bluuebunny/crossref_metadata_2025 huggingface dataset:
INFLUENCE OF HIGH PRESSURE ON THE TEMPERATURE-DEPENDENCE OF THE PSEUDO-GAP IN OXYGEN DEFICIENT YBa2Cu3O7-δ SINGLE CRYSTALS
Authors: VOVK R. V. , ZAVGORODNIY A. A. , OBOLENSKII M. A. , GOULATIS I. L. , CHRONEOS A. , SIMOES V. M. PINTO
Published: August 2010

The influence of high pressure on the conductivity in the ab-plane of the oxygen deficient YBa 2 Cu 3 O 7-δ single crystals is investigated. It is determined that excess conductivity Δσ(T) in the YBa 2 Cu 3 O 7-δ single crystals in a wide temperature interval (Tc < T < T*, where Tc is the critical temperature and T* is the temperature that the PG regime begins) obeys an exponential temperature-dependence. The description of the excess conductivity with [Formula: see text]) can be interpreted in terms of mean field theory. The temperature-dependence of the pseudo-gap is well described in the framework of the Bardeen–Cooper–Schrieffer (BCS) to the Bose–Einstein condensate (BEC) crossover theory. Increasing the applied pressure leads to the effect of narrowing the temperature range of implementation of the PG regime, thus extending the area of linear ρ(T) dependence in the ab-plane.
INTERACTION EFFECTS IN THE EQUATION OF STATE OF BARYONIC AND QUARK MATTER FOR DENSE STARS
Authors: BRAGHIN F. L.
Published: August 2010

Some specific aspects of the equation of state of strongly interacting baryonic and quark matter are addressed by substituting (at least in part) the usual numerical self-consistency of the mean field equations, eventually with corrections, by an analytical treatment of the dynamic equations of the components of such system. Several solutions can be found yielding different behaviors. The mean field solutions are partially extended.
MASS–RADIUS RELATION FOR MAGNETIZED STRANGE QUARKS STARS
Authors: MARTÍNEZ A. P. , FELIPE R. G. , PARET D. M.
Published: August 2010

We review the stability of magnetized strange quark matter (MSQM) within the phenomenological MIT bag model, taking into account the variation of the relevant input parameters, namely, the strange quark mass, baryon density, magnetic field and bag parameter. A comparison with magnetized asymmetric quark matter in β-equilibrium as well as with strange quark matter (SQM) is presented. We obtain that the energy per baryon for MSQM decreases as the magnetic field increases, and its minimum value at vanishing pressure is lower than the value found for SQM, which implies that MSQM is more stable than non-magnetized SQM. The mass–radius relation for magnetized strange quark stars is also obtained in this framework.
DIVERGENCE-TYPE THEORY OF CONFORMAL FIELDS
Authors: PERALTA-RAMOS J. , CALZETTA E.
Published: August 2010

We present a nonlinear hydrodynamical description of a conformal plasma within the framework of divergence-type theories (DTTs), which are not based on a gradient expansion. We compare the equations of the DTT and the second-order theory (based on conformal invariants), for the case of Bjorken flow. The approach to ideal hydrodynamics is faster in the DTT, indicating that our results can be useful in the study of early-time dynamics in relativistic heavy-ion collisions.
HIGH-ENERGY NEUTRINO ASTRONOMY WITH THE ANTARES TELESCOPE
Authors:   on behalf of the ANTARES Collaboration, VERNIN P.
Published: August 2010

Since its completion in 2008, ANTARES is the largest neutrino telescope operating in the Northern hemisphere. High-energy muon-neutrinos originating from galactic and extra-galactic sources cross the earth and produce up-going muons by charged current interaction in the medium just below the bottom of the sea or in the water around it. These muons travel through the water with the emission of Cerenkov light detected by a three-dimensional array of photomultipliers tubes (PMT). The performances and the first results of the telescope will be discussed.
EXOTIC PHASES IN HOT NEUTRON–PROTON–ELECTRON (NPE) MATTER
Authors: AVANCINI S. S. , MARINELLI J. R. , MENEZES D. P. , MORAES M. M. W. , PROVIDÊNCIA C. , SANTOS A. M.
Published: August 2010

In the present paper, we study exotic phases in hot neutron–proton–electron (NPE) matter. It is shown that for densities lower than the normal nuclear matter inhomogeneous (exotic or pasta) phases may be present. This is believed to occur due to the so-called frustration mechanism, i.e., a close competition between the surface and Coulomb energy which, in certain cases, favors exotic phases instead of homogeneous matter. These structures may have important effects in the cooling of neutron stars, for example, affecting the neutrino opacity.
THERE ARE NO BLACK HOLES — PSEUDO-COMPLEX GENERAL RELATIVITY: REVIEW AND SOME PREDICTIONS
Authors: HESS P. O. , MAGHLAOUI L. , GREINER W.
Published: August 2010

The pseudo-complex extension of general relativity will be reviewed, and as a special case the pseudo-complex Schwarzschild metric will be discussed. As a consequence of the pseudo-complex extension, dark energy which accumulates around central mass concentrations arises. The collapse of a large mass will be avoided due to the presence of dark energy. Some experimental consequences will be discussed, like the redshift around large mass concentrations and the perihelion shift of Mercury.
GALAXY EVOLUTION THROUGH THE COSMIC TIME
Authors: IDIART T. P. , PACHECO J. A. F. , SILK J.
Published: August 2010

Elliptical galaxies are the best systems to study the early star formation activity in the universe. This work aims to understand the formation and evolution of these objects through the study of the integrated properties of their stellar populations. Here an evolutionary model is developed and their predicted spectrophotometric properties are presented.
BLACK HOLE–NEUTRON STAR COALESCING BINARIES
Authors: FERRARI V. , GUALTIERI L. , PANNARALE F.
Published: August 2010

Coalescing black hole–neutron star binaries have been invoked as possible progenitors of short gamma-ray bursts and are also among the most promising gravitational wave sources to be detected by ground-based laser interferometers. When the star is disrupted by tidal interactions before reaching the innermost stable circular orbit, the gravitational wave signal emitted by the system is expected to exhibit a cutoff frequency which is a distinctive feature of the waveform. We evaluate this frequency for several equations of state, describing the matter inside the neutron star, and combinations of the binary parameters. We show that, if this frequency will be found in a detected gravitational wave, it will provide valuable information on the behavior of matter in the stellar core.
Regulation of serum response factor activity and smooth muscle cell apoptosis by chromodomain helicase DNA-binding protein 8
Authors: Rodenberg Jennifer M. , Hoggatt April M. , Chen Meng , Touw Ketrija , Jones Rebekah , Herring B. Paul
Published: August 2010

Serum response factor (SRF) is a widely expressed protein that plays a key role in the regulation of smooth muscle differentiation, proliferation, migration, and apoptosis. It is generally accepted that one mechanism by which SRF regulates these diverse functions is through pathway-specific cofactor interactions. A novel SRF cofactor, chromodomain helicase DNA binding protein 8 (CHD8), was isolated from a yeast two-hybrid screen using SRF as bait. CHD8 is highly expressed in adult smooth muscle tissues. Coimmunoprecipitation assays from A10 smooth muscle cells demonstrated binding of endogenous SRF and CHD8. Data from GST-pulldown assays indicate that the NH2-terminus of CHD8 can interact directly with the MADS domain of SRF. Adenoviral-mediated knockdown of CHD8 in smooth muscle cells resulted in attenuated expression of SRF-dependent, smooth muscle-specific genes. Knockdown of CHD8, SRF, or CTCF, a previously described binding partner of CHD8, in A10 VSMCs also resulted in a marked induction of apoptosis. Mechanistically, apoptosis induced by CHD8 knockdown was accompanied by attenuated expression of the anti-apoptotic proteins, Birc5, and CARD10, whereas SRF knockdown attenuated expression of CARD10 and Mcl-1, but not Birc5, and CTCF knockdown attenuated expression of Birc5. These data suggest that CHD8 plays a dual role in smooth muscle cells modulating SRF activity toward differentiation genes and promoting cell survival through interactions with both SRF and CTCF to regulate expression of Birc5 and CARD10.
Imaging signal transduction during phagocytosis: phospholipids, surface charge, and electrostatic interactions
Authors: Grinstein Sergio
Published: August 2010

Together with the development of genetically encoded fluorescent probes, digital imaging has provided great impetus to the study of cell signaling by providing enhanced sensitivity and much-improved spatial and temporal resolution. We have used phagocytosis as a paradigm of signal transduction, taking advantage of the generous size of phagosomes and of their comparatively leisurely rate of formation. Aided by the design of specific probes, we demonstrated a highly localized and elegantly choreographed sequence of changes in the level of several phosphoinositides and were able to also monitor the fate of phosphatidylserine. The net changes in the content of these anionic phospholipids are accompanied by marked alterations in the surface charge of the membrane of nascent phagosomes. These, in turn, cause the relocation of proteins that associate with the membrane by electrostatic interactions. Our studies suggest that anionic lipids control protein targeting not only through stereospecific recognition by specialized domains but also by electrostatic association mediated by polycationic motifs. The “electrostatic switch” can be turned on or off by altering the charge of the protein ligand (e.g., by phosphorylation) or, alternatively, by modifying the lipid composition of the target membrane.
Orai1 interacts with STIM1 and mediates capacitative Ca2+ entry in mouse pulmonary arterial smooth muscle cells
Authors: Ng Lih Chyuan , Ramduny Deepa , Airey Judith A. , Singer Cherie A. , Keller Phillip S. , Shen Xiao-Ming , Tian Honglin , Valencik Maria , Hume Joseph R.
Published: August 2010

Previous studies in mouse pulmonary arterial smooth muscle cells (PASMCs) showed that cannonical transient receptor potential channel TRPC1 and stromal interaction molecule 1 (STIM1) mediate the sustained component of capacitative Ca2+ entry (CCE), but the molecular candidate(s) that mediate the transient component of CCE remain unknown. The aim of the present study was to examine whether Orai1 mediates the transient component of CCE through activation of STIM1 in mouse PASMCs. In primary cultured mouse PASMCs loaded with fura-2, cyclopiazonic acid (CPA) caused a transient followed by a sustained rise in intracellular Ca2+ concentration ([Ca2+]i). The transient but not the sustained rise in [Ca2+]i was partially inhibited by nifedipine. The nifedipine-insensitive transient rise in [Ca2+]i and the increase in Mn2+ quench of fura-2 fluorescence caused by CPA were both reduced in cells treated with Orai1 siRNA. These responses to CPA were further reduced in cells treated with Orai1 and STIM1 small interfering (si)RNA. Moreover, overexpression of STIM1 enhanced the rise in [Ca2+]i and the increase in Mn2+ quench of fura-2 fluorescence caused by CPA, and these responses were reduced in cells treated with Orai1 siRNA. RT-PCR revealed Orai1 and STIM1 mRNAs, and Western blot analysis identified Orai1 and STIM1 proteins in mouse PASMCs. Furthermore, Orai1 was found to coimmunoprecipitate with STIM1, and the precipitation level of Orai1 was increased in cells subjected to store-depletion. Immunostaining revealed colocalization of Orai1 and STIM1 proteins, and the colocalization of these proteins was more apparent after store-depletion. These data provide direct evidence that the transient component of CCE is mediated by Orai1 channel as a result of STIM1 activation in mouse PASMCs.
Glucose-induced ERM protein activation and translocation regulates insulin secretion
Authors: Lopez James P. , Turner Jerrold R. , Philipson Louis H.
Published: August 2010

A key step in regulating insulin secretion is insulin granule trafficking to the plasma membrane. Using live-cell time-lapse confocal microscopy, we observed a dynamic association of insulin granules with filamentous actin and PIP2-enriched structures. We found that the scaffolding protein family ERM, comprising ezrin, radixin, and moesin, are expressed in β-cells and target both F-actin and PIP2. Furthermore, ERM proteins are activated via phosphorylation in a glucose- and calcium-dependent manner. This activation leads to a translocation of the ERM proteins to sites on the cell periphery enriched in insulin granules, the exocyst complex docking protein Exo70, and lipid rafts. ERM scaffolding proteins also participate in insulin granule trafficking and docking to the plasma membrane. Overexpression of a truncated dominant-negative ezrin construct that lacks the ERM F-actin binding domain leads to a reduction in insulin granules near the plasma membrane and impaired secretion. Conversely, overexpression of a constitutively active ezrin results in more granules near the cell periphery and an enhancement of insulin secretion. Diabetic mouse islets contain less active ERM, suggestive of a novel mechanism whereby impairment of insulin granule trafficking to the membrane through a complex containing F-actin, PIP2, Exo70, and ERM proteins contributes to defective insulin secretion.
Sterol regulatory element binding protein and dietary lipid regulation of fatty acid synthesis in the mammary epithelium
Authors: Rudolph Michael C. , Monks Jenifer , Burns Valerie , Phistry Meridee , Marians Russell , Foote Monica R. , Bauman Dale E. , Anderson Steven M. , Neville Margaret C.
Published: August 2010

The lactating mammary gland synthesizes large amounts of triglyceride from fatty acids derived from the blood and from de novo lipogenesis. The latter is significantly increased at parturition and decreased when additional dietary fatty acids become available. To begin to understand the molecular regulation of de novo lipogenesis, we tested the hypothesis that the transcription factor sterol regulatory element binding factor (SREBF)-1c is a primary regulator of this system. Expression of Srebf1c mRNA and six of its known target genes increased ≥2.5-fold at parturition. However, Srebf1c-null mice showed only minor deficiencies in lipid synthesis during lactation, possibly due to compensation by Srebf1a expression. To abrogate the function of both isoforms of Srebf1, we bred mice to obtain a mammary epithelial cell-specific deletion of SREBF cleavage-activating protein (SCAP), the SREBF escort protein. These dams showed a significant lactation deficiency, and expression of mRNA for fatty acid synthase ( Fasn), insulin-induced gene 1 ( Insig1), mitochondrial citrate transporter ( Slc25a1), and stearoyl-CoA desaturase 2 ( Scd2) was reduced threefold or more; however, the mRNA levels of acetyl-CoA carboxylase-1α ( Acaca) and ATP citrate lyase ( Acly) were unchanged. Furthermore, a 46% fat diet significantly decreased de novo fatty acid synthesis and reduced the protein levels of ACACA, ACLY, and FASN significantly, with no change in their mRNA levels. These data lead us to conclude that two modes of regulation exist to control fatty acid synthesis in the mammary gland of the lactating mouse: the well-known SREBF1 system and a novel mechanism that acts at the posttranscriptional level in the presence of SCAP deletion and high-fat feeding to alter enzyme protein.
Cloning and characterization of a zebrafish homologue of human AQP1: a bifunctional water and gas channel
Authors: Chen Li-Ming , Zhao Jinhua , Musa-Aziz Raif , Pelletier Marc F. , Drummond Iain A. , Boron Walter F.
Published: August 2010

The mammalian aquaporins AQP1, AQP4, and AQP5 have been shown to function not only as water channels but also as gas channels. Zebrafish have two genes encoding an AQP1 homologue, aqp1a and aqp1b. In the present study, we cloned the cDNA that encodes the zebrafish protein Aqp1a from the 72-h postfertilization (hpf) embryo of Danio rerio, as well as from the swim bladder of the adult. The deduced amino-acid sequence of aqp1a consists of 260 amino acids and is 59% identical to human AQP1. By analyzing the genomic DNA sequence, we identified four exons in the aqp1a gene. By in situ hybridization, aqp1a is expressed transiently in the developing vasculature and in erythrocytes from 16 to 48 h of development. Later, at 72 hpf, aqp1a is expressed in dermal ionocytes and in the swim bladder. Western blot analysis of adult tissues reveals that Aqp1a is most highly expressed in the eye and swim bladder. Xenopus oocytes expressing aqp1a have a channel-dependent (*) osmotic water permeability (Pf*) that is indistinguishable from that of human AQP1. On the basis of the magnitude of the transient change in surface pH (ΔpHS) that were recorded as the oocytes were exposed to either CO2or NH3, we conclude that zebrafish Aqp1a is permeable to both CO2and NH3. The ratio (ΔpHS*)CO2/Pf*is about half that of human AQP1, and the ratio (ΔpHS*)NH3/Pf*is about one-quarter that of human AQP1. Thus, compared with human AQP1, zebrafish Aqp1a has about twice the selectivity for CO2over NH3.
High-protein-induced glomerular hyperfiltration is independent of the tubuloglomerular feedback mechanism and nitric oxide synthases
Authors: Sällström Johan , Carlström Mattias , Olerud Johan , Fredholm Bertil B. , Kouzmine Mattias , Sandler Stellan , Persson A. Erik G.
Published: August 2010

A high protein intake is associated with increased glomerular filtration rate (GFR), which has been suggested to be mediated by reduced signaling of the tubuloglomerular feedback (TGF) mechanism. Nitric oxide (NO) has been shown to contribute to high protein-induced glomerular hyperfiltration, but the specific NO synthase (NOS) isoform responsible is not clear. In this study, a model for high-protein-induced hyperfiltration in conscious mice was developed. Using this model, we investigated the role of TGF using adenosine A1-receptor knockout mice lacking the TGF mechanism. Furthermore, the role of the different NOS isoforms was studied using neuronal-, inducible-, and endothelial-NOS knockout mice, and furthermore, wild-type mice acutely administered with the unspecific NOS inhibitor Nω-nitro-l-arginine methyl ester (100 mg/kg). GFR was measured consecutively in mice given a low-protein diet (8% casein) for 10 days, followed by a high-protein diet (50% casein) for 10 days. All mice developed high protein-induced hyperfiltration to a similar degree. These results demonstrate that high protein-induced glomerular hyperfiltration is independent of the TGF mechanism and NOS isoforms.
TNFR1-deficient mice display altered blood pressure and renal responses to ANG II infusion
Authors: Chen Chun Cheng Andy , Pedraza Paulina L. , Hao Shoujin , Stier Charles T. , Ferreri Nicholas R.
Published: August 2010

The hypothesis that TNF receptor 1-deficient (TNFR1−/−) mice display blood pressure (BP) and renal functional responses that differ from wild-type (WT) mice was tested in an angiotensin II (ANG II)-dependent model of hypertension. Basal systolic BP (SBP), mean arterial pressure, diastolic BP, heart rate (HR), and pulse pressure were similar in WT and TNFR1−/−mice. Infusion of ANG II for 7 days elevated SBP to a greater extent in TNFR1−/−compared with WT mice; pulse pressure was also elevated in TNFR1−/−. HR decreased in TNFR1−/−mice infused with ANG II, an effect prominent on day 1. Basal urinary albumin excretion was similar in WT and TNFR1−/−mice but was higher in TNFR1−/−in response to ANG II infusion. Water intake and urine volume were increased by ANG II infusion; this increase was higher in TNFR1−/−vs. WT mice, whereas body weight and food intake were unaffected. Baseline creatinine clearance (Ccr), urinary sodium excretion, and fractional excretion of sodium (FENa%) were similar in vehicle-treated WT and TNFR1−/−mice. ANG II infusion for 7 days increased Ccr and filtered load of sodium in TNFR1−/−but not WT mice, whereas it elicited an increase in FENa% and urinary sodium excretion in WT but not TNFR1−/−mice. ANG II also inhibited renal TNFR1 mRNA accumulation while increasing that of TNFR2. These findings indicate deletion of TNFR1 is associated with an exacerbated SBP response, decrease in HR, and altered renal function in ANG II-dependent hypertension.
Decoding and Cortical Source Localization for Intended Movement Direction With MEG
Authors: Wang Wei , Sudre Gustavo P. , Xu Yang , Kass Robert E. , Collinger Jennifer L. , Degenhart Alan D. , Bagic Anto I. , Weber Douglas J.
Published: August 2010

Magnetoencephalography (MEG) enables a noninvasive interface with the brain that is potentially capable of providing movement-related information similar to that obtained using more invasive neural recording techniques. Previous studies have shown that movement direction can be decoded from multichannel MEG signals recorded in humans performing wrist movements. We studied whether this information can be extracted without overt movement of the subject, because the targeted users of brain-controlled interface (BCI) technology are those with severe motor disabilities. The objectives of this study were twofold: 1) to decode intended movement direction from MEG signals recorded during the planning period before movement onset and during imagined movement and 2) to localize cortical sources modulated by intended movement direction. Ten able-bodied subjects performed both overt and imagined wrist movement while their cortical activities were recorded using a whole head MEG system. The intended movement direction was decoded using linear discriminant analysis and a Bayesian classifier. Minimum current estimation (MCE) in combination with a bootstrapping procedure enabled source-space statistical analysis, which showed that the contralateral motor cortical area was significantly modulated by intended movement direction, and this modulation was the strongest ∼100 ms before the onset of overt movement. These results suggest that it is possible to study cortical representation of specific movement information using MEG, and such studies may aid in presurgical localization of optimal sites for implanting electrodes for BCI systems.
Multiple Somatotopic Representations of Heat and Mechanical Pain in the Operculo-Insular Cortex: A High-Resolution fMRI Study
Authors: Baumgärtner Ulf , Iannetti Gian Domenico , Zambreanu Laura , Stoeter Peter , Treede Rolf-Detlef , Tracey Irene
Published: August 2010

Whereas studies of somatotopic representation of touch have been useful to distinguish multiple somatosensory areas within primary (SI) and secondary (SII) somatosensory cortex regions, no such analysis exists for the representation of pain across nociceptive modalities. Here we investigated somatotopy in the operculo-insular cortex with noxious heat and pinprick stimuli in 11 healthy subjects using high-resolution (2 × 2 × 4 mm) 3T functional magnetic resonance imaging (fMRI). Heat stimuli (delivered using a laser) and pinprick stimuli (delivered using a punctate probe) were directed to the dorsum of the right hand and foot in a balanced design. Locations of the peak fMRI responses were compared between stimulation sites (hand vs. foot) and modalities (heat vs. pinprick) within four bilateral regions of interest: anterior and posterior insula and frontal and parietal operculum. Importantly, all analyses were performed on individual, non-normalized fMRI images. For heat stimuli, we found hand-foot somatotopy in the contralateral anterior and posterior insula [hand, 9 ± 10 (SD) mm anterior to foot, P < 0.05] and in the contralateral parietal operculum (SII; hand, 7 ±10 mm lateral to foot, P < 0.05). For pinprick stimuli, we also found somatotopy in the contralateral posterior insula (hand, 9 ±10 mm anterior to foot, P < 0.05). Furthermore, the response to heat stimulation of the hand was 11 ± 12 mm anterior to the response to pinprick stimulation of the hand in the contralateral (left) anterior insula ( P < 0.05). These results indicate the existence of multiple somatotopic representations for pain within the operculo-insular region in humans, possibly reflecting its importance as a sensory-integration site that directs emotional responses and behavior appropriately depending on the body site being injured.
Activity-Dependent Regulation of the Binomial Parameters p and n at the Mouse Neuromuscular Junction In Vivo
Authors: Wang Xueyong , Wang Qingbo , Engisch Kathrin L. , Rich Mark M.
Published: August 2010

Block of neurotransmission at the mammalian neuromuscular junction triggers an increase in the number of vesicles released (quantal content). The increase occurs whether nerve and muscle activity are both blocked by placement of a tetrodotoxin (TTX) containing cuff on the nerve or whether muscle activity is selectively blocked by injection of α-bungarotoxin (BTX). We used ANOVA to examine whether the mechanism underlying the increase in quantal content differed between the two types of activity blockade. We found that TTX-induced blockade increased the probability of release ( p), whereas BTX-induced blockade increased the number of releasable vesicles ( n). The lack of increase in p when postsynaptic activity was blocked with BTX suggests that block of presynaptic activity triggers the increase. To determine whether n is regulated by mismatch of pre- and postsynaptic activity introduced by BTX injection we combined BTX and TTX and still found an increase in n. We conclude that block of acetylcholine binding to acetylcholine receptors during spontaneous release triggers the increase in n.
Prognostic Gene Expression Signature for Squamous Cell Carcinoma of Lung
Authors: Zhu Chang-Qi , Strumpf Dan , Li Chun-Yan , Li Qing , Liu Ni , Der Sandy , Shepherd Frances A. , Tsao Ming-Sound , Jurisica Igor
Published: August 2010

Purpose: This study aimed to identify and validate a gene expression signature for squamous cell carcinoma of the lung (SQCC).

Experimental Design: A published microarray dataset from 129 SQCC patients was used as a training set to identify the minimal gene set prognostic signature. This was selected using the MAximizing R Square Algorithm (MARSA), a novel heuristic signature optimization procedure based on goodness-of-fit (R square). The signature was tested internally by leave-one-out-cross-validation (LOOCV), and then externally in three independent public lung cancer microarray datasets: two datasets of non–small cell lung cancer (NSCLC) and one of adenocarcinoma (ADC) only. Quantitative-PCR (qPCR) was used to validate the signature in a fourth independent SQCC cohort.

Results: A 12-gene signature that passed the internal LOOCV validation was identified. The signature was independently prognostic for SQCC in two NSCLC datasets (total n = 223) but not in ADC. The lack of prognostic significance in ADC was confirmed in the Director's Challenge ADC dataset (n = 442). The prognostic significance of the signature was validated further by qPCR in another independent cohort containing 62 SQCC samples (hazard ratio, 3.76; 95% confidence interval, 1.10-12.87; P = 0.035).

Conclusions: We identified a novel 12-gene prognostic signature specific for SQCC and showed the effectiveness of MARSA to identify prognostic gene expression signatures. Clin Cancer Res; 16(20); 5038–47. ©2010 AACR.
Obsessive-Compulsive Behavior as a Symptom of Dementia in Progressive Supranuclear Palsy
Authors: Fukui T. , Lee E. , Hosoda H. , Okita K.
Published: August 2010

Aims: To describe obsessive-compulsive symptoms (OCS) as under-recognized behavioral and psychological symptoms of dementia of progressive supranuclear palsy (PSP) and to discuss possible mechanisms based on MRI and SPECT findings. Methods: We studied 74 PSP patients. OCS are defined as persistent and unreasonable, but non-delusional/hallucinatory, ideas and behaviors. Demography, cognition, the widths of middle cerebellar peduncles (MCP) and the inter-caudate distances (ICD), both corrected by the intracranial size (MCP and ICD ratios), and changes on voxel-based SPECT were compared between the subgroups with and without OCS. Finally, the predicative power of various factors to OCS was investigated. Results: We observed OCS in 18 patients (24%). They were obsessed with daily trifles and physical symptoms among other things. OCS was not associated with demography or cognitive levels. OCS-positive patients had significantly smaller MCP and ICD ratios and showed marked uptake decreases in the orbitofrontal cortex, caudate and thalamus. Relative uptake increases in the cerebellum, specifically the tonsils, were milder in OCS-positive than -negative patients. A smaller right MCP, a smaller ICD ratio and lower uptake increases in the right cerebellar were the significant predictors of OCS. Conclusions: OCS are frequent but under-recognized behavioral and psychological symptoms of dementia in PSP. Dysfunction of the fronto-caudate-thalamus-cerebellum circuit may be involved.
Aortic Pressures, Stiffness and Left Ventricular Function in Coronary Slow Flow Phenomenon
Authors: Tanriverdi Halil , Evrengul Harun , Kilic I. Dogu , Taskoylu Ozgur , Dogan Güllü , Alpsoy Seref
Published: August 2010

Background: Coronary slow flow (CSF) phenomenon is characterized by delayed opacification of coronary vessels in a normal coronary angiogram. Although clinical and pathological features have been previously described, the underlying pathophysiology has not been fully elucidated. In this study, we aimed to evaluate central aortic pressure, aortic stiffness and left ventricular (LV) function in patients with coronary slow flow. Method and Results: The study population consisted of 154 patients who underwent coronary angiography because of typical and quasi-typical symptoms of angina. 81 patients with angiographically proven CSF and 73 cases with normal coronary flow pattern with similar risk profiles were enrolled in the study. Aortic pressures and indexes of elastic properties were evaluated using invasive methods. Aortic pulse pressure (mm Hg) and pulsality index of patients with CSF were found to be significantly higher than those of controls (60.8 ± 13.8 vs. 53.7 ± 14.5, p = 0.002; 0.84 ± 0.22 vs. 0.67 ± 0.18, p = 0.0001, respectively). LV Doppler parameters were deteriorated in patients with CSF. Aortic fractional pulse pressure and pulsality index were significantly correlated with the mean TIMI frame count and LV diastolic parameters in correlation analysis. Conclusion: The present findings allow us to conclude that impaired aortic elasticity in patients with CSF may also be responsible for the impaired LV diastolic parameters.
Effect of Pioglitazone on Platelet Aggregation in a Healthy Cohort
Authors: Chokesuwattanaskul Warangkana , Yaqub Yasir , Suarez Jose A. , Simoni Jan , Simoni Grace , Nugent Kenneth M. , Jimenez Rosalinda , Perez-Verdia Alejandro
Published: August 2010

Background: Peroxisome proliferator-activated receptor (PPAR) agonists can favorably influence atheroma proliferation, lipoprotein metabolism and macrovascular complications. Pioglitazone, one of the thiazolidinedione compounds, is a PPAR ligand activator and a clinically important PPAR agonist. There is controversy in the literature about its potential antiplatelet effects. Its direct platelet inhibition is a novel hypothesis tested in animal models and in human populations with underlying diabetic and/or cardiovascular diseases. The present study was aimed to test the hypothesis of direct platelet aggregation inhibition with the use of pioglitazone in a healthy population. Methods: This prospective study was started after obtaining institutional review board approval. The platelet aggregation response to adenosine diphosphate, epinephrine, collagen and arachidonic acid was measured in healthy subjects before and after treatment with pioglitazone. The fasting lipid profile including total cholesterol, low-density lipoprotein, very-low-density lipoprotein and high-density lipoprotein was also measured. Results: Twenty subjects, 12 males and 8 females, were enrolled with a mean age of 31.5 ± 7.6 years (range 24–46). Two subjects did not complete the study and were excluded. The mean HbA1C was 5.4% (range 4.7–5.7). The study showed a non-significant platelet aggregation reduction after taking a 7-day pioglitazone course. The adenosine diphosphate-mediated platelet aggregation difference was not significant (p = 0.99); the arachidonic acid-mediated platelet aggregation difference was 0.6% (p = 0.93), for epinephrine 0.9% (p = 0.88) and for collagen 0.2% (p = 0.94). Further, it did not show a favorable response of lipoprotein profile with a non-significant reduction in all lipid panel values even though there is a slight reduction in total cholesterol, triglyceride, low-density lipoprotein and very low-density lipoprotein and a slight increase in high-density lipoprotein. Conclusions: We conclude that pioglitazone does not have a direct platelet aggregation inhibition effect in a healthy population, nor does it have a favorable effect on lipoprotein profile after a short treatment period.
Psychometric Properties of the PAT: An Assessment Tool for ADL Performance of Older People Living in Residential Homes
Authors: Weening-Dijksterhuis Elizabeth , Kamsma Yvo P.T. , van Heuvelen Marieke J.G.
Published: August 2010

Background: As the world population ages, the number of people with diminished performance on the Activities of Daily Living (ADL) increases. A reliable and valid measure needs to be developed to determine the effects of interventions focused at increasing self-care abilities. We developed the Performance ADL Test (PAT) for this purpose. Objective: The aim of this study was to investigate the reliability and validity of the PAT in older people living in residential homes. Methods: The PAT contains 16 test items, covering the entire range of Basic ADL and Instrumental ADL performance in elderly people. For this assessment, 40 older people (mean age of 85 ± 7.5 years) participated. All 40 subjects lived in residential institutions in the Netherlands, were able to walk at least 10 m, could understand instructions spoken in Dutch, and had no cognitive impairment. During the first test session, subjects completed the PAT, the Groningen Activity Restriction Scale (GARS), and performance-based physical fitness tests. Two weeks later, subjects were retested on the PAT. Results: Factor analysis revealed three subscales: Organization of Performance, Gross Motor Function, and Fine Motor Function. Internal consistency (Cronbach’s α) of all scales and subscales ranged from 0.731 to 0.881. Test-retest reliability (intraclass correlation) ranged from 0.316 to 0.950. Paired sample t-tests revealed no significant differences between subject performance obtained during the two test periods. Pearson’s correlations between the PAT and the GARS ranged from 0.490 to 0.831, and between the PAT and the fitness tests from 0.317 to 0.781. Conclusion: Although the number of participants was limited (n = 40), the PAT seems to be a useful instrument for assessing ADL performance in older people living in residential homes. In general, internal consistency, test-retest reliability, and validity were satisfactory.
Damage to the Upper Portion of Area 19 and the Deep White Matter in the Left Inferior Parietal Lobe, Including the Superior Longitudinal Fasciculus, Results in Alexia with Agraphia
Authors: Shinoura Nobusada , Onodera Toshiyuki , Kurokawa Kotoyo , Tsukada Masanobu , Yamada Ryozi , Tabei Yusuke , Koizumi Tomoyuki , Yagi Kazuo
Published: August 2010

Analysis of lesions and symptoms in patients with brain tumors combined with information from diffusion tensor imaging provides direct evidence of the anatomical localization of brain function. Using these methods, we evaluated 8 patients who underwent surgery for metastatic brain tumors located in the left occipital lobes between 2007 and 2009. Preoperatively, 4 patients (cases 1–4) had alexia with agraphia while the other 4 patients (cases 5–8) did not. Tractography for the superior longitudinal fasciculus (SLF) was performed before surgery in case 1. The common brain tumors in cases 1–4 were located in the upper portion of area 19, and peritumor edema in that area resulted in compromise of the deep white matter of the inferior parietal lobe (IPL). The SLF was compressed and disrupted in the white matter of the IPL near the upper portion of area 19 in case 1. In cases 5–8, the brain tumors were not located in the upper portion of area 19. These results suggest that damage to the upper portion of area 19 and to the white matter in the left IPL, including the SLF, resulted in alexia with agraphia.
Sevoflurane Protects against Acute Kidney Injury in a Small-Size Liver Transplantation Model
Authors: Kong H.Y. , Zhu S.M. , Wang L.Q. , He Y. , Xie H.Y. , Zheng S.S.
Published: August 2010

Background: Living donor liver transplantation (LDLT) patients run the risk of developing acute kidney injury (AKI) and subsequent chronic kidney disease, affecting morbidity and mortality. Sevoflurane has anti-inflammation properties, and renal ischemia/reperfusion under sevoflurane anesthesia resulted in drastic improvements in renal function. Extrahepatic metabolism of sevoflurane has been reported in patients undergoing liver transplantation, and might lead to nephrotoxicity. However, whether sevoflurane anesthesia is safe with regard to renal function in small-size liver transplantation needs further investigation. As neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of AKI, we looked at the renal effects of sevoflurane in a rat liver transplantation model using small-for-size grafts to investigate the changes of NGAL level and kidney histology. Methods: Sixty male Sprague-Dawley rats were randomly divided into 2 groups after 50% size liver transplantation. Rats were anesthetized with chloral hydrate or with sevoflurane and subjected to liver transplantation. Twelve rats in each group were used for the survival study and 6 rats were used for the hemodynamic study. Six rats in each group were sacrificed 2 or 24 h after reperfusion. We harvested kidneys and serum for further analysis, including histological and functional parameters; TNF-α, IL-6 and NGAL immunoassay; expressions of myeloperoxidase (MPO) activity; and NF-ĸB in renal tissues. Results: Rats in the sevoflurane group had significantly lower Scr 24 h after reperfusion compared with those in the chloral hydrate group. Rats in the sevoflurane group demonstrated significantly reduced NGAL concentrations compared with rats in the chloral hydrate group 2 h after reperfusion. Epithelial necrosis in the chloral hydrate group (3.2 ± 0.8) was greater than that in the sevoflurane group (1.5 ± 1.1; p < 0.05). Sevoflurane anesthesia resulted in significantly lower plasma TNF-α and IL-6 concentrations and reduced MPO concentrations 2 h after reperfusion (p < 0.05). NF-ĸB protein levels 2 h after reperfusion increased by at least 110% in the chloral hydrate group relative to the sevoflurane group 2 h after reperfusion (p < 0.05). However, the urine inorganic fluoride concentrations increased significantly (p < 0.001) 2 h after reperfusion in the sevoflurane group (6.1 ± 1.5 µmol·l–1) compared with the chloral hydrate group. Conclusions: Sevoflurane anesthesia can attenuate renal injury and modulate inflammatory cascades in small-size liver transplantation using rat models.
Liquid Drugs and High Dead Space Syringes May Keep HIV and HCV Prevalence High – A Comparison of Hungary and Lithuania
Authors: Gyarmathy V. Anna , Neaigus Alan , Li Nan , Ujhelyi Eszter , Caplinskiene Irma , Caplinskas Saulius , Latkin Carl A.
Published: August 2010

Despitevery similar political, drug policy and HIV prevention backgrounds, HIV and HCV prevalence is considerably different in Hungary (low HIV and moderate HCV prevalence) and Lithuania (high HCV and moderate HIV prevalence). Wecompared the drug use profile of Hungarian (n = 215) and Lithuanian (n = 300) injecting drug users (IDUs). Overall, compared with IDUs in Hungary, IDUs in Lithuania often injected opiates purchased in liquid form (‘shirka’), used and shared 2-piece syringes (vs. 1-piece syringes) disproportionately more often, were less likely to acquire their syringes from legal sources and had significantly more experience with injected and less experience with non-injected drugs. It may not be liquid drugs per se that contribute to a higher prevalence of HCV and/or HIV, but it is probably factors associated with the injecting of liquid drugs, such as the wide-spread use and sharing of potentially contaminated 2-piece syringes acquired often from non-legal sources, and syringe-mediated drug sharing with 2-piece syringes. Scaling up substitution therapy, especially heroin replacement, combined with reducing the supply of liquid drugs may decrease the prevalence of high-risk injecting behaviours related to the injecting of liquid drugs and drug injecting-related infections among IDUs in Lithuania.
The Significance of Fibroblast Growth Factor Receptor 2 Expression in Differentiation of Hepatocellular Carcinoma
Authors: Harimoto Norifumi , Taguchi Kenichi , Shirabe Ken , Adachi Eisuke , Sakaguchi Yoshihisa , Toh Yasushi , Okamura Takeshi , Kayashima Hiroto , Taketomi Akinobu , Maehara Yoshihiko
Published: August 2010

Fibroblast growth factor receptors (FGFRs) have been reported to be involved in the progression of many cancers. The aim of this study is to clarify the significance of FGFR2 expression in the differentiation of hepatocellular carcinoma (HCC). One nodule-in-nodule HCC sample was obtained from a patient to analyze the different expression in well- to moderately differentiated HCC and poorly differentiated HCC using microarray technique. The expression of FGFR2 in 46 patients with surgically resected HCC was immunohistochemically examined and analyzed in relation to their clinicopathological factors. Fgfr2 was 4.7 times up-regulated in poorly differentiated HCC from a nodule-in-nodule sample. The high expression group was 16 cases and the low expression group was 30 cases. The high FGFR2 expression correlated significantly with a poor histological differentiation, a higher incidence of portal vein and a high level of alpha-fetoprotein. The overall survival rates and the disease-free survival rates in high expression were significantly worse than those in low. In conclusion, a high FGFR2 expression plays an important role in poor differentiation, portal vein invasion, high alpha-fetoprotein production, and poor prognosis. These data suggest that FGFR2 may be a potentially useful biological marker of tumor invasiveness in HCC as well as a novel molecular target for HCC.
Predictive Factors of Complete Response to Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer
Authors: Carlomagno Chiara , Pepe Stefano , D’Armiento Francesco Paolo , D’Armiento Maria , Cannella Lucia , De Stefano Alfonso , Crispo Anna , Giordano Marcella , De Placido Sabino
Published: August 2010

Purpose: Pathological complete response (pCR) after neoadjuvant chemoradiotherapy is a favorable prognosticator in rectal cancer patients. We investigated whether the biological features of the primary tumor affect pCR. Materials and Methods:Forty-six patients treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy were considered. Forty-three patients underwent surgery, and the pathologic response was scored according to the tumor regression grade (TRG) scale. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor, poly(adenosine diphosphate-ribose) polymerase-1, X-ray cross-complimenting, thymidylate synthase (TS) and Ki67 expression were evaluated by immunohistochemistry on rectal biopsies obtained before chemoradiotherapy, and scored as the percentage of positive cells. Cutoffs were selected based on ROC analysis. The correlation between the biological factors and the TRG coded as TRG1 (pCR) versus TRG ≧2 (no pCR) was assessed by the χ2 test and logistic regression analysis. Results: Low EGFR (p = 0.007), high TS (p = 0.002), and high Ki67 (p = 0.05) were strongly associated with pCR. Upon univariate analysis, TRG significantly affected disease-free survival (p = 0.03). Conclusions: pCR was significantly associated with high TS, high Ki67 and low EGFR expression. Patients with pCR have a significantly lower incidence of relapse.
The Development of Aortic Insufficiency in Left Ventricular Assist Device-Supported Patients
Authors: Cowger Jennifer , Pagani Francis D. , Haft Jonathan W. , Romano Matthew A. , Aaronson Keith D. , Kolias Theodore J.
Published: August 2010

Background—

Aortic insufficiency (AI) following left ventricular assist device (LVAD) placement can affect device performance. The aim of this study was to examine AI development following LVAD implantation.

Methods and Results—

Echocardiograms (n=315) from 78 subjects undergoing HeartMate-XVE (n=25 [32%]) or HeartMate-II (n=53 [68%]) implantations from 2004 to 2008 were reviewed. Studies were obtained preoperatively and at 1, 3, 6, 12, 18, and 24 months after surgery. AI was graded on an interval scale (0=none, 0.5=trivial, 1=mild, 1.5=mild-moderate, 2=moderate, 2.5=moderate-severe, 3=severe), and the change in AI at follow-up was analyzed with significance tests. Kaplan–Meier estimates for freedom from moderate or worse AI at follow-up were generated. Mixed-model linear regression was used to identify correlates of AI progression during LVAD support. The median (25th, 75th percentile) duration of LVAD support was 239 (112, 455) days, and preoperative AI grade was 0.0 (0.0, 0.0). At 6 months, 89±4% of subjects (n=49 at risk) were free from moderate or worse AI, but this was reduced to 74±7% (n=29 at risk) and 49±13% (n=13 at risk) by 12 and 18 months, respectively. Correlates (slope±SE) of AI progression included female sex (0.002±0.001;
P
=0.01), smaller body surface area (−0.003±0.001 per m
2
;
P
=0.0017), and HeartMate-II model type (0.002±0.001;
P
=0.039). Correlates (β±SE) of progressive AI on postoperative echocardiogram included increasing aortic sinus diameter (0.04±0.01 per mm;
P
=0.001), an aortic valve that remained closed (0.42±0.06;
P
<0.001) or only intermittently opened (0.34±0.09;
P
<0.001), and lower left ventricular diastolic (−0.002±0.0004 per cm
3
;
P
<0.001) and systolic (−0.002±0.0004 per cm
3
;
P
<0.001) volumes.

Conclusions—

AI progresses over time in LVAD-supported patients. As we move toward an era of long-term cardiac support, more studies are needed to determine the clinical significance of these findings.
Monetary Non-neutrality in a Multisector Menu Cost Model
Authors: Nakamura Emi , Steinsson Jón
Published: August 2010

Empirical evidence suggests that as much as one-third of the U.S. business cycle is due to nominal shocks. We calibrate a multisector menu cost model using new evidence on the cross-sectional distribution of the frequency and size of price changes in the U.S. economy. We augment the model to incorporate intermediate inputs. We show that the introduction of heterogeneity in the frequency of price change triples the degree of monetary non-neutrality generated by the model. We furthermore show that the introduction of intermediate inputs raises the degree of monetary non-neutrality by another factor of three, without adversely affecting the model's ability to match the large average size of price changes. A single-sector model with a frequency of price change equal to the median, rather than the mean, generates monetary non-neutrality similar to that in our multisector model. Our multisector model with intermediate inputs generates variation in real output in response to calibrated aggregate nominal shocks that can account for roughly 23% of the U.S. business cycle.