bluuebunny/crossref_metadata_2025 huggingface dataset:
Discontinuous drug combination therapy in autoimmune ocular disorders
Authors: Orsoni Jelka G. , Zavota Laura , Mora Paolo , Rubino Pierangela , Manzotti Francesca , Pellistri Isabella
Published: September 2008

Purpose:  This study aimed to assess the effectiveness of a steroid‐sparing immunosuppressive treatment (IST) protocol in the control of severe or steroid‐resistant autoimmune ocular inflammatory diseases.

Methods:  We carried out a prospective, non‐randomized clinical study. Patients presenting with ocular inflammations that failed to respond adequately to steroids alone after monotherapy for a mean period of 9 ± 2 months (internal control) were offered the option to switch to a combined IST. The protocol consisted of different immunosuppressive drugs added in a stepladder sequence, where each drug (including the steroids) was administered discontinuously. Main outcome measures were control of inflammation, visual acuity and safety of treatment.

Results:  A total of 76 subjects (121 affected eyes) enrolled in the IST protocol. Mean length of follow‐up was 43 ± 15 months. Complete control of inflammation was achieved in 86% of patients. During the first year of IST, the rate of inflammatory recurrences/patient was 0.78 ± 1.13. This ratio diminished further during succeeding follow‐up. Mean best corrected visual acuity improved from 0.31 logMAR to 0.24 logMAR (p < 0.001). Blood pressure and uric acid blood levels significantly altered for the worse in the study group.

Conclusions:  Immunosuppressive treatment was effective in achieving inflammatory quiescence in a large majority of patients. The study also demonstrated the longterm safety of the protocol and its steroid‐sparing effect.
Metabolic profiles in goat does in late pregnancy with and without subclinical pregnancy toxemia
Authors: Bani Ismail Z.A. , Al‐Majali A.M. , Amireh F. , Al‐Rawashdeh O.F.
Published: September 2008

Background: Pregnant goat does can develop various metabolic diseases during late pregnancy that may have profound effects on their health and productivity, including subclinical pregnancy toxemia.

Objectives: This study was performed to evaluate serum biochemical findings in goats in late pregnancy with and without subclinical pregnancy toxemia.

Methods: Serum samples were obtained from 153 clinically healthy goats in the last trimester of pregnancy from 14 herds in central and northern Jordan. Serum was analyzed for the following constituents: 3‐hydroxybutyrate (3‐HB), glucose, total protein, albumin, urea, creatinine, aspartate aminotransferase, alkaline phosphatase, cholesterol, triglycerides, cortisol, T3, T4, total calcium, magnesium, and phosphorus, using commercially available kits. Goats were classified as having subclinical pregnancy toxemia or as controls on the basis of 3‐HB results. Biochemical results were compared between the 2 groups using nonparametric statistical tests.

Results: Fifty‐three does had subclinical pregnancy toxemia (3‐HB>0.86 mmol/L) and 100 were pregnant control does (3‐HB≤0.86 mmol/L). Does with subclinical pregnancy toxemia had significantly lower glucose concentrations (P<.001) and significantly higher urea (P=.042) and total protein (P=.048) concentrations compared with pregnant control does. 3‐HB concentration was significantly correlated with glucose (r=0.290, P=.035), phosphorus (r=0.351, P=.01), and cortisol (r=0.394, P=.004) concentrations in goats with subclinical toxemia.

Conclusions: Results of this study indicate that the biochemical profile of does with subclinical pregnancy toxemia differs from that of other pregnant goats. 3‐HB should be measured in pregnant does in late stages of gestation with hypoglycemia or with elevated urea and total protein concentrations.
CONTROLLING TURBULENCE VIA TARGET WAVES GENERATED BY LOCAL PHASE SPACE COMPRESSION
Authors: GAO JIHUA , ZHENG ZHIGANG , MA JUN
Published: September 2008

The control of spatiotemporal chaos by developing target waves via local phase space compression in dynamical systems described by partial differential equation is reported. By considering spatially one-dimensional (1D) and two-dimensional (2D) complex Ginzburg–Landau equations (CGLE), we find that by using local system perturbation and confining variable in a finite range within a controlled area, periodic signals are generated and spread into an uncontrolled area in 1D spatiotemporal systems with weak turbulence. In 2D systems, target waves can be developed to suppress spatiotemporal chaos by using this compression technique in the convective instability area. The controllable parameters are investigated by performing numerical simulations.
ELECTRONIC STRUCTURE OF KINETIC ENERGY DRIVEN CUPRATE SUPERCONDUCTORS
Authors: FENG SHIPING , GUO HUAIMING , LAN YU , CHENG LI
Published: September 2008

In this paper, we review the low energy electronic structure of the kinetic energy driven d-wave cuprate superconductors. We give a general description of the charge-spin separation fermion-spin theory, where the constrained electron is decoupled as the gauge invariant dressed holon and spin. In particular, we show that under the decoupling scheme, the charge-spin separation fermion-spin representation is a natural representation of the constrained electron defined in a restricted Hilbert space without double electron occupancy. Based on the charge-spin separation fermion-spin theory, we have developed the kinetic energy driven superconducting mechanism, where the superconducting state is controlled by both superconducting gap parameter and quasiparticle coherence. Within this kinetic energy driven superconductivity, we have discussed the low energy electronic structure of the single layer and bilayer cuprate superconductors in both superconducting and normal states, and qualitatively reproduced all main features of the angle-resolved photoemission spectroscopy measurements on the single layer and bilayer cuprate superconductors. We show that the superconducting state in cuprate superconductors is the conventional Bardeen-Cooper-Schrieffer like with the d-wave symmetry, so that the basic Bardeen-Cooper-Schrieffer formalism with the d-wave gap function is still valid in discussions of the low energy electronic structure of cuprate superconductors, although the pairing mechanism is driven by the kinetic energy by exchanging spin excitations. We also show that the well-pronounced peak-dip-hump structure of the bilayer cuprate superconductors in the superconducting state and double-peak structure in the normal state are mainly caused by the bilayer splitting.
FIRST PRINCIPLES STUDY OF THE EFFECT OF ORBITAL-DEPENDENT EXCHANGE-CORRELATION POTENTIAL ON THE ELECTRONIC AND OPTICAL PROPERTIES OF Pb(Zr1-xTix)O3
Authors: BAEDI J. , HOSSEINI S. M. , KOMPANY A.
Published: September 2008

Ab initio calculations have been performed on the electrical and optical properties of Pb ( Zr 1-x Ti x) O 3 ceramics with x = 0.5, which is a perovskite type compound. The Kohn–Sham equations were solved using the full potential linear Augmented Plane Wave approach (FP-LAPW). We used GGA, LDA + U and GGA + U approximations for the exchange correlation potential. The results show that with a proper choice of U eff = U - J, for any atoms of the compound, the theoretical values of band gap and the refractive index have been improved compared to their experimented values.
SQUEEZING ENHANCED THREE-MODE ENTANGLED STATE
Authors: HU LI-YUN , FAN HONG-YI
Published: September 2008

By virtue of the technique of integration within an ordered product of operators (Fan et al., Ann. Phys.321 (2006) 480) we construct a kind of three-mode entangled squeezed state in the Fock space, which exhibits stronger squeezing in one quadrature than that of the usual two-mode squeezed vacuum state.
KHASARE'S EQUATION OF STATE TO SOME FLUID MIXTURES: 1-4 DIOXANE IN BENZENE, TETRAHYDROFURAN AND CARBON TETRACHLORIDE
Authors: DESHPANDE M. S.
Published: September 2008

A number of equations have been proposed by workers in the field of liquid state and, upon exploration, these have been found to meet success of varying degrees. Khasare has proposed a new equation of state involving intermolecular potential with three-model parameters. This equation of state has been applied to the binary liquid mixture of benzene, tetrahydrofuran and carbon tetrachloride in 1-4 dioxane. It is observed that there is a close agreement with experimental values for ultrasonic wave velocity, molar volume and, to some degree, volume expansion coefficient. Model parameters are fairly constant over the liquid phase 10 K above m.p. and 10 K below b.p.
EFFECT OF VARIOUS MATERIAL PARAMETERS ON THE CALCULATED VELOCITY-FIELD RELATION IN Al0.2Ga0.8N AT ROOM TEMPERATURE
Authors: ARABSHAHI H. , FARZANE-KORD A. , ROKN-ABADI M. REZAEE , DASTRAS M.
Published: September 2008

The results of an ensemble Monte Carlo simulation of the steady-state electron drift velocity as a function of applied electric field in Al 0.2 Ga 0.8 N are presented. The effect of various material parameters on the calculated velocity is assessed by varying each parameter independently by ± 30%. It is found that both the optical phonon energy and intervalley separation energy alter the peak electron velocity. Variations in the dielectric constants and central valley effective mass have more effect upon the peak drift velocity and act to alter the threshold electric field. The combined effects of a greater central valley effective mass and a larger phonon energy in Al 0.2 Ga 0.8 N result in a greater threshold field.
Barrett's Esophagus and Esophageal Adenocarcinoma
Authors: Bresalier Robert S.
Published: September 2008

The incidence of esophageal adenocarcinoma (EAC) has risen dramatically over the past three decades in western countries. The importance of Barrett's esophagus (BE) derives from its potential to transform to adenocarcinoma. BE is characterized by endoscopically recognized displacement of the squamocolumnar junction proximal to the gastroesophageal junction, with replacement of squamous mucosa with columnar lined mucosa. Adenocarcinomas of the esophagus appear to arise from Barrett's mucosa through progressive degrees of dysplasia, but the pathogenesis and natural history of this process are still unclear. Much of our knowledge regarding BE and the risk of EAC is based on observational and cross-sectional analyses, and recommendations regarding management have traditionally represented “expert opinion.” The past few years have seen an explosion in new information and the initiation of longitudinal studies to define the risk of adenocarcinoma in BE, the identification of predictive and prognostic markers of cancer risk, sensitive and cost-effective methods of surveillance, and methods of management of dysplasia and early neoplasia including disease prevention.
Metabolism of very-low-density lipoprotein and chylomicrons by streptozotocin-induced diabetic rat heart: effects of diabetes and lipoprotein preference
Authors: Niu You-Guo , Evans Rhys D.
Published: September 2008

Very-low-density lipoprotein (VLDL) and chylomicrons (CM) are major sources of fatty acid supply to the heart, but little is known about their metabolism in diabetic myocardium. To investigate this, working hearts isolated from control rats and diabetic rats 2 wk following streptozotocin (STZ) injection were perfused with control and diabetic lipoproteins. Analysis of the diabetic lipoproteins showed that both VLDL and CM were altered compared with control lipoproteins; both were smaller and had different apolipoprotein composition. Heparin-releasable lipoprotein lipase (HR-LPL) activity was increased in STZ-induced diabetic hearts, but tissue residual LPL activity was decreased; moreover, diabetic lipoproteins stimulated HR-LPL activity in both diabetic and control hearts. Diabetic hearts oxidized lipoprotein-triacylglycerol (TAG) to a significantly greater extent than controls (>80% compared with deposition as tissue lipid), and the oxidation rate of exogenous lipoprotein-TAG was increased significantly in diabetic hearts regardless of TAG source. Significantly increased intracardiomyocyte TAG accumulation was found in diabetic hearts, although cardiac mechanical function was not inhibited, suggesting that lipotoxicity precedes impaired cardiac performance. Glucose oxidation was significantly decreased in diabetic hearts; additionally, however, diabetic lipoproteins decreased glucose oxidation in diabetic and control hearts. These results demonstrate increased TAG-rich lipoprotein metabolism concomitant with decreased glucose oxidation in type 1 diabetic hearts, and the alterations in cardiac lipoprotein metabolism may be due to the properties of diabetic TAG-rich lipoproteins as well as the diabetic state of the myocardium. These changes were not related to cardiomyopathy at this early stage of diabetes.
Contractile C2C12myotube model for studying exercise-inducible responses in skeletal muscle
Authors: Nedachi Taku , Fujita Hideaki , Kanzaki Makoto
Published: September 2008

Adequate exercise leads to a vast variety of physiological changes in skeletal muscle as well as other tissues/organs and is also responsible for maintaining healthy muscle displaying enhanced insulin-responsive glucose uptake via GLUT4 translocation. We generated highly developed contractile C2C12myotubes by manipulating intracellular Ca2+transients with electric pulse stimulation (EPS) that is endowed with properties similar to those of in vivo skeletal muscle in terms of 1) excitation-induced contractile activity as a result of de novo sarcomere formation, 2) activation of both the AMP kinase and stress-activated MAP kinase cascades, and 3) improved insulin responsiveness as assessed by GLUT4 recycling. Tbc1d1, a Rab-GAP implicated in exercise-induced GLUT4 translocation in skeletal muscle, also appeared to be phosphorylated on Ser231after EPS-induced contraction. In addition, a switch in myosin heavy-chain (MHC) expression from “fast type” to “slow type” was observed in the C2C12myotubes endowed with EPS-induced repetitive contractility. Taking advantage of these highly developed contractile C2C12myotubes, we identified myotube-derived factors responsive to EPS-evoked contraction, including the CXC chemokines CXCL1/KC and CXCL5/LIX, as well as IL-6, previously reported to be upregulated in contracting muscles in vivo. Importantly, animal treadmill experiments revealed that exercise significantly increased systemic levels of CXCL1/KC, perhaps derived from contracting muscle. Taken together, these results confirm that we have established a specialized muscle cell culture model allowing contraction-inducible cellular responses to be explored. Utilizing this model, we identified contraction-inducible myokines potentially linked to the metabolic alterations, immune responses, and angiogenesis induced by exercise.
12-Lipoxygenase-knockout mice are resistant to inflammatory effects of obesity induced by western diet
Authors: Nunemaker Craig S. , Chen Meng , Pei Hong , Kimble Sarah D. , Keller Susanna R. , Carter Jeffrey D. , Yang Zandong , Smith Kellie M. , Wu Runpei , Bevard Melissa H. , Garmey James C. , Nadler Jerry L.
Published: September 2008

Inflammation is a key pathological process in the progression of atherosclerosis and type 2 diabetes. 12/15-lipoxygenase (12-LO), an enzyme involved in fatty acid metabolism, may contribute to inflammatory damage triggered by stressors such as obesity and insulin resistance. We hypothesized that mice lacking 12-LO are protected against inflammatory-mediated damage associated with a “western” diet. To test this hypothesis, age-matched male 12-LO knockout (12-LOKO) and wild-type C57BL/6 (B6) mice were fed either a standard chow or western diet and assessed for several inflammatory markers. Western-fed B6 mice showed expected reductions in glucose and insulin tolerance compared with chow-fed mice. In contrast, western-fed 12-LOKO mice maintained glucose and insulin tolerance similar to chow-fed mice. Circulating proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, were increased in western B6 mice but not 12-LOKO mice, whereas the reported protective adipokine, adiponectin, was decreased only in western B6 mice. 12-LO activity was significantly elevated by western diet in islets from B6 mice. Islets from 12-LOKO mice did not show western-diet-induced islet hyperplasia or increases in caspase-3 apoptotic staining observed in western-fed B6 mice. Islets from 12-LOKO mice were also protected from reduced glucose-stimulated insulin secretion observed in islets from western-fed B6 mice. In visceral fat, macrophage numbers and monocyte chemoattractant protein-1 expression were elevated in western B6 mice but not 12-LOKO mice. These data suggest that 12-LO activation plays a role in western-diet-induced damage in visceral fat and islets. Inhibiting 12-LO may provide a new therapeutic approach to prevent inflammation-mediated metabolic consequences of excess fat intake.
Mathematical models of diabetes progression
Authors: De Gaetano Andrea , Hardy Thomas , Beck Benoit , Abu-Raddad Eyas , Palumbo Pasquale , Bue-Valleskey Juliana , Pørksen Niels
Published: September 2008

Few attempts have been made to model mathematically the progression of type 2 diabetes. A realistic representation of the long-term physiological adaptation to developing insulin resistance is necessary for effectively designing clinical trials and evaluating diabetes prevention or disease modification therapies. Writing a good model for diabetes progression is difficult because the long time span of the disease makes experimental verification of modeling hypotheses extremely awkward. In this context, it is of primary importance that the assumptions underlying the model equations properly reflect established physiology and that the mathematical formulation of the model give rise only to physically plausible behavior of the solutions. In the present work, a model of the pancreatic islet compensation is formulated, its physiological assumptions are presented, some fundamental qualitative characteristics of its solutions are established, the numerical values assigned to its parameters are extensively discussed (also with reference to available cross-sectional epidemiologic data), and its performance over the span of a lifetime is simulated under various conditions, including worsening insulin resistance and primary replication defects. The differences with respect to two previously proposed models of diabetes progression are highlighted, and therefore, the model is proposed as a realistic, robust description of the evolution of the compensation of the glucose-insulin system in healthy and diabetic individuals. Model simulations can be run from the authors' web page.
In situ profiling of adipokines in subcutaneous microdialysates from lean and obese individuals
Authors: Murdolo Giuseppe , Herder Christian , Wang Zhaohui , Rose Bettina , Schmelz Martin , Jansson Per-Anders
Published: September 2008

Adipose tissue (AT) had emerged as an endocrine organ and a key regulator of the metabolically triggered inflammation. The aims of this study were 1) to investigate the usefulness of a multiplexed bioassay in characterizing a panel of adipokines in subcutaneous (sc) microdialysate samples and 2) to determine whether lean and obese individuals differ in their interstitial adipokines levels following microdialysis (MD) probe insertion. Ultrafiltrating MD membranes were inserted in opposite sites of the sc abdominal AT of six lean (L) and six obese (OB) males at the beginning (M1) and during the last 120 min (M2) of the study. Interstitial and serum concentrations of adipokines were quantified using the Luminex technique and ELISA at 60-min intervals for 5 h. In comparison with L subjects, OB subjects exhibited elevated interstitial leptin ( P < 0.001), IL-8 ( P < 0.05), and IL-18 levels ( P = 0.05), as well as higher serum concentrations of leptin ( P < 0.0001), IL-6 ( P < 0.0001), tumor necrosis factor-α ( P < 0.001), IL-8 ( P = 0.01) and interferon-γ-inducible protein 10 ( P < 0.05). In samples from the M1 membranes, leptin decreased and IL-1α, IL-18, and RANTES (regulated on activation, normal T-cell expressed and secreted) remained relatively stable, whereas IL-6, IL-8, and monocyte chemoattractant protein-1 significantly increased after the first hour ( P < 0.0001 vs. baseline). Notably, either the magnitude of increase from the initial values or the time pattern of all the adipokines in M1 and M2 dialysates were similar between the groups. In conclusion, the current work provides valuable information on the optimal time frame to collect in situ AT microdialysate samples. Further studies are needed, however, to unravel the intricate interplay of cytokines in AT interstitial fluid.
Neuronal functions, feeding behavior, and energy balance inSlc2a3+/−mice
Authors: Schmidt Stefan , Richter Miriam , Montag Dirk , Sartorius Tina , Gawlik Verena , Hennige Anita M. , Scherneck Stephan , Himmelbauer Heinz , Lutz Stefan Z. , Augustin Robert , Kluge Reinhart , Ruth Peter , Joost Hans-Georg , Schürmann Annette
Published: September 2008

Homozygous deletion of the gene of the neuronal glucose transporter GLUT3 ( Slc2a3) in mice results in embryonic lethality, whereas heterozygotes ( Slc2a3+/−) are viable. Here, we describe the characterization of heterozygous mice with regard to neuronal function, glucose homeostasis, and, since GLUT3 might be a component of the neuronal glucose-sensing mechanism, food intake and energy balance. Levels of GLUT3 mRNA and protein in brain were reduced by 50% in Slc2a3+/−mice. Electrographic features examined by electroencephalographic recordings give evidence for slightly but significantly enhanced cerebrocortical activity in Slc2a3+/−mice. In addition, Slc2a3+/−mice were slightly more sensitive to an acoustic startle stimulus (elevated startle amplitude and reduced prepulse inhibition). However, systemic behavioral testing revealed no other functional abnormalities, e.g., in coordination, reflexes, motor abilities, anxiety, learning, and memory. Furthermore, no differences in body weight, blood glucose, and insulin levels were detected between wild-type and Slc2a3+/−littermates. Food intake as monitored randomly or after intracerebroventricular administration of 2-deoxyglucose or d-glucose, or food choice for carbohydrates/fat was not affected in Slc2a3+/−mice. Taken together, our data indicate that, in contrast to Slc2a1, a single allele of Slc2a3 is sufficient for maintenance of neuronal energy supply, motor abilities, learning and memory, and feeding behavior.
Neural and cardiovascular responses to emotional stress in humans
Authors: Carter Jason R. , Durocher John J. , Kern Rosalie P.
Published: September 2008

Sympathetic neural responses to mental stress are well documented but controversial, whereas sympathetic neural responses to emotional stress are unknown. The purpose of this study was to investigate neural and cardiovascular responses to emotional stress evoked by negative pictures and reexamine the relationship between muscle sympathetic nerve activity (MSNA) and perceived stress. Mean arterial pressure (MAP), heart rate (HR), MSNA, and perceived stress levels were recorded in 18 men during three randomized trials: 1) neutral pictures, 2) negative pictures, and 3) mental stress. MAP and HR increased during mental stress (Δ14 ± 2 mmHg and Δ15 ± 2 beats/min, P < 0.001) but did not change during viewing of negative or neutral pictures. MSNA did not change during viewing of neutral (Δ1 ± 1 burst/min, n = 16) or negative (Δ0 ± 1 burst/min, n = 16) pictures or during mental stress (Δ1 ± 2 burst/min, n = 13). Perceived stress levels were higher during mental stress (3 ± 0 arbitrary units) than during viewing negative pictures (2 ± 0 arbitrary units, P < 0.001). Perceived stress levels were not correlated to changes in MSNA during negative pictures ( r = 0.10, P = 0.84) or mental stress ( r = 0.36, P = 0.23). In conclusion, our results demonstrate robust increases in MAP and HR during mental stress, but not during emotional stress evoked by negative pictures. Although the influence of mental stress on MSNA remains unresolved, our findings challenge the concept that perceived stress levels modulate MSNA during mental stress.
Coenzyme Q10 supplementation rescues renal disease in Pdss2kd/kd mice with mutations in prenyl diphosphate synthase subunit 2
Authors: Saiki Ryoichi , Lunceford Adam L. , Shi Yuchen , Marbois Beth , King Rhonda , Pachuski Justin , Kawamukai Makoto , Gasser David L. , Clarke Catherine F.
Published: September 2008

Homozygous mice carrying kd (kidney disease) mutations in the gene encoding prenyl diphosphate synthase subunit 2 ( Pdss2 kd/kd) develop interstitial nephritis and eventually die from end-stage renal disease. The PDSS2 polypeptide in concert with PDSS1 synthesizes the polyisoprenyl tail of coenzyme Q (Q or ubiquinone), a lipid quinone required for mitochondrial respiratory electron transport. We have shown that a deficiency in Q content is evident in Pdss2 kd/kd mouse kidney lipid extracts by 40 days of age and thus precedes the onset of proteinuria and kidney disease by several weeks. The presence of the kd (V117M) mutation in PDSS2 does not prevent its association with PDSS1. However, heterologous expression of the kd mutant form of PDSS2 together with PDSS1 in Escherichia coli recapitulates the Q deficiency observed in the Pdss2 kd/kd mouse. Dietary supplementation with Q10 provides a dramatic rescue of both proteinuria and interstitial nephritis in the Pdss2 kd/kd mutant mice. The results presented suggest that Q may be acting as a potent lipid-soluble antioxidant, rather than by boosting kidney mitochondrial respiration. Such Q10 supplementation may have profound and beneficial effects in treatment of certain forms of focal segmental glomerulosclerosis that mirror the renal disease of the Pdss2 kd/kd mouse.
Caloric Restriction Does Not Offset Age-Associated Changes in the Biophysical Properties of Motoneurons
Authors: Kalmar Jayne M. , Button Duane C. , Gardiner Kalan , Cahill Farrell , Gardiner Phillip F.
Published: September 2008

Age-associated changes in neuromuscular function may be due to a loss of motor neurons as well as changes in their biophysical properties. Neuronal damage imposed by reactive oxygen species may contribute to age-related deficits in CNS function. Thus we hypothesized that aging would alter the functional properties of motoneurons and that caloric-restriction would offset these changes. Intracellular recordings were made from lumbar motoneurons of old Fisher Brown Norway (FBN) fed ad libitum (oldAL, 30.8 ± 1.3 mo) or on a fortified calorie-restricted diet from 14 wk of age (oldCR, 31.0 ± 1.8 mo). Basic and rhythmic firing properties recorded from these aged motoneurons (MNs) were compared with properties recorded from young FBN controls (young, 8.4 ± 4.6 mo). Compared with young MNs, old MNs had a 104% greater ( P < 0.001) afterhyperpolarization potential (AHP), a 21.1% longer AHP half-decay time ( P < 0.05), 28.7% lower rheobase ( P < 0.001), 49.7% greater ( P < 0.001) input resistance, 21.1% ( P < 0.0001) less spike frequency adaptation, lower minimal (30.2%, P < 0.0001) and maximal (16.7%, P < 0.0001) steady-state firing frequencies, a lower (35.5%, P < 0.0001) frequency-current slope, and an increased incidence of persistent inward current. Because basic properties became more diverse in old MNs and the slope of the frequency-current relationship, which is normally similar for high- and low-threshold MNs, was lower in the old group, we conclude that aging alters the biophysical properties of MNs in a fashion that cannot be simply attributed to a loss of high-threshold MNs. Surprisingly, caloric restriction, which is known to attenuate aging-associated changes in hindlimb muscles, had no effect on the progress of aging in the innervating MNs.
Effect of Inactivation of the Cortical Frontal Eye Field on Saccades Generated in a Choice Response Paradigm
Authors: Keller Edward L. , Lee Kyoung-Min , Park Se-Woong , Hill Jessica A.
Published: September 2008

Previous studies using muscimol inactivations in the frontal eye fields (FEFs) have shown that saccades generated by recall from working memory are eliminated by these lesions, whereas visually guided saccades are relatively spared. In these experiments, we made reversible inactivations in FEFs in alert macaque monkeys and examined the effect on saccades in a choice response task. Our task required monkeys to learn arbitrary pairings between colored stimuli and saccade direction. Following inactivations, the percentage of choice errors increased as a function of the number of alternative (NA) pairings. In contrast, the percentage of dysmetric saccades (saccades that landed in the correct quadrant but were inaccurate) did not vary with NA. Saccade latency increased postlesion but did not increase with NA. We also made simultaneous inactivations in both FEFs. The results following bilateral lesions showed approximately twice as many choice errors. We conclude that the FEFs are involved in the generation of saccades in choice response tasks. The dramatic effect of NA on choice errors, but the lack of an effect of NA on motor errors or response latency, suggests that two types of processing are interrupted by FEF lesions. The first involves the formation of a saccadic intention vector from associate memory inputs, and the second, the execution of the saccade from the intention vector. An alternative interpretation of the first result is that a role of the FEFs may be to suppress incorrect responses. The doubling of choice errors following bilateral FEF lesions suggests that the effect of unilateral lesions is not caused by a general inhibition of the lesioned side by the intact side.
In vivo analysis of key elements within the renin regulatory region
Authors: Glenn Sean T. , Jones Craig A. , Pan Li , Gross Kenneth W.
Published: September 2008

Renin is responsible for initiating the enzymatic cascade that results in the production of angiotensin II, the major effector molecule of the renin-angiotensin system (RAS). Extensive information on the regulatory region of the renin gene has been derived by transient transfection studies in vitro, particularly using the As4.1 cell line. To verify key factors within the regulatory region of renin in vivo, homologous recombination was used to introduce a green fluorescent protein (GFP) cassette into exon one of the renin gene contained within a 240 kb bacterial artificial chromosome (BAC) to create a construct that has GFP expression controlled by the renin regulatory region (RenGFP BAC). Within the regulatory region of the RenGFP BAC construct we independently deleted the enhancer, as well as mutated the HOX-PBX site within the proximal promoter element. Transgenic lines were generated for each of these BAC constructs and GFP expression was analyzed throughout a spectrum of tissues positive for renin expression including the kidney, adrenal gland, gonadal artery, and submandibular gland. The results described within this manuscript support the interpretation that the renin enhancer is critical for regulating baseline expression where as the Hox/Pbx site is important for the tissue specificity of renin expression.
Key pathways associated with heart failure development revealed by gene networks correlated with cardiac remodeling
Authors: Gao Zhong , Barth Andreas S. , DiSilvestre Deborah , Akar Fadi G. , Tian Yanli , Tanskanen Antti , Kass David A. , Winslow Raimond L. , Tomaselli Gordon F.
Published: September 2008

Heart failure (HF) is the leading cause of morbidity and mortality in the industrialized world. While the transcriptomic changes in end-stage failing myocardium have received much attention, no information is available on the gene expression patterns associated with the development of HF in large mammals. Therefore, we used a well-controlled canine model of tachycardia-induced HF to examine global gene expression in left ventricular myocardium with Affymetrix canine oligonucleotide arrays at various stages after initiation of rapid ventricular pacing ( days 3, 7, 14, and 21). The gene expression data were complemented with measurements of action potential duration, conduction velocity, and left ventricular end diastolic pressure, and dP/d t(max) over the time course of rapid ventricular pacing. As a result, we present a phenotype-centered gene association network, defining molecular systems that correspond temporally to hemodynamic and electrical remodeling processes. Gene Ontology analysis revealed an orchestrated regulation of oxidative phosphorylation, ATP synthesis, cell signaling pathways, and extracellular matrix components, which occurred as early as 3 days after the initiation of ventricular pacing, coinciding with the early decline in left ventricular pump function and prolongation of action potential duration. The development of clinically overt left ventricular dysfunction was associated with few additional changes in the myocardial transcriptome. We conclude that the majority of tachypacing-induced transcriptional changes occur early after initiation of rapid ventricular pacing. As the transition to overt HF is characterized by few additional transcriptional changes, posttranscriptional modifications may be more critical in regulating myocardial structure and function during later stages of HF.
Meta-analysis and profiling of cardiac expression modules
Authors: Akavia Uri David , Benayahu Dafna
Published: September 2008

Heart failure is a complex, complicated disease that is not yet fully understood. We used the Module Map algorithm to uncover groups of genes that have a similar pattern of expression under various conditions of heart stress. These groups of genes are called modules and may serve as computational predictions of biological pathways for the various clinical situations. The Module Map algorithm allows a large-scale analysis of genes expressed. We applied this algorithm to 700 different mouse experiments downloaded from the Gene Expression Omnibus database, which identified 884 modules. The analysis reconstructed partially known principles that play a role in governing the response of heart to stress, thus demonstrating the strength of the method. We have shown a role of genes related to the immune system in conditions of heart remodeling and failure. We have also shown changes in the expression of genes involved with energy metabolism and changes in the expression of contractile proteins of the heart following myocardial infarction. When focusing on another module we noted a new correlation between genes related to osteogenesis and heart failure, including Runx2 and Ahsg, whose role in heart failure was unknown so far. Despite a lack of prior biological knowledge, the Module Map algorithm has reconstructed known pathways, which demonstrates the strength of this new method for analyzing gene profiles related to clinical phenomenon. The method and the analysis presented are a new avenue to uncover the correlation of clinical conditions to the molecular level.
Near‐Infrared Resonance Energy Transfer Glucose Biosensors in Hybrid Microcapsule Carriers
Authors: Chinnayelka Swetha , Zhu Huiguang , McShane Mike
Published: September 2008

Fluorescence‐based sensing systems offer potential for noninvasive monitoring with implantable devices, but require carrier technologies that provide suitable immobilization, accessibility, and biocompatibility. Recent developments towards this goal include a competitive binding assay for glucose that has been encapsulated in semipermeable microcapsule carriers. This paper describes an extension of this work to increase the applicability to in vivo monitoring, wherein two significant developments are described: (1) a near‐infrared resonance energy transfer system for transducing glucose concentration, and (2) novel hybrid organic‐inorganic crosslinked microcapsules as carriers. The quenching‐based assay is a competitive binding (CB) system based on apo‐glucose oxidase (AG) as the receptor and dextran as the competitive ligand. The encapsulated quencher‐labeled dextran and near infrared donor‐labeled glucose receptor showed a stable and reversible response with tunable sensitivity of 1–5%/mM over the physiological range, making these transducers attractive for continuous monitoring for biomedical applications.
Regulation of FoxP3+Regulatory T Cells and Th17 Cells by Retinoids
Authors: Kim Chang H.
Published: September 2008

Vitamin A has both positive and negative regulatory functions in the immune system. While vitamin A is required for normal formation of immune cells and epithelial cell barriers, vitamin A deficiency can lead to increased inflammatory responses and tissue damage. The mechanism with which vitamin A and its metabolites such as retinoids negatively regulate inflammatory responses has not been clearly defined. Recently, it has been established that retinoids promote the generation of immune-suppressive FoxP3+regulatory T cells while they suppress the T cell differentiation into inflammatory Th17 cells in the periphery such as intestine. These novel functions of retinoids provide a potentially important immune regulatory mechanism. In this review, we discuss the functions of retinoids in the development of the FoxP3+cells and Th17 cells, the phenotype and functions of retinoid-induced FoxP3+T cells, and the impact of retinoid-induced FoxP3+T cells on the immune tolerance.
Comparative Vibration Analysis of a Parametrically Nonlinear Excited Oscillator Using HPM and Numerical Method
Authors: Khatami I. , Pashai M. H. , Tolou N.
Published: September 2008

The objective of this paper is to present an analytical investigation to analyze the vibration of parametrically excited oscillator with strong cubic negative nonlinearity based on Mathieu‐Duffing equation. The analytic investigation was conducted by using He′s homotopy‐perturbation method (HPM). In order to obtain the analytical solution of Mathieu‐Duffing equation, homotopy‐perturbation method has been utilized. The Runge‐Kutta′s (RK) algorithm was used to solve the governing equation via numerical solution. Finally, to demonstrate the validity of the proposed method, the response of the oscillator, which was obtained from approximate solution, has been shown graphically and compared with that of numerical solution. Afterward, the effects of variation of the parameters on the accuracy of the homotopy‐ perturbation method were studied.
On the State and Prospects of the Study of Zoroastrianism
Authors: Stausberg Michael
Published: September 2008

The academic study of Zoroastrianism goes back to the seventeenth century. It was a classic topic in the History of Religions as an academic discipline throughout its formative period. Zoroastrianism has become less visible on the field of the History of Religions since the 1970s. This, however, does not mean that there was no progress in Zoroastrian Studies since that time. Quite to the contrary, despite the customary tendency to paint a gloomy picture of the progress of Zoroastrian Studies, scholarship in this field has advanced considerably in recent decades. The present article sketches eighteen major subjects of innovative recent research activities. Topics include textual studies, law, astrology, secondary sources, religion and politics, regional diversity, marginalization, impact on and interaction with other religious traditions, the modern communities in India, Iran, and various "diasporic" settings as well as gender, rituals, and outside reception. e article concludes by sketching some prospects for the study of Zoroastrianism.
Asceticism in Transition: Exploring the Concepts of Memory, Performance and Ambiguity in 20th Century Dutch Monastic Life
Authors: Bosgraaf Emke
Published: September 2008

Asceticism is a topic of interest among a wide range of scholars. In the past two decades the corpus on asceticism has been growing steadily and contributions have been made from a variety of perspectives (for an overview see Wimbusch and Valantasis, Asceticism [1995]). In this article I will focus on the almost unknown history of asceticism in 20th century Dutch monastic life. This is a history that, especially after the 1950s, reflects a period of transition in which a radical erosion of asceticism occurred. In order to understand and explore asceticism in this specific period and context, I will discuss the demarcation of asceticism that Gavin Flood outlined in his thought-provoking study of 2004, The Ascetic Self: Subjectivity, Memory and Tradition. In this book Flood distinguishes three central parameters of asceticism, in short: memory, performance and ambiguity. These three concepts are applied to research material that is based upon a historical study of Catholic spiritual literature (1930–1965) and eighteen interviews with members of Dutch religious communities who personally experienced ascetic practices during their religious lives. I will argue that the memory of ascetic tradition is no longer being appropriated, which has specific consequences for examining the two parameters of performance and ambiguity.
Joseph and Aseneth in Rumania
Authors: Burchard Christoph
Published: September 2008

The article offers a survey of the text-forms of "Joseph and Aseneth" in Serbo-Slavonic, Greek, and Rumanian which circulated in Rumania in the 17th to the middle of the 19th centuries, especially a Rumanian condensation produced by orthodox monks in the early 18th century for moral education. Particular attention is paid to textual contamination among the forms. This is the end of the long history of vernacular versions and adaptations of the story which started around 600 C.E. with the Syriac translation.
The Special Tribunal for Lebanon: A Court “Off the Shelf” for a Divided Country
Authors: Wetzel Jan Erik , Mitri Yvonne
Published: September 2008

The Special Tribunal for Lebanon is the most recently established international criminal tribunal. Controversially created by the UN Security Council in 2007 amid rising political tensions in the country, it is designed to investigate a number of politically motivated killings, including the assassination of the former Lebanese Prime Minister Rafik Hariri in 2005. It shares many characteristics of other hybrid (or “internationalized”) criminal tribunals, especially the Special Court for Sierra Leone, which facilitated its speedy establishment. But it breaks new ground as an international effort to specifically end impunity for terrorist acts. This article argues that in many respects, the legal framework of the Special Tribunal distills the “best practices” of prior tribunals. At the same time, the debate over its creation and its chances to assist the peace process in Lebanon continues.
Regulating Immigration Control: Carrier Sanctions in the Netherlands
Authors: Scholten Sophie , Minderhoud Paul
Published: September 2008

This article attempts to put carrier sanctions policies in a broad perspective by looking at the immigration context, the rationale behind the policy, the changing character of borders and the regulatory environment of this policy. Carrier sanction legislation can be understood as a remote control instrument, which is supplementary to controls before and at the border and internal controls, whereby the concept of the border as a line between states is abandoned. The second part of the article focuses on the implementation of the carrier sanctions policy in the Netherlands. The Dutch government tries to overcome the principal-agent dilemma arising from involving a third party in enforcement, by installing a system of 'contiguous measures', both negative and positive, to stimulate carriers to perform controls on their passengers' documents. Responsibilities are imposed on carriers but the state, by using 'soft' and 'hard touch' legislation, remains in control.
Case Report on Laval, 18 December 2007 (Case C-341/05) and Viking, 11 December 2007 (Case C-438/05)
Authors: Tans Simon
Published: September 2008

This case report examines the ECJ cases Laval and Viking focusing on three important issues. First, regarding Directive 96/71/EC and the posting of workers, the report provides a clarification of the key arguments submitted in the Laval case explaining that the collective agreement at issue falls outside the scope of the Directive. In doing so, background information on relevant rules and cases on cross-border posting of workers will be provided. Second, the report explains the Court's approach to horizontal implications of Articles 43 EC and 49 EC for trade unions. It is submitted that the Court uses the same, well-known, approach used earlier in regard to sporting associations and bar associations. Such private entities can, under specific circumstances, have the obligation to act in conformity with Articles 43 EC and 49 EC. Due attention is given to possible justification grounds. Finally, this case note investigates the implications of Laval and Viking from a fundamental rights perspective. The Court recognises collective action as a fundamental right under Community law, thereby relying on the Charter of fundamental rights. The use of this source by the ECJ receives specific attention as does the relationship between fundamental freedoms and fundamental rights.
Governance and Networks at the Limits of Representation
Authors: Catlaw Thomas J.
Published: September 2008

Integrating literatures from public administration and social and political theory, this article provides a critical analysis of the political theory of democratic network governance. The article contends that critics and advocates alike have misrecognized the potentially transformative logic of networks by tacitly embedding their arguments and research in the taken-for-granted assumptions of representative government and its determination of political community as “the People.” This determination carries with it a number of assumptions and biases that are especially problematic in the contemporary world. The article argues that a new metaphor of and new style for imagining political community can be extracted from the network and that this can open a new avenue for reconsidering the nature of public administrative practice and pedagogy.
Toward a Screening Tool for Housing Accessibility Problems
Authors: Carlsson Gunilla , Schilling Oliver , Slaug Björn , Fänge Agneta , Ståhl Agneta , Nygren Carita , Iwarsson Susanne
Published: September 2008

To present a reduced version of the Housing Enabler, useful as a screening tool in practice contexts and in research, this study identifies the core items of the environmental component of the instrument, that is, the items most important in terms of the instrument's overall validity to measure accessibility problems. Utilizing cross-national data and interdisciplinary knowledge through an iterative process, a set of core items was identified. The environmental component of the reduced version comprises 61 items, compared to 188 in the original instrument. The rank correlation between the accessibility scores generated by the original and reduced versions was r ≥ .97 ( p < .001). Based on comprehensive empirical research in three countries, the reduced version of the Housing Enabler is a time-efficient and valid screening instrument. It is a powerful tool for research and interventions focusing on housing accessibility problem identification.
Friendships Influence Hispanic Students' Implicit Attitudes Toward White Non-Hispanics Relative to African Americans
Authors: Aberson Christopher L. , Porter Michael K. , Gaffney Amber M.
Published: September 2008

This study examined the role of Hispanic students' friendships with White non-Hispanics (n-Hs) and African Americans (AAs) in predicting implicit and explicit prejudices toward these groups. Participants ( N = 73) completed implicit and explicit attitude measures and a friendship questionnaire. Friendships were associated with implicit attitudes such that participants with more White n-H than AA friends exhibited implicit favoritism for White n-Hs. Friendships did not influence explicit attitudes. The authors discuss findings relative to the unique contributions Hispanic samples make to research on the contact hypothesis, systems justification, and environmental association models of implicit attitudes.