bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling and Theory of Intermittent Motions in a Machine Tool With a Friction Boundary
Authors: Gegg Brandon C. , Suh Steve C. S. , Luo Albert C. J.
Published: August 2010

In this paper the simplified mechanical model for a machine-tool system is presented. The state and domains are defined with respect to the (contact and frictional force) boundaries in this system. The switching sets for this machine-tool will be defined for all the boundaries considered herein. The forces and force product components at the switching points are determined according to discontinuous systems theory. The forces and force product govern the passability of the machine-tool through the respective boundary. Mapping definitions and notations are developed through the switching sets for the boundaries. A mapping structure and notation for one type of intermittent cutting periodic motion is defined as an example.
AWJ Milling of Gamma Titanium Aluminide
Authors: Hashish Mohamed
Published: August 2010

A study was undertaken to determine the feasibility of the AWJ process for controlled depth milling of gamma Titanium Aluminide tiles. It was demonstrated that milling can be accomplished to 0.025-mm accuracy. To overcome undercutting near rib roots, the jet was clock-angled at about 15 deg to the vertical every set of passes. This allowed the milling to thin skins of about 0.5-mm. It was observed that as the material is milled, stresses were relieved, and either deformation or cracking may result. Accordingly, parts need to be annealed before milling. The milling to thin skins was successfully demonstrated on 150×300 mm2 parts without adverse effects. Also, the process of milling of the dual rib height was developed using the dual mask approach. Abrasive particle embedding on the milled surfaces was observed to be about 0.15% of the area, but cleaning with plain waterjets showed that all embedded particles can be removed. A detailed economic analysis confirmed that the AWJ milling process is relatively inexpensive and highly productive. The complete cost of milling including mask cutting, overhead, capital, and running cost is less than 300 USD/ft2.
Time Domain Models for Damping-Controlled Fluidelastic Instability Forces in Tubes With Loose Supports
Authors: Hassan Marwan , Hossen Achraf
Published: August 2010

This paper presents simulations of a loosely supported cantilever tube subjected to turbulence and fluidelastic instability forces. Several time domain fluid force models are presented to simulate the damping-controlled fluidelastic instability mechanism in tube arrays. These models include a negative damping model based on the Connors equation, fluid force coefficient-based models (Chen, 1983, “Instability Mechanisms and Stability Criteria of a Group of Cylinders Subjected to Cross-Flow. Part 1: Theory,” Trans. ASME, J. Vib., Acoust., Stress, Reliab. Des., 105, pp. 51–58; Tanaka and Takahara, 1981, “Fluid Elastic Vibration of Tube Array in Cross Flow,” J. Sound Vib., 77, pp. 19–37), and two semi-analytical models (Price and Païdoussis, 1984, “An Improved Mathematical Model for the Stability of Cylinder Rows Subjected to Cross-Flow,” J. Sound Vib., 97(4), pp. 615–640; Lever and Weaver, 1982, “A Theoretical Model for the Fluidelastic Instability in Heat Exchanger Tube Bundles,” ASME J. Pressure Vessel Technol., 104, pp. 104–147). Time domain modeling and implementation challenges for each of these theories were discussed. For each model, the flow velocity and the support clearance were varied. Special attention was paid to the tube/support interaction parameters that affect wear, such as impact forces and normal work rate. As the prediction of the linear threshold varies depending on the model utilized, the nonlinear response also differs. The investigated models exhibit similar response characteristics for the lift response. The greatest differences were seen in the prediction of the drag response, the impact force level, and the normal work rate. Simulation results show that the Connors-based model consistently underestimates the response and the tube/support interaction parameters for the loose support case.
An Experimental Study on Cutting Forces in the Threading and the Side Cut Turning With Coated and Uncoated Grades
Authors: Kafkas Firat
Published: August 2010

The objective of this study is to obtain the cutting force components on the threading insert. The cutting force data used in the analysis are measured by a three-dimensional dynamic force dynamometer. The AISI 4140 and AISI 4340 low alloy steels are selected for the experiment on the threading and the side cut turning. The inserts used for testing is the TiAlN coated and uncoated grades. LT22NR35ISO type insert is used in the experiment. During the experiments, no cutting fluid and a constant spindle speed is used. The thread pitch and the depth of cut were kept fixed at 3.5 mm and 0.05 mm for the radial feed per pass, respectively. The study emphasizes on the effects on the workpiece material and the cutting tool grade of the cutting force components that occur during the threading. Also, these results are compared with the findings that are obtained during the side cut turning. It is determined that the measured primary cutting and radial forces during the threading are approximately three times bigger than those during the side cut turning, although feed forces during the threading are approximately 30 times lower compared with the side cut turning. The TiAlN coated WC/Co grade shows the best performance with respect to the cutting force components. The specific cutting forces are determined in order to understand the interference of chips that occur during the threading. With the increase in the cumulative radial feed, the corresponding specific cutting forces become higher. It is reasoned that the difference in the specific cutting forces results from the alteration of the interference of the flowing chips. The specific cutting forces decrease in the beginning of the threading and then increases with the cumulative radial feed. The results show that the interference of the chip flow influences the threading force components to a very large extent.
Effect of a Flexible Wall on a Reattaching Turbulent Shear Layer
Authors: Velikorodny Alexey , Duck Graham , Oshkai Peter
Published: August 2010

Digital particle image velocimetry was applied to investigate turbulent flow of air between a flexible wall and a rigid surface containing a backward-facing step (BFS). The inflow condition corresponded to a Coanda jet issuing from a nozzle that was located upstream of the BFS. The flexible wall was represented by a sheet of paper under tension that was positioned above the BFS. Two additional configurations, which involved the BFS without the flexible wall and the BFS in proximity to an inclined rigid upper wall, were considered in this study. In all three cases, the flow fields were characterized in terms of patterns of time-averaged velocity, out-of-plane vorticity, streamline topology, and turbulence statistics. High-speed photography and unsteady pressure measurements were employed to characterize the flow-induced deformation of the flexible wall and the flow oscillations. The profile of the paper sheet could be approximated by linear segments, which, in conjunction with the rigid surface that contained the BFS, formed a diverging channel configuration. Confinement of the incoming flow by the flexible wall delayed flow reattachment to the rigid bottom surface downstream of the BFS. Patterns of turbulence statistics in the presence of the flexible wall shared qualitative similarity with the corresponding parameters of diverging channel flows as well as classical Couette–Poiseuille flows.
Height Control in Laser Cladding Using Adaptive Sliding Mode Technique: Theory and Experiment
Authors: Zeinali Meysar , Khajepour Amir
Published: August 2010

A closed-loop control of the laser cladding process is desired due to difficulties encountered in depositing a layer with acceptable quality from both geometrical and metallurgical point of views. One of the main parameters to achieve the desired geometry in laser cladding process is the height of the deposited layers. In this paper, a real-time measurement and control of the clad height is presented. Due to complex nature of the process and presence of uncertainties, a robust and adaptive sliding mode control is proposed and implemented to control the clad height. The velocity of the substrate is used as a control input while the molten pool height, which is obtained using a charge-coupled device (CCD) camera and an image processing algorithm is used as a feedback signal. Stability of the controller is proven in the presence of time-varying uncertainties and the performance of the closed-loop system is validated by simulation and experiments. The experimental results are promising and show that the geometrical accuracy of the deposited layers can be improved significantly.
Instability of Pressure Relief Valves in Water Pipes
Authors: Moussou P. , Gibert R. J. , Brasseur G. , Teygeman Ch. , Ferrari J. , Rit J. F.
Published: August 2010

Pressure relief valves in water pipes are known to sometimes chatter when the inlet pressure slightly exceeds the set pressure. While these devices are responsible for numerous fatigue issues in process industries, there is a relatively low number of technical publications covering their performance, especially in heavy fluid applications. The present study is intended as a contribution to the understanding of pressure relief valve dynamics, taking into account fluid-structure interactions. A series of tests were performed with a water relief valve in a test rig. Adjusting the set pressure of the valve to about 30 bars, an upstream pressure varying from 20 bars to 35 bars was imposed, so that the valve opened and the water flow varied from a few m3/h to about 80 m3/h. During the tests, the pipe was equipped upstream and downstream of the valve with static pressure sensors and a flowmeter, the disk lift was measured with a laser displacement sensor, and the spring force was recorded simultaneously. Several fluctuating pressure sensors were also installed in the inlet pipe. Static instability is investigated by comparing the spring force to the hydraulic force. Dynamic instability is observed and it is shown that the resonant behavior of the disk generates an apparent negative pressure drop coefficient at some frequencies. This negative pressure drop coefficient can trigger a dynamic instability in a manner similar to the negative damping effect in leakage-flow vibrations.
Strange Metal Transport Realized by Gauge/Gravity Duality
Authors: Faulkner Thomas , Iqbal Nabil , Liu Hong , McGreevy John , Vegh David
Published: August 2010

Black Holes as Tools

When confronted with a difficult problem, physicists often resort to mapping it to a more tractable one. A good example of this strategy is provided by new developments linking string theory and condensed-matter physics to make theoretical connections between gravity and complex systems of interacting electrons. This theoretical convergence provides a description of Fermi liquids, which can be thought of as interacting systems of electrons whose excitations can be expressed in terms of non-interacting quasiparticles. Several interesting systems elude quasiparticle description, but

Faulkner
et al.

(p.
1043
, published online 5 August) have now developed a mathematical framework that describes the non-Fermi liquid represented by the strange metal phase of cuprate high-temperature superconductors. They calculate the electronic response and, for a particular value of a tunable parameter, recover the linear resistivity. Further development of this framework may allow elucidation of other exotic properties of the cuprates and similar complex systems.
Glutamine Deamidation and Dysfunction of Ubiquitin/NEDD8 Induced by a Bacterial Effector Family
Authors: Cui Jixin , Yao Qing , Li Shan , Ding Xiaojun , Lu Qiuhe , Mao Haibin , Liu Liping , Zheng Ning , Chen She , Shao Feng
Published: August 2010

Gee-Up, NEDD8

Diverse bacterial pathogens, such as
Burkholderia pseudomallei
and enteropathogenic
Escherichia coli
(EPEC), inject effector proteins into eukaryotic host cells to subvert host cell biology.

Cui
et al.

(p.
1215
; published online 5 August) show that certain bacterial effector proteins promoted the glutamine deamidation of ubiquitin and the ubiquitin-related protein, NEDD8. The modification of ubiquitin inhibited the formation of polyubiquitin chains while, unexpectedly, the same chemical alteration on NEDD8 interfered with the cell cycle, offering insights not only into the cytopathic effects of bacterial infection but also into mechanisms that may operate during viral infection and cancer.
Evolving role of cardiac CT in the diagnosis of coronary artery disease
Authors: Yerramasu Ajay , Venuraju Shreenidhi , Lahiri Avijit
Published: August 2010

Non-invasive assessment of coronary artery patency has been attempted with different imaging modalities over the last few decades. The continuous motion of the heart, the respiratory movement, together with the small and tortuous nature of the coronary arteries, made this a technically challenging task. Over the last decade, significant advances in computed tomography (CT) technology helped CT coronary angiography (CTCA) to evolve as a non-invasive alternative to conventional catheter based coronary angiography. Clinical experience with CTCA has since grown rapidly and led to its acceptance as a useful diagnostic technique for coronary artery disease in certain patient populations. Recently, there has been exponential growth in the availability and use of CTCA in several centres across the world. In order to appreciate the potential impact of CTCA on current clinical practice, it is important to understand its advantages and limitations and its clinical performance in comparison with established techniques.
Concurrent comparison of epidemiology, clinical presentation and outcome between adult patients suffering from the pandemic influenza A (H1N1) 2009 virus and the seasonal influenza A virus infection
Authors: To Kelvin K W , Wong Samson S Y , Li Iris W S , Hung Ivan F N , Tse Herman , Woo Patrick C Y , Chan Kwok-Hung , Yuen Kwok-Yung
Published: August 2010

Purpose of study

The demographics, clinical features and outcome of patients with pandemic influenza A (H1N1) 2009 infection were compared with a concurrent cohort of patients with seasonal influenza A infection.

Study design

The clinical and microbiological data of hospitalised adult patients admitted between 29 June and 28 October 2009, with pandemic A (H1N1) 2009 or seasonal influenza A infection, were analysed.

Results

A total of 186 patients including 69 pandemic A (H1N1) and 117 seasonal influenza were analysed. The majority (75%) under 50 years of age had pandemic A (H1N1). Compared with seasonal influenza, pandemic A (H1N1) patients were younger (median age 47 years vs 76 years, p<0.001), less likely to have lower respiratory tract symptoms (46.4% vs 66.7%, p=0.007), but more likely to be obese (5.8% vs 0%, p=0.018), pregnant (7.2% vs 0.9%, p=0.027) or have no underlying predisposing factors (24.6% vs 5.1%, p<0.001). Patients with pandemic A (H1N1) were more likely to receive oseltamivir (91.3% vs 40.2%, p<0.001), but less likely to receive antibiotics (75.4% vs 90.6%, p=0.005). Respiratory failure was the reason for intensive care unit admission for all four patients with pandemic A (H1N1), but only for one of three patients with seasonal influenza. There were no statistical significant differences in the rate of intensive care unit admission or death.

Conclusions

In addition to age, several clinical parameters were different between pandemic A (H1N1) and seasonal influenza. However, since both seasonal and pandemic influenza can lead to significant morbidity and mortality, the impact of pre-existing seasonal influenza should not be underestimated during the pandemic period.
HIF-1 mediates pathogenic inflammatory responses to intestinal ischemia-reperfusion injury
Authors: Feinman Rena , Deitch Edwin A. , Watkins Anthony C. , Abungu Billy , Colorado Iriana , Kannan Kolenkode B. , Sheth Sharvil U. , Caputo Francis J. , Lu Qi , Ramanathan Madhuri , Attan Shirhan , Badami Chirag D. , Doucet Danielle , Barlos Dimitrios , Bosch-Marce Marta , Semenza Gregg L. , Xu Da-Zhong
Published: August 2010

Acute lung injury (ALI) and the development of the multiple organ dysfunction syndrome (MODS) are major causes of death in trauma patients. Gut inflammation and loss of gut barrier function as a consequence of splanchnic ischemia-reperfusion (I/R) have been implicated as the initial triggering events that contribute to the development of the systemic inflammatory response, ALI, and MODS. Since hypoxia-inducible factor (HIF-1) is a key regulator of the physiological and pathophysiological response to hypoxia, we asked whether HIF-1 plays a proximal role in the induction of gut injury and subsequent lung injury. Utilizing partially HIF-1α-deficient mice in a global trauma hemorrhagic shock (T/HS) model, we found that HIF-1 activation was necessary for the development of gut injury and that the prevention of gut injury was associated with an abrogation of lung injury. Specifically, in vivo studies demonstrated that partial HIF-1α deficiency ameliorated T/HS-induced increases in intestinal permeability, bacterial translocation, and caspase-3 activation. Lastly, partial HIF-1α deficiency reduced TNF-α, IL-1β, cyclooxygenase-2, and inducible nitric oxide synthase levels in the ileal mucosa after T/HS whereas IL-1β mRNA levels were reduced in the lung after T/HS. This study indicates that prolonged intestinal HIF-1 activation is a proximal regulator of I/R-induced gut mucosal injury and gut-induced lung injury. Consequently, these results provide unique information on the initiating events in trauma-hemorrhagic shock-induced ALI and MODS as well as potential therapeutic insights.
Loss of protein tyrosine phosphatase N2 potentiates epidermal growth factor suppression of intestinal epithelial chloride secretion
Authors: Scharl Michael , Rudenko Ivan , McCole Declan F.
Published: August 2010

The Crohn's disease candidate gene, protein tyrosine phosphatase nonreceptor type 2 (PTPN2), has been shown to regulate epidermal growth factor (EGF)-induced phosphatidylinositol 3-kinase (PI3K) activation in fibroblasts. In intestinal epithelial cells (IECs), EGF-induced EGF receptor (EGFR) activation and recruitment of PI3K play a key role in regulating many cellular functions including Ca2+-dependent Cl−secretion. Moreover, EGFR also serves as a conduit for signaling by other non-growth factor receptor ligands such as the proinflammatory cytokine, IFN-γ. Here we investigated a possible role for PTPN2 in the regulation of EGFR signaling and Ca2+-dependent Cl−secretion in IECs. PTPN2 knockdown enhanced EGF-induced EGFR tyrosine phosphorylation in T84cells. In particular, PTPN2 knockdown promoted EGF-induced phosphorylation of EGFR residues Tyr-992 and Tyr-1068 and led subsequently to increased association of the catalytic PI3K subunit, p110, with EGFR and elevated phosphorylation of the downstream marker, Akt. As a functional consequence, loss of PTPN2 potentiated EGF-induced inhibition of carbachol-stimulated Ca2+-dependent Cl−secretion. In contrast, PTPN2 knockdown affected neither IFN-γ-induced EGFR transactivation nor EGF- or IFN-γ-induced phosphorylation of ERK1/2. In summary, our data establish a role for PTPN2 in the regulation of EGFR signaling in IECs in response to EGF but not IFN-γ. Knockdown of PTPN2 directs EGFR signaling toward increased PI3K activation and increased suppression of epithelial chloride secretory responses. Moreover, our findings suggest that PTPN2 dysfunction in IECs leads to altered control of intestinal epithelial functions regulated by EGFR.
Colon luminal content and epithelial cell morphology are markedly modified in rats fed with a high-protein diet
Authors: Andriamihaja Mireille , Davila Anne-Marie , Eklou-Lawson Mamy , Petit Nathalie , Delpal Serge , Allek Fadhila , Blais Anne , Delteil Corine , Tomé Daniel , Blachier François
Published: August 2010

Hyperproteic diets are used in human nutrition to obtain body weight reduction. Although increased protein ingestion results in an increased transfer of proteins from the small to the large intestine, there is little information on the consequences of the use of such diets on the composition of large intestine content and on epithelial cell morphology and metabolism. Rats were fed for 15 days with either a normoproteic (NP, 14% protein) or a hyperproteic isocaloric diet (HP, 53% protein), and absorptive colonocytes were observed by electron microscopy or isolated for enzyme activity studies. The colonic luminal content was recovered for biochemical analysis. Absorbing colonocytes were characterized by a 1.7-fold reduction in the height of the brush-border membranes ( P = 0.0001) after HP diet consumption when compared with NP. This coincided in the whole colon content of HP animals with a 1.8-fold higher mass content ( P = 0.0020), a 2.2-fold higher water content ( P = 0.0240), a 5.2-fold higher protease activity ( P = 0.0104), a 5.5-fold higher ammonia content ( P = 0.0008), and a more than twofold higher propionate, valerate, isobutyrate, and isovalerate content ( P < 0.05). The basal oxygen consumption of colonocytes was similar in the NP and HP groups, but ammonia was found to provoke a dose-dependent decrease of oxygen consumption in the isolated absorbing colonocytes. The activity of glutamine synthetase (which condenses ammonia and glutamate) was found to be much higher in colonocytes than in small intestine enterocytes and was 1.6-fold higher ( P = 0.0304) in colonocytes isolated from HP animals than NP. Glutaminase activity remained unchanged. Thus hyperproteic diet ingestion causes marked changes both in the luminal environment of colonocytes and in the characteristics of these cells, demonstrating that hyperproteic diet interferes with colonocyte metabolism and morphology. Possible causal relationships between energy metabolism, reduced height of colonocyte brush-border membranes, and reduced water absorption are discussed.
Roles of lysosomal proteolytic systems in AQP5 degradation in the submandibular gland of rats following chorda tympani parasympathetic denervation
Authors: Azlina Ahmad , Javkhlan Purevjav , Hiroshima Yuka , Hasegawa Takahiro , Yao Chenjuan , Akamatsu Tetsuya , Hosoi Kazuo
Published: August 2010

Chorda tympani denervation (CTD) of rats was earlier shown to result in loss of submandibular gland (SMG) weight (at only 1 wk) and in continued reduction in aquaporin 5 (AQP5) protein expression (until 4 wk), without affecting its mRNA synthesis (Li X, Azlina A, Karabasil MR, Purwanti N, Hasegawa T, Yao C, Akamatsu T, Hosoi K. Am J Physiol Gastrointest Liver Physiol 295: G112–G123, 2008). The present study indicated that despite elevation of bax, a proapoptosis protein, by CTD, the operation also increased the level of bcl-2, an antiapoptosis protein, in the SMG. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) showed no increase in the number of apoptotic cells in the SMG. CTD, however, induced strongly and transiently (at 1–3 days) the protein expression of LC3B-II, a marker protein of autophagosomes, suggesting that the reduction in the gland weight was due to onset of autophagy by CTD. Upon CTD, Lamp2, a lysosomal marker, gradually increased in amount, reaching a peak at the 14th day. Immunohistochemical analysis revealed an increase in the number of lysosome-like structures positive for both AQP5 and Lamp2 in the acinar cells of the SMG after CTD; similar changes were observed also for AQP5 and LC3Bs. These data suggest that AQP5 in the SMG entered autophagosomes and/or lysosomes for degradation upon CTD. In vitro AQP5-degrading activity was found in the SMG extracts, and such activity was shown to be increased by CTD. Inhibitor experiments implied cathepsins B and L to be candidate enzymes for this degradation under normal and CTD conditions, respectively.
Identification of microRNAs during rat liver regeneration after partial hepatectomy and modulation by ursodeoxycholic acid
Authors: Castro Rui E. , Ferreira Duarte M. S. , Zhang Xiaoxiao , Borralho Pedro M. , Sarver Aaron L. , Zeng Yan , Steer Clifford J. , Kren Betsy T. , Rodrigues Cecília M. P.
Published: August 2010

New gene regulation study tools such as microRNA (miRNA or miR) analysis may provide unique insights into the remarkable ability of the liver to regenerate. In addition, we have previously shown that ursodeoxycholic acid (UDCA) modulates mRNA levels during liver regeneration. Bile acids are also homeotrophic sensors of functional hepatic capacity. The present study was designed to determine whether miRNAs are modulated in rats following 70% partial hepatectomy (PH) and elucidate the role of UDCA in regulating miRNA expression during liver regeneration (LR). Total RNA was isolated from livers harvested at 3–72 h following 70% PH or sham operations, from both 0.4% (wt/wt) UDCA and control diet-fed animals. By using a custom microarray platform we found that several miRNAs are significantly altered after PH by >1.5-fold, including some previously described as modulators of cell proliferation, differentiation, and death. In particular, expression of miR-21 was increased after PH. Functional modulation of miR-21 in primary rat hepatocytes increased cell proliferation and viability. Importantly, UDCA was a strong inducer of miR-21 both during LR and in cultured HepG2 cells. In fact, UDCA feeding appeared to induce a sustained increase of proliferative miRNAs observed at early time points after PH. In conclusion, miRNAs, in particular miR-21, may play a significant role in modulating proliferation and cell cycle progression genes after PH. miR-21 is additionally induced by UDCA in both regenerating rat liver and in vitro, which may represent a new mechanism behind UDCA biological functions.
Increased renal α-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy
Authors: West Crystal , Zhang Zheng , Ecker Geoffrey , Masilamani Shyama M. E.
Published: August 2010

Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na+/H+exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy ( days 18–20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (UNaV postbenzamil-UNaV postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.
Energy expenditure in obesity-prone and obesity-resistant rats before and after the introduction of a high-fat diet
Authors: Jackman Matthew R. , MacLean Paul S. , Bessesen Daniel H.
Published: August 2010

While most rats gain weight when placed on a high-fat diet (HFD), some strains resist HFD-induced weight gain. To maintain weight, obesity-resistant (OR) rats must either eat less than obesity-prone (OP) rats or increase total energy expenditure (TEE). To determine if changes in TEE predispose to or protect from weight gain, energy expenditure, energy intake, and weight gain were measured in male and female OP and OR rats consuming a low-fat diet (LFD) and for 5 days after switching to a HFD. After 5 days on a HFD, OP rats gained significantly more weight (male: 42.8 ± 6.9 g, female: 25.5 ± 3.0 g) than their OR counterparts (male: 24.0 ± 7.5 g, female: 13.7 ± 1.4 g). Both male and female rats significantly increased their energy intake when transitioned to the HFD, and TEE increased modestly in all groups. Compared with female OP rats, female OR rats had a significantly greater increase in TEE on the HFD. This was due to an increase in both resting and nonresting energy expenditure. In contrast, the effect of the HFD in males was minor. TEE was also measured in female rats consuming a HFD, pair fed to LFD calories. The increase in TEE of pair-fed female OR rats was substantially less than what was seen in the HFD ad libitum condition. Physical activity was also measured in female rats. There was no evidence that increases in physical activity were the cause of the increased TEE seen in female OR rats consuming a HFD. These results suggest that resistance to HFD-induced weight gain in female OR rats may be due in part to an increase in TEE and a greater reliance on lipid as an energy source. Changes in TEE appear to be triggered by overconsumption of the HFD and not simply the diet composition.
Hypoxia-induced intrapulmonary arteriovenous shunting at rest in healthy humans
Authors: Laurie Steven S. , Yang Ximeng , Elliott Jonathan E. , Beasley Kara M. , Lovering Andrew T.
Published: August 2010

Intrapulmonary arteriovenous (IPAV) shunting has been shown to occur at rest in some subjects breathing a hypoxic gas mixture [fraction of inspired oxygen (FiO2) = 0.12] for brief periods of time. In the present study we set out to determine if IPAV shunting could be induced at rest in all subjects exposed to hypoxia for 30 min. Twelve subjects (6 women) breathed four levels of hypoxia (FiO2 = 0.16, 0.14, 0.12, and 0.10) for 30 min each in either an ascending or descending order with a 15-min normoxic break between bouts. Saline contrast echocardiography was used to detect IPAV shunt and a shunt score (0–5) was assigned based on contrast in the left ventricle with a shunt score ≥ 2 considered significant. Pulmonary artery systolic pressure (PASP) was determined using Doppler ultrasound. The total number of subjects demonstrating shunt scores ≥ 2 for FiO2 = 0.16, 0.14, 0.12, and 0.10 was 1/12, 7/12, 9/12, and 12/12, respectively. Shunt scores were variable between subjects but significantly greater than normoxia for FiO2 = 0.12 and 0.10. Shunt scores correlated with peripheral measurements of arterial oxygen saturation (SpO2) ( r w = −0.67) and PASP ( r w = 0.44), despite an increased shunt score but no increase in PASP while breathing an FiO2 = 0.12. It is unknown how hypoxia induces the opening of IPAV shunts, but these vessels may be controlled via similar mechanisms as systemic vessels that vasodilate in response to hypoxia. Despite intersubject variability our results indicate significant IPAV shunting occurs at rest in all subjects breathing an FiO2 = 0.10 for 30 min.
Mechanisms of aerobic performance impairment with heat stress and dehydration
Authors: Cheuvront Samuel N. , Kenefick Robert W. , Montain Scott J. , Sawka Michael N.
Published: August 2010

Environmental heat stress can challenge the limits of human cardiovascular and temperature regulation, body fluid balance, and thus aerobic performance. This minireview proposes that the cardiovascular adjustments accompanying high skin temperatures (Tsk), alone or in combination with high core body temperatures (Tc), provide a primary explanation for impaired aerobic exercise performance in warm-hot environments. The independent (Tsk) and combined (Tsk+ Tc) effects of hyperthermia reduce maximal oxygen uptake (V̇o2max), which leads to higher relative exercise intensity and an exponential decline in aerobic performance at any given exercise workload. Greater relative exercise intensity increases cardiovascular strain, which is a prominent mediator of rated perceived exertion. As a consequence, incremental or constant-rate exercise is more difficult to sustain (earlier fatigue) or requires a slowing of self-paced exercise to achieve a similar sensation of effort. It is proposed that high Tskand Tcimpair aerobic performance in tandem primarily through elevated cardiovascular strain, rather than a deterioration in central nervous system (CNS) function or skeletal muscle metabolism. Evaporative sweating is the principal means of heat loss in warm-hot environments where sweat losses frequently exceed fluid intakes. When dehydration exceeds 3% of total body water (2% of body mass) then aerobic performance is consistently impaired independent and additive to heat stress. Dehydration augments hyperthermia and plasma volume reductions, which combine to accentuate cardiovascular strain and reduce V̇o2max. Importantly, the negative performance consequences of dehydration worsen as Tskincreases.
Derivation of a finite-element model of lingual deformation during swallowing from the mechanics of mesoscale myofiber tracts obtained by MRI
Authors: Mijailovich Srboljub M. , Stojanovic Boban , Kojic Milos , Liang Alvin , Wedeen Van J. , Gilbert Richard J.
Published: August 2010

To demonstrate the relationship between lingual myoarchitecture and mechanics during swallowing, we performed a finite-element (FE) simulation of lingual deformation employing mesh aligned with the vector coordinates of myofiber tracts obtained by diffusion tensor imaging with tractography in humans. Material properties of individual elements were depicted in terms of Hill's three-component phenomenological model, assuming that the FE mesh was composed of anisotropic muscle and isotropic connective tissue. Moreover, the mechanical model accounted for elastic constraints by passive and active elements from the superior and inferior directions and the effect of out-of-plane muscles and connective tissue. Passive bolus effects were negligible. Myofiber tract activation was simulated over 500 ms in 1-ms steps following lingual tip association with the hard palate and incorporated specifically the accommodative and propulsive phases of the swallow. Examining the displacement field, active and passive muscle stress, elemental stretch, and strain rate relative to changes of global shape, we demonstrate that lingual reconfiguration during these swallow phases is characterized by (in sequence) the following: 1) lingual tip elevation and shortening in the anterior-posterior direction; 2) inferior displacement related to hyoglossus contraction at its inferior-most position; and 3) dominant clockwise rotation related to regional contraction of the genioglossus and contraction of the hyoglossus following anterior displacement. These simulations demonstrate that lingual deformation during the indicated phases of swallowing requires temporally patterned activation of intrinsic and extrinsic muscles and delineate a method to ascertain the mechanics of normal and pathological swallowing.
Adhesion-Induced Drug Resistance in Leukemia Stem Cells
Authors: Funayama Keiji , Murai Fumihiko , Shimane Miyuki , Nomura Hitoshi , Asano Shigetaka
Published: August 2010

The co-culture of TF-1 leukemia cells and MS-5 stromal cells produces a cobblestone area which partially mimics the leukemia stem cell niche. The adhering leukemia cells are shown to become less sensitive to cytarabine, etoposide and daunorubicin. These changes are associated with an increased proportion of the G0/G1 phase, increased upregulation of cyclin-dependent kinase inhibitors, and increased levels of Bcl-2, but not with any change in the expression of BAX or drug transporters such as ABCG2 and MDR1, compared to monocultured leukemic cells. In addition, we demonstrate using a bioimaging technique that daunorubicin accumulates in the lysosomes of the adherent leukemic cells and that V-ATPase is activated. These findings suggest that adhesion alone can lead to drug resistance in leukemic stem cells by various mechanisms.
Gestational and Neonatal Iron Deficiency Alters Apical Dendrite Structure of CA1 Pyramidal Neurons in Adult Rat Hippocampus
Authors: Brunette Katyarina E. , Tran Phu V. , Wobken Jane D. , Carlson Erik S. , Georgieff Michael K.
Published: August 2010

The hippocampus develops rapidly during the late fetal and early postnatal periods. Fetal/neonatal iron deficiency anemia (IDA) alters the genomic expression, neurometabolism and electrophysiology of the hippocampus during the period of IDA and, strikingly, in adulthood despite neonatal iron treatment. To determine how early IDA affects the structural development of the apical dendrite arbor in hippocampal area CA1 in the offspring, pregnant rat dams were given an iron-deficient (ID) diet between gestational day 2 and postnatal day (P) 7 followed by rescue with an iron-sufficient (IS) diet. Apical dendrite morphology in hippocampus area CA1 was assessed at P15, P30 and P70 by Scholl analysis of Golgi-Cox-stained neurons. Messenger RNA levels of nine cytoplasmic and transmembrane proteins that are critical for dendrite growth were analyzed at P7, P15, P30 and P65 by quantitative real-time polymerase chain reaction. The ID group had reduced transcript levels of proteins that modify actin and tubulin dynamics [e.g. cofilin-1 (Cfl-1), profilin-1 (Pfn-1), and profilin-2 (Pfn-2)] at P7, followed at P15 by a proximal shift in peak branching, thinner third-generation dendritic branches and smaller-diameter spine heads. At P30, iron treatment since P7 resulted in recovery of all transcripts and structural components except for a continued proximal shift in peak branching. Nevertheless, at P65–P70, the formerly ID group showed a 32% reduction in 9 mRNA transcripts, including Cfl-1 and Pfn-1 and Pfn-2, accompanied by 25% fewer branches, that were also proximally shifted. These alterations may be due to early-life programming of genes important for structural plasticity during adulthood and may contribute to the abnormal long-term electrophysiology and recognition memory behavior that follows early iron deficiency.
Effects of Amphetamine on Conditioned Place Preference and Locomotion in the Male Green Tree Frog, Hyla cinerea
Authors: Presley Gina M. , Lonergan William , Chu Joanne
Published: August 2010

Neural systems mediating motivation and reward have been well described in mammalian model systems, especially with reference to reward properties of drugs of abuse. Far less is known of the neural mechanisms underlying motivation and reward in non-mammals. The behavioral procedure conditioned place preference (CPP) is often used to quantify reward properties of psychoactive drugs. The indirect dopamine agonist d-amphetamine (AMPH) is known for its properties for inducing CPP in mammals and for inducing dose-related stereotypic movements. We used the green tree frog, Hyla cinerea, to examine whether AMPH could induce both CPP and a dose response change in motor behaviors. We demonstrated that H. cinerea can show place conditioning to AMPH following 14 days of training and that AMPH can cause reversal of a strong baseline place preference. Amphetamine-treated animals (20 mg/kg b.w.) received the drug paired with the previously non-preferred context, and vehicle paired with the preferred context. Control animals received vehicle in both preferred and non-preferred contexts. Amphetamine-treated animals switched context preference following conditioning, whereas control animals did not. We also demonstrated in an open-field experiment that AMPH did not cause any noticeable changes in motor movement or behaviors across a range of doses (0, 10, 20 mg/kg b.w.). This study represents the first examination of the behavioral effects of AMPH in amphibians. These results may contribute to a better understanding of the function and pharmacology of a reward system that may mediate natural behaviors in frogs and other vertebrates.
The Role of Peroxisome Proliferator-Activated Receptor-γ and Estrogen Receptors in Genistein-Induced Regulation of Vascular Tone in Female Rat Aortas
Authors: Xiang Qiuling , Lin Guiping , Fu Xiaodong , Wang Shuzhen , Wang Tinghuai
Published: August 2010

Background: Genistein (GST) is a phytoestrogen that binds estrogen receptors (ER) to produce a protective cardiovascular effect. It also has been shown binding peroxisome proliferator-activated receptor-γ (PPAR-γ). Methods: In the present study, we assessed the role of PPAR-γ and ER in GST-mediated regulation of vascular tone in female rat aortas by in vitro tension measurement, immunohistochemistry, immunofluorescence, immunoprecipitation and Western blot analysis. Results: In aortas pretreated with GW9662 (inhibitor of PPAR-γ), ICI182780 (inhibitor of ER) and a combination of GW9662 and ICI182780, the magnitudes of GST-induced dilatation were attenuated. N(G)-nitro-L-arginine methyl ester had a similar effect. ER-β and PPAR-γ colocalized in all 3 layers of the aortas, while ER-α and PPAR-γ colocalized only in the vascular endothelium and adventitia. In GST-treated whole-cell protein samples, we demonstrated coimmunoprecipitation of ER-β (not ER-α) and PPAR-γ. The expression of ER-β and PPAR-γ in nuclear protein from GST-treated samples increased, which was partially reversed by either GW9662 or ICI182780 and more efficiently reversed using a combination of GW9662 and ICI182780. Conclusion: Our findings suggest that GST can relax phenylephrine-induced vascular contraction in female rat aortas, which is mediated by PPAR-γ and ER-β.
Effect of Ramipril Alone Compared to Ramipril with Eplerenone on Diabetic Nephropathy in Streptozocin-Induced Diabetic Rats
Authors: Mavrakanas Thomas A. , Cheva Angeliki , Kallaras Konstantinos , Karkavelas Georgios , Mironidou-Tzouveleki Maria
Published: August 2010

Background/Aims: We studied the effect of the combined treatment with an angiotensin-converting enzyme (ACE) inhibitor (ramipril) and eplerenone compared with ramipril alone in streptozocin-induced diabetic rats. Methods: Wistar rats were divided into 4 groups: nondiabetic controls, streptozocin-treated diabetic rats (50 mg/kg), diabetic rats receiving ramipril (1 mg/kg) and diabetic rats treated with the combination of ramipril (1 mg/kg) and eplerenone (100 mg/kg) for 8 weeks. Our model produced early-stage diabetic nephropathy. Results: The diabetic rats developed polyuria, proteinuria, hyperfiltration (assessed by creatinine clearance) and histopathological evidence of renal injury including glomerular hypertrophy and mesangial expansion. Ramipril reduced proteinuria but its combination with eplerenone did not produce any greater benefit. Both treatment approaches prevented glomerular hypertrophy. Addition of eplerenone to ramipril prevented glomerular hyperfiltration. Conclusion: Whether eplerenone should be used in addition to an ACE inhibitor or an angiotensin receptor blocker at an early stage of diabetic nephropathy remains questionable.
Oral Protein Therapy for the Future – Transport of Glycolipid-Modified Proteins: Vision or Fiction
Authors: Müller Günter
Published: August 2010

The reliable and early diagnosis of common complex multifactorial diseases depends on the individual determination of all (or as many as possible) polymorphisms of each susceptibility gene together with amount and type of the corresponding gene products and their downstream effects, including the synthesis and flux of metabolites and regulation of signalling processes. In addition, this system’s biology-driven personalized diagnosis must be accompanied by options for personalized reliable and early therapy. In the mid-term, the direct substitution or inhibition of the proteins encoded by the corresponding defective gene products of the susceptibility genes exerting lower or higher activity by administration of the ‘normal’ proteins or inhibitory antibodies, respectively, seems to be most promising. The critical hurdle of oral bioavailability as well as transport into the cytoplasm of the target cells, if required, could be overcome by therapeutic proteins with carboxy-terminal modification by glycosylphosphatidylinositol (GPI). This may be deduced from recent experiments with rat adipocytes. Here this membrane-anchoring glycolipid structure induces the sequential transport of proteins from special regions of the plasma membrane via the surface of intracellular lipid droplets to special membrane vesicles, which are finally released from the adipocytes together with the associated GPI proteins. It remains to be studied whether similar molecular mechanisms operate in intestinal epithelial cells and may enable the transport of GPI proteins from the intestinal lumen into the blood stream. If so, modification of proteins encoded by (combinations of) susceptibility genes with GPI could significantly facilitate the personalized therapy of common diseases on the basis of ‘inborn’ safety, efficacy, rapid realization and oral application.
Individual Behavioral and Neuronal Phenotypes for Arginine Vasotocin Mediated Courtship and Aggression in a Territorial Teleost
Authors: Santangelo Nick , Bass Andrew H.
Published: August 2010

The neuropeptide arginine vasotocin (AVT) is well known to modulate both aggression and affiliation, yet few studies relate individual behavioral state to a quantitative assessment of AVT distribution in the brain. Here, using a wild population of beaugregory damselfish, Stegastes leucostictus, we assess: (1) the effect of AVT on courtship, and (2) with reference to our previous study on AVT modulation of aggression in this species, the relationship between AVT-like immunoreactive (ir) fiber distribution in the forebrain’s preoptic area and individual courtship and aggression levels. Exogenous AVT did not affect courtship, yet Manning compound, an arginine vasopressin (AVP) V1a receptor antagonist, significantly lowered but did not eradicate courtship. Consistent with AVT’s known facilitation of aggression in this species, the density of AVT-ir fibers in the preoptic area was significantly negatively correlated to aggression. Our findings match similar behavioral and immunoreactive patterns of neuropeptide secretion in other taxa. Unlike aggression, preoptic AVT-ir fiber density was not significantly correlated to individual courtship levels. The results suggest a differential involvement of preoptic AVT neurons and/or their receptors in supporting the expression of aggression and courtship.
Behavioural Effects of Co-Administration of Δ9-Tetrahydrocannabinol with Fluoxetine in Rats
Authors: Goddard Matthew , Smith Paul F. , Ashton John C.
Published: August 2010

Previous studies have suggested panic induced by cannabinoids may be potentiated by concurrently using selective serotonin reuptake inhibitors. We therefore tested for panic and anxiety-related behaviour in rats coadministered with the selective serotonin reuptake inhibitor fluoxetine hydrochloride and the CB1 agonist Δ9-tetrahydrocannabinol. Although each drug alone elicited behaviours consistent with previous studies, we did not find that coadministration of these drugs potentiated or reduced the effects of either drug alone. Specifically, fluoxetine treatment did not cause any increase in freezing behaviour, decrease in social interaction or exploration in an adverse environment, change preference for outer or inner zones, or modulate rearing behaviour in rats receiving Δ9-tetrahydrocannabinol.