bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive sparse representations of ultrasonic signals for acoustic microimaging
Authors: Zhang Guang-Ming , Harvey David M. , Braden Derek R.
Published: August 2006

Acoustic microimaging (AMI) is a common nondestructive tool for failure analysis of microelectronic packages. Accurate estimation of the reflected ultrasonic echoes is essential for detection and location of defects inside the microelectronic packages. In this paper, an advanced AMI technique based on adaptive sparse representations is proposed to estimate the ultrasonic echoes and recover the reflectivity function. An adapted overcomplete dictionary capable of concise expression of ultrasonic signals is first learned by the focal underdetermined system solver-based column normalized dictionary learning algorithm. The ultrasonic A-scans generated by an AMI system are then decomposed into adaptive sparse representations over the learned dictionary using a sparse basis selection algorithm. Echo selection and echo estimation are further performed from the resulting adaptive sparse representations. The proposed technique offers a solution to the blind source separation problem for restoration of the reflectivity function and can separate closely spaced overlapping echoes beyond the resolution of the AMI system. Experimental verifications are carried out using both synthetic and measured data. The results show the proposed technique produces high resolution and accurate estimates for ultrasonic echoes.
Effects of level and frequency on the audibility of partials in inharmonic complex tones
Authors: Moore Brian C. J. , Glasberg Brian R. , Low Kai En , Cope Thomas , Cope Wei
Published: August 2006

The effect of level and frequency on the audibility of partials was measured for complex tones with partials uniformly spaced on an equivalent rectangular bandwidth (ERBN) number scale. On each trial, subjects heard a sinusoidal “probe” followed by a complex tone. The probe was mistuned downwards or upwards (at random) by 4.5% from the frequency of one randomly selected partial in the complex. The subject indicated whether the probe was higher or lower in frequency than the nearest partial in the complex. The frequencies were roved from trial to trial, keeping frequency ratios fixed. In experiment 1, the level per partial, L, was 40 or 70dB SPL and the mean frequency of the central partial, fc, was 1201Hz. Scores for the highest and lowest partials in the complexes were generally high for all spacings. Scores for the inner partials were close to chance at 0.75-ERBN spacing, and improved as the spacing was increased up to 2 ERBN. For intermediate spacings, performance was better for the lower level used. In experiment 2, L was 70dB SPL and fc was 3544Hz. Performance worsened markedly for partial frequencies above 3544Hz, consistent with a role of phase locking.
Adaptive control of vowel formant frequency: Evidence from real-time formant manipulation
Authors: Purcell David W. , Munhall Kevin G.
Published: August 2006

Auditory feedback during speech production is known to play a role in speech sound acquisition and is also important for the maintenance of accurate articulation. In two studies the first formant (F1) of monosyllabic consonant-vowel-consonant words (CVCs) was shifted electronically and fed back to the participant very quickly so that participants perceived the modified speech as their own productions. When feedback was shifted up (experiment 1 and 2) or down (experiment 1) participants compensated by producing F1 in the opposite frequency direction from baseline. The threshold size of manipulation that initiated a compensation in F1 was usually greater than 60Hz. When normal feedback was returned, F1 did not return immediately to baseline but showed an exponential deadaptation pattern. Experiment 1 showed that this effect was not influenced by the direction of the F1 shift, with both raising and lowering of F1 exhibiting the same effects. Experiment 2 showed that manipulating the number of trials that F1 was held at the maximum shift in frequency (0, 15, 45 trials) did not influence the recovery from adaptation. There was a correlation between the lag-one autocorrelation of trial-to-trial changes in F1 in the baseline recordings and the magnitude of compensation. Some participants therefore appeared to more actively stabilize their productions from trial-to-trial. The results provide insight into the perceptual control of speech and the representations that govern sensorimotor coordination.
The Opi1p Transcription Factor Affects Expression of
FLO11
, Mat Formation, and Invasive Growth in
Saccharomyces cerevisiae
Authors: Reynolds Todd B.
Published: August 2006

Mat formation in the bakers' yeast
Saccharomyces cerevisiae
is a surface-associated phenomenon in which yeast cells spread over the surface of a low-density agar petri plate as a complex film. This spreading growth occurs by sliding motility and is dependent on the adhesion protein (adhesin) Flo11p. In order to identify molecular pathways that govern mat formation, whole-genome transcriptional profiling was used to compare cells growing as a mat to cells growing in a suspension culture (planktonic cells). This analysis revealed that
S. cerevisiae
upregulates a subset of genes in response to growth on a surface. These genes included the
INO1
gene, which encodes the
myo
-inositol-1-phosphate synthase, which carries out the rate-limiting step in inositol biosynthesis. Further inquiry revealed that a transcription factor that controls
INO1
expression, called Opi1p, participates in the regulation of mat formation. Opi1p appears to modulate mat formation by influencing the expression of
FLO11
. The
opi1Δ
mutant was found to exhibit reduced
FLO11
levels. Consequently, the
opi1Δ
mutant perturbs the
FLO11
-dependent phenotype of invasive growth. The
opi1Δ
mutant's defects in mat formation and invasive growth are dependent on the transcriptional activator Ino2p. These results indicate that Opi1p affects mat formation and invasive growth by participating in the regulation of
FLO11
.
Trypanosoma congolense
Procyclins: Unmasking Cryptic Major Surface Glycoproteins in Procyclic Forms
Authors: Utz Silvia , Roditi Isabel , Kunz Renggli Christina , Almeida Igor C. , Acosta-Serrano Alvaro , Bütikofer Peter
Published: August 2006

In the tsetse fly, the protozoan parasite
Trypanosoma congolense
is covered by a dense layer of glycosylphosphatidylinositol (GPI)-anchored molecules. These include a protease-resistant surface molecule (PRS), which is expressed by procyclic forms early in infection, and a glutamic acid- and alanine-rich protein (GARP), which appears at later stages. Since neither of these surface antigens is expressed at intermediate stages, we investigated whether a GPI-anchored protein of 50 to 58 kDa, previously detected in procyclic culture forms, might constitute the coat of these parasites. We therefore partially purified the protein from
T. congolense
Kilifi procyclic forms, obtained an N-terminal amino acid sequence, and identified its gene. Detailed analyses showed that the mature protein consists almost exclusively of 13 heptapeptide repeats (EPGENGT). The protein is densely N glycosylated, with up to 13 high-mannose oligosaccharides ranging from Man
5
GlcNAc
2
to Man
9
GlcNAc
2
linked to the peptide repeats. The lipid moiety of the glycosylphosphatidylinositol is composed of
sn
-1-stearoyl-2-
lyso
-glycerol-3-HPO
4
-1-(2-
O
-acyl)-
d
-
myo
-inositol. Heavily glycosylated proteins with similar repeats were subsequently identified in
T. congolense
Savannah procyclic forms. Collectively, this group of proteins was named
T. congolense
procyclins to reflect their relationship to the EP and GPEET procyclins of
T. brucei
. Using an antiserum raised against the EPGENGT repeat, we show that
T. congolense
procyclins are expressed continuously in the fly midgut and thus form the surface coat of cells that are negative for both PRS and GARP.
Membrane Topology and Transient Acylation ofToxoplasma gondiiGlycosylphosphatidylinositols
Authors: Kimmel Jürgen , Smith Terry K. , Azzouz Nahid , Gerold Peter , Seeber Frank , Lingelbach Klaus , Dubremetz Jean-François , Schwarz Ralph T.
Published: August 2006

Using hypotonically permeabilizedToxoplasma gondiitachyzoites, we investigated the topology of the free glycosylphosphatidylinositols (GPIs) within the endoplasmic reticulum (ER) membrane. The morphology and permeability of parasites were checked by electron microscopy and release of a cytosolic protein. The membrane integrity of organelles (ER and rhoptries) was checked by protease protection assays. In initial experiments, GPI biosynthetic intermediates were labeled with UDP-[6-3H]GlcNAc in permeabilized parasites, and the transmembrane distribution of the radiolabeled lipids was probed with phosphatidylinositol-specific phospholipase C (PI-PLC). A new early intermediate with an acyl modification on the inositol was identified, indicating that inositol acylation also occurs inT. gondii. A significant portion of the early GPI intermediates (GlcN-PI and GlcNAc-PI) could be hydrolyzed following PI-PLC treatment, indicating that these glycolipids are predominantly present in the cytoplasmic leaflet of the ER. PermeabilizedT. gondiiparasites labeled with either GDP-[2-3H]mannose or UDP-[6-3H]glucose showed that the more mannosylated and side chain (Glc-GalNAc)-modified GPI intermediates are also preferentially localized in the cytoplasmic leaflet of the ER.
GPR-4 Is a Predicted G-Protein-Coupled Receptor Required for Carbon Source-Dependent Asexual Growth and Development inNeurospora crassa
Authors: Li Liande , Borkovich Katherine A.
Published: August 2006

The filamentous fungusNeurospora crassais able to utilize a wide variety of carbon sources. Here, we examine the involvement of a predicted G-protein-coupled receptor (GPCR), GPR-4, during growth and development in the presence of different carbon sources inN. crassa. Δgpr-4mutants have reduced mass accumulation compared to the wild type when cultured on high levels of glycerol, mannitol, or arabinose. The defect is most severe on glycerol and is cell density dependent. The genetic and physical relationship between GPR-4 and the threeN. crassaGα subunits (GNA-1, GNA-2, and GNA-3) was explored. All three Gα mutants are defective in mass accumulation when cultured on glycerol. However, the phenotypes of Δgna-1and Δgpr-4Δgna-1mutants are identical, introduction of a constitutively activatedgna-1allele suppresses the defects of the Δgpr-4mutation, and the carboxy terminus of GPR-4 interacts most strongly with GNA-1 in the yeast two-hybrid assay. Although steady-state cyclic AMP (cAMP) levels are normal in Δgpr-4strains, exogenous cAMP partially remediates the dry mass defects of Δgpr-4mutants on glycerol medium and Δgpr-4strains lack the transient increase in cAMP levels observed in the wild type after addition of glucose to glycerol-grown liquid cultures. Our results support the hypothesis that GPR-4 is coupled to GNA-1 in a cAMP signaling pathway that regulates the response to carbon source inN. crassa. GPR-4-related GPCRs are present in the genomes of several filamentous ascomycete fungal pathogens, raising the possibility that a similar pathway regulates carbon sensing in these organisms.
Postconditioning fails to prevent radial artery endothelial dysfunction induced by ischemia and reperfusion: evidence from a human in vivo study
Authors: Dragoni Saverio , Di Stolfo Giuseppe , Sicuro Silvia , Lisi Monica , Parker John D. , Forconi Sandro , Gori Tommaso
Published: August 2006

Animal studies have shown that, as compared with unrestricted reperfusion, exposure to brief periods of controlled ischemia (postconditioning) at the end of a prolonged ischemia reduces the extent of tissue damage. We set out to test whether postconditioning can prevent endothelial dysfunction induced by ischemia and reperfusion in a human in vivo model. Ten healthy young non-smoking volunteers were enrolled in this cross-over, controlled, investigator-blinded study. Subjects were exposed to 15 min of forearm ischemia followed by either unrestricted reperfusion or postconditioning (3 periods of 20 s of ischemia separated by 10 s of reperfusion). Endothelium-dependent flow-mediated dilation (FMD) was measured at the level of the radial artery before and after ischemia (with or without postconditioning). Forearm ischemia blunted FMD in both study visits (unrestricted reperfusion visit: before ischemia, 7.7% ± 1.3%; after ischemia, 2.5% ± 1.4%; and postconditioning visit: before, 7.3% ± 1.2%; after, 2.6 ± 1.6%; P < 0.05 for both, P = not significant (NS) between visits). In contrast with data from animal studies, postconditioning (20 s ischemia – 10 s reperfusion repeated 3 times) does not limit post-ischemic endothelial dysfunction in this human in vivo model. Further human studies are necessary to evaluate other reperfusion protocols in an attempt to limit post-ischemic tissue damage.
Inhibitory effects of astragaloside IV on diabetic peripheral neuropathy in rats
Authors: Yu Junxian , Zhang Yindi , Sun Shi , Shen Jianping , Qiu Jun , Yin Xiaoxing , Yin Honglin , Jiang Shaojun
Published: August 2006

Astragaloside IV (AGS-IV), a new glycoside of cycloartane-type triterpene isolated from the root of Astragalus membranaceus (Fisch.) Bunge, has been used experimentally for its potent immune-stimulating, anti-inflammatory, and antioxidative actions. A recent study has shown AGS-IV to be an aldose-reductase inhibitor and a free-radical scavenger. This study examined the effects of AGS-IV on motor nerve conduction velocity (MNCV), tailflick threshold temperature, biochemical indexes, and the histology of the sural nerve after diabetes was induced in rats with 75 mg/kg streptozotocin (STZ). AGS-IV (3, 6, 12 mg/kg, twice a day) was administered by oral gavage for 12 weeks after diabetes was induced. Compared with control (nondiabetic) rats, obvious changes in physiological behaviors and a significant reduction in sciatic MNCV in diabetic rats were observed after 12 weeks of STZ administration. Morphological analysis showed that AGS-IV suppressed a decrease in myelinated fiber area, an increase in myelinated fiber density, and an increase in segmental demyelination in diabetic rats. The protective mechanism of AGS-IV involved a decrease in declining blood glucose concentration and HbA1C levels, and an increase in plasma insulin levels. AGS-IV increased the activity of glutathione peroxidase in nerves, depressed the activation of aldose reductase in erythrocytes, and decreased the accumulation of advanced glycation end products in both nerves and erythrocytes. Moreover, AGS-IV elevated Na+,K+-ATPase activity in both the nerves and erythrocytes of diabetic rats. These results indicate that AGS-IV exerts protective effects against the progression of peripheral neuropathy in STZ-induced diabetes in rats through several interrelated mechanisms.
Effect of AT2 blockade on cardiac hypertrophy as induced by high dietary salt in the proatrial natriuretic peptide (ANP) gene-disrupted mouse
Authors: Angelis Ekaterini , Tse M. Yat , Adams Michael A. , Pang Stephen C.
Published: August 2006

The role of the angiotensin II type 2 receptor (AT2) during alterations in cardiac size remains largely unclear. Through employment of an AT2 antagonist, the present study explored a possible involvement of the AT2 receptor during salt-induced cardiac hypertrophy in the proatrial natriuretic peptide gene-disrupted mouse (ANP−/−). ANP−/− mice received either saline solution or the AT2 antagonist, PD123319, and were then placed on a high salt diet (8.0% NaCl) for 3 weeks. Cardiac and pulmonary size, expression of the renin–angiotensin system (RAS), and the behaviour of various hypertrophy marker genes were assessed. PD123319 caused enhanced expression of the systemic RAS, yet the cardiac RAS was largely unaffected. Although AT2 blockade did not alter whole cardiac mass, right ventricle mass, as well as pulmonary mass-to-body mass ratios were significantly decreased. Collagen type I was decreased in the latter tissues, likely contributing to the regression in mass. Several players essential in the maintenance of myocardial extracellular matrix homeostasis including B-type natriuretic peptide, matrix metalloproteinase-2, tumour necrosis factor, and transforming growth factor were also significantly altered by PD123319. These data suggest that AT2 blockade is involved in significant changes in myocardial extracellular matrix components translating into decreases in tissue mass in the salt-sensitive ANP−/− animal.
MØLLER ENERGY–MOMENTUM PRESCRIPTION FOR A LOCALLY ROTATIONALLY SYMMETRIC SPACE–TIME
Authors: AYDOGDU OKTAY
Published: August 2006

The energy distribution in the Locally Rotationally Symmetric (LRS) Bianchi type II space–time is obtained by considering the Møller energy–momentum definition in both Einstein's theory of general relativity and teleparallel theory of relativity. The energy distribution which includes both the matter and gravitational field is found to be zero in both of these different gravitation theories. This result agrees with previous works of Cooperstock and Israelit, Rosen, Johri et al., Banerjee and Sen, Vargas, and Aydogdu and Salti. Our result — the total energy of the universe is zero — supports the view points of Albrow and Tryon.
${\mathcal N} = 2$ CONFORMAL SUPERGRAVITY FROM TWISTOR-STRING THEORY
Authors: AHN CHANGHYUN
Published: August 2006

A chiral superfield strength in [Formula: see text] conformal supergravity at linearized level is obtained by acting two superspace derivatives on [Formula: see text] chiral superfield strength which can be described in terms of [Formula: see text] twistor superfields. By decomposing SU (4)R representation of [Formula: see text] twistor superfields into the SU (2)R representation with an invariant U (1)R charge, the surviving [Formula: see text] twistor superfields contain the physical states of [Formula: see text] conformal supergravity. These [Formula: see text] twistor superfields are functions of homogeneous coordinates of weighted complex projective space WCP3|4 where the two weighted fermionic coordinates have weight -1 and 3.
VIBRATION AND TRANSONIC FLUTTER ANALYSIS FOR F-16 STORES CONFIGURATION CLEARANCE
Authors: CANFIELD ROBERT A. , TOTH RAYMOND G. , MELVILLE REID
Published: August 2006

This paper supports quick and accurate prediction of the flutter onset speed of an F-16 Block 40/50 configured with external stores in the transonic flight regime. Current flutter prediction methods are reviewed and hypothesized mechanisms for limit cycle oscillation (LCO) are summarized. New efforts to correlate transonic small disturbance (TSD) theory methods with flight tests are outlined. Vibration analysis and structural optimization of an F-16 finite element model were used to match ground vibration testing results. Frequency tuning was found to be critical for accurate flutter speed predictions. Sensitivity to nonlinear aerodynamic effects and store modeling was examined.
EIGENFREQUENCY SHIFT IN THE NEWMARK TIME INTEGRATOR
Authors: ASKES HARM , PAVIC ALEKSANDAR
Published: August 2006

This technical note aims to clarify the influence of numerical time integration schemes (such as the Newmark method) on the eigenfrequency of the system. With a straightforward analysis of three consecutive time instants it is shown that the eigenfrequency of the time-discretized system is different from the eigenfrequency of the original (continuous) system, and that this frequency shift depends on the magnitude of the applied time step. As such, it affects both free and forced vibrations. In particular, for the analysis of forced vibrations at resonance the excitation frequency must be matched with the eigenfrequency of the time-discretized system rather than the eigenfrequency of the system prior to time discretization.
Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions
Authors: Taylor A. F. , Saunders M. M. , Shingle D. L. , Cimbala J. M. , Zhou Z. , Donahue H. J.
Published: August 2006

The strong correlation between a bone's architectural properties and the mechanical forces that it experiences has long been attributed to the existence of a cell that not only detects mechanical load but also structurally adapts the bone matrix to counter it. One of the most likely cellular candidates for such a “mechanostat” is the osteocyte, which resides within the mineralized bone matrix and is perfectly situated to detect mechanically induced signals. However, as osteocytes can neither form nor resorb bone, it has been hypothesized that they orchestrate mechanically induced bone remodeling by coordinating the actions of cells residing on the bone surface, such as osteoblasts. To investigate this hypothesis, we developed a novel osteocyte-osteoblast coculture model that mimics in vivo systems by permitting us to expose osteocytes to physiological levels of fluid shear while shielding osteoblasts from it. Our results show that osteocytes exposed to a fluid shear rate of 4.4 dyn/cm2 rapidly increase the alkaline phosphatase activity of the shielded osteoblasts and that osteocytic-osteoblastic physical contact is a prerequisite. Furthermore, both functional gap junctional intercellular communication and the mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2 signaling pathway are essential components in the osteoblastic response to osteocyte communicated mechanical signals. By utilizing other nonosteocytic coculture models, we also show that the ability to mediate osteoblastic alkaline phosphatase levels in response to the application of fluid shear is a phenomena unique to osteocytes and is not reproduced by other mesenchymal cell types.
Influences of calorie restriction and age on energy expenditure in the rhesus monkey
Authors: Raman Aarthi , Ramsey Jon J. , Kemnitz Joseph W. , Baum Scott T. , Newton Wendy , Colman Ricki J. , Weindruch Richard , Beasley Mark T. , Schoeller Dale A.
Published: August 2006

Caloric restriction (CR) is known to retard the aging process, and a marker of aging is decreased energy expenditure (EE). To assess longitudinal effects of CR on EE in rhesus monkeys ( Macaca mulatta), data from 41 males (M) and 26 females (F) subjected to 9 or 15 yr of CR were studied. EE and body composition of monkeys 11–28 yr of age were measured using indirect calorimetry and dual X-ray absorptiometry. Total EE (24-h EE) was divided into daytime (day EE), nighttime (night EE), and daytime minus nighttime (D − N EE). M calorie-restricted monkeys showed a lower 24-h EE (means ± SD = 568 ± 96 kcal/day, P < 0.0001) than controls (C; 630 ± 129 kcal/day). Calorie-restricted M had a lower night EE (difference = 36 kcal P < 0.0001) compared with C M, but after adjusting for FFM and FM, night EE was not different between calorie-restricted and C males ( P = 0.72). The 24-h EE decreased with age (13 kcal decrease/yr, P < 0.0001), but there was no difference between CR and C. Adjusted for FFM and FM, D − N EE decreased with age (9 kcal/yr, P < 0.0001), with no interaction with age ( P = 0.72). The F were compared with age-matched M selected from the male cohort. F had a lower 24-h EE (496 ± 84 kcal/day) than M (636 ± 139 kcal/day) ( P < 0.0001). Adjusting for FFM and FM, night EE was lower in F compared with M (difference = 18 kcal, P = 0.077). Night EE did not differ between calorie-restricted and C younger monkeys after adjusting for FFM and FM. In conclusion, CR did not alter the age-related decrease in EE with CR.
Cellular distribution of the potassium channel KCNQ1 in normal mouse kidney
Authors: Zheng Wencui , Verlander Jill W. , Lynch I. Jeanette , Cash Melanie , Shao Jiahong , Stow Lisa R. , Cain Brian D. , Weiner I. David , Wall Susan M. , Wingo Charles S.
Published: August 2006

Mechanisms of K+secretion and absorption along the collecting duct are not understood fully. Because KCNQ1 participates in K+secretion within the inner ear and stomach, distribution of KCNQ1 in mouse kidney was studied using Northern and Western analyses, RT-PCR of isolated tubules, and immunohistochemistry. Northern blots demonstrated KCNQ1 transcripts in whole kidney. RT-PCR showed KCNQ1 mRNA in isolated distal convoluted tubule (DCT), connecting segment (CNT), collecting ducts (CD), and glomeruli. Immunoblots of kidney and stomach revealed a ∼75-kDa protein, the expected mobility for KCNQ1. KCNQ1 was detected by immunohistochemistry throughout the distal nephron and CD. Thick ascending limbs exhibited weak basolateral immunolabel. In DCT and CNT cells, immunolabel was intense and basolateral, although KCNQ1 label was stronger in late than in early DCT. Initial collecting tubule and cortical CD KCNQ1 immunolabel was predominantly diffuse, but many cells exhibited discrete apical label. Double-labeling experiments demonstrated that principal cells, type B intercalated cells, and a few type A intercalated cells exhibited distinct apical KCNQ1 immunolabel. In inner medullary CD, principal cells exhibited distinct basolateral KCNQ1 immunolabel, whereas intercalated cells showed diffuse cytoplasmic staining. Thus KCNQ1 protein is widely distributed in mouse distal nephron and CD, with significant axial and cellular heterogeneity in location and intensity. These findings suggest that KCNQ1 has cell-specific roles in renal ion transport and may participate in K+secretion and/or absorption along the thick ascending limb, DCT, connecting tubule, and CD.
Prostaglandin D2inhibits TGF-β1-induced epithelial-to-mesenchymal transition in MDCK cells
Authors: Zhang Aihua , Dong Zheng , Yang Tianxin
Published: August 2006

In a separate study, we identified PGE2as a potent inhibitor of TGF-β1-induced epithelial-mesenchymal transition (EMT) in cultured Madin-Darby canine kidney (MDCK) cells (Zhang A, Wang M-H, Dong Z, and Yang T. Am J Physiol Renal Physiol 291: F1323–F1331, 2006). This finding prompted us to examine the roles of other prostanoids: PGD2, PGF2α, PGI2, and thromboxane A2(TXA2). Treatment with 10 ng/ml TGF-β1for 3 days induced EMT as reflected by conversion to the spindle-like morphology, loss of E-cadherin, and activation of α-smooth muscle actin (α-SMA). Treatment with PGD2remarkably preserved the epithelial-like morphology, restored the expression of E-cadherin, and abolished the activation of α-SMA. In contrast, PGF2α, carbocyclic thromboxane A2, PGI2and its stable analog beraprost were without an effect. MDCK cells expressed DP1and DP2receptors; however, the effect of PGD2was neither prevented by DP1antagonist BW-A868C or DP2antagonist BAY-u3405 nor was mimicked by DP1agonist BW-245C. cAMP-elevating agents forskolin and 8-Br-cAMP blocked EMT. However, cAMP blockers H89 and Rp-cAMP failed to block the effect of PGD2. PGD2did not seem to act via its metabolites as 15-deoxy-Delta( 12 , 14 )-prostaglandin J2(15d-PGJ2) levels in the medium following incubation with 3 μM PGD2were well below the values predicted from the cross activity of the assay. Exposure to TGF-β1induced a threefold increase in reactive oxygen species production that was completely abolished by PGD2. We conclude that 1) PGD2, but not PGI2, PGF2α, and TXA2inhibit EMT, 2) PGD2inhibits EMT independently of DP1and DP2receptors, and 3) PGD2exhibits antioxidant property which may, in part, account for the antifibrotic action of this PG.
Novel mouse strain with Cre recombinase in 11β-hydroxysteroid dehydrogenase-2-expressing cells
Authors: Náray-Fejes-Tóth Anikó , Fejes-Tóth Géza
Published: August 2006

Here we describe the generation and characterization of a mouse strain that expresses an improved Cre (iCre) recombinase ( 48 ) under the control of the endogenous 11β-hydroxysteroid dehydrogenase type 2 (11HSD2) promoter. Progeny of 11HSD2/iCre and ROSA26 reporter mice were used to determine the pattern of iCre expression by measuring the activity of the LacZ gene product β-galactosidase in a panel of tissues. On Cre recombinase activity, intense β-galactosidase activity (X-gal staining) was observed in the classic mineralocorticoid target segments of the kidney, as well as in the colon, and both female and male reproductive organs. Weaker iCre expression was detected in the lung and heart. In the brain, strong iCre activity was present in cardiovascular centers that are known to express 11HSD2 and mineralocorticoid receptors [nucleus tractus solitarius (NTS) and amygdala] as well as in the granular layer of the cerebellum. iCre expression was weaker in neonatal kidney and colon than in the adult but was present in the hair follicles and cartilage. These results indicate that in the 11HSD2/iCre strain iCre expression faithfully represents the expression pattern of endogenous 11HSD2. Thus this mouse model represents the first Cre deleter strain that can be used to eliminate desired genes in every mineralocorticoid target tissue. This mouse model should serve as a useful resource for investigators who want to study the function of genes involved in aldosterone action and genes in other pathways that are selectively expressed in these cells.
Early Detection of Chemoradioresponse in Esophageal Carcinoma by 3′-Deoxy-3′-3H-Fluorothymidine Using Preclinical Tumor Models
Authors: Apisarnthanarax Smith , Alauddin Mian M. , Mourtada Firas , Ariga Hisanori , Raju Uma , Mawlawi Osama , Han Dongmei , Bornmann William G. , Ajani Jaffer A. , Milas Luka , Gelovani Juri G. , Chao K.S. Clifford
Published: August 2006

Purpose: Early identification of esophageal cancer patients who are responding or resistant to combined chemoradiotherapy may lead to individualized therapeutic approaches and improved clinical outcomes. We assessed the ability of 3′-deoxy-3′-18F-fluorothymidine positron emission tomography (FLT-PET) to detect early changes in tumor proliferation after chemoradiotherapy in experimental models of esophageal carcinoma.

Experimental Design: The in vitro and ex vivo tumor uptake of [3H]FLT in SEG-1 human esophageal adenocarcinoma cells were studied at various early time points after docetaxel plus irradiation and validated with conventional assessments of cellular proliferation [thymidine (Thd) and Ki-67] and [18F]FLT micro-PET imaging. Imaging-histologic correlation was determined by comparing spatial Ki-67 and [18F]FLT distribution in autoradiographs. Comparison with fluorodeoxyglucose (FDG) was done in all experiments.

Results: In vitro [3H]FLT and [3H]Thd uptake rapidly decreased in SEG-1 cells 24 hours after docetaxel with a maximal reduction of over 5-fold (P = 0.005). The [3H]FLT tumor-to-muscle uptake ratio in xenografts declined by 75% compared with baseline (P < 0.005) by 2 days after chemoradiotherapy, despite the lack of change in tumor size. In contrast, the decline of [3H]FDG uptake was gradual and less pronounced. Tumor uptake of [3H]FLT was more closely correlated with Ki-67 expression (r = 0.89, P < 0.001) than was [3H]FDG (r = 0.39, P = 0.08). Micro-PET images depicted similar trends in reduction of [18F]FLT and [18F]FDG tumor uptake. Autoradiographs displayed spatial correlations between [18F]FLT uptake and histologic Ki-67 distribution in preliminary studies.

Conclusions: FLT-PET is suitable and more specific than FDG-PET for depicting early reductions in tumor proliferation that precede tumor size changes after chemoradiotherapy.
Intratumoral Therapy with IL13-PE38 Results in Effective CTL-Mediated Suppression of IL-13Rα2-Expressing Contralateral Tumors
Authors: Kawakami Koji , Terabe Masaki , Kioi Mitomu , Berzofsky Jay A. , Puri Raj K.
Published: August 2006

Purpose: IL13-PE38, a targeted cytotoxin comprised of interleukin 13 (IL-13) and a mutated form of Pseudomonas exotoxin, induces specific killing of tumor cells expressing abundant levels of the IL-13Rα2 chain. We hypothesized that tumor cells killed by the cytotoxin may release antigens and/or apoptotic bodies when cells are dying, which then induce adoptive immunity, and that the PE38 portion of IL13-PE38 may act as a stimulant for the induction of a CTL response.

Experimental Design: To test this hypothesis, we established D5 melanoma tumors with or without expression of the IL-13Rα2 chain in both flanks of C57BL/6 mice, and then IL13-PE38 was injected in the right flank tumors only.

Results and Conclusions: When animals with IL-13Rα2-expressing D5 tumor (right) were injected with IL13-PE38, right flank tumors expressing the IL-13Rα2 chain not only showed dramatic regression but contralateral tumors (left flank) also showed tumor regression. Cell depletion experiments in tumor-bearing animals indicated that both CD8+ and CD4+ T cells contribute to the regression of contralateral tumors through CTL activation in the periphery and cellular infiltration into tumors. In addition, intratumoral treatment into s.c. tumors of mice bearing metastatic lung tumors with IL13-PE38 showed not only the reduction of treated s.c. tumor but also the reduction of lung metastasis. Thus, IL13-PE38 mediates an antitumor effect not only directly but also indirectly by inducing a host CD8+ T cell immune response. Accordingly, targeted cytotoxins may be used to treat local disease even if they cannot be administered systemically, and yet may still induce a reasonable systemic antitumor response.
Effect of Altering Dietary ω-6/ω-3 Fatty Acid Ratios on Prostate Cancer Membrane Composition, Cyclooxygenase-2, and Prostaglandin E2
Authors: Kobayashi Naoko , Barnard R. James , Henning Susanne M. , Elashoff David , Reddy Srinivasa T. , Cohen Pinchas , Leung Pak , Hong-Gonzalez Jenny , Freedland Stephen J. , Said Jonathan , Gui Dorina , Seeram Navindra P. , Popoviciu Laura M. , Bagga Dilprit , Heber David , Glaspy John A. , Aronson William J.
Published: August 2006

Purpose: To determine whether altering the dietary content of ω-6 (n-6) and ω-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E2 (PGE2) levels.

Experimental Design: Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection.

Results: Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase–mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE2 levels, and decreased vascular endothelial growth factor expression.

Conclusion: These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE2 and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.
Expression of Annexin A1 in Esophageal and Esophagogastric Junction Adenocarcinomas: Association with Poor Outcome
Authors: Wang Kim L. , Wu Tsung-Teh , Resetkova Erika , Wang Huamin , Correa Arlene M. , Hofstetter Wayne L. , Swisher Stephen G. , Ajani Jaffer A. , Rashid Asif , Hamilton Stanley R. , Albarracin Constance T.
Published: August 2006

Purpose: Annexin A1 (ANXA1) is a calcium-binding protein involved in arachidonic acid metabolism and epidermal growth factor receptor tyrosine kinase pathway. ANXA1 has been implicated in early squamous cell carcinogenesis of esophagus and correlates with degree of tumor differentiation. However, the role of ANXA1 in esophageal adenocarcinoma is unclear. Our goal was to evaluate ANXA1 expression and determine its prognostic significance in adenocarcinoma of the esophagus and esophagogastric junction.

Experimental Design: This study included 104 consecutive patients with primary resected esophageal and esophagogastric junction adenocarcinomas (11 stage I, 24 stage II, 53 stage III, and 16 stage IV). ANXA1 protein expression in each tumor was assessed by immunohistochemical staining of tissue microarrays. ANAX1 expression level was classified as high (≥25% of tumor cells with cytoplasmic staining), low (<25% of tumor cells with cytoplasmic staining), or negative; and was correlated with clinicopathologic features and patients' outcomes.

Results: High ANXA1 expression was present in 39% (41 of 104) of tumors and was associated with higher pathologic T stage (P = 0.03) and distant metastasis (P = 0.04). High ANXA1 expression correlated with increased recurrence rate (P = 0.004) and decreased overall survival (P = 0.003) in univariate analysis. In multivariate analysis, ANXA1 expression and pN stage significantly correlated with recurrence rate (P = 0.008 and P < 0.001, respectively) and overall survival (P = 0.02 and P < 0.001, respectively) independent of T stage.

Conclusion: Our results indicate that high ANXA1 expression is frequent in esophageal and esophagogastric junction adenocarcinomas, correlates with more advanced pathologic T stage and the presence of distant metastasis, and is an independent prognostic factor for patient survival.
Psychological Aspects of Primary Aldosteronism
Authors: Sonino Nicoletta , Fallo Francesco , Fava Giovanni A.
Published: August 2006

Background: Except for 3 case reports of Conn’s syndrome presenting as depression, psychosocial factors have not been explored in primary aldosteronism. We investigated psychological correlates in primary aldosteronism using methods that were found to be sensitive and reliable in psychosomatic research. Method: Ten consecutive newly diagnosed patients with primary aldosteronism were studied: 5 males/5 females; mean age (±SD) 45.5 ± 6.6 years, age range 34–54 years; 4 with an aldosterone-producing adenoma and 6 with idiopathic aldosteronism; systolic/diastolic blood pressure 189 ± 20/111 ± 7.7 mm Hg; upright plasma aldosterone 40.0 ± 18.3 ng/dl; upright plasma renin activity (PRA) 0.2 ± 0.1 ng/ml/h; aldosterone/PRA ratio 229.2 ± 191.0; serum K+ 3.5 ± 0.5 mmol/l. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for eliciting psychiatric diagnoses, and a shortened version of the structured interview for subclinical psychological syndromes, the Diagnostic Criteria for Psychosomatic Research (DCPR), were administered. Results: Seven patients (2 with aldosterone-producing adenoma and 5 with idiopathic hyperaldosteronism) received both DSM-IV and DCPR diagnoses, while 3 had neither. As to DSM-IV, generalized anxiety disorder was detected in 6 cases (in 1 it was associated with panic disorder and in 1 with major depression) and obsessive-compulsive disorder in 1. The most frequent DCPR cluster was demoralization (5 cases), while persistent somatization occurred in 2 cases (associated with demoralization in 1) and irritable mood in 1. Conclusions: The occurrence of anxiety disorders in patients with primary aldosteronism was much higher than that found in the general population and in primary care. Since an association between hyperaldosteronism and anxiety has also been suggested in previous animal studies, it seems worthwhile to gain further knowledge on clinical aspects by larger population studies.
Actions of Mibefradil, Efonidipine and Nifedipine Block of Recombinant T- and L-Type Ca2+ Channels with Distinct Inhibitory Mechanisms
Authors: Lee Tae-Seong , Kaku Toshihiko , Takebayashi Satoshi , Uchino Tomoko , Miyamoto Shinji , Hadama Tetsuo , Perez-Reyes Edward , Ono Katsushige
Published: August 2006

We compared detailed efficacy of efonidipine and nifedipine, dihydropyridine analogues, and mibefradil using recombinant T- and L-type Ca2+ channels expressed separately in mammalian cells. All these Ca2+ channel antagonists blocked T-type Ca2+ channel currents (ICa(T)) with distinct blocking manners: ICa(T) was blocked mainly by a tonic manner by nifedipine, by a use-dependent manner by mibefradil, and by a combination of both manners by efonidipine. IC50s of these Ca2+ channel antagonists to ICa(T) and L-type Ca2+ channel current (ICa(L)) were 1.2 µmol/l and 0.14 nmol/l for nifedipine; 0.87 and 1.4 µmol/l for mibefradil, and 0.35 µmol/l and 1.8 nmol/l for efonidipine, respectively. Efonidipine, a dihydropyridine analogue, showed high affinity to T-type Ca2+ channel.
Regional Pattern of Increased Water Diffusivity in Hippocampus and Corpus Callosum in Mild Cognitive Impairment
Authors: Wang Huali , Su Min-Ying
Published: August 2006

Background: Corpus callosum atrophy possibly indicates neuronal degeneration in association cortex in Alzheimer’s disease (AD). Water diffusivity allows detecting physiological changes that probably occur earlier than structural shrinkage in cerebral regions during the development of AD. Objective: To simultaneously investigate the focal volumetric and early structural changes with apparent diffusion coefficient (ADC) of corpus callosum in mild cognitive impairment (MCI), and to explore the regional pattern of ADC increase in hippocampus and corpus callosum. Methods: Thirteen subjects with MCI and 13 healthy age-matched control subjects were studied. With three-dimensional volumetric spoiled gradient recalled echo MRI images, we measured the volume of hippocampus and corpus callosum. Using MRI-guided diffusion-weighted imaging analysis, we calculated ADCs from hippocampus and corpus callosum. Within the receiver-operation curve (ROC) statistical framework, areas under ROC curves from hippocampal and callosal ADCs were compared in differentiating between MCI and controls. Results: After normalization to intracranial volume, hippocampal, not callosal, volume was significantly reduced in MCI. ADC values were increased in hippocampus and corpus callosum in MCI. The extent of ADC increase was similar between hippocampus and corpus callosum. Conclusion: Alterations in water diffusivity may precede corpus callosum atrophy during the development of MCI. Diffusion changes might occur simultaneously in allocortex and neocortex in MCI.
Nature, Development and Disaster in Postwar Kobe: An Exploration of the Environmental Thinking of Japanese Local Politicians
Authors: Tsu Timothy Yun Hui
Published: August 2006

Postwar Kobe prides itself on being a "progressive" city. It attracted nation-wide attention in the Fifties and Sixties for bold and innovative infrastructure construction. Since the Seventies, without slowing down the pace of construction, it has acquired the reputation for being "environmentally enlightened." The city therefore appears to have achieved a balance between the imperatives of the "construction nation" and "green nation." This paper examines the thinking of two Kobe mayors and two governors of Hyōgo prefecture, wherein the city is located, to shed light on an aspect of environmental change in modern Japan that has been overlooked by scholars. By showing how the four heads of local government, by their own account, have tried to resolve the conflicting demands of development and conservation, this paper argues that local political leaders, in contrary to the conventional view of Japanese government, do contribute—sometimes even taking the lead—to the physical and cultural transformation of the territory under their charge.
The Medical Ethics of Professionalised Āyurveda
Authors: Benner Dagmar
Published: August 2006

In 1982, the Central Council for Indian Medicine (CCIM) issued guidelines on medical education and practice and a code of ethics for practitioners of Indian medicine, i.e. āyurveda, unani and siddha. These were at least partly based on the traditions of the respective medical systems and have been revised and adapted over the years. The ethical guidelines, however, followed standards set by the World Medical Association in the Declaration of Geneva of 1948 and the International Code of Ethics of 1949 and have not been updated since they were first issued. Rather than being a self-expression of the indigenous medical professions and their traditional values, the CCIM code of ethics aligned itself with international standards, thus ideologically placing the Indian systems of medicine on a par with biomedicine. This echoes developments in the early history of āyurvedic professionalisation, which was strongly influenced by the regulation and formalisation of medicine in Britain. In this article, I will trace the historical development of āyurvedic professional ethics, highlighting links with British health care regulations and international developments in the field of medical ethics.
Chinese Medicine and the Problem of Tradition
Authors: Scheid Volker
Published: August 2006

In the West, but not only in the West, Asian medicines continue to be understood and promoted through a discourse that emphasises their status as 'traditions'. Chinese medicine, widely referred to throughout the world as 'Traditional Chinese Medicine' (TCM), is an obvious example. The problematic nature of this practice, which uses tradition as the 'other' of modernity, has often been criticised, yet no alternative has yet emerged. One solution may be to redefine the notion of tradition in an effort to accord it value in and of itself. This article is a contribution to this process. It combines two different sections from a forthcoming book Currents ef Tradition in Chinese Medicine, 1624–2005. The first section briefly reviews the complex history of the concept of tradition in western social thought. The second section, written in a very different style, uses eating—and specifically the meals that the author shared with his informants during his fieldwork—as an analogy for grasping some of the essential practices that define the scholarly tradition in Chinese medicine. Introductory in nature and intention, this article is intended to stimulate debate rather than provide a definite answer to the question it raises.
A Method of Inspecting Non-woven Basis Weight Using the Exponential Law of Absorption and Image Processing
Authors: Lien Hsin-Chung , Liu Chih-Hua
Published: August 2006

This article explores a method of inspecting the non-woven basis weight on-line, by combining the exponential law of absorption and image processing technique. In the experiment, a theoretic equation for the charge-coupled device image-capture transmittance and non-woven basis weight was acquired through the exponential law of absorption. By using light source compensation and the least-squares approximation, the best approximate equations of transmittance and basis weight were acquired. According to the experimental results, the method of inspecting non-woven basis weight by image processing as proposed in this paper can reduce the uniformity of image gray scale from a coefficient of variation (C.V.) of 5.5 to 0.7%, raise the R2 of basis weight and transmittance to 0.998, and decrease the basis weight inspection error to 0.33%. The proposed method effectively enhances the accuracy and stability of non-contact inspection of non-woven basis weight. The result acquired herein can also be applied to the on-line uniformity inspection system with web as the basic material.