bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple and intuitive procedure for evaluating mode degeneracy in photonic crystal fibers
Authors: Uranus H. P.
Published: February 2006

A simple and intuitive procedure for evaluating the degeneracy of the modes of photonic crystal fibers is presented. The procedure requires only a visual inspection of the vector plots of the transverse modal field profiles and can be applied without knowing group theory and without doing extra computations. Several examples are given.
Statistical mechanics of colloids and Boltzmann’s definition of the entropy
Authors: Swendsen Robert H.
Published: February 2006

The Boltzmann entropy as traditionally presented in statistical mechanics textbooks is only a special case and not Boltzmann's fundamental definition. The difference becomes important when the traditional expression for the entropy is applied to colloids, for which it makes incorrect predictions. Boltzmann's original definition of the entropy in terms of the probabilities of states of composite systems leads to consistent and correct statistical mechanics and thermodynamics.
Progressive Disruption of Cellular Protein Folding in Models of Polyglutamine Diseases
Authors: Gidalevitz Tali , Ben-Zvi Anat , Ho Kim H. , Brignull Heather R. , Morimoto Richard I.
Published: February 2006

Numerous human diseases are associated with the chronic expression of misfolded and aggregation-prone proteins. The expansion of polyglutamine residues in unrelated proteins is associated with the early onset of neurodegenerative disease. To understand how the presence of misfolded proteins leads to cellular dysfunction, we employed
Caenorhabditis elegans
polyglutamine aggregation models. Here, we find that polyglutamine expansions disrupted the global balance of protein folding quality control, resulting in the loss of function of diverse metastable proteins with destabilizing temperature-sensitive mutations. In turn, these proteins, although innocuous under normal physiological conditions, enhanced the aggregation of polyglutamine proteins. Thus, weak folding mutations throughout the genome can function as modifiers of polyglutamine phenotypes and toxicity.
DILATON STABILIZATION AND INFLATION IN THE D-BRANE WORLD
Authors: KIM HANG BAE
Published: February 2006

We study possible mechanisms of the dilaton stabilization in the D-brane world in which a compactified D-brane constitutes our universe. The dilaton can be stabilized due to the interplay between the D-brane tension and the negative scalar curvature of extra dimensions. Cosmic evolution of the dilaton is investigated with the obtained dilaton potential and it is found that inflation can be realized before the settlement of the dilaton.
PENNING DISCHARGE PLASMA SOURCE AND ITS APPLICATION TO SYNTHESIS OF NANOSTRUCTURED AlN FILMS
Authors: FENG P. X. , LI Y. H. , WEINER BRAD
Published: February 2006

Penning discharge (PD) sputtering deposition technique is developed and first used in synthesis of nanostructured aluminum nitride (AlN) films. The advantage of the present PD is that discharge current is linearly dependent on power supply voltage. Maximal discharge current up to 180 mA is obtained for power supply voltage of 5 kV with a ballast resistor of 25 kΩ. In contrast, the discharge voltage is only 290 V. Installation of smaller value of the ballast resistor will yield larger discharge current, whereas discharge voltage remains nearly unchanged, which is an important factor employed to the synthesis of high quality of AlN films.

The preferred orientations of nanoscale AlN particles distributions on the surface of the substrates are observed. The increase of the power voltage (discharge current) for sputtering deposition yields different patterns of the nanoscale particles, but sizes of the particles are unchanged. Typical A 1– TO and A1– LO bands in Raman spectra of the films are identified, respectively.
THE ELECTRICAL RESISTIVITY OF LIQUIDPb-BiALLOY
Authors: LI QIANG , ZU FANG-QIU , LI XIAN-FEN , XI YUN
Published: February 2006

Different from the conventional liquid theory, experimental evidence suggests that there might be discontinuous liquid-liquid (L-L) structure transitions for some alloys. By the resistivity experiments, it is assumed that a temperature-induced L-L structure transition might occur in liquid lead-bismuth ( PbBi ) alloy. The electrical resistivity of four compositions for PbBi alloy versus temperature was precisely measured in our experiment. It was found that the resistivity increases linearly with temperature rising in a certain range of temperature above the melting point. During subsequent calefaction, the results obviously showed that a turning point appears in the resistivity-temperature (R-T) curve for every composition at a certain temperature. The turning temperature depends on composition. It can be considered that there is L-L structure transition in some regions of high temperature for PbBi alloy.
AHARONOV–CASHER PHASE AND SPIN MOTIVE FORCE
Authors: CHOI TAESEUNG
Published: February 2006

We have studied the spin motive force induced by the time-dependent nonadiabatic Aharonov–Casher (AC) phase. It has been shown that the spin motive force has the new term explicitly dependent on the Aharonov–Anandan (AA) phase. This AA phase dependent term could be obtained both in the canonical and path-integral formulations. In path-integral formulations this AA dependent term originates from the nontrivial path-ordering nature of a non-Abelian spin gauge group. We also have shown that this term can be understood as the rotating frame effect in the classical equation of motion for the spin angular momentum. With this term the duality between the Aharonov–Bohm and the AC effect reaches the Newton's third law in the classical limit.
STUDY ON CONDUCTANCE IMPROVEMENT OF THE CATHODE MATERIALS OF LiCo0.92M0.08O2 (M=Ni, Zn) BY AB INITIO CALCULATIONS
Authors: DENG BIN , DING KE , GU CHANG-XIN , LING LI , SUN QI
Published: February 2006

Electronic structures of LiCo 0.92 M 0.08 O 2 ( M=Ni , Zn ) have been studied by the first principle theory based on the density-functional theory in this paper in order to understand their electronic conductivity improvement mechanism. Their DOS (density of state) and PDOS (partial density of state) have been calculated and compared with those of LiCoO 2. The calculated results show that although the total DOS maintain unchanged, the distributions of DOS and PDOS are different from those of the undoped LiCoO 2. DOS of [Formula: see text] of Co -3d electrons in LiCo 0.92 M 0.08 O 2 ( M=Ni , Zn ) increases while [Formula: see text] and t2g decrease, and O atoms have more closed-shell characteristics and become more highly ionized, which induce the conductivity enhancement of LiCoO 2 after it is M -doped. A possible reason, which is the charge compensation mechanism, is adopted for explaining this improvement.
THE DETERMINANTS OF CREDIT DEFAULT SWAP RATES: AN EXPLANATORY STUDY
Authors: ABID FATHI , NAIFAR NADER
Published: February 2006

The aim of this paper is to explain empirically the determinants of credit default swap rates using a linear regression. We document that the majority of variables, detected from the credit risk pricing theories, explain more than 60% of the total level of credit default swap. These theoretical variables are credit rating, maturity, riskless interest rate, slope of the yield curve and volatility of equities. The estimated coefficients for the majority of these variables are consistent with theory and they are significant both statistically and economically. We conclude that credit rating is the most determinant of credit default swap rates.
COMPACTNESS AND GLOBAL ESTIMATES FOR A FOURTH ORDER EQUATION OF CRITICAL SOBOLEV GROWTH ARISING FROM CONFORMAL GEOMETRY
Authors: HEBEY EMMANUEL , ROBERT FRÉDÉRIC , WEN YULIANG
Published: February 2006

Given (M,g) a smooth compact Riemannian manifold of dimension n ≥ 5, we investigate compactness for fourth order critical equations like Pgu = u2♯-1, where [Formula: see text] is a Paneitz–Branson operator with constant coefficients b and c, u is required to be positive, and [Formula: see text] is critical from the Sobolev viewpoint. We prove that such equations are compact on locally conformally flat manifolds, unless b lies in some closed interval associated to the spectrum of the smooth symmetric (2,0)-tensor field involved in the definition of the geometric Paneitz–Branson operator.
TWISTED REPRESENTATIONS OF VERTEX OPERATOR SUPERALGEBRAS
Authors: DONG CHONGYING , ZHAO ZHONGPING
Published: February 2006

This paper gives an analogue of Ag(V) theory for a vertex operator superalgebra V and an automorphism g of finite order. The relation between the g-twisted V-modules and Ag(V)-modules is established. It is proved that if V is g-rational, then Ag(V) is finite-dimensional semi-simple associative algebra and there are only finitely many irreducible g-twisted V-modules.
Laser ablation
40
Ar/
39
Ar dating of metamorphic fabrics in the Caledonides of north Ireland
Authors: Condon D.J. , Hodges K.V. , Alsop G.I. , White A.
Published: February 2006

In situ
40
Ar/
39
Ar dating of two texturally distinct biotite generations within a phyllite from the Caledonian orogen of Ireland was performed using a high spatial resolution laser microprobe. In this sample, an older generation of biotite (Bt
1
) is aligned subparallel to a steeply dipping crenulation foliation, which itself is overprinted by a regionally developed shallow-dipping foliation. The second biotite generation (Bt
2
) occurs as randomly oriented porphyroblasts that overprint and therefore postdate both foliations. A dataset of 89 ages from a single thick section was acquired for six Bt
1
and eight Bt
2
crystals. The two biotite generations yielded two statistically distinct age distributions with Bt
1
maxima at
c
. 433 Ma and Bt
2
maxima at
c
. 417 Ma. A small number of analyses (11% Bt
1
and 26% Bt
2
) from within crystals yielded ‘main population’ ages that conflict with the dominant age populations and relative chronology established by field relationships. Discordant analyses from the earlier Bt
1
crystals are younger (than the Bt
2
population) and probably reflect intracrystalline partial resetting during a later thermal perturbation. The discordant Bt
2
analyses are predominantly older (than the Bt
2
population) and are interpreted as indicating localized excess
40
Ar. Such dis cordant analyses indicate intracrystalline variation reflecting both excess
40
Ar (Bt
2
population) and
40
Ar loss (Bt
1
population), and were therefore discarded when determining geologically meaningful ages.
Kinematics of the Høybakken detachment zone and the Møre–Trøndelag Fault Complex, central Norway
Authors: Osmundsen P.T. , Eide E.A. , Haabesland N.E. , Roberts D. , Andersen T.B. , Kendrick M. , Bingen B. , Braathen A. , Redfield T.F.
Published: February 2006

The tectonic disintegration of the Caledonian orogen through combined extension, contraction and strike-slip was characterized by spatial and temporal strain partitioning through a period of at least 30 Ma. Early to Mid-Devonian exhumation of the Central Norway basement window was associated with retrograde, top-to-the-SW extensional shearing in the Høybakken detachment zone, sinistral shearing along the Møre–Trøndelag Fault Complex, and formation of extension-parallel folds. Progressive exhumation led to increasing strain localization and to the transition from ductile to brittle deformation. In the interval between
c
. 370 and 320 Ma, the Høybakken detachment fault cut previously folded detachment mylonites, capturing mylonites in its hanging wall.
40
Ar/
39
Ar mica and K-feldspar ages indicate a Late Devonian or younger age for the uppermost parts of the adjacent ‘Old Red’ basin. Gentle folding of this stratigraphic level attests to the continuation of shortening and orogen-oblique extension into Late Devonian–Carboniferous time. Shortening was intensified along strands of the Møre–Trøndelag Fault Complex, as shown by mutually cross-cutting reverse and strike-slip faults. ‘Flower structures’ may be particularly common in constrictional strain systems where strike-slip faults develop parallel to the principal elongation trend, but normal to the principal axis of shortening.
The SNC meteorites: basaltic igneous processes on Mars
Authors: Bridges J.C. , Warren P.H.
Published: February 2006

A group of 32 meteorites, the SNC (
S
hergotty,
N
akhla,
C
hassigny) group, was derived from Mars as a product of 4–7 ejection events, probably from Tharsis and Elysium–Amazonis. The SNCs either have basaltic mineralogy or some are ultramafic cumulates crystallized from basaltic melts. The SNCs can be classified both petrographically and geochemically. We classify the shergottite SNC meteorites on the basis of their light rare earth element (LREE) depletion into highly depleted, moderately depleted and slightly depleted. The slightly depleted samples (which are mainly but not exclusively aphyric basalts) show high log
10
f
O
2
values (QFM −1.0, where QFM is quartz–fayalite–magnetite). Highly depleted samples, which are mainly olivine-phyric basalts, have low log
10
f
O
2
values (QFM −3.5). On the basis of mixing calculations between La/Lu and
87
Sr/
86
Sr we favour models linking the correlation between LREE abundances and log
10
f
O
2
to mantle heterogeneity rather than contamination by oxidized, LREE-rich crustal fluids. SNC chemistry in general reflects the Fe-rich mantle of Mars (which contains twice as much FeO as the Earth's mantle), the late accretion of chondritic material into the mantle, and possibly the presence of a plagioclase-rich magma ocean, which acted to variably deplete the mantle in Al. The high FeO contents of the SNC melts are associated with high melt densities (allowing the ponding of large magma bodies) and low viscosities, both of which are consistent with the large scale of many observed martian lava flows.
The geological evolution of Atai Mons, Venus: a volcano–corona ‘hybrid’
Authors: Grindrod P.M. , Stofan E.R. , Brian A.W. , Guest J.E.
Published: February 2006

Atai Mons, Venus, is classified as a large volcano yet displays characteristics that are typical of coronae. Coronae are widespread volcano-tectonic features that are apparently unique to Venus. Detailed analysis of Atai Mons using photogeological and geophysical techniques illustrates that it has experienced a complex history and may still be active. We show that processes found at both coronae and large volcanoes have occurred throughout the history of Atai Mons with no definite temporal preference. It does not have an evolution that can be described simply as the evolution of one feature into another. These results suggest that large volcanoes and coronae are more intimately linked than previously thought, and that detailed mapping and gravity surveys are reliable ways of establishing the evolution of hybrid features.
The specification of armourstone gradings and EN 13383 (2002)
Authors: Latham J.-P. , Van Meulen J. , Dupray S.
Published: February 2006

The grading, whether in terms of mass or size distribution of rock, is critical in the design of hydraulic civil engineering works such as breakwaters, coastal protection revetments, river training works and dam face protection. In the quarry, more effort is needed to control these rock properties than all the others. However, in practice, a poor level of understanding of relatively simple statistical concepts and the recent introduction of an elaborate specification system have contributed to many pitfalls in quality control. The acceptable size and mass ranges for consignments of rock materials are set down in the European standard for armourstone, EN 13383:2002 (
BSI 2002
). Armourstone pieces are substantially coarser than traditional aggregates and typically include large rock blocks sometimes weighing several tonnes. This standard, in force since 2004, introduced a system of standard gradings and requirements. Although similar to that promoted in
CIRIA/CUR (1991)
, a detailed explanation is long overdue. In this paper, the Rosin–Rammler equation for cumulative mass and size distributions is adopted. A purchaser or designer can then visualize from a single idealized curve, together with acceptance limits, the most reasonable expectation for a specified grading, rather than work with an envelope of acceptable grading limits. The research also draws upon actual mass distributions measured from projects dating from 1991. These are combined with theoretical data sets. The result is a new expression for what has become a contractually important ratio. The ratio is that between the mean mass as given by bulk weighing and counting, and the median mass used by designers. Non-standard grading specification is also treated, providing further background to recommended best practice as presented in the forthcoming update to the 1991 rock manual.
Impact of incretin hormones on β-cell function in subjects with normal or impaired glucose tolerance
Authors: Muscelli Elza , Mari Andrea , Natali Andrea , Astiarraga Brenno D. , Camastra Stefania , Frascerra Silvia , Holst Jens J. , Ferrannini Ele
Published: February 2006

The mechanisms by which the enteroinsular axis influences β-cell function have not been investigated in detail. We performed oral and isoglycemic intravenous (IV) glucose administration in subjects with normal (NGT; n = 11) or impaired glucose tolerance (IGT; n = 10), using C-peptide deconvolution to calculate insulin secretion rates and mathematical modeling to quantitate β-cell function. The incretin effect was taken to be the ratio of oral to IV responses. In NGT, incretin-mediated insulin release [oral glucose tolerance test (OGTT)/IV ratio = 1.59 ± 0.18, P = 0.004] amounted to 18 ± 2 nmol/m2 (32 ± 4% of oral response), and its time course matched that of total insulin secretion. The β-cell glucose sensitivity (OGTT/IV ratio = 1.52 ± 0.26, P = 0.02), rate sensitivity (response to glucose rate of change, OGTT/IV ratio = 2.22 ± 0.37, P = 0.06), and glucose-independent potentiation were markedly higher with oral than IV glucose. In IGT, β-cell glucose sensitivity (75 ± 14 vs. 156 ± 28 pmol·min−1·m−2·mM−1 of NGT, P = 0.01) and potentiation were impaired on the OGTT. The incretin effect was not significantly different from NGT in terms of plasma glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide responses, total insulin secretion, and enhancement of β-cell glucose sensitivity (OGTT/IV ratio = 1.73 ± 0.24, P = NS vs. NGT). However, the time courses of incretin-mediated insulin secretion and potentiation were altered, with a predominance of glucose-induced vs. incretin-mediated stimulation. We conclude that, under physiological circumstances, incretin-mediated stimulation of insulin secretion results from an enhancement of all dynamic aspects of β-cell function, particularly β-cell glucose sensitivity. In IGT, β-cell function is inherently impaired, whereas the incretin effect is only partially affected.
Chronic selective glycogen synthase kinase-3 inhibition enhances glucose disposal and muscle insulin action in prediabetic obese Zucker rats
Authors: Dokken Betsy B. , Henriksen Erik J.
Published: February 2006

Increasing evidence supports a negative role of glycogen synthase kinase-3 (GSK-3) in regulation of skeletal muscle glucose transport. We assessed the effects of chronic treatment of insulin-resistant, prediabetic obese Zucker ( fa/ fa) rats with a highly selective GSK-3 inhibitor (CT118637) on glucose tolerance, whole body insulin sensitivity, plasma lipids, skeletal muscle insulin signaling, and in vitro skeletal muscle glucose transport activity. Obese Zucker rats were treated with either vehicle or CT118637 (30 mg/kg body wt) twice per day for 10 days. Fasting plasma insulin and free fatty acid levels were reduced by 14 and 23% ( P < 0.05), respectively, in GSK-3 inhibitor-treated animals compared with vehicle-treated controls. The glucose response during an oral glucose tolerance test was reduced by 18% ( P < 0.05), and whole body insulin sensitivity was increased by 28% ( P < 0.05). In vivo insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (50%) and IRS-1-associated phosphatidylinositol-3′ kinase (79%) relative to fasting plasma insulin levels were significantly elevated ( P < 0.05) in plantaris muscles of GSK-3 inhibitor-treated animals. Whereas basal glucose transport in isolated soleus and epitrochlearis muscles was unaffected by chronic GSK-3 treatments, insulin stimulation of glucose transport above basal was significantly enhanced (32–60%, P < 0.05). In summary, chronic treatment of insulin-resistant, prediabetic obese Zucker rats with a specific GSK-3 inhibitor enhances oral glucose tolerance and whole body insulin sensitivity and is associated with an amelioration of dyslipidemia and an improvement in IRS-1-dependent insulin signaling in skeletal muscle. These results provide further evidence that selective targeting of GSK-3 in muscle may be an effective intervention for the treatment of obesity-associated insulin resistance.
Differential regulation of the JNK/AP-1 pathway byS-adenosylmethionine and methylthioadenosine in primary rat hepatocytes versus HuH7 hepatoma cells
Authors: Ansorena Eduardo , Berasain Carmen , Zabalza María J. López , Ávila Matías A. , García-Trevijano Elena R. , Iraburu María J.
Published: February 2006

S-adenosylmethionine (AdoMet) and 5′-methylthioadenosine (MTA) exert a protective action on apoptosis induced by okadaic acid in primary rat hepatocytes but not in human transformed HuH7 cells. In the present work, we analyzed the role played by the JNK/activator protein (AP)-1 pathway in this differential effect. Okadaic acid induced the phosphorylation of JNK and c-Jun and the binding activity of AP-1 in primary hepatocytes, and pretreatment with either AdoMet or MTA prevented those effects. In HuH7 cells, pretreatment with either AdoMet or MTA did not affect JNK and c-Jun activation or AP-1 binding induced by okadaic acid. In both cell types, p38 was activated by okadaic acid, but neither AdoMet nor MTA presented a significant effect on its activity. Therefore, the differential effect of both AdoMet and MTA on the JNK/AP-1 pathway could explain their antiapoptotic effect on primary hepatocytes and the lack of protection they show against okadaic acid-induced apoptosis in hepatoma cells.
Short-chain fatty acid mediated phosphorylation of heat shock protein 25: effects on camptothecin-induced apoptosis
Authors: Parhar Kuljit , Baer Kathy A. , Parker Kristy , Ropeleski Mark J.
Published: February 2006

Although short-chain fatty acid (SCFA)-induced heat shock protein 25 (Hsp25) is associated with increased cellular resistance to injury, withdrawal of lumenal butyrate in vivo is associated with intestinal epithelial injury and apoptosis. Recognizing that SCFA-dependent posttranslational modification of Hsp25 may involve altered Hsp25 phosphorylation, we hypothesized that butyrate regulates Hsp25 phosphorylation and secondarily affects cellular responses to apoptosis-inducing agents. Intestinal epithelial crypt IEC-18 cells were treated with butyrate, propionate, or the histone deacetylase inhibitor trichostatin A for 6–24 h. Immunolocalization of Hsp25 was examined by confocal laser microscopy. Hsp25 phosphorylation was characterized using two-dimensional isoelectric focusing gel electrophoresis. Hsp25 accumulation in cytoskeletal- and mitochondrial-enriched fractions was examined by immunoblotting. The activation of p38 MAP kinase was determined using phospho-specific antibodies and MAPKAPK 2 kinase assays. The effects of SCFA on apoptosis were studied by ELISA detection of cleaved DNA and using antibodies recognizing cleaved caspase-3. Five-millimolar butyrate induced no significant injury to IEC-18 cells. Hsp25 did not accumulate in Triton X-100-insoluble cytoskeletal fractions with butyrate treatment but did localize to mitochondria in a p38 MAP kinase-dependent manner. Hsp25 phosphorylation was induced by butyrate, propionate, and trichostatin A. Butyrate-mediated changes in Hsp25 phosphorylation coincide with the activation of the p38 MAP kinase and MAPKAPK 2. Butyrate, propionate, and low-dose trichostatin A confer significant protection from camptothecin-induced apoptosis, which was not reversed by the p38 inhibitor SB203580. We conclude that butyrate-mediated phosphorylation of Hsp25 is associated with significant resistance to apoptosis, which appears to be independent of p38-mediated targeting of Hsp25 to mitochondria.
Molecular mechanism of tumor necrosis factor-α modulation of intestinal epithelial tight junction barrier
Authors: Ye Dongmei , Ma Iris , Ma Thomas Y.
Published: February 2006

A TNF-α-induced increase in intestinal epithelial tight junction (TJ) permeability has been proposed to be an important proinflammatory mechanism contributing to intestinal inflammation in Crohn's disease and other inflammatory conditions. Previous studies from our laboratory suggested that the TNF-α-induced increase in intestinal TJ permeability was mediated by an increase in myosin light chain kinase (MLCK) protein expression. However, the molecular mechanisms that mediate the TNF-α increase in intestinal TJ permeability and MLCK protein expression remain unknown. The purpose of this study was to delineate the intracellular and molecular mechanisms that mediate the TNF-α-induced increase in intestinal TJ permeability; using an in vitro intestinal epithelial model system consisting of filter-grown Caco-2 intestinal epithelial monolayers. To examine the molecular mechanisms involved in the TNF-α regulation of intestinal TJ barrier, we identified and cloned for the first time a functionally active MLCK promoter region. TNF-α treatment of filter-grown Caco-2 monolayers transfected with plasmid vector containing the MLCK promoter region produced an increase in MLCK promoter activity and MLCK transcription. The TNF-α-induced increase in MLCK transcription corresponded to a sequential increase in MLCK protein expression, MLCK activity, and Caco-2 TJ permeability. The TNF-α-induced increase in MLCK promoter activity was mediated by NF-κB activation, and the inhibition of NF-κB activation prevented the TNF-α-induced increase in promoter activity and the subsequent increase in MLCK protein expression and Caco-2 TJ permeability. The TNF-α-induced activation of MLCK promoter was mediated by binding of the activated NF-κB p50/p65 dimer to the downstream κB binding site (−84 to −75) on the MLCK promoter region; deletion of the κB binding site prevented the TNF-α increase in promoter activity. Additionally, siRNA silencing of NF-κB p65 also prevented the TNF-α increase in MLCK promoter activity. In conclusion, our findings indicated that the TNF-α-induced increase in intestinal epithelial TJ permeability was mediated by NF-κB p50/p65 binding and activation of the MLCK promoter. NF-κB p50/p65 activation of the MLCK promoter then leads to a stepwise increase in MLCK transcription, expression and activity, and MLCK-mediated opening of the intestinal TJ barrier.
Effect of aging on bolus kinematics during the pharyngeal phase of swallowing
Authors: Bardan Eytan , Kern Mark , Arndorfer Ronald C. , Hofmann Candy , Shaker Reza
Published: February 2006

Swallowing difficulty is a common complaint in the elderly and, although there are data for the biomechanics of liquid swallows, little is known about solid bolus motion, or kinematics, in the elderly. The aims of this study were as follows: 1) to characterize and compare solid and liquid bolus kinematics in the elderly and compare the findings with those in young subjects and 2) to correlate bolus kinematics and dynamics. Concurrent manometric-fluoroscopic techniques were used to study eight young and eight elderly subjects. The subjects performed four swallows each of 0.2-cm-diameter solid barium pellets and 5 ml of liquid barium during sagittal fluoroscopy and six-channel pharyngoesophageal manometry. Images were digitized for analysis of kinematic properties such as velocity and acceleration. Dynamic pressures were recorded and coordinated with kinematic events. Image analysis showed that velocity varied as the pellet passed through the hypopharynx, pharynx, and upper esophageal sphincter. In young subjects, pellet kinematics were characterized by two zones of pellet acceleration: one over the tongue base and another as the pellet passed through the upper esophageal sphincter. Although the elderly showed a similar zone of acceleration over the base of the tongue, the second zone of pellet acceleration was not seen. Decreasing pressure gradients immediately distal to the position of the solid pellet and liquid bolus characterized dynamics for all subjects. This decreasing pressure gradient was significantly larger in elderly than in young subjects. Bolus kinematics and dynamics were significantly altered among elderly compared with young subjects. Among these differences were the absence of hypopharyngeal bolus acceleration and a significant increase in the transsphincteric pressure gradient in the elderly.
Angiotensin II type 1 receptors and the intestinal microvascular dysfunction induced by ischemia and reperfusion
Authors: Petnehazy Thomas , Cooper Dianne , Stokes Karen Y. , Russell Janice , Wood Katherine C. , Granger D. Neil
Published: February 2006

The acute phase of intestinal ischemia-reperfusion (I/R) injury is mediated by leukocytes and is characterized by oxidative stress and blood cell recruitment. Upregulation of angiotensin II type 1 receptors (AT1-R) has been implicated in the pathogenesis of conditions associated with oxidative stress. The AT1-R-antagonist Losartan (Los) attenuates leukocyte recruitment following I/R. However, the role of AT1-R in intestinal I/R injury and the associated platelet-leukocyte interactions remains unclear. The objective of this study was to define the contribution of AT1-R to I/R-induced blood cell recruitment in intestinal venules. Leukocyte and platelet adhesion were quantified by intravital microscopy in the small bowel of C57Bl/6 [wild-type (WT)] mice exposed to sham operation or 45 min of ischemia and 4 h of reperfusion. A separate WT group received Los for 7 days before gut I/R (WT-I/R + Los). AT1-R bone marrow chimeras that express AT1-R on the vessel wall but not blood cells also underwent I/R. Platelet and leukocyte adhesion as well as AT1-R expression in the gut microvasculature were significantly elevated after I/R. All of these responses were attenuated in the WT-I/R + Los group, compared with untreated I/R mice. A comparable abrogation of I/R-induced blood cell adhesion was noted in AT1-R bone marrow chimeras. I/R-induced platelet adhesion was unaltered in mice overexpressing Cu,Zn-SOD or mice deficient in NAD(P)H oxidase. These data suggest that although gut I/R upregulates endothelial expression of AT1-R, engagement of these angiotensin II receptors on blood cells is more important in eliciting the prothrombogenic and proinflammatory state observed in postischemic gut venules, through a superoxide-independent pathway.
Improvement of pulmonary hypoplasia associated with congenital diaphragmatic hernia by in utero CFTR gene therapy
Authors: Larson Janet E. , Cohen J. Craig
Published: February 2006

Congenital diaphragmatic hernia (CDH) may be an ideal candidate disease for in utero gene therapy as disrupted fetal lung growth plays a significant role in disease outcome. We previously demonstrated that transient in utero overexpression of CFTR during fetal development resulted in lung epithelial proliferation and differentiation. We hypothesized that gene therapy with CFTR would improve the pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH). CDH was induced by the herbicide 2,4-dichlorophenyl-4-nitrophyl ether (nitrofen) following maternal ingestion at either 10 or 13 days gestation. In utero gene transfer of the CFTR gene was subsequently performed at 16 days gestation. Examination of the fetuses at 22 days gestation revealed little improvement in the CFTR-treated lungs following induction of hernias with nitrofen at 10 days gestation. However, the CFTR gene treatment significantly improved internal surface area, saccular density, overall saccular number, and amount of saccular air space in the lungs that were treated with nitrofen at 13 days gestation. RT-PCR demonstrated that gene transfer occurred following treatment at 13 days gestation but not in the lungs treated with nitrofen at 10 days gestation, despite gene transfer at the same gestational age (16 days) in both groups. As disruption of lung development correlates with the gestational stage at which nitrofen exposure occurs, these results confirmed previous findings that in utero gene transfer efficiency depends on the stage of lung development. Lung development may be significantly delayed in human CDH to allow for successful gene transfer later in gestation, providing a substantial therapeutic window.
Androgens augment renal vascular responses to ANG II in New Zealand genetically hypertensive rats
Authors: Song Jin , Kost Curtis K. , Martin Douglas S.
Published: February 2006

Males develop higher blood pressure than do females. This study tested the hypothesis that androgens enhance responsiveness to ANG II during the development of hypertension in New Zealand genetically hypertensive (NZGH) rats. Male NZGH rats were obtained at 5 wk of age and subjected to sham operation (Sham) or castration (Cas) then studied at three age groups: 6–7, 11–12, and 16–17 wk. Mean arterial blood pressure (MAP), heart rate (HR), and renal blood flow (RBF) measurements were recorded under Inactin anesthesia. These variables were measured after enalapril (1 mg/kg) treatment and during intravenous ANG II infusion (20, 40, and 80 ng/kg/min). Plasma testosterone was measured by ELISA. Angiotensin type 1 (AT1) receptor expression was assessed by Western blot analysis and RT-PCR. ANG II-induced MAP responses were significantly attenuated in Cas NZGH rats. At the highest ANG II dose, MAP increased by 40 ± 4% in Sham vs. 22 ± 1% in Cas NZGH rats of 16–17 wk of age. Similarly, renal vascular resistance (RVR) responses to ANG II were reduced by castration (209 ± 20% in Sham vs. 168 ± 10% in Cas NZGH rats at 16–17 wk of age). Castration also reduced MAP recorded in conscious NZGH rats of this age group. Testosterone replacement restored baseline MAP and the pressor and RVR responses to ANG II. Castration reduced testosterone concentrations markedly. Testosterone treatment restored these concentrations. Neither castration nor castration+testosterone treatment affected AT1 receptor mRNA or protein expression. Collectively, these data suggest that androgens modulate renal and systemic vascular responsiveness to ANG II, which may contribute to androgen-induced facilitation of NZGH rat hypertension.
A novel approach to assess insulin sensitivity reveals no increased insulin sensitivity in mice with a dominant-negative mutant hepatocyte nuclear factor-1α
Authors: Ahrén B. , Pacini G.
Published: February 2006

In phenotype experiments in mice, determination of dynamic insulin sensitivity often uses the insulin tolerance test. However, the interpretation of this test is complicated by the counterregulation occurring at low glucose. To overcome this problem, we determined the dynamic insulin sensitivity after inhibition of endogenous insulin secretion by diazoxide (25 mg/kg) in association with intravenous administration of glucose plus insulin (the DSGIT technique). Estimation of insulin sensitivity index (SI) by this technique showed good correlation to SI from a regular intravenous glucose tolerance test ( r = 0.87; P < 0.001; n = 15). With DSGIT, we evaluated dynamic insulin sensitivity in mice with a rat insulin promoter (β-cell-targeted) dominant-negative mutation of hepatic nuclear factor (HNF)-1α [RIP-DN HNF-1α (Tg) mice]. When insulin was administered exogenously at the same dose in Tg and wild-type (WT) mice, plasma insulin levels were higher in WT, indicating an increased insulin clearance in Tg mice. When the diazoxide test was used, different doses of insulin were therefore administered (0.1 and 0.15 U/kg in WT and 0.2 and 0.25 U/kg in Tg) to achieve similar insulin levels in the groups. Minimal model analysis showed that SI was the same in the two groups (0.78 ± 0.21 × 10−4 min·pmol−1·l−1 in WT vs. 0.60 ± 0.11 in Tg; P = 0.45) as was the glucose elimination rate ( P = 0.27). We conclude that 1) the DSGIT technique determines the in vivo dynamic insulin action in mice, 2) insulin clearance is increased in Tg mice, and 3) chronic islet dysfunction in RIP-DN HNF-1α mice is not compensated with increased insulin sensitivity.
Effects of prenatal ethanol exposure and sex on the arginine vasopressin response to hemorrhage in the rat
Authors: Bird Danielle N. , Sato Aileen K. , Knee Daniel S. , Uyehara Catherine F. T. , Person Donald A. , Claybaugh John R.
Published: February 2006

AVP synthesis, storage, and osmotically stimulated release are reduced in young adult rats exposed prenatally to ethanol (PE). Whether the reduced release of AVP to the osmotic stimulus is due to impairment of the vasopressin system or specifically to an osmoreceptor-mediated release is not known. The present experiments were done, therefore, to determine whether a hemorrhage-induced AVP response would also be diminished in PE-exposed rats. Pregnant rats were fed either a control liquid diet [no prenatal ethanol (NPE)] or a liquid diet with 35% of the calories from ethanol from days 7– 21 of pregnancy. Offspring were weaned at 3 wk of life. At 11 wk of age, femoral arterial catheters were surgically placed, and blood volumes were determined at 12 wk. Three days later, two hemorrhages of 10% of the blood volume were performed with samples taken before and 10 min after the hemorrhages. After a 20% blood loss, plasma AVP was 19% higher in NPE rats than in the PE rats despite no differences in mean arterial blood pressure (MABP). Also, hypothalamic AVP mRNA and pituitary AVP content were reduced in PE rats. Furthermore, confirming an earlier report of sex differences in AVP release, the hemorrhage-induced hormone response was twofold greater in female rats than male rats, regardless of previous ethanol exposure. These studies demonstrate that the AVP response to hemorrhage is reduced in PE rats independently of differences in MABP. The data are compatible with a theory of a reduced number of hemorrhage-responsive vasopressinergic neurons capable of stimulated AVP release in PE rats.
Internuclear coupling of hypothalamic magnocellular nuclei by glutamate synaptic circuits
Authors: Boudaba Cherif , Tasker Jeffrey G.
Published: February 2006

Magnocellular neurons of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) display bursting activity that is synchronized under certain conditions. They receive excitatory synaptic inputs from intrahypothalamic glutamate circuits, some of which are activated by norepinephrine. Ascending noradrenergic afferents and intrahypothalamic glutamate circuits may be responsible for the generation of synchronous bursting among oxytocin neurons and/or asynchronous bursting among vasopressin neurons located in the bilateral supraoptic and paraventricular nuclei. Here, we tested whether magnocellular neurons of the PVN receive excitatory synaptic input from the contralateral PVN and the region of the retrochiasmatic SON (SONrx) via norepinephrine-sensitive internuclear glutamate circuits. Whole cell patch-clamp recordings were performed in PVN magnocellular neurons in coronal hypothalamic slices from male rats, and the ipsilateral SONrx region and contralateral PVN were stimulated using electrical and chemical stimulation. Electrical and glutamate microdrop stimulation of the ipsilateral SONrx region or contralateral PVN elicited excitatory postsynaptic potentials/currents (EPSP/Cs) in PVN magnocellular neurons mediated by glutamate release, revealing internuclear glutamatergic circuits. Microdrop application of norepinephrine also elicited EPSP/Cs, suggesting that these circuits could be activated by activation of noradrenergic receptors. Repetitive electrical stimulation and drop application of norepinephrine, in some cases, elicited bursts of action potentials. Our data reveal glutamatergic synaptic circuits that interconnect the magnocellular nuclei and that can be activated by norepinephrine. These internuclear glutamatergic circuits may provide the functional architecture to support burst generation and/or burst synchronization in hypothalamic magnocellular neurons under conditions of activation.
Hypothermia-enhanced splenic cytokine gene expression is independent of the sympathetic nervous system
Authors: Ganta Chanran K. , Helwig Bryan G. , Blecha Frank , Ganta Roman R. , Cober Richard , Parimi Sujatha , Musch Timothy I. , Fels Richard J. , Kenney Michael J.
Published: February 2006

Splenic nerve denervation abrogates enhanced splenic cytokine gene expression responses to acute heating, demonstrating that hyperthermia-induced activation of splenic sympathetic nerve discharge (SND) increases splenic cytokine gene expression. Hypothermia alters SND responses; however, the role of the sympathetic nervous system in mediating splenic cytokine gene expression responses to hypothermia is not known. The purpose of the present study was to determine the effect of hypothermia on the relationship between the sympathetic nervous system and splenic cytokine gene expression in anesthetized F344 rats. Gene expression analysis was performed using a microarray containing 112 genes, representing inflammatory cytokines, chemokines, cytokine/chemokine receptors and housekeeping genes. A subset of differentially expressed genes was verified by real-time RT-PCR analysis. Splenic SND was decreased significantly during cooling (core temperature decreased from 38 to 30°C) in splenic-intact rats but remained unchanged in sham-cooled splenic-intact rats (core temperature maintained at 38°C). Hypothermia upregulated the transcripts of several genes, including, chemokine ligands CCL2, CXCL2, CXCL10, and CCL20, and interleukins IL-1α, IL-1β, and IL-6. Gene expression responses to hypothermia were similar for the majority of cytokine genes in splenic-intact and splenic-denervated rats. These results suggest that hypothermia-enhanced splenic cytokine gene expression is independent of splenic SND.
Differences in the time course of proximal and distal airway response to inhaled histamine studied by synchrotron radiation CT
Authors: Bayat Sam , Porra Liisa , Suhonen Heikki , Nemoz Christian , Suortti Pekka , Sovijärvi Anssi R. A.
Published: February 2006

We studied the kinetics of proximal and distal bronchial response to histamine aerosol in healthy anesthetized and mechanically ventilated rabbits up to 60 min after histamine administration using a novel xenon-enhanced synchrotron radiation computed tomography imaging technique. Individual proximal airway constriction was assessed by measuring the luminal cross-sectional area. Distal airway obstruction was estimated by measuring the ventilated alveolar area after inhaled xenon administration. Respiratory system conductance was assessed continuously. Proximal airway cross-sectional area decreased by 57% of the baseline value by 20 min and recovered gradually but incompletely within 60 min. The ventilated alveolar area decreased immediately after histamine inhalation by 55% of baseline value and recovered rapidly thereafter. The results indicate that the airway reaction to inhaled histamine and the subsequent recovery are significantly slower in proximal than in distal bronchi in healthy rabbit. The findings suggest that physiological reaction mechanisms to inhaled histamine in the airway walls of large and small bronchi are not similar.
Acclimatory-phase specificity of gene expression during the course of heat acclimation and superimposed hypohydration in the rat hypothalamus
Authors: Schwimmer Hagit , Eli-Berchoer Luba , Horowitz Michal
Published: February 2006

The induction of the heat-acclimated phenotype involves reprogramming the expression of genes encoding both constitutive and inducible proteins. In this investigation, we studied the global genomic response in the hypothalamus during heat acclimation, with and without combined hypohydration stress. Rats were acclimated for 2 days (STHA) or for 30 days (LTHA) at 34°C. Hypohydration (10% decrease in body weight) was attained by water deprivation. 32P-labeled RNA samples from the hypothalamus were hybridized onto cDNA Atlas array (Clontech no. 1.2) membranes. Clustering and functional analyses of the expression profile of a battery of genes representing various central regulatory functions of body homeostasis demonstrated a biphasic acclimation profile with a transient upregulation of genes encoding ion channels, transporters, and transmitter signaling upon STHA. After LTHA, most genes returned to their preacclimation expression levels. In both STHA and LTHA, genes encoding hormones and neuropeptides, linked with metabolic rate and food intake, were downregulated. This genomic profile, demonstrating an enhanced transcription of genes linked with neuronal excitability during STHA and enhanced metabolic efficiency upon LTHA, is consistent with our previously established integrative acclimation model. The response to hypohydration was characterized by an upregulation of a large number of genes primarily associated with the regulation of ion channels, cell volume, and neuronal excitability. During STHA, the response was transiently desensitized, recovering upon LTHA. We conclude that hypohydration overrides the heat acclimatory status. It is notable that STHA and hypohydration gene profiles are analogous with the physiological profile described in the response to various types of brain injury.
Effect of short-term sprint interval training on human skeletal muscle carbohydrate metabolism during exercise and time-trial performance
Authors: Burgomaster Kirsten A. , Heigenhauser George J. F. , Gibala Martin J.
Published: February 2006

Our laboratory recently showed that six sessions of sprint interval training (SIT) over 2 wk increased muscle oxidative potential and cycle endurance capacity (Burgomaster KA, Hughes SC, Heigenhauser GJF, Bradwell SN, and Gibala MJ. J Appl Physiol 98: 1895–1900, 2005). The present study tested the hypothesis that short-term SIT would reduce skeletal muscle glycogenolysis and lactate accumulation during exercise and increase the capacity for pyruvate oxidation via pyruvate dehydrogenase (PDH). Eight men [peak oxygen uptake (V̇o2 peak) = 3.8 ± 0.2 l/min] performed six sessions of SIT (4–7 × 30-s “all-out” cycling with 4 min of recovery) over 2 wk. Before and after SIT, biopsies (vastus lateralis) were obtained at rest and after each stage of a two-stage cycling test that consisted of 10 min at ∼60% followed by 10 min at ∼90% of V̇o2 peak. Subjects also performed a 250-kJ time trial (TT) before and after SIT to assess changes in cycling performance. SIT increased muscle glycogen content by ∼50% (main effect, P = 0.04) and the maximal activity of citrate synthase (posttraining: 7.8 ± 0.4 vs. pretraining: 7.0 ± 0.4 mol·kg protein −1·h−1; P = 0.04), but the maximal activity of 3-hydroxyacyl-CoA dehydrogenase was unchanged (posttraining: 5.1 ± 0.7 vs. pretraining: 4.9 ± 0.6 mol·kg protein −1·h−1; P = 0.76). The active form of PDH was higher after training (main effect, P = 0.04), and net muscle glycogenolysis (posttraining: 100 ± 16 vs. pretraining: 139 ± 11 mmol/kg dry wt; P = 0.03) and lactate accumulation (posttraining: 55 ± 2 vs. pretraining: 63 ± 1 mmol/kg dry wt; P = 0.03) during exercise were reduced. TT performance improved by 9.6% after training (posttraining: 15.5 ± 0.5 vs. pretraining: 17.2 ± 1.0 min; P = 0.006), and a control group ( n = 8, V̇o2 peak = 3.9 ± 0.2 l/min) showed no change in performance when tested 2 wk apart without SIT (posttraining: 18.8 ± 1.2 vs. pretraining: 18.9 ± 1.2 min; P = 0.74). We conclude that short-term SIT improved cycling TT performance and resulted in a closer matching of glycogenolytic flux and pyruvate oxidation during submaximal exercise.