than commercial WPC 35. The HHP treatment of 300 MPa for 0 min did not improve foam stability of WPC. However, WPC treated at 300 or 400 MPa for 15 min and 600 MPa for 0 min exhibited significantly greater foam stability than commercial WPC 35. The HHP treatment was beneficial to enhance overrun and foam stability of WPC, showing promise for ice cream and whipping cream applications.     

Fouling of microfiltration and ultrafiltration membranes by natural waters

Membrane filtration (microfiltration and ultrafiltration) has become an accepted process for drinking water treatment, but membrane fouling remains a significant problem. The objective of this study was to systematically investigate the mechanisms and components in natural waters that contribute to fouling. Natural waters from five sources were filtered in a benchtop filtration system. A sequential filtration process was used in most experiments. The first filtration steps removed specific components from the water, and the latter filtration steps investigated membrane fouling by the remaining components. Particulate matter (larger than 0.45 microm) was relatively unimportant in fouling as compared to dissolved matter. Very small colloids, ranging from about 3-20 nm in diameter, appeared to be important membrane foulants based on this experimental protocol. The colloidal foulants included both inorganic and organic matter, but the greatest fraction of material was organic. When the colloidal fraction of material was removed, the remaining dissolved organic matter (DOM), which was smaller than about 3 nm and included about 85-90% of the total DOM, caused very little fouling. Thus, although other studies have identified DOM as a major foulant during filtration of natural waters, this work shows that a small fraction of DOM may be responsible for fouling. Adsorption was demonstrated to be an important mechanism for fouling by colloids.     

Lymphatic fatty acids from rats fed human milk and formula supplemented with fish oil

Absorption of long-chain polyunsaturated fatty acids from human milk and formula supplemented with fish oil was studied to determine if the distribution route into lymphatic triacylglycerol (TAG) and phospholipid (PL) varies with the dietary source. Rats were intraduodenally infused with human milk or formula containing graded amounts of fish oil (0, 0.5, or 1.0 g/100 mL), and the mesenteric lymph was collected. Arachidonic acid (20∶4n−6) levels in lymphatic TAG and PL were highest from animals fed human milk. In the animals infused with formula containing fish oil, as the amount of eicosapentaenoic acid (EPA, 20∶5n−3) infused increased, there was essentially an equal increase of EPA associated with both lymphatic TAG and PL. Animals intraduodenally infused with human milk or formula without fish oil had only minor levels (less than 1%) of EPA in the lymph. In the fish oil-treated animals, as the amount of docosahexaenoic acid (DHA, 22∶6n−3) infused increased, there was a 16-fold increase in DHA associated with lymphatic TAG, but only a 3-fold increase in DHA associated with lymphatic PL. The highest level of DHA in rats infused with human milk was observed in lymphatic PL. Hence, fish oil can be added to formula as a source of long-chain polyunsaturated fatty acids, but the distribution of fatty acids into lymphatic TAG and PL is not the same as that observed with human milk.     

Stereospecificity of premature human infant lingual lipase

The lingual lipase in gastric aspirates from premature infants was found to be partially stereospecific forsn-3 esters of synthetic enantiometric triacylglycerols containing 18∶1 and 16∶0. Thesn-3 ester was hydrolyzed about 4 times faster than the acid at thesn-1 position with no difference in rates between 18∶1 and 16∶0. Thesn-2 was also hydrolyzed to some extent. Scientific contribution no. 949, Storrs Agricultural Experiment Station, University of Connecticut, Storrs, Ct 06268.     

Effects of feed intake and sodium bicarbonate on milk production and concentrations of hormones and metabolites in plasma of cows

Eight Holstein cows were used to investigate the effects of DM intake and sodium bicarbonate on lactational performance and concentrations of hormones and metabolites in plasma. Cows were fed a diet with or without 1.0% sodium bicarbonate (dry matter basis) in a switchback design. Four cows were fed ad libitum and four cows were fed approximately 80% of their recommended nutrient requirements by restriction of DM intake throughout the three 21-d periods. Supplementing the diet with sodium bicarbonate increased DM intake of cows fed ad libitum. There was a feed intake by sodium bicarbonate interaction for production of 4% FCM. This interaction may be explained by the difference in DM intake of cows fed ad libitum or restricted amounts of feed and supplemented with sodium bicarbonate. Cows fed restricted amounts of feed had lower milk, milk fat, milk protein, milk SNF, and milk energy yields. Restriction of feed intake increased plasma concentrations of somatotropin and nonesterified fatty acids but decreased concentrations of insulin, triidothyronine, thyroxine, glucagon, and prolactin. In contrast, feeding supplemental sodium bicarbonate did not affect concentrations of hormones or metabolites in plasma at either feed intake.