bluuebunny/crossref_metadata_2025 huggingface dataset:
Delirious Cities and Their Cinema: On Koolhaas and Film Studies
Authors: Tweedie James
Published: May 2010

Using contemporary Chinese and Hong Kong cinema, the large body of writing on media emanating from Koolhaas and his atelier, and the headquarters for China Central Television as its primary touchstones, this essay examines the relationship between the current media environment in East Asia and the architectural practice and theory produced by Koolhaas. The paper argues that his virtuoso designs and enormously productive critical work reach an impasse at precisely the moment when his conception of cinema is exhausted and he embraces the increasingly influential theoretical model drawn from digital media. While his notion of the generic city is modeled on the film studio set, with its utterly flexible and ephemeral structures expanded to the scale of the city, and his more recent structures embody the promises of a network society, Koolhaas fails to consider other image-making practices that remain vibrant and rely on diametrically opposed conceptions of the moving image, most notably the documentary-derived cinema of filmmakers like Jia Zhangke.
On variances of partial volumes of the typical cell of a Poisson-Voronoi tessellation and large-dimensional volume degeneracy
Authors: Yao Yi-Ching
Published: May 2010

For a typical cell of a homogeneous Poisson-Voronoi tessellation in ℝd, it is shown that the variance of the volume of the intersection of the typical cell with any measurable subset of ℝd is bounded by the variance of the volume of the typical cell. It is also shown that the variance of the volume of the intersection of the typical cell with a translation of itself is bounded by four times the variance of the volume of the typical cell. These bounds are applied to show large-dimensional volume degeneracy as d tends to ∞. An extension to the kth nearest-point Poisson-Voronoi tessellation for k ≥ 2 is also considered.
Aggregation of a random-coefficient ar(1) process with infinite variance and idiosyncratic innovations
Authors: Puplinskaitė Donata , Surgailis Donatas
Published: May 2010

Contemporaneous aggregation ofNindependent copies of a random-coefficient AR(1) process with random coefficienta∈ (−1, 1) and independent and identically distributed innovations belonging to the domain of attraction of an α-stable law (0 < α < 2) is discussed. We show that, under the normalizationN1/α, the limit aggregate exists, in the sense of weak convergence of finite-dimensional distributions, and is a mixed stable moving average as studied in Surgailis, Rosiński, Mandrekar and Cambanis (1993). We focus on the case where the slope coefficientahas probability density vanishing regularly ata= 1 with exponentb∈ (0, α − 1) for α ∈ (1, 2). We show that in this case, the limit aggregate {X̅t} exhibits long memory. In particular, for {X̅t}, we investigate the decay of the codifference, the limit of partial sums, and the long-range dependence (sample Allen variance) property of Heyde and Yang (1997).
Evidence for within-individual energy reallocation in cold-challenged, egg-producing birds
Authors: Salvante Katrina G. , Vézina François , Williams Tony D.
Published: May 2010

Recent studies have shown that the metabolic cost of avian egg production involves a 16–27% increase in metabolic rate (MR) above non-reproductive basal or resting values (BMR and RMR, respectively). To determine how the metabolic cost of egg production interacted with the costs of other essential processes (such as cold acclimation and active heat production), we measured the MR of non-breeding and egg-producing zebra finches (Taeniopygia guttata) while (a) warm-acclimated (to 19–21°C) and measured within their thermoneutral zone (at 35°C), (b) cold-acclimated (to 7°C) and measured at thermoneutrality (at 35°C, i.e. not actively producing heat), and (c) cold-acclimated and measured below thermoneutrality (at 7°C) (i.e. during active heat production). The metabolic cost of egg production was small (24% above BMR) compared with the additive costs of cold acclimation and active heat production (224% above BMR). Exposure to low ambient temperatures was accompanied by an increase in seed consumption (by 72%) and a decrease in locomotor activity (by 72%) compared with warm-acclimated, non-breeding values. By contrast, egg production in heat-producing females was associated with an 11% decrease in MR and a 22% decrease in seed consumption compared with non-breeding thermoregulating values. Our data suggest that while the increase in MR associated with egg production is small in relation to the birds' capacity to increase MR in response to other energetically demanding processes, the addition of egg production to these metabolically costly activities may be enough to necessitate the use of energy-saving strategies, such as internal energy reallocation, to cope with the additional energetic demands.
Directional constraint of endpoint force emerges from hindlimb anatomy
Authors: Bunderson Nathan E. , McKay J. Lucas , Ting Lena H. , Burkholder Thomas J.
Published: May 2010

Postural control requires the coordination of force production at the limb endpoints to apply an appropriate force to the body. Subjected to horizontal plane perturbations, quadruped limbs stereotypically produce force constrained along a line that passes near the center of mass. This phenomenon, referred to as the force constraint strategy, may reflect mechanical constraints on the limb or body, a specific neural control strategy or an interaction among neural controls and mechanical constraints. We used a neuromuscular model of the cat hindlimb to test the hypothesis that the anatomical constraints restrict the mechanical action of individual muscles during stance and constrain the response to perturbations to a line independent of perturbation direction. In a linearized neuromuscular model of the cat hindlimb, muscle lengthening directions were highly conserved across 10,000 different muscle activation patterns, each of which produced an identical, stance-like endpoint force. These lengthening directions were closely aligned with the sagittal plane and reveal an anatomical structure for directionally constrained force responses. Each of the 10,000 activation patterns was predicted to produce stable stance based on Lyapunov stability analysis. In forward simulations of the nonlinear, seven degree of freedom model under the action of 200 random muscle activation patterns, displacement of the endpoint from its equilibrium position produced restoring forces, which were also biased toward the sagittal plane. The single exception was an activation pattern based on minimum muscle stress optimization, which produced destabilizing force responses in some perturbation directions. The sagittal force constraint increased during simulations as the system shifted from an inertial response during the acceleration phase to a viscoelastic response as peak velocity was obtained. These results qualitatively match similar experimental observations and suggest that the force constraint phenomenon may result from the anatomical arrangement of the limb.
To eat or not to eat: the effect of AICAR on food intake regulation in yellow-bellied marmots (Marmota flaviventris)
Authors: Florant Gregory L. , Fenn Ashley M. , Healy Jessica E. , Wilkerson Gregory K. , Handa Robert J.
Published: May 2010

Mammals that hibernate (hibernators) exhibit a circannual rhythm of food intake and body mass. In the laboratory during the winter hibernation period, many hibernators enter a series of multi-day torpor bouts, dropping their body temperature to near ambient, and cease to feed even if food is present in their cage. The mechanism(s) that regulates food intake in hibernators is unclear. Recently, AMP-activated protein kinase (AMPK) has been shown to play a key role in the central regulation of food intake in mammals. We hypothesized that infusing an AMPK activator, 5-aminoimidazole-4-carboxamide 1 B-D-ribofuranoside (AICAR), intracerebroventricularly (ICV) into the third ventricle of the hypothalamus would stimulate yellow-bellied marmots (Marmota flaviventris) to feed during their hibernation season. Infusion of AICAR ICV into marmots at an ambient temperature of 22°C caused a significant (P<0.05) increase in food intake. In addition, animals stimulated to feed did not enter torpor during the infusion period. Marmots ICV infused with saline did not increase food intake and these animals continued to undergo torpor at an ambient temperature of 22°C. Our results suggest that AICAR stimulated the food intake pathway, presumably by activating AMPK. These results support the hypothesis that AMPK may be involved in regulating food intake in hibernators and that there may be common neural pathways involved in regulating feeding and eliciting torpor.
Physiological and immunocytochemical evidence that glutamatergic neurotransmission is involved in the activation of arm autotomy in the featherstarAntedon mediterranea(Echinodermata: Crinoidea)
Authors: Wilkie I. C. , Barbaglio A. , Maclaren W. M. , Carnevali M. D. Candia
Published: May 2010

The crinoid echinoderm Antedon mediterranea autotomises its arms at specialised skeletal joints known as syzygies that occur at regular intervals along the length of each arm. Detachment is achieved through the nervously mediated destabilisation of ligament fibres at a particular syzygy. The aim of this investigation was to identify neurotransmitters that are involved in the autotomy response. Physiological experiments were conducted on isolated preparations of syzygial joints, which can be induced to undergo autotomy-like fracture by applying stimulatory agents such as elevated [K+]o. Initial experiments with elevated [K+]o showed that the autotomy threshold (the minimum amount of stimulation required to provoke autotomy) is lowest in syzygies at the arm base and rises distally. Of a range of neurotransmitter agonists tested, only l-glutamate invoked syzygial destabilisation, as did its analogues l-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate, but not l-(+)-2-amino-4-phosphonobutyrate (l-AP4) or N-methyl-d-aspartate (NMDA). The implication that l-glutamate stimulates syzygial fracture through AMPA/kainate-like receptors was supported by the finding that the action of l-glutamate was inhibited by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Acetylcholine depressed the response of syzygial preparations to l-glutamate, suggesting a possible mechanism by which the autotomy threshold could be varied constitutively and facultatively. An immunocytochemical method employing a polyclonal antibody against l-glutamate conjugated to glutaraldehyde revealed l-glutamate-like immunoreactivity in all components of the putative neural pathway controlling the autotomy reflex, including the epidermis, brachial nerve, syzygial nerves and cellular elements close to the syzygial ligaments. We conclude that it is highly probable that l-glutamate acts as an excitatory neurotransmitter in the activation of arm autotomy in A. mediterranea.
Effects of static magnetic fields on the development and aging ofCaenorhabditis elegans
Authors: Hung Yao-Ching , Lee Jia-Huey , Chen Huang-Meng , Huang Guewha Steven
Published: May 2010

The current study investigated the possible effects of static magnetic fields (SMFs) on the developmental and aging processes of Caenorhabditis elegans. Nematodes were grown in the presence of SMFs of strengths varying from 0 to 200 mT. The rate of development and the lifespan were recorded. Treatment with a 200 mT SMF reduced the development time from the L2 to the L3 stage by 20%, from L3 to L4 by 23%, and from L4 to young adult by 31%. After SMF treatment, the average lifespan was reduced from 31 days to 24 days for wild-type nematodes. The up-regulation of clk-1, lim-7, daf-2, unc-3 and age-1 after SMF treatment was verified by quantitative real-time RT-PCR. Apparently, induction of gene expression is selective and dose dependent. The total developmental time was significantly reduced for the lin-4, lin-14, lin-41 and lim-7 mutants, but not for the let-7, clk-1, unc-3 and age-1 mutants. Lifespan analyses revealed that the let-7, unc-3 and age-1 mutants were not affected by SMF treatment. Here we show that SMFs accelerate nematode development and shorten nematode lifespan through pathways associated with let-7, clk-1, unc-3 and age-1.
Numerical simulation of a pectoral fin during labriform swimming
Authors: Shoele Kourosh , Zhu Qiang
Published: May 2010

We numerically examine the fluid–structure interaction and force generation of a skeleton-reinforced fin that geometrically, structurally and kinematically resembles the pectoral fin of a fish during labriform swimming. This fin contains a soft membrane with negligible bending stiffness and 12 embedded rays (modeled as beams). A potential flow-based boundary element model is applied to solve the fluid flow around the fin, in which the vorticity field is modeled as thin vorticity sheets shed from prescribed locations (the sharp trailing edge). The fin motion is actuated by dorsoventral and anteroposterior rotations of the rays (the motion of each ray is controlled individually), as well as pitching motion of the baseline. Consequently, the fin undergoes a combination of flapping (lift-based) and rowing (drag-based) motions typical in labriform swimming. The fin motion contains two strokes: a recovery stroke and a power stroke. The performance of the fin depends upon kinematic parameters such as the Strouhal number, the phase lag between rays, the pitching motion of the baseline and the passive deformations of the rays. The most interesting finding is that the strengthening of the ray at the leading edge plays a pivotal role in performance enhancement by reducing the effective angle of attack and decreasing the power expenditure during the recovery stroke.
Feasting, fasting and freezing: energetic effects of meal size and temperature on torpor expression by little brown batsMyotis lucifugus
Authors: Matheson Amanda L. , Campbell Kevin L. , Willis Craig K. R.
Published: May 2010

Torpor is an adaptation for energy conservation employed by many species of small-bodied endotherms. However, surprisingly little is known regarding proximate factors influencing day-to-day variation in torpor expression in the wild. We used open-flow respirometry to quantify torpor expression in nine little brown bats (Myotis lucifugus, LeConte 1831) at two ambient temperatures (7°C and 17°C) following either sham feeding or consumption of a high-protein meal (50% or 100% of the mass required to reach satiation for each individual). Food consumption significantly increased the time spent normothermic before torpor entry but did not affect either the rate of body cooling or torpid metabolic rate. Bats did not fully exploit potential energy savings by maximising their use of torpor. Instead they varied torpor expression such that total energy expenditure over the course of each 22-h trial was balanced against gross energy intake immediately before the trial, independent of ambient temperature. This was accomplished by adjusting the timing of entry into torpor (thus altering the time spent torpid), rather than by modulating torpid metabolic rate. However, pre-trial body mass was also a significant predictor of torpor expression, which suggests that energy reserves combine with recent foraging success to influence individuals' decisions about depth and duration of their torpor bouts. We also present evidence that little brown bats use the heat generated through digestion (i.e. the heat increment of feeding) to substitute for active thermogenesis at sub-thermoneutral temperatures, thereby reducing the energetic costs of thermoregulation prior to torpor entry.
G-proteins modulate invertebrate synaptic calcium channel (LCav2) differently from the classical voltage-dependent regulation of mammalian Cav2.1 and Cav2.2 channels
Authors: Huang Xuan , Senatore Adriano , Dawson Taylor F. , Quan Quyen , Spafford John David
Published: May 2010

Voltage-gated calcium channels in the Cav2 channel class are regulators of synaptic transmission and are highly modified by transmitter inputs that activate synaptic G-protein-coupled receptors (GPCRs). A ubiquitous form of G-protein modulation involves an inhibition of mammalian Cav2.1 and Cav2.2 channels by Gβγ dimers that can be relieved by high-frequency trains of action potentials. Here, we address whether the ubiquitous and versatile form of G-protein regulation in mammals is also found in simpler invertebrate nervous systems. Remarkably, the invertebrate LCav2 channel from the pond snail, Lymnaea stagnalis, does not bear any of the hallmarks of mammalian, voltage-dependent G-protein inhibition of Cav2.2. Swapping either the I-II linker or N-terminus of Cav2.2, which serve as key binding domains for G-protein inhibition, does not endow invertebrate LCav2 channels with voltage-dependent G-protein modulatory capacity. Instead, in vitro expressed LCav2 channels are inhibited slowly by the activation of cAMP, in a manner that depends on G-proteins but does not depend on Gβγ subunits. A similar G-protein and cAMP-dependent inhibition of nifedipine-insensitive LCav2 currents is also consistent in native and identified Lymnaea VD4 neurons. The slower inhibition using a cellular messenger such as cAMP may meet the modulatory needs in invertebrates while an activity-dependent regulation, evolving in vertebrates, provides a more dynamic, fine-tuning of neurosecretion by regulating the influence of neurotransmitter inputs through presynaptic GPCRs.
Aquatic feeding in pipid frogs: the use of suction for prey capture
Authors: Carreño Carrie A. , Nishikawa Kiisa C.
Published: May 2010

Inertial suction feeding is the most common method of prey capture among aquatic vertebrates. However, it had been unclear whether the aquatic frogs in the family Pipidae also used inertial suction for prey capture. In this study, we examined feeding behavior in four species of pipids, Pipa pipa, Xenopus laevis, Hymenochirus boettgeri and Pseudhymenochirus merlini. Pressure in the buccopharyngeal cavity was measured during prey capture. These pressure measurements were coupled with high-speed recordings of feeding behavior. For each species, the internal buccopharyngeal pressure was found to drop significantly below ambient pressure, and changes in pressure corresponded with the onset of mouth opening. Kinematic analysis revealed that all species of pipids generated subambient pressure during prey capture; H. boettgeri and P. merlini relied solely on inertial suction feeding. Pipa pipa and X. laevis additionally employed forelimb scooping during prey capture but both of these species demonstrated the ability to capture prey with inertial suction alone. Based on buccopharyngeal pressure measurements as well as kinematic analyses, we conclude that inertial suction feeding is used during prey capture in these four species of pipids.
Optimization of conventional spinning process parameters by means of numerical simulation and statistical analysis
Authors: Essa K , Hartley P
Published: May 2010

Research in sheet metal spinning has increased due to a greater demand, especially in the transportation industries, for parts with very high strength-to-weight ratios with low cost. Spinning processes are efficient in producing such characteristics and there is great flexibility in the process with a relatively low tool cost. The objectives of this investigation are to define the critical working parameters in spinning, show the effects of these factors on product quality characteristics, and to optimize the working parameters. The example used is the conventional spinning of a cylindrical cup. Optimization of the process is undertaken through the use of statistical analysis tools applied to the data produced from three-dimensional finite element simulations of the process. This has been achieved by generating two ‘designs of experiments’. The first identifies the most critical parameters for product formability and the second shows how these critical parameters affect the product quality. The results show that feed rate, relative clearance, and roller nose radius are the most important working parameters and significantly affect average thickness, thickness variation, and springback of the cylindrical cup. An additional 22 per cent improvement in the product quality characteristic is gained through using the optimum working parameters.
On milling of thin-walled tubular geometries
Authors: Bera T C , Desai K A , Rao P V M
Published: May 2010

Machining of thin-walled tubular geometries poses interesting problems from a process planning perspective. In machining of such geometries by milling, cutting force-induced tool and workpiece deflections have to be overcome in order to realize part accuracies without compromising productivity. This calls for a systematic study of surface errors on machined parts due to both tool and workpiece deflections. The present paper investigates the effect of cutter and workpiece flexibilities on surface error during peripheral milling of thin-walled tubular geometries. Unlike previous attempts to study milling of thin-walled straight geometries, the present work focuses mainly on machining of tubular geometries. Tubular geometries need to be treated differently from a process planning perspective by exploiting the workpiece rigidity they offer. The process planner has an option of synclastic and anticlastic machining possibilities during machining of tubular geometries which needs to be explored and understood. More importantly, the complex and varying profile of surface error with cutting conditions has to be accounted for. From the outcomes of the present work it can be summarized that surface errors in machining of closed tubular geometries are due to multiple factors which include workpiece rigidity, tool overhang, curvature effects, thinning effects, and nature of tool and workpiece engagements. All of these parameters are affected by process parameters chosen during machining. The present study also demonstrates that the understanding of surface error profiles due to cutter and workpiece deflections not only helps in realizing dimensional accuracy, but geometric tolerances as well.
Performance analyses and economic evaluation of a hybrid thermoelectric solar water heater
Authors: Lertsatitthanakorn C , Therdyothin A , Soponronnarit S
Published: May 2010

Performance and economic analyses of a hybrid thermoelectric (TE) solar water heater have been studied. The hybrid TE solar water heater was composed of transparent glass, air gap, an absorber plate, TE modules, water-cooled heat sinks, and storage water tank. The incident solar radiation heats up the absorber plate creating a temperature difference between the TE modules that generate a direct current. Only a small part of the absorbed solar radiation is converted to electricity, while the rest increases the temperature of the absorber plate. The water flows through each heat sink located under the TE modules to gain heat. The heated water then flows to the upper section of the absorber plate where it receives additional heating from the absorber plate. Improvements to the thermal and overall efficiency of the system can be achieved by the use of the double-pass collector system and TE technology. The experiment shows that the thermal and overall efficiencies increase as the water flowrate increases. The maximum and overall efficiencies were 74.9 per cent and 77.3 per cent, respectively, at the water flowrate of 0.33 kg/s. Meanwhile, the electrical-power output and the electrical-power generation efficiency depended on the temperature difference between the hot and cold sides of the TE modules. At a temperature difference of 27.1 °C, the unit achieved a power output of 3.6 W and the electrical-power generation efficiency of 0.87 per cent. Moreover, economic analysis indicates that the payback period of the hybrid TE solar water heater operating at the water flowrate of 0.33 kg/s is shorter and yields a higher internal rate of return.
Hybrid non-singular terminal sliding-mode controller design for an electric vehicle system with a brushless d.c. motor
Authors: Wang Y N , Zhang X Z , Yuan X F
Published: May 2010

The present paper proposes an efficient and robust control scheme for an electric vehicle (EV) with a brushless d.c. motor. First, after analysing the control principle for the brushless d.c. motor, the equivalent circuits of the control system are depicted and the mathematical models under normal driving and energy regeneration are derived, respectively. Then, by combining the merits and defects of the non-singular terminal sliding-mode (NTSM) with the high-order sliding-mode (HOSM) method, a hybrid non-singular terminal sliding-mode control scheme (HTSM) for robust control of the EV is put forward to guarantee both system performance and robust stability. The experimental results show that the scheme exhibits better performance and higher efficiency than the traditional proportional-integral-derivative (PID) controller. Furthermore, more energy is recovered and the proposed scheme improves the driving range by 5.7 per cent more than the PID controller.
Parameter identification of a cage induction motor using particle swarm optimization
Authors: Nikranajbar A , Ebrahimi M K , Wood A S
Published: May 2010

The current paper presents an adaptive system identification/parameter estimation algorithm for a three-phase cage induction motor based on particle swarm optimization (PSO). The performance of the proposed algorithm is emphasized by comparing its results with those of the well-known stochastic optimization techniques of genetic algorithm (GA) and simulated annealing (SA) for the benchmark application with six unknown parameters to identify. The dynamic inertia-weighted PSO algorithm significantly outperformed the GA and SA techniques. The achievement of the presented methodology in confronting a rather complicated non-linear dynamic engineering application underlines the ability of the algorithm to be used for a range of real-world problems, and moreover justifies and motivates the development of more advanced techniques.
Roles of Mono- and Divalent Cations in DNA Compaction Induced by Histone-Mimic Nanoparticles
Authors: Takenaka Toshio , Zinchenko Anatoly A , Yoshikawa Kenichi , Murata Shizuaki
Published: May 2010

The compaction of gene-size T4 DNA induced by the action of silica nanoparticles (10–100 nm diameter), the surfaces of which were modified to various degrees by a 3-aminopropylsilyl groups, was monitored by a fluorescent microscope in an aqueous solution. It was found that DNA compaction was facilitated by mono- and divalent cations such as Na+, K+, Mg2+, and Ca2+. This promotion by cations was the result of charge-neutralization of DNA and was more remarkable in compaction by histone-size nanoparticles (10 nm) than in that by larger ones (>15 nm). Divalent metal ions were more effective at promoting compaction due to their greater charge-neutralizing character, but a quaternary diammonium derivative of 1,3-propanediamine deactivated DNA compaction by 10-nm nanoparticles. Although metal ions binding to DNA can reduce electrostatic tension on DNA and provide flexibility to create a DNA loop with a small diameter, such ammonium dication does not make DNA sufficiently flexible.
Regulation of interferon-γ, interleukin-4 and interleukin-2 bySchizonepeta tenuifoliathrough differential effects on nuclear factor-κB, NFATc2 and STAT4/6
Authors: Kang Hee , Moon Ja-Young , Sohn Nak-Won
Published: May 2010

Contact with antigen on T-cells is made via the T-cell receptor/CD3 complex plus CD28, resulting in the production of cytokines including interleukin (IL)-2, IL-4 and interferon (IFN)-γ. In particular, dysregulation of IFN-γ and IL-4 accounts in part for organ-specific autoimmune diseases, allergic inflammation and other chronic inflammatory disorders. The dried above-ground parts of Schizonepeta tenuifolia Briq are used for the treatment of common cold and skin rashes observed in allergic dermatitis, psoriasis and other dermatological disorders in oriental medicine. In the present study, we investigated whether S. tenuifolia water extract (STE) may modulate systemic levels of IFN-γ, IL-4 and IL-2 in anti-CD3-stimulated mice and the production of those cytokines in anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs). In addition, the effects of STE on anti-CD3-induced activation of several transcription factors were examined. Oral administration of STE significantly reduced the serum levels of IFN-γ and IL-4 from anti-CD3-treated mice but enhanced those of IL-2. Similar patterns were demonstrated in anti-CD3-stimulated splenocytes and PBMCs in vitro. Further analysis showed that STE enhanced the nuclear translocation of nuclear factor of activated T cells (NFAT)c2 but reduced that of the nuclear factor (NF)-κB. The downregulation of IFN-γ and IL-4 was not mediated by its effects on signal transducer and activator of transcription (STAT)4 and STAT6 activation. These results suggest that the differential regulation of STE on IFN-γ, IL-4 and IL-2 may be due to its suppression of NF-κB, concomitant with its enhancement of NFATc2. Further mechanistic work is required to investigate the role of STE on its modulation of anti-CD3-induced cytokines.
The influence of gestational zinc deficiency on the fetal insulin-like growth factor axis in the rat
Authors: Hanna Lynn A , Clegg Michael S , Ellis-Hutchings Robert G , Niles Brad J , Keen Carl L
Published: May 2010

The insulin-like growth factor (IGF) axis, a key regulator of embryonic growth and development, is exquisitely sensitive to the nutrient status of the animal. In addition to macronutrient deficiencies, zinc deficiency can impact the IGF axis. Gestational zinc deficiency is teratogenic, resulting in intrauterine growth retardation and structural abnormalities. The aim of this study was to investigate the effects of gestational zinc deficiency on the fetal IGF axis in a rat model. From gestation day (GD) 0.5, dams consumed zinc-deficient (ZD, 0.3 mg zinc/kg) or control (25 mg zinc/kg) diet ad libitum, while a third group of dams consumed the control diet in amounts equivalent to the food intake of the ZD dams (Paired group). On GD 19.5 fetal tissue, blood and amniotic fluid were collected. Fetal growth was significantly reduced by zinc deficiency compared with the Paired and Control groups. Fetuses from the Paired group were smaller compared with the Control, but only ZD fetuses had structural malformations. Amniotic fluid IGF-1 concentrations were significantly lower in the Paired group than in the ZD and Control groups. Plasma of ZD fetuses contained lower levels of IGF binding protein-1 when compared with fetuses in the Paired and Control groups. Fetal liver IGF-1 mRNA levels were lower in the ZD fetuses than in the Paired and Control fetuses. These observations suggest that differences in the fetal IGF axis between ZD and Paired groups contribute to the poor pregnancy outcome and enhanced fetal growth retardation observed with zinc deficiency.
Glucose intolerance and decreased early insulin response in mice with severe hypertriglyceridemia
Authors: Ding Yi-Lei , Wang Yu-Hui , Huang Wei , Liu George , Ross Colin , Hayden Michael R , Yang Jin-Kui
Published: May 2010

Hypertriglyceridemia (HTG) is one of the key features of dyslipidemia in type 2 diabetes, caused by the overproduction and/or decreased clearance of triglyceride (TG)-rich lipoproteins, and significantly promotes the development of cardiovascular diseases in diabetes. However, the effect of severe HTG on glucose metabolism has not previously been determined. Lipoprotein lipase (LPL) deficiency results in severe HTG in humans. By using LPL-deficient mice with severe HTG, we assessed the impact of severe HTG on insulin secretion and glucose tolerance in the present study. While young LPL-deficient mice (4 months of age) showed higher fasting blood glucose (7.42 ± 0.84 versus 4.8 ± 0.80 mmol/L, P < 0.01) and lower insulin concentrations (0.16 ± 0.03 versus 0.48 ± 0.14 ng/mL, P < 0.05), old mice (12 months of age) had higher insulin (1.70 ± 0.35 versus 0.77 ± 0.04 ng/mL, P < 0.05) but normal fasting blood glucose concentrations. Both young and old mice had elevated free fatty acid (FFA) concentrations and exhibited decreased early insulin response; however, only old mice showed impaired glucose tolerance, as compared with wild-type mice of a similar age. Morphological assessment showed enlarged islets in old LPL-deficient mice. These findings suggest that different tests for glucose homeostasis may be needed for patients with LPL deficiency and severe HTG, even though their glucose concentrations are normal at initial screening.
Evidence for the hypothesis that 10-formyldihydrofolate is the in vivo substrate for aminoimidazolecarboxamide ribotide transformylase
Authors: Baggott Joseph E , Tamura Tsunenobu
Published: May 2010

We postulate that 10-formyl-7,8-dihydrofolate (10-HCO-H2folate), not 10-formyl-5,6,7,8-tetrahydrofolate (10-HCO-H4folate), is the predominant in vivo substrate for mammalian aminoimidazolecarboxamide ribotide (AICAR) transformylase, an enzyme in purine nucleotide biosynthesis de novo, which introduces carbon 2 (C2) into the purine ring. 10-HCO-H2folate exists in vivo as labeled 10-formyl-folic acid (10-HCO-folic acid: an oxidation product of 10-HCO-H4folate and 10-HCO-H2folate) and is found after doses of labeled folic acid in humans or laboratory animals. The bioactivity of the unnatural isomer, [6 R]-5-formyltetrahydrofolate, in humans is explained by its in vivo conversion to 10-HCO-H2folate. The structure and active site of AICAR transformylase are not consistent with other enzymes that utilize 10-HCO-H4folate. Because 10-HCO-H4folate is rapidly oxidized in vitro to 10-HCO-H2folate by cytochrome C alone and in mitochondria, it is hypothesized that this process takes place in vivo. In vitro data indicate that 10-HCO-H2folate is kinetically preferred over 10-HCO-H4folate by AICAR transformylase and that this enzyme may not have access to sufficient supplies of 10-HCO-H4folate. Methotrexate blockage of the AICAR transformylase process in patients with rheumatoid arthritis suggests that dihydrofolate (H2folate) reductase is involved and is consistent with H2folate and 10-HCO-H2folate being the product and substrate for AICAR transformylase. The labeling of purine C2 by an oral dose of [6 RS]-5-H[13C]O-H4folate in a human subject is consistent with 10-H[13C]O-H2folate formation from unnatural isomer, [6 R]-5-H[13C]O-H4folate, and it being a substrate for AICAR transformylase. In vitro exchange reactions of purine C2 using H4folate coenzymes are not duplicated in vivo and is consistent with H2folate coenzymes being used in vivo by AICAR transformylase.
Aerobic exercise training improves Ca2+ handling and redox status of skeletal muscle in mice
Authors: Ferreira Julio C B , Bacurau Aline V , Bueno Carlos R , Cunha Telma C , Tanaka Leonardo Y , Jardim Maira A , Ramires Paulo R , Brum Patricia C
Published: May 2010

Exercise training is known to promote relevant changes in the properties of skeletal muscle contractility toward powerful fibers. However, there are few studies showing the effect of a well-established exercise training protocol on Ca2+ handling and redox status in skeletal muscles with different fiber-type compositions. We have previously standardized a valid and reliable protocol to improve endurance exercise capacity in mice based on maximal lactate steady-state workload (MLSSw). The aim of this study was to investigate the effect of exercise training, performed at MLSSw, on the skeletal muscle Ca2+ handling-related protein levels and cellular redox status in soleus and plantaris. Male C57BL/6J mice performed treadmill training at MLSSw over a period of eight weeks. Muscle fiber-typing was determined by myosin ATPase histochemistry, citrate synthase activity by spectrophotometric assay, Ca2+ handling-related protein levels by Western blot and reduced to oxidized glutathione ratio (GSH:GSSG) by high-performance liquid chromatography. Trained mice displayed higher running performance and citrate synthase activity compared with untrained mice. Improved running performance in trained mice was paralleled by fast-to-slow fiber-type shift and increased capillary density in both plantaris and soleus. Exercise training increased dihydropyridine receptor (DHPR) α2 subunit, ryanodine receptor and Na+/Ca2+ exchanger levels in plantaris and soleus. Moreover, exercise training elevated DHPR β1 subunit and sarcoplasmic reticulum Ca2+-ATPase (SERCA) 1 levels in plantaris and SERCA2 levels in soleus of trained mice. Skeletal muscle GSH content and GSH:GSSG ratio was increased in plantaris and soleus of trained mice. Taken together, our findings indicate that MLSSw exercise-induced better running performance is, in part, due to increased levels of proteins involved in skeletal muscle Ca2+ handling, whereas this response is partially dependent on specificity of skeletal muscle fiber-type composition. Finally, we demonstrated an augmented cellular redox status and GSH antioxidant capacity in trained mice.
Molecular dynamics simulations of rupture in lipid bilayers
Authors: Tomasini Michael D , Rinaldi Carlos , Tomassone M Silvina
Published: May 2010

Magnetic fluid hyperthermia is a promising cancer therapy in which magnetic nanoparticles are acted upon by a high-frequency oscillating magnetic field. While the accepted mechanism is localized hyperthermia, it is plausible that shear stresses due to nanoparticles rotating near a cell membrane may induce rupture, enhancing the effectiveness of the treatment. With the goal of understanding this further, molecular dynamics simulations were carried out on a model cell membrane. A bilayer composed of dipalmitoylphosphatidylcholine lipids was subjected to an incremental tension as well as an incremental shear stress. In both cases, it was found that the bilayer could withstand a surface tension of approximately 90 mN/m prior to rupture. Under tension, the bilayer ruptured at double its initial area, whereas under shear, the bilayer ruptured at 1.8 times its initial area. The results show that both incremental tension and incremental shearing are able to produce bilayer rupture, with shear being more injurious, yielding a larger surface tension for a smaller deformation. This information allows for comparison between the estimated energy required to rupture a cell membrane and the energy that a magnetic nanoparticle would be able to generate while rotating in a cellular environment. Our estimates indicate that magnetically blocked nanoparticles with diameters larger than 50 nm may result in rupture due to shear.
Are purified or expanded cord blood-derived CD133+cells better at improving cardiac function?
Authors: Senegaglia Alexandra C , Barboza Laura A , Dallagiovanna Bruno , Aita Carlos A M , Hansen Paula , Rebelatto Carmen L K , Aguiar Alessandra M , Miyague Nelson I , Shigunov Patrícia , Barchiki Fabiane , Correa Alejandro , Olandoski Marcia , Krieger Marco A , Brofman Paulo R S
Published: May 2010

Endothelial progenitor cells (EPCs), which express the CD133 marker, can differentiate into mature endothelial cells (ECs) and create new blood vessels. Normal angiogenesis is unable to repair the injured tissues that result from myocardial infarction (MI). Patients who have high cardiovascular risks have fewer EPCs and their EPCs exhibit greater in vitro senescence. Human umbilical cord blood (HUCB)-derived EPCs could be an alternative to rescue impaired stem cell function in the sick and elderly. The aim of this study was to purify HUCB-derived CD133+cells, expand them in vitro and evaluate the efficacy of the purified and expanded cells in treating MI in rats. CD133+cells were selected for using CD133-coupled magnetic microbeads. Purified cells stained positive for EPC markers. The cells were expanded and differentiated in media supplemented with fetal calf serum and basic fibroblast growth factor, insulin-like growth factor-I and vascular endothelial growth factor (VEGF). Differentiation was confirmed by lack of staining for EPC markers. These expanded cells exhibited increased expression of mature EC markers and formed tubule-like structures in vitro. Only the expanded cells expressed VEGF mRNA. Cells were expanded up to 70-fold during 60 days of culture, and they retained their functional activity. Finally, we evaluated the therapeutic potential of purified and expanded CD133+cells in treating MI by intramyocardially injecting them into a rat model of MI. Rats were divided into three groups: A (purified CD133+cells-injected); B (expanded CD133+cells-injected) and C (saline buffer-injected). We observed a significant improvement in left ventricular ejection fraction for groups A and B. In summary, CD133+cells can be purified from HUCB, expanded in vitro without loosing their biological activity, and both purified and expanded cells show promising results for use in cellular cardiomyoplasty. However, further pre-clinical testing should be performed to determine whether expanded CD133+cells have any clinical advantages over purified CD133+cells.
Current trends in mathematical modeling of tumor–microenvironment interactions: a survey of tools and applications
Authors: Rejniak Katarzyna A , McCawley Lisa J
Published: May 2010

In its simplest description, a tumor is comprised of an expanding population of transformed cells supported by a surrounding microenvironment termed the tumor stroma. The tumor microcroenvironment has a very complex composition, including multiple types of stromal cells, a dense network of various extracellular matrix (ECM) fibers interpenetrated by the interstitial fluid and gradients of several chemical species that either are dissolved in the fluid or are bound to the ECM structure. In order to study experimentally such complex interactions between multiple players, cancer is dissected and considered at different scales of complexity, such as protein interactions, biochemical pathways, cellular functions or whole organism studies. However, the integration of information acquired from these studies into a common description is as difficult as the disease itself. Computational models of cancer can provide cancer researchers with invaluable tools that are capable of integrating the complexity into organizing principles as well as suggesting testable hypotheses. We will focus in this Minireview on mathematical models in which the whole cell is a main modeling unit. We will present a current stage of such cell-focused mathematical modeling incorporating different stromal components and their interactions with growing tumors, and discuss what modeling approaches can be undertaken to complement the in vivo and in vitro experimentation.
Suprachiasmatic nucleus neurons display endogenous resistance to excitotoxicity
Authors: Bottum Kathleen , Poon Emily , Haley Benjamin , Karmarkar Sumedha , Tischkau Shelley A
Published: May 2010

A comprehensive understanding of neuroprotective pathways is essential to progress in the battle against numerous neurodegenerative conditions. The hypothalamic suprachiasmatic nucleus (SCN) is endogenously resistant to glutamate (Glu) excitotoxicity in vivo. This study was designed to determine whether immortalized SCN neurons (SCN2.2 cells) retain this characteristic. We first established that SCN2.2 cells retained the ability to respond to Glu. SCN2.2 cells expressed N-methyl-d-aspartate (NMDA) receptor subtypes NR1 and NR2A/2B, suggesting the presence of functional receptors. mRNA for the NMDA receptor subunits NR2A and NR2B were higher in the SCN2.2 than in the control hypothalamic neurons (GT1-7). Specific NMDA receptor antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate and d-(–)-2-amino-5-phosphonovaleric acid blocked Glu-induced activation of gene expression. SCN2.2 cells were resistant to Glu excitotoxicity compared with GT1-7 neurons as assessed with a mitochondrial function assay, cell death by trypan blue exclusion and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling. SCN2.2 resistance to Glu excitoxicity was retained in the presence of the broad spectrum Glu transport inhibitor, l-trans-pyrrolidine-2,4 dicarboxylate, excluding glial Glu uptake as a major neuroprotective mechanism. Collectively, these observations demonstrate endogenous neuroprotection in SCN2.2 cells; this cell line is resistant to excitotoxicity under conditions that are toxic to other immortalized cell lines. Thus, the SCN2.2 cell line may provide insights into the molecular mechanisms that confer endogenous neuroprotection in the SCN.
Effect of swirling flow on the uptakes of native and oxidized LDLs in a straight segment of the rabbit thoracic aorta
Authors: Ding Zufeng , Fan Yubo , Deng Xiaoyan , Zhan Fan , Kang Hongyan
Published: May 2010

To elucidate the physiological significance of the spiral flow in the arterial system from the viewpoint of atherogenic lipid transport, an ex vivo experimental comparative study was designed to investigate the effect of swirling flow on the distribution of native 3,3′-dioctadecylindocarbocyanine-low-density lipoprotiens (DiI-LDL) and DiI-ox-LDL uptakes by segments of the rabbit thoracic aorta. The experimental results showed that when compared with the normal flow, the swirling flow generated in the test arteries significantly reduced the DiI-LDL and DiI-ox-LDL uptakes by the arterial walls. The results also showed that the values of DiI-ox-LDL uptake were higher than those of DiI-LDL uptake at the same sample position in both the normal flow group and the swirling flow group. Most interestingly, the experimental results found that the percentage increase in DiI-ox-LDL uptake was much larger than that in DiI-LDL uptake when the perfusion duration increased from 3 to 24 h. In conclusion, the present study substantiated the hypothesis that the spiral flow in the arterial system plays a beneficial role in protecting the arterial wall from atherogenesis. Meanwhile, it supported the concept that the receptor-mediated bindings of LDL uptake, the barrier function of the arterial endothelial linings and the mass transport phenomenon of LDL concentration polarization are all involved in the infiltration/accumulation of atherogenic lipids within the arterial wall.
Exogenous ghrelin regulates proliferation and apoptosis in the hypotrophic gut mucosa of the rat
Authors: de Segura Ignacio A Gómez , Vallejo-Cremades María Teresa , Lomas Jesús , Sánchez Miriam F , Caballero María Isabel , Largo Carlota , De Miguel Enrique
Published: May 2010

Ghrelin is the natural endogenous ligand for growth hormone secretagogue receptors. This peptide regulates energy homeostasis and expenditure and is a potential link between gut absorptive function and growth. We hypothesized that ghrelin may induce a proliferative and antiapoptotic action promoting the recovery of the hypotrophic gut mucosa. Therefore, the aim of the study was to determine the action of exogenous ghrelin following gut mucosal hypotrophia in rats fed an elemental diet. An elemental diet provides readily absorbable simple nutrients and is usually given to patients with absorptive dysfunction. Male Wistar rats ( n = 48) were fed the elemental diet for one week to induce mucosal hypotrophy and then treated for another week with systemic ghrelin and pair-fed with either a normoproteic or hyperproteic isocaloric liquid diet. Another group received a standard diet instead of the elemental diet and served as control (normotrophy). The elemental diet induced intestinal hypotrophia characterized by decreased proliferation in the ileum and increased apoptosis in jejunum and ileum. Ghrelin administration restored normal levels of proliferation in the ileum and apoptosis in the jejunum, with partial apoptosis restoration in the ileum. Ghrelin levels in plasma and fundus were increased in all groups, although the highest levels were found in rats treated with exogenous ghrelin. Ghrelin administration has a positive effect in the hypotrophic gut, regulating both proliferation and apoptosis towards a physiological balance counteracting the negative changes induced by an elemental diet in the intestines.