bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical capacity in relation to low back, neck, or shoulder pain in a working population
Authors: Hamberg-van Reenen H H , Ariëns G A M , Blatter B M , Twisk J W R , van Mechelen W , Bongers P M
Published: May 2006

Aims:To investigate the longitudinal relation between physical capacity (isokinetic lifting strength, static endurance of the back, neck, and shoulder muscles, and mobility of the spine) and low back, neck, and shoulder pain.

Methods:In this prospective cohort study, 1789 Dutch workers participated. At baseline, isokinetic lifting strength, static endurance of the back, neck, and shoulder muscles, and mobility of the spine were measured in the pain free workers, as well as potential confounders, including physical workload. Low back, neck, and shoulder pain were self-reported annually at baseline and three times during follow up.

Results:After adjustment for confounders, Poisson generalised estimation equations showed an increased risk of low back pain among workers in the lowest sex specific tertile of performance in the static back endurance tests compared to workers in the reference category (RR = 1.42; 95% CI 1.19 to 1.71), but this was not found for isokinetic trunk lifting strength or mobility of the spine. An increased risk of neck pain was shown for workers with low performance in tests of isokinetic neck/shoulder lifting strength (RR = 1.31; 95% CI 1.03 to 1.67) and static neck endurance (RR = 1.22; 95% CI 1.00 to 1.49). Among workers in the lowest tertiles of isokinetic neck/shoulder lifting strength or endurance of the shoulder muscles, no increased risk of shoulder pain was found.

Conclusions:The findings of this study suggest that low back or neck endurance were independent predictors of low back or neck pain, respectively, and that low lifting neck/shoulder strength was an independent predictor of neck pain. No association was found between lifting trunk strength, or mobility of the spine and the risk of low back pain, nor between lifting neck/shoulder strength or endurance of the shoulder muscles and the risk of shoulder pain.
SOME POLICY IMPLICATIONS OF BEHAVIORAL ECONOMICS AND HAPPINESS STUDIES FOR SINGAPORE: WITH SPECIAL REFERENCE TO CASINOS
Authors: NG YEW-KWANG
Published: May 2006

Behavioral economics is the study of economic behavior beyond the traditional simple economic models of constrained maximization with purely economic objectives (consumption/profits). Some policy implications of the findings of behavioral economics, happiness studies and beyond are outlined, with special reference to excessive volatility in business cycles and the optimal level of public spending. Though behavioral economics potentially provides more support for the restriction of gambling, an outright ban need not be optimal. Though legal casinos may increase some crimes, it will decrease crimes associated with illegal gambling. Some restrictions of problem gambling will be needed. Apart from (if not rather than) the attraction of tourists/visitors, the consumer surplus associated with responsible pleasure gambling is likely to be the major benefits of legalizing casinos. The proposed entry fee may be better replaced by a membership system, as the former is unfair to locals and will lead to unhealthy gambling.
GOVERNMENT SPENDING ON PUBLIC GOODS, SPECIALIZATION-BASED EXTERNAL ECONOMIES AND PATTERN OF TRADE
Authors: ANWAR SAJID
Published: May 2006

This paper examines the link between government spending on a public good and pattern of trade in the presence of specialization-based external economies. The results presented in this paper are based on a simple model of an economy that produces one industrial, one agricultural, one public good and a large number of varieties of professional services. It is shown that, when the agricultural and the public goods are non-traded, the country where government spending is relatively large is a net-exporter of varieties of professional services; if varieties of professional services are equally (or more) capital intensive as compared to the industrial good. When the public good and varieties of professional services are non-traded, the country where government spending is relatively large may export the industrial good in exchange for the agricultural good; if the combined capital intensity of professional services and the industrial good is greater than the capital intensity of the agricultural good and the size of specialization-based external economies is sufficiently small.
DO MONEY AND INTEREST RATES MATTER FOR STOCK PRICES? AN ECONOMETRIC STUDY OF SINGAPORE AND USA
Authors: WONG WING-KEUNG , KHAN HABIBULLAH , DU JUN
Published: May 2006

This paper examines the long-term as well as short-term equilibrium relationships between the major stock indices and selected macroeconomic variables (such as money supply and interest rate) of Singapore and the United States by employing the advanced time series analysis techniques that include cointegration, Johansen multivariate cointegrated system, fractional cointegration and Granger causality. The cointegration results based on data covering the period January 1982 to December 2002 suggest that Singapore's stock prices generally display a long-run equilibrium relationship with interest rate and money supply (M1) but a similar relationship does not hold for the United States. To capture the short-run dynamics of the relationship, we replicate the same experiments with different subsets of data representing shorter time periods. It is evident that stock markets in Singapore moved in tandem with interest rate and money supply before the Asian Crisis of 1997, but this pattern was not observed after the crisis. In the United States, stock prices were strongly cointegrated with macroeconomic variables before the 1987 equity crisis but the relationships gradually weakened and totally disappeared with the emergence of Asian Crisis that also indirectly affected the United States. The results of fractional cointegration and the Johansen multivariate system are consistent with the earlier cointegration results that both Singapore and US stock markets did possess equilibrium relationships with M1 and interest rate at the early days. However, the stability of the systems was disturbed by a series of well-known financial turbulence in the past two decades and eventually weakened for Singapore and completely disappeared for the US. This may imply that monetary authority may take action to respond to the asset price turbulence in order to maintain the stability of monetary economy and thus break the existing equilibrium between stock markets and macroeconomic variables like interest rate and M1. Another possible explanation is that the market became more efficient after 1997 Asian crisis. Finally, the results of Granger causality tests uncover some systematic causal relationships, implying that stock market performance might be a good gauge for Central Bank's monetary policy adjustment.
VECTOR AUTOREGRESSION EVIDENCE ON MONETARISM: A FOCUS ON SOME DEVELOPING ECONOMIES IN SOUTH ASIA
Authors: AHMED MUDABBER , RAO U. L. G.
Published: May 2006

The objective of this paper is to test the validity of two views of monetarism in Bangladesh, India, and Pakistan. A Structural Vector Autoregressive (SVAR) model is developed and the objective is accomplished by conducting Granger causality tests and estimating variance decompositions and impulse response functions. The first view of monetarism that changes in the quantity of money cause, lead and are positively related to changes in prices at least in the medium to long time horizon is supported in Bangladesh, India, and Pakistan. The second view of monetarism that changes in the quantity of money cause, lead and are positively related to changes in output at least in the short to medium time horizon is not supported. The implication of such a result is that an expansionary monetary policy only fuels prices with insignificant effects on output. It supports the view of real business cycle theorists who postulate that policy changes only affect prices.
A CRITICAL ASSESSMENT OF PAST INVESTIGATIONS INTO SINGAPORE'S SAVING BEHAVIOR
Authors: HOPF GREGOR
Published: May 2006

This article aims to show that the literature so far has not been able to present a statistically robust answer to the question of what drove Singapore's spectacular savings rates. A substantial part of the literature — particularly earlier studies — must be rejected on methodological grounds since the time-series properties of the respective data series were not taken into consideration when choosing the appropriate testing method. Others have omitted potentially crucial determinants of savings or have wrongly disaggregated Gross National Savings. This unsatisfactory state of investigation into Singapore's saving behavior is unfortunate because savings play such a central role in Singapore's economic history since the country's independence. For future research the article also supplies new data series, which disaggregate Singapore's national savings after taking the country's peculiarities into consideration. The critical assessment is also intended as a guideline to future researchers of which mistakes to avoid and where potential pitfalls lie.
IN-PLANE NONLINEAR BEHAVIOUR OF CIRCULAR PINNED ARCHES WITH ELASTIC RESTRAINTS UNDER THERMAL LOADING
Authors: BRADFORD M. A.
Published: May 2006

This paper considers the nonlinear in-plane behaviour of a circular arch subjected to thermal loading only. The arch is pinned at its ends, with the pins being on roller supports attached to longitudinal elastic springs that model an elastic foundation, or the restraint provided by adjacent members in a structural assemblage. By using a nonlinear formulation of the strain-displacement relationship, the principle of virtual work is used to produce the differential equations of in-plane equilibrium, as well as the statical boundary conditions that govern the structural behaviour under thermal loading. These equations are solved to produce the equilibrium equations in closed form. The possibility of thermal buckling of the arch is addressed by considering an adjacent buckled equilibrium configuration, and the differential equilibrium equations for this buckled state are also derived from the principle of virtual work. It is shown that unless the arch is flat, in which case it replicates a straight column, thermal buckling of the arch in the plane of its curvature cannot occur, and the arch deflects transversely without bound in the elastic range as the temperature increases. The nonlinear behaviour of a flat arch (with a small included angle) is similar to that of a column with a small initial geometric imperfection under axial loading, while the nonlinearity and magnitude of the deflections decrease with an increase of the included angle at a given temperature. By using the closed form solutions for the problem, the influence of the stiffness of the elastic spring supports is considered, as is the attainment of temperature-dependent first yielding of a steel arch.
NONLINEAR ANALYSIS OF FRAMES INCLUDING SHEAR DEFORMATION
Authors: PETROLITO J. , LEGGE K. A.
Published: May 2006

In this paper, we consider the nonlinear analysis of frames with shear deformation, and present a series of benchmark solutions for a variety of problems and modelling assumptions. The benchmarks enable users and developers of nonlinear analysis software to test the accuracy of their procedures when including shear deformation.
VIBRATION OF PARABOLIC TIED-ARCH BEAMS DUE TO MOVING LOADS
Authors: YAU JONG-DAR
Published: May 2006

This paper intends to study the train-induced vibration of a parabolic tied-arch bridge using an analytical approach. The train loads over the bridge are regarded as a sequence of equidistant moving loads with identical weights. The tied-arch bridge considered is modeled as the combination of a parabolic flat-rise arch with two-hinged supports and a simple beam suspended by densely distributed vertical cables connected to the arch rib. Using the normal coordinate transformation method, the coupled equations of motion of the arch rib and suspended beam are converted into a set of uncoupled equations. Then, one can derive closed form solutions for the response of the tied-arch beam to successive moving loads, by which the resonant conditions of higher modes of the suspended beam can be identified. According to the present study, the critical position for the maximum acceleration on the suspended beam depends upon the vibration shape that has been excited. Moreover, the numerical results indicate that the lower the rise of the arch rib, the larger the acceleration response of the main beam suspended by the arch.
FLUTTER STABILITY BEHAVIOR OF FREE–FREE COLUMN WITH A MOVABLE MASS SUBJECTED TO FOLLOWER DRAG FORCE
Authors: PRABHAKARA D. L. , DHARSHAN M. D. , UTHPAL U. J.
Published: May 2006

The stability behavior of a prismatic free–free column, carrying a movable mass and subjected to the action of follower end thrust and follower frictional resistance has been investigated. A finite element model of the beam is formulated using the modified Hamilton's principle. The eigenvalues of the characteristic equation of the governing differential equation of motion are extracted using the Q-R algorithm. The parameters considered in the investigation include: (i) ratio of the movable mass to the total mass, (ii) position of the movable mass, and (iii) ratio of resultant frictional drag to the magnitude of the end thrust. Some of the interesting results conducted in this study may be useful to the design engineers. Depending on the various parameters used, the column may lose stability either by divergence or by flutter. The first two frequencies vanish when the column is subjected to only an end thrust without any extra mass and/or frictional drag, indicating the occurrence of both the rigid body translation and rotation. However, only one vanishing frequency is observed when the column is carrying a movable mass and is subjected to a frictional drag (irrespective of their values), indicating the occurrence of only one rigid body motion.
ELECTROMECHANICAL DYNAMICS FOR MICRO BEAMS
Authors: XU LIZHONG , JIA XIAOLI
Published: May 2006

In this paper, an electromechanical coupled dynamic equation of a micro beam under an electrostatic force as well as under an electromechanical coupled force is presented. The linearization of above dynamic equation is made, allowing the equation to be divided into a linear dynamic equation for dynamic displacement and a static balance equation for static displacement. Using the balance equation, the changes of the voltage along with displacement are studied. It is shown that there is a critical voltage at which the micro beam will buckle. From the linear dynamic equation, natural frequencies and vibration modes of the micro beam, and its forced responses to voltage excitation are derived. The results show that the natural frequencies and vibrating magnitudes of the micro beam are affected by mechanical and electric parameters. Smaller beam length and voltage as well as larger beam thickness and clearance should be selected in order to obtain smaller vibrating magnitudes. It is also shown that for higher vibration modes, more positions of the peak dynamic displacements occur.
NONLINEAR DYNAMICS OF POLAR-ORTHOTROPIC CIRCULAR PLATES
Authors: AKOUR SALIH N. , NAYFEH JAMAL F.
Published: May 2006

The dynamics of nonlinear polar orthotropic circular plates with simply supported boundary condition are investigated. Kirchhoff strain displacement relations for thin plates plus next higher-order nonlinear terms (von Karman type geometric nonlinearity) are considered. Lagrangian density function and Hamilton's principle are utilized to derive Lagrange's equations, from which the equations of motion and associated boundary conditions are derived. Analytical solution is obtained by the perturbation techniques and numerical solution by the Runge–Kutta method. Phase diagrams, discrete Fast Fourier Transform (FFT diagrams) and time history responses are presented for studying the forced vibration behavior. The sub-harmonic and primary resonances are studied as well as the effect of adding damping foil layers. The quadratic term in the governing equation plays a softening role on the overall behavior of the plate due to its relatively large coefficient. The increase of damping tends to smooth out the unstable region (i.e. jump phenomenon) in the system.
AXI-SYMMETRIC WAVE PROPAGATION OF CARBON NANOTUBES WITH NON-LOCAL ELASTIC SHELL MODEL
Authors: WANG Q.
Published: May 2006

A non-local elastic shell model is proposed for the first time in this study for considering the small-scale effect in axi-symmetric wave propagation in carbon nanotubes (CNTs). Two coupled radial and longitudinal modes, and one decoupled torsional mode, are derived from the developed non-local shell model. The small-scale effect on wave propagation is numerically studied and discussed. In addition, the cut-off frequency based on the non-local shell model is obtained, which is found to be free of the small-scale effect. It is interesting to note that only one asymptotic phase velocity exists in the CNTs using the non-local shell model, whereas two asymptotic phase velocities can be predicted using the classical or local elastic shell model. It is hoped the research presented herein can be used as a benchmark for future studies on the wave propagation of CNTs with non-local continuum models.
A “how to” guide for developing a publishable Scholarship of Teaching project
Authors: O'Loughlin Valerie Dean
Published: May 2006

In order for the efforts of scholarly teaching to be recognized, the work must become public and presented to peers for review. Scholarship of Teaching is not only improving instruction and learning but also methodically assessing whether specific teaching interventions have had the desired effect. In this paper, the author presents a step-by-step guide for how to develop a Scholarship of Teaching project that is well thought out and worthy of publication. Factors to consider before performing such pedagogical research include developing a clear research hypothesis for the classroom, reviewing the background literature, obtaining Institutional Review Board (Human Subjects) approval, and determining which methods of assessment may be used. This “how to” guide discusses how to handle all of these factors and prepare the data for publication and introduces the reader to references related to the Scholarship of Teaching and learning as well as educational research and theory.
Angelo Mosso and muscular fatigue: 116 years after the first congress of physiologists: IUPS commemoration
Authors: Giulio Camillo Di , Daniele Franca , Tipton Charles M.
Published: May 2006

At the first International Congress of Physiologists in Basel, Switzerland, the Italian physiologist Angelo Mosso (1846–1910) discussed his findings on muscular fatigue while demonstrating the functioning of an ergograph (work recorder). One hundred sixteen years later, Mosso's career, scientific accomplishments, and legacy in the study of muscular fatigue were commemorated at the 2005 International Congress of Physiological Sciences. After receiving his degree in Medicine and Surgery from Turin, Italy, in 1870, Mosso was able to study and interact with renowned physiologists as Wilhelm Ludwig, Du Bois-Reymond, Hugo Kronecker, and Etienne Marey. By 1879, he was Professor of Physiology at the University in Turin, where he conducted research pertaining to blood circulation, respiration, physical education, high-altitude physiology, and muscular fatigue. Using tracings from the ergograph (concentric contractions of the flexor muscles of the middle finger that were volitionally or electrically stimulated), he was able to characterize muscle fatigue and to associate its occurrence with central or peripheral influences. He demonstrated that exercise would increase muscular strength and endurance while prolonging the occurrence of fatigue, which he postulated was a chemical process that involved the production of toxic substances such as carbonic acid. The phenomenon of contracture was described, and his collective studies led to the formulation of laws pertaining to exhaustion and to the 1891 publication of La Fatica (Fatigue). Besides La Fatica, Mosso will be remembered as a scientist with a love for physiology, a concern for the social welfare of his countrymen, and as one who sought to integrate physiological, philosophical, and psychological concepts in his experimental studies.
Using a classic paper by Gottschalk and Mylle to teach the countercurrent model of urinary concentration
Authors: Tauck David L.
Published: May 2006

Most undergraduates lack the scientific background to read and appreciate much of the primary literature in physiology. Even when the underlying concepts are elegantly simple, the inherent complexity of contemporary papers often makes the work inaccessible to them. However, with a little help, they can be guided to an understanding of the creative thought processes that underlie the research and to appreciate its significance. This is especially true of many classic papers in physiology that often rely on easily comprehensible techniques. Moreover, the American Physiological Society (APS) has invited prominent scientists to select important papers in their fields and to write essays that both put the work into historical context and explain why it is scientifically important. The APS Legacy Project makes these classic papers freely available online. One such paper by Gottschalk and Mylle presents data from a series of micropuncture studies that confirm all of the predictions of the countercurrent exchange model of concentrated urine production ( 2 ). The included handout of questions for discovery learning and teaching points suggest ways to use the paper as an instructional resource.
Teaching from classic papers: Hill's model of muscle contraction
Authors: Holmes Jeffrey W.
Published: May 2006

A. V. Hill's 1938 paper “The heat of shortening and the dynamic constants of muscle” is an enduring classic, presenting detailed methods, meticulous experiments, and the model of muscle contraction that now bears Hill's name. Pairing a simulation based on Hill's model with a reading of his paper allows students to follow his thought process to discover key principles of muscle physiology and gain insight into how to develop quantitative models of physiological processes. In this article, the experience of the author using this approach in a graduate biomedical engineering course is outlined, along with suggestions for adapting this approach to other audiences.
The Opinion Editorial: teaching physiology outside the box
Authors: Poronnik Philip , Moni Roger W.
Published: May 2006

Improving the public understanding of science is an important challenge for the future professional scientists who are our current undergraduates. In this paper, we present a conceptual model that explores the role of mass media as community gatekeepers of new scientific findings. This model frames the benefits for undergraduate science students to learn about media genres so that they can learn to communicate science more effectively to nonprofessional audiences. Informed by this Media Role model, we then detail a novel writing task for undergraduate physiology students, the Opinion Editorial (Op-Ed), and an accompanying Peer Review. The Op-Ed genre was directly taught to the students by a professional journalist. As an assessment task, students presented a recent, highly technical paper as an Op-Ed. This was assessed by both faculty members and peers using a detailed assessment rubric. Most students were able to replicate the features of Op-Eds and attained high grades on their writing tasks. Survey data from final-year physiology students ( n = 230) were collected before and after the implementation of the Op-Ed/Peer Review. These indicated that most students were aware of the importance of scientists to effectively communicate their knowledge to nonprofessional audiences, that the Op-Ed writing task was challenging, and that they believed that their ability to write to nonprofessional audiences was improved after explicit teaching and feedback.
A classic learning opportunity from Fenn, Rahn, and Otis (1946): the alveolar gas equation
Authors: Curran-Everett Douglas
Published: May 2006

The alveolar gas equation, the focus of a classic paper by Fenn, Rahn, and Otis, provides a framework for understanding the mechanisms involved in pulmonary gas exchange as well as the limits of human performance. The classic 1946 paper by Fehn, Rahn, and Otis gives your students an opportunity to learn about the alveolar gas equation from the physiologists who pioneered it and demonstrates that mathematics and data graphics are fundamental tools with which to learn respiratory physiology. In this essay, I outline avenues of discovery by which your students can explore the alveolar gas equation. Meaningful learning stems from inspiration: to learn, you must be inspired to learn. If anyone can inspire learning in respiratory physiology, it is Wallace Fenn, Hermann Rahn, and Arthur Otis.
ATP and PIP2 dependence of the magnesium-inhibited, TRPM7-like cation channel in cardiac myocytes
Authors: Gwanyanya Asfree , Sipido Karin R. , Vereecke Johan , Mubagwa Kanigula
Published: May 2006

The Mg2+-inhibited cation (MIC) current ( IMIC) in cardiac myocytes biophysically resembles currents of heterologously expressed transient receptor potential (TRP) channels, particularly TRPM6 and TRPM7, known to be important in Mg2+ homeostasis. To understand the regulation of MIC channels in cardiac cells, we used the whole cell voltage-clamp technique to investigate the role of intracellular ATP in pig, rat, and guinea pig isolated ventricular myocytes. IMIC, studied in the presence or absence of extracellular divalent cations, was sustained for ≥50 min after patch rupture in ATP-dialyzed cells, whereas in ATP-depleted cells IMIC exhibited complete rundown. Equimolar substitution of internal ATP by its nonhydrolyzable analog adenosine 5′-(β,γ-imido)triphosphate failed to prevent rundown. In ATP-depleted cells, inhibition of lipid phosphatases by fluoride + vanadate + pyrophosphate prevented IMIC rundown. In contrast, under similar conditions neither the inhibition of protein phosphatases 1, 2A, 2B or of protein tyrosine phosphatase nor the activation of protein kinase A (forskolin, 20 μM) or protein kinase C (phorbol myristate acetate, 100 nM) could prevent rundown. In ATP-loaded cells, depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) by prevention of its resynthesis (10 μM wortmannin or 15 μM phenylarsine oxide) induced rundown of IMIC. Finally, loading ATP-depleted cells with exogenous PIP2 (10 μM) prevented rundown. These results suggest that PIP2, likely generated by ATP-utilizing lipid kinases, is necessary for maintaining cardiac MIC channel activity.
The human NBCe1-A mutant R881C, associated with proximal renal tubular acidosis, retains function but is mistargeted in polarized renal epithelia
Authors: Toye Ashley M. , Parker Mark D. , Daly Christopher M. , Lu Jing , Virkki Leila V. , Pelletier Marc F. , Boron Walter F.
Published: May 2006

The human electrogenic renal Na-HCO3 cotransporter (NBCe1-A; SLC4A4) is localized to the basolateral membrane of proximal tubule cells. Mutations in the SLC4A4 gene cause an autosomal recessive proximal renal tubular acidosis (pRTA), a disease characterized by impaired ability of the proximal tubule to reabsorb HCO3− from the glomerular filtrate. Other symptoms can include mental retardation and ocular abnormalities. Recently, a novel homozygous missense mutant (R881C) of NBCe1-A was reported from a patient with a severe pRTA phenotype. The mutant protein was described as having a lower than normal activity when expressed in Xenopus oocytes, despite having normal Na+ affinity. However, without trafficking data, it is impossible to determine the molecular basis for the phenotype. In the present study, we expressed wild-type NBCe1-A (WT) and mutant NBCe1-A (R881C), tagged at the COOH terminus with enhanced green fluorescent protein (EGFP). This approach permitted semiquantification of surface expression in individual Xenopus oocytes before assay by two-electrode voltage clamp or measurements of intracellular pH. These data show that the mutation reduces the surface expression rather than the activity of the individual protein molecules. Confocal microscopy on polarized mammalian epithelial kidney cells [Madin-Darby canine kidney (MDCK)I] expressing nontagged WT or R881C demonstrates that WT is expressed at the basolateral membrane of these cells, whereas R881C is retained in the endoplasmic reticulum. In summary, the pathophysiology of pRTA caused by the R881C mutation is likely due to a deficit of NBCe1-A at the proximal tubule basolateral membrane, rather than a defect in the transport activity of individual molecules.
Loss of flow induces leukocyte-mediated MMP/TIMP imbalance in dynamic in vitro blood-brain barrier model: role of pro-inflammatory cytokines
Authors: Krizanac-Bengez Ljiljana , Hossain Mohammed , Fazio Vince , Mayberg Marc , Janigro Damir
Published: May 2006

There is substantial evidence linking blood-brain barrier (BBB) failure during cerebral ischemia to matrix metalloproteinases (MMP). BBB function may be affected by loss of shear stress under normoxia/normoglycemia, as during cardiopulmonary bypass procedures. The present study used an in vitro flow-perfused BBB model to analyze the individual contributions of flow, cytokine levels, and circulating blood leukocytes on the release/activity of MMP-9, MMP-2, and their endogenous inhibitors, the tissue inhibitors of MMPs (TIMPs), TIMP-1, and TIMP-2. The presence of circulating blood leukocytes under normoxic/normoglycemic flow cessation/reperfusion significantly increased the luminal levels of MMP-9 and activity of MMP-2, accompanied by partial reduction of TIMP-1, complete reduction of TIMP-2 and increased BBB permeability. These changes were not observed during constant flow with circulating blood leukocytes, or after normoxic/normoglycemic or hypoxic/hypoglycemic flow cessation/reperfusion without circulating blood leukocytes. The addition of anti-IL-6 or anti-TNF-α antibody in the lumen before reperfusion suppressed the levels of MMP-9 and activity of MMP-2, had no effect on TIMP-1, and completely restored TIMP-2 and BBB integrity. Injection of TIMP-2 in the lumen before reperfusion prevented the activation of MMP-2 and BBB permeability. These data indicate that blood leukocytes and loss of flow are major factors in the activation of MMP-2, and that cytokine-mediated differential regulation of TIMP-1 and TIMP-2 may contribute significantly to BBB failure.
Comparative effects of a low-carbohydrate diet and exercise plus a low-carbohydrate diet on muscle sarcoplasmic reticulum responses in males
Authors: Duhamel T. A. , Green H. J. , Perco J. G. , Ouyang J.
Published: May 2006

We employed a glycogen-depleting session of exercise followed by a low-carbohydrate (CHO) diet to investigate modifications that occur in muscle sarcoplasmic reticulum (SR) Ca2+-cycling properties compared with low-CHO diet alone. SR properties were assessed in nine untrained males [peak aerobic power (V̇o2 peak) = 43.6 ± 2.6 (SE) ml·kg−1·min−1] during prolonged cycle exercise to fatigue performed at ∼58% V̇o2 peak after 4 days of low-CHO diet (Lo CHO) and after glycogen-depleting exercise plus 4 days of low-CHO (Ex+Lo CHO). Compared with Lo CHO, Ex+Lo CHO resulted in 12% lower ( P < 0.05) resting maximal Ca2+-ATPase activity ( Vmax = 174 ± 12 vs. 153 ± 10 μmol·g protein−1·min−1) and smaller reduction in Vmax induced during exercise. A similar effect was observed for Ca2+ uptake. The Hill coefficient, defined as slope of the relationship between cytosolic free Ca2+ concentration and Ca2+-ATPase activity, was higher ( P < 0.05) at rest (2.07 ± 0.15 vs. 1.90 ± 0.10) with Ex+Lo CHO, an effect that persisted throughout the exercise. The coupling ratio, defined as the ratio of Ca2+ uptake to Vmax, was 23–30% elevated ( P < 0.05) at rest and during the first 60 min of exercise with Ex+Lo CHO. The ∼27 and 34% reductions ( P < 0.05) in phase 1 and phase 2 Ca2+ release, respectively, observed during exercise with Lo CHO were not altered by Ex+Lo CHO. These results indicate that when prolonged exercise precedes a short-term Lo CHO diet, Ca2+ sequestration properties and efficiency are improved compared with those during Lo CHO alone.
Role of mTOR signaling in intestinal cell migration
Authors: Rhoads J. Marc , Niu Xiaomei , Odle Jack , Graves Lee M.
Published: May 2006

An early signaling event activated by amino acids and growth factors in many cell types is the phosphorylation of the mammalian target of rapamycin (mTOR; FRAP), which is functionally linked to ribosomal protein s6 kinase (p70s6k), a kinase that plays a critical regulatory role in the translation of mRNAs and protein synthesis. We previously showed that intestinal cell migration, the initial event in epithelial restitution, is enhanced by l-arginine (ARG). In this study, we used amino acids as prototypic activators of mTOR and ARG, IGF-1, or serum as recognized stimulators of intestinal cell migration. We found that 1) protein synthesis is required for intestinal cell migration, 2) mTOR/p70s6k pathway inhibitors (rapamycin, wortmannin, and intracellular Ca2+ chelation) inhibit cell migration, 3) ARG activates migration and mTOR/p70s6k (but not ERK-2) in migrating enterocytes, and 4) immunocytochemistry reveals abundant p70s6k staining in cytoplasm, whereas phospho-p70s6k is virtually all intranuclear in resting cells but redistributes to the periphery on activation by ARG. We conclude that mTOR/p70s6k signaling is essential to intestinal cell migration, is activated by ARG, involves both nuclear and cytoplasmic events, and may play a role in intestinal repair.
Influence of body heat content on hand function during prolonged cold exposures
Authors: Flouris A. D. , Cheung S. S. , Fowles J. R. , Kruisselbrink L. D. , Westwood D. A. , Carrillo A. E. , Murphy R. J. L.
Published: May 2006

We examined the influence of 1) prior increase [preheating (PHT)], 2) increase throughout [heating (HT)], and 3) no increase [control (Con)] of body heat content (Hb) on neuromuscular function and manual dexterity of the hands during a 130-min exposure to −20°C (coldEx). Ten volunteers randomly underwent three passive coldEx, incorporating a 10-min moderate-exercise period at the 65th min while wearing a liquid conditioning garment (LCG) and military arctic clothing. In PHT, 50°C water was circulated in the LCG before coldEx until core temperature was increased by 0.5°C. In HT, participants regulated the inlet LCG water temperature throughout coldEx to subjective comfort, while the LCG was not operating in Con. Thermal comfort, rectal temperature, mean skin temperature, mean finger temperature (T̄fing), change in Hb (ΔHb), rate of body heat storage, Purdue pegboard test, finger tapping, handgrip, maximum voluntary contraction, and evoked twitch force of the first dorsal interosseus muscle were recorded. Results demonstrated that, unlike in HT and PHT, thermal comfort, rectal temperature, mean skin temperature, twitch force, maximum voluntary contraction, and finger tapping declined significantly in Con. In contrast, T̄fing and Purdue pegboard test remained constant only in HT. Generalized estimating equations demonstrated that ΔHb and T̄fing were associated over time with hand function, whereas no significant association was detected for rate of body heat storage. It is concluded that increasing Hb not only throughout but also before a coldEx is effective in maintaining hand function. In addition, we found that the best indicator of hand function is ΔHb followed by T̄fing.
Motor Adaptation to Single Force Pulses: Sensitive to Direction but Insensitive to Within-Movement Pulse Placement and Magnitude
Authors: Fine Michael S. , Thoroughman Kurt A.
Published: May 2006

Although previous experiments have identified that errors in movement induce adaptation, the precise manner in which errors determine subsequent control is poorly understood. Here we used transient pulses of force, distributed pseudo-randomly throughout a movement set, to study how the timing of feedback within a movement influenced subsequent predictive control. Human subjects generated a robust adaptive response in postpulse movements that opposed the pulse direction. Regardless of the location or magnitude of the pulse, all pulses yielded similar changes in predictive control. All current supervised and unsupervised theories of motor learning presume that adaptation is proportional to error. Current neural models that broadly encode movement velocity and adapt proportionally to motor error can mimic human insensitivity to pulse location, but cannot mimic human insensitivity to pulse magnitude. We conclude that single trial adaptation to force pulses reveals a categorical strategy that humans adopt to counter the direction, rather than the magnitude, of movement error.
Dynamical Mechanisms of Odor Processing in Olfactory Bulb Mitral Cells
Authors: Rubin Daniel B. , Cleland Thomas A.
Published: May 2006

In the olfactory system, the contribution of dynamical properties such as neuronal oscillations and spike synchronization to the representation of odor stimuli is a matter of substantial debate. While relatively simple computational models have sufficed to guide current research in large-scale network dynamics, less attention has been paid to modeling the membrane dynamics in bulbar neurons that may be equally essential to sensory processing. We here present a reduced, conductance-based compartmental model of olfactory bulb mitral cells that exhibits the complex dynamical properties observed in these neurons. Specifically, model neurons exhibit intrinsic subthreshold oscillations with voltage-dependent frequencies that shape the timing of stimulus-evoked action potentials. These oscillations rely on a persistent sodium conductance, an inactivating potassium conductance, and a calcium-dependent potassium conductance and are reset via inhibitory input such as that delivered by periglomerular cell shunt inhibition. Mitral cells fire bursts, or clusters, of spikes when continuously stimulated. Burst properties depend critically on multiple currents, but a progressive deinactivation of IAover the course of a burst is an important regulator of burst termination. Each of these complex properties exhibits appropriate dynamics and pharmacology as determined by electrophysiological studies. Additionally, we propose that a second, inconsistently observed form of infrathreshold bistability in mitral cells may derive from the activation of ATP-activated potassium currents responding to hypoxic conditions. We discuss the integration of these cellular properties in the larger context of olfactory bulb network operations.
5-HT Modulation of Identified Segmental Premotor Interneurons in the Lamprey Spinal Cord
Authors: Biró Zoltán , Hill Russell H. , Grillner Sten
Published: May 2006

Ipsilaterally projecting spinal excitatory interneurons (EINs) generate the hemisegmental rhythmic locomotor activity in lamprey, while the commissural interneurons ensure proper left-right alternation. 5-HT is a potent modulator of the locomotor rhythm and is endogenously released from the spinal cord during fictive locomotion. The effect of 5-HT was investigated for three segmental premotor interneuron types: EINs, commissural excitatory and commissural inhibitory interneurons. All three types of interneurons produced chemical postsynaptic potentials in motoneurons, but only those from EINs had an electrical component. The effect of 5-HT was studied on the slow afterhyperpolarization, involved in spike frequency regulation, and on the segmental synaptic transmission to motoneurons. 5-HT induced a reduction in the slow afterhyperpolarization and a depression of synaptic transmission in all three types of segmental interneurons. Thus 5-HT is a very potent modulator of membrane properties and synaptic transmission of last-order segmental premotor interneurons. Such modulation of locomotor network interneurons can partially account for the observed effects of 5-HT on the swimming pattern in lamprey.
GABAA-Receptor Blockade Reverses the Injury-Induced Sensitization of Nociceptor-Specific (NS) Neurons in the Spinal Dorsal Horn of the Rat
Authors: Garcia-Nicas Esther , Laird Jennifer M. A. , Cervero Fernando
Published: May 2006

Single-unit electrical activity was recorded from 80 nociceptor-specific (NS) neurons in the dorsal horn of the lumbar spinal cord of pentobarbital anesthetized rats. Their responses to low- and high-intensity mechanical stimulation of their receptive fields (RFs) were recorded before and after the application of irritant agents [capsaicin (CAP) or mustard oil (MO)] to the RF. Before the applications of the irritants the neurons responded only to high-intensity stimuli, but after this procedure 20 of 28 neurons tested were sensitized, i.e., gave increased responses to high-intensity stimuli and showed novel responses to low-intensity mechanical stimulation as well as an Aβ-fiber afferent drive. CAP was more likely to induce sensitization than MO and the majority of sensitized neurons were located in the superficial dorsal horn. No relationship was found between the magnitude of the response to the sensitizing agent and the presence or absence of sensitization. Cumulative doses of two γ-aminobutyric acid type A (GABAA)–receptor antagonists, picrotoxin and bicuculline, were administered systemically or applied directly over the spinal cord. The GABAA antagonists reversed the sensitization of the neurons by reducing the novel low-threshold responses. These results show that NS neurons in the spinal dorsal horn can be sensitized by a sustained afferent discharge in peripheral nociceptors and that this sensitization can be reduced or reversed by low doses of GABAA-receptor antagonists. This provides evidence for a mechanism in which an enhanced GABAergic transmission can lead to hyperexcitability and sensitization of NS neurons in the dorsal horn.
Effect of Texture of Plastic and Elastic Model Foods on the Parameters of Mastication
Authors: Foster K. D. , Woda A. , Peyron M. A.
Published: May 2006

Mastication is continually modified throughout the chewing sequence in response to the texture of the food. The aim of this work was to compare the effects of an increase in hardness of two model food types, presenting either elastic or plastic rheological properties, on mastication. Each model food type consisted of four products of different hardness. Sensory testing experiments conducted with one group of 14 subjects showed significant perceived differences between products in terms of their increasing hardness. Fifteen other volunteers were asked to chew three replicates of each elastic and plastic product during two sessions. EMGs of masseter and temporalis muscles were recorded simultaneously with jaw movement during chewing. Numerous variables were analyzed from these masticatory recordings. Multiple linear regression analyses were used to assess the respective effects of food hardness and rheological properties on variables characterizing either the whole masticatory sequence or different stages of the sequence. Muscle activities were significantly affected by an increase in hardness regardless of the food type, whereas the shape of the cycles depended on the rheological properties. The masticatory frequency was affected by hardness at the initial stage of the sequence but overall frequency adaptation was better explained by a change in rheological behavior, with plastic products being chewed at a slower frequency. A dual hypothesis was proposed, implicating first a cortical–brain stem preprogrammed mechanism to adapt the shape of the jaw movements to the rheological properties of the food, and second, a brain stem mechanism with mainly sensory feedback from the mouth to adapt muscle force to the food hardness.
Nerve Growth Factor Decreases Potassium Currents and Alters Repetitive Firing in Rat Sympathetic Neurons
Authors: Luther Jason A. , Birren Susan J.
Published: May 2006

The sympathetic nervous system is an essential regulator of the cardiovascular system and interactions with target tissue regulate sympathetic neuronal properties. The heart produces nerve growth factor (NGF), which promotes sympathetic noradrenergic innervation of cardiac tissue and affects sympathetic synaptic strength. Neurotrophins, including NGF, are important modulators of synaptic plasticity and membrane electrical properties. Here we show that acute application of NGF causes a change in the repetitive firing pattern of cultured sympathetic neurons of the rat superior cervical ganglion. Neurons fire fewer action potentials in NGF, but with increased frequency, demonstrating an NGF-dependent change from a tonic to a phasic firing pattern. Additionally, NGF decreases the spike time variance, making spikes more tightly time locked to stimulus onset. NGF causes a decrease in the amplitude of both calcium-dependent and -independent potassium currents, and inhibition of calcium-dependent potassium currents using CdCl2reproduces some, but not all, of the firing properties induced by NGF. This study suggests that NGF release from cardiac tissue may act to modulate the repetitive firing properties of sympathetic neurons to tune their output to meet the physiological needs of the organism.
Electrophysiological Classification of Somatostatin-Positive Interneurons in Mouse Sensorimotor Cortex
Authors: Halabisky Brian , Shen Fran , Huguenard John R. , Prince David A.
Published: May 2006

Classification of inhibitory interneurons is critical in determining their role in normal information processing and pathophysiological conditions such as epilepsy. Classification schemes have relied on morphological, physiological, biochemical, and molecular criteria; and clear correlations have been demonstrated between firing patterns and cellular markers such as neuropeptides and calcium-binding proteins. This molecular diversity has allowed generation of transgenic mouse strains in which GFP expression is linked to the expression of one of these markers and presumably a single subtype of neuron. In the GIN mouse (E GFP-expressing Inhibitory Neurons), a subpopulation of somatostatin-containing interneurons in the hippocampus and neocortex is labeled with enhanced green fluorescent protein (EGFP). To optimize the use of the GIN mouse, it is critical to know whether the population of somatostatin–EGFP-expressing interneurons is homogeneous. We performed unsupervised cluster analysis on 46 EGFP-expressing interneurons, based on data obtained from whole cell patch-clamp recordings. Cells were classified according to a number of electrophysiological variables related to spontaneous excitatory postsynaptic currents (sEPSCs), firing behavior, and intrinsic membrane properties. EGFP-expressing interneurons were heterogeneous and at least four subgroups could be distinguished. In addition, multiple discriminant analysis was applied to data collected during whole cell recordings to develop an algorithm for predicting the group membership of newly encountered EGFP-expressing interneurons. Our data are consistent with a heterogeneous population of neurons based on electrophysiological properties and indicate that EGFP expression in the GIN mouse is not restricted to a single class of somatostatin-positive interneuron.