bluuebunny/crossref_metadata_2025 huggingface dataset:
Annoyance from environmental noise across the lifespan
Authors: Van Gerven Pascal W. M. , Vos Henk , Van Boxtel Martin P. J. , Janssen Sabine A. , Miedema Henk M. E.
Published: July 2009

Curvilinear effects of age on self-reported annoyance from environmental noise were investigated in a pooled international and a Dutch sample of in total 62,983 individuals aged between 15 and 102years. All respondents were frequently exposed to varying levels of transportation noise (i.e., aircraft, road traffic, and railway noise). Results reveal an inverted U-shaped pattern, where the largest number of highly annoyed individuals was found in the middle-aged segment of the sample (peaking around 45years) while the lowest number was found in the youngest and oldest age segments. This pattern was independent of noise exposure level and self-reported noise sensitivity. The inverted U-shape explains the absence of linear age effects in previous studies. The results are discussed in light of theories predicting an age-related vulnerability to noise.
Temperature modes for nonlinear Gaussian beams
Authors: Myers Matthew R. , Soneson Joshua E.
Published: July 2009

In assessing the influence of nonlinear acoustic propagation on thermal bioeffects, approximate methods for quickly estimating the temperature rise as operational parameters are varied can be very useful. This paper provides a formula for the transient temperature rise associated with nonlinear propagation of Gaussian beams. The pressure amplitudes for the Gaussian modes can be obtained rapidly using a method previously published for simulating nonlinear propagation of Gaussian beams. The temperature-mode series shows that the nth temperature mode generated by nonlinear propagation, when normalized by the fundamental, is weaker than the nth heat-rate mode (also normalized by the fundamental in the heat-rate series) by a factor of log(n)/n, where n is the mode number. Predictions of temperature rise and thermal dose were found to be in close agreement with full, finite-difference calculations of the pressure fields, temperature rise, and thermal dose. Applications to non-Gaussian beams were made by fitting the main lobe of the significant modes to Gaussian functions.
Evoked response study tool: A portable, rugged system for single and multiple auditory evoked potential measurements
Authors: Finneran James J.
Published: July 2009

Although the potential of using portable auditory evoked potential systems for field testing of stranded cetaceans has been long recognized, commercial systems for evoked potential measurements generally do not possess the bandwidth required for testing odontocete cetaceans and are not suitable for field use. As a result, there have been a number of efforts to develop portable evoked potential systems for field testing of cetaceans. This paper presents another such system, called the evoked response study tool (EVREST). EVREST is a Windows-based hardware/software system designed for calibrating sound stimuli and recording and analyzing transient and steady-state evoked potentials. The EVREST software features a graphical user interface, real-time analysis and visualization of recorded data, a variety of stimulus options, and a high level of automation. The system hardware is portable, rugged, battery-powered, and possesses a bandwidth that encompasses the audible range of echolocating odontocetes, making the system suitable for field testing of stranded or rehabilitating cetaceans.
Natural frequency of a gas bubble in a tube: Experimental and simulation results
Authors: Jang Neo W. , Gracewski Sheryl M. , Abrahamsen Ben , Buttaccio Travis , Halm Robert , Dalecki Diane
Published: July 2009

Use of ultrasonically excited microbubbles within blood vessels has been proposed for a variety of clinical applications. In this paper, an axisymmetric coupled boundary element and finite element code and experiments have been used to investigate the effects of a surrounding tube on a bubble’s response to acoustic excitation. A balloon model allowed measurement of spherical gas bubble response. Resonance frequencies match one-dimensional cylindrical model predictions for a bubble well within a rigid tube but deviate for a bubble near the tube end. Simulations also predict bubble translation along the tube axis and aspherical oscillations at higher amplitudes.
High frequency measurements of sound speed and attenuation in water-saturated glass-beads of varying size
Authors: Lee Keunhwa , Park Eungkyu , Seong Woojae
Published: July 2009

Acoustic measurements of p-wave speed and attenuation were made for water-saturated granular medium, consisting of six kinds of glass-beads with mean grain size ranging from 90 to 875 μm, at frequency range between 400 kHz and 1.1 MHz. Sound speed and attenuation were obtained using the inter-receiver broadband estimation technique. The measured data exhibit various frequency dependencies for the different mean grain sizes, consistent with earlier measurements from other researches. These results reveal that the trend of dispersion relation for the sound speed and attenuation, in the high frequency region, is strongly dependent on the range of Rayleigh parameter kd.
Nocardia nova
as the Causative Agent in Spondylodiscitis and Psoas Abscess
Authors: Hamdad Farida , Vidal Barbara , Douadi Youcef , Laurans Genevieve , Canarelli Brigitte , Choukroun Gabriel , Rodriguez-Nava Veronica , Boiron Patrick , Beaman Blaine , Eb François
Published: July 2009

We describe here the first case of
Nocardia nova
spondylodiscitis accompanied by a psoas abscess due to spreading from pulmonary nocardiosis.
Nocardia
was cultured from all affected sites. After 1 year of an appropriate antimicrobial therapy and a surgical drainage of the abscess that was required, the patient's clinical condition had improved.
New Exploration and Understanding of Traditional Chinese Medicine
Authors: Xutian Stevenson , Zhang Jun , Louise Wozniak
Published: July 2009

Traditional Chinese Medicine (TCM), originating from oriental philosophy and culture, has been developing through a series of special research and experiments with meditation, accumulation of experiences, and a complete comprehension of ancient theories and methods. However, compared with Conventional Western Medicine (CWM), the theory of TCM is complicated and not easily accepted by Westerners. It is important to explore TCM by using modern scientific techniques and theories. Utilizing his frontier experience and up-to-date scientific knowledge, Dr. Qian Xuesen has been trying to incorporate some key principles with the comprehensive understanding of TCM and clarify difficult but important concepts and principles. Some examples are the existence of invisible matter; 'Qi' and 'Qi monism'; the Heart representing the 'whole will' of human beings; the water environment functioning as a fundamental condition of life; the human body being united with nature and universe as one; the spirit and physical body always being considered unified and connected with the five viscera, especially with the Heart; and the Chinese herbal formula working with different principles than CWM drugs. These works are important for understanding the essence of TCM, the promoting of the modernization of TCM theories by means of the latest of achievements in scientific developments, establishing the direction for future medicines with TCM characteristics, uniting Chinese and Western medicines, and exploiting a bright future for the health of mankind.
Gingko biloba Extract (EGb 761) Prevents Ischemic Brain Injury by Activation of the Akt Signaling Pathway
Authors: Cho Jae-Hyeon , Sung Jin-Hee , Cho Eun-Hae , Won Chung-Kil , Lee Hyo-Jong , Kim Myeong-Ok , Koh Phil-Ok
Published: July 2009

EGb 761 is a standardized extract of Gingko biloba that exerts protective effects against ischemic brain injury. This study investigated whether EGb 761 modulates the neuroprotective effects through Akt and its downstream targets, Bad and FKHR. Adult male rats were treated with EGb 761 (100 mg/kg) or vehicle prior to middle cerebral artery occlusion (MCAO). Brains were collected 24 hours after MCAO and infarct volumes were analyzed. EGb 761 significantly reduced infarct volume. Potential activation was mearsured by phosphorylation of Akt at Ser473, Bad at Ser136, and FKHR at Ser256 using Western blot analysis. EGb 761 prevented the injury-induced decrease of pAkt and its down stream targets, pBad and pFKHR. Furthermore, EGb 761 prevented the injury-induced increase of cleaved caspase-3 levels. In conclusion, this study suggests that EGb 761 prevents cell death due to brain injury and that EGb 761 protection is affected by preventing the injury-induce decrease of Akt phosphorylation.
Potential Anti-Cancer Activities of Furanodiene, A Sesquiterpene from Curcuma wenyujin
Authors: Sun Xiu-Yan , Zheng Yan-Ping , Lin Dong-Hai , Zhang Hui , Zhao Feng , Yuan Chun-Su
Published: July 2009

Furanodiene is a sesquiterpene extracted from the essential oil of the rhizome of Curcuma wenyujin Y.H. Chen et C. Ling (Wen Ezhu). Furanodiene is the primary component in Wen Ezhu's essential oil, accounting for more than 20% by weight. In vitro, MTT assay was used to compare the inhibitory effects of furanodiene and Wen Ezhu's essential oil on 11 human cancer cell lines. Compared to the essential oil, furanodiene showed stronger growth inhibitions on Hela, Hep-2, HL-60, PC3, SGC-7901 and HT-1080 cells with IC50 between 0.6–4.8 μg/ml. In vivo, furanodiene was also found to exhibit inhibitory effects on the growth of uterine cervical (U14) and sarcoma 180 (Sl80) tumors in mice. Our data suggests that furanodiene, an active component from the essential oil of Wen Ezhu, possesses efficacy against uterine cervical cancer.
Effect ofZizyphus jujubaExtract on the Inhibition of Adipogenesis in 3T3-L1 Preadipocytes
Authors: Kubota Hiroaki , Morii Risako , Kojima-Yuasa Akiko , Huang Xuedan , Yano Yosihisa , Matsui-Yuasa Isao
Published: July 2009

Obesity, the leading metabolic disease in the world, is a serious health problem in industrialized countries. The Zizyphus jujuba fruit has been used as traditional Chinese medicinal herb and considered to affect various physiological functions in the body for thousands of years. We investigated the anti-obesity effect of Z. jujuba on adipocyte differentiation of 3T3-L1 preadipocytes and found that treatment with an extract of Z. jujuba suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity without affecting cell viability. Further fractionation of the initial Z .jujuba extract with organic solvent revealed that the chloroform fraction ( CHCl3- F ) elicited the most inhibitory effect, which involved significant attenuation of the expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)γ and CCAAT enhancer binding proteins (C/EBPs) at the protein level. These results suggest that CHCl3- F may block adipogenesis, at least in part, by decreasing the expression of PPARγ, C/EBPα and β.
EFFECT OF NANO-SIZED OXALATE PRECURSOR ON THE FORMATION OF GdBa2Cu3O7-δ PHASE VIA COPRECIPITATION METHOD
Authors: HAMADNEH I. , AHMAD A. M. , WAHID M. H. , ZAINAL Z. , ABD-SHUKOR R.
Published: July 2009

The formation of GdBa 2 Cu 3 O 7-δ( Gd123 ) from metal oxalate precursor with average grain size less than 40 nm using the coprecipitation method is reported. The coprecipitated powders were heated at 900°C for 12 hours, pelletized and then sintered at 920°C for 15, 20 and 25 hours, respectively. All samples showed a dominant Gd123 phase with the orthorhombic structure. The amount of impurity phase Gd 2 BaCuO 5( Gd211 ) can be controlled by varying the sintering time. This work shows that nano-sized oxalate powders produced via coprecipitation method can be an effective technique to synthesize high quality GdBa 2 Cu 3 O 7-δ samples where the amount of ( Gd211 ) can be controlled by varying the sintering duration. The percentage of Gd211 impurity decreased with increase in sintering time. This result is useful in utilizing the Gd211 phase as pinning center in enhancing the transport properties.
STUDY ON ELASTIC ANALYSIS OF CRACK PROBLEM OF TWO-DIMENSIONAL DECAGONAL QUASICRYSTALS OF POINT GROUP 10, $\overline {10}$
Authors: LI WU , FAN TIAN YOU
Published: July 2009

By introducing a stress potential function, we transform the plane elasticity equations of two-dimensional quasicrystals of point group 10, [Formula: see text] to a partial differential equation. And then we use the complex variable function method for classical elasticity theory to that of the quasicrystals. As an example, a decagonal quasicrystal in which there is an arc is subjected to a uniform pressure p in the elliptic notch of the decagonal quasicrystal is considered. With the help of conformal mapping, we obtain the exact solution for the elliptic notch problem of quasicrystals. The work indicates that the stress potential and complex variable function methods are very useful for solving the complicated boundary value problems of higher order partial differential equations which originate from quasicrystal elasticity.
ANALYTIC EQUATION OF STATE FOR EXP-6 POTENTIAL FLUID AND APPLICATION TO N2 FLUID
Authors: XUE XINYING , SUN JIUXUN , TIAN RONGGANG , YU FEI , YANG WEI
Published: July 2009

An analytical expression for the equation of state and thermo-physical quantities of exponential-6 ( exp- 6) fluid are derived based on the Ross variational perturbation theory. The developed formalism is applied to N 2 fluid. Comparisons of theory and simulations for exp- 6 potential fluid are presented. The agreement of numerical results of pressure and internal energy with Monte Carlo (MC) simulations show that the theoretical model is satisfactory except where a few points from metastable ones appeared in literature. The expression has been applied to fluid nitrogen and the fitting to experimental data of fluid N 2 is surprisingly good. The predictions of pressure in the range of high temperature and high density are satisfactory. It has also been found that the analytic equation of state for exp- 6 potential fluid based on RDF proposed by Sun et al. is better in a wide range of pressures and temperatures than that derived from PY expression. Comparisons show that a potential dependence on temperature and density (or volume) may be necessary for the understanding of interaction between N 2 molecules. The equation of state can also be extended to application of important real gases such as H 2, O 2, CH 4, CO and CO 2.
A MoSi2–SiC–Si/MoSi2 COATING TO PROTECT CARBON/CARBON COMPOSITES AGAINST OXIDATION AT 1700°C
Authors: FU QIAN-GANG , LI HE-JUN , WANG YONG-JIE , LI KE-ZHI , WU HENG
Published: July 2009

In order to protect carbon/carbon ( C / C ) composites from oxidation at 1700°C, a MoSi 2– SiC – Si / MoSi 2 coating was prepared on the surface of these composites by a simple and effective method. The MoSi 2– SiC – Si inner layer was obtained by pack cementation, and the MoSi 2 outer layer was prepared by slurry coating using silicon-sol as the caking agent. The microstructures of the as-prepared coating were examined by X-ray diffraction and scanning electron microscope. Oxidation test shows that, the as-received coating can protect C / C composites from oxidation for more than 107 h at 1700°C in air. The excellent anti-oxidation ability of this coating is attributed to its dense structure and the formation of the SiO 2 film on the coating surface during oxidation.
Neo-luddism and the demonisation of technology
Authors: Bowman Don
Published: July 2009

The Internet is a primary engine of innovation, communication, and entertainment in our society. It is used by diverse and potentially conflicting interests. When these interests collide in the form of technology, should the Internet stay true to its roots and let things take their course naturally, or should regulation and legislation be enacted to control what may or may not be done. This author believes public opinion is best served by light regulation and a strong focus on allowing technological innovation to take its natural course.
Research challenges in future networks
Authors: Medhi Deep , Freeman Peter A.
Published: July 2009

A US-Japan Workshop on Future Networks was held in Palo Alto, CA on October 31 - November 1, 2008. This workshop brought together leading US and Japanese network researchers and network research infrastructure developers who are interested in future networks. The focus was on research issues and experimental infrastructure to support research on future generation networks. The goal was to foster cooperation and communication between peers in the two countries. Through this workshop, a number of research challenges were identified. The workshop also made recommendations to: create a new funding mechanism to foster special collaborations in networking and experimentation, extend current national testbeds with international connectivity; and urge the respective governments to exert strong leadership to ensure that collaborative research for creating future networks is carried out.
The ACM SIGCOMM 2009 technical program committee process
Authors: Papagiannaki Konstantina , Rizzo Luigi
Published: July 2009

Selecting a technical program for a conference, and running the process so that decisions are well received by authors and participants, is a challenging task. We report our experience in running the SIGCOMM 2009 Technical Program Committee (TPC). The purpose of this article is to document the process that we followed, and discuss it critically. This should let authors get a better understanding of what led to the final acceptance or rejection of their work, and hopefully allow colleagues in charge of similar tasks make use of our experience.
Pancreatic β-cell overexpression of the glucagon receptor gene results in enhanced β-cell function and mass
Authors: Gelling Richard W. , Vuguin Patricia M. , Du Xiu Quan , Cui Lingguang , Rømer John , Pederson Raymond A. , Leiser Margarita , Sørensen Heidi , Holst Jens J. , Fledelius Christian , Johansen Peter B. , Fleischer Norman , McIntosh Christopher H. S. , Nishimura Erica , Charron Maureen J.
Published: July 2009

In addition to its primary role in regulating glucose production from the liver, glucagon has many other actions, reflected by the wide tissue distribution of the glucagon receptor (Gcgr). To investigate the role of glucagon in the regulation of insulin secretion and whole body glucose homeostasis in vivo, we generated mice overexpressing the Gcgr specifically on pancreatic β-cells (RIP-Gcgr). In vivo and in vitro insulin secretion in response to glucagon and glucose was increased 1.7- to 3.9-fold in RIP-Gcgr mice compared with controls. Consistent with the observed increase in insulin release in response to glucagon and glucose, the glucose excursion resulting from both a glucagon challenge and intraperitoneal glucose tolerance test (IPGTT) was significantly reduced in RIP-Gcgr mice compared with controls. However, RIP-Gcgr mice display similar glucose responses to an insulin challenge. β-Cell mass and pancreatic insulin content were also increased (20 and 50%, respectively) in RIP-Gcgr mice compared with controls. When fed a high-fat diet (HFD), both control and RIP-Gcgr mice developed similar degrees of obesity and insulin resistance. However, the severity of both fasting hyperglycemia and impaired glucose tolerance (IGT) were reduced in RIP-Gcgr mice compared with controls. Furthermore, the insulin response of RIP-Gcgr mice to an IPGTT was twice that of controls when fed the HFD. These data indicate that increased pancreatic β-cell expression of the Gcgr increased insulin secretion, pancreatic insulin content, β-cell mass, and, when mice were fed a HFD, partially protected against hyperglycemia and IGT.
Motor unit number estimate as a predictor of motor dysfunction in an animal model of type 1 diabetes
Authors: Souayah Nizar , Potian Joseph G. , Garcia Carmen C. , Krivitskaya Natalia , Boone Christine , Routh Vanessa H. , McArdle Joseph J.
Published: July 2009

Peripheral neuropathy is a common complication of diabetes that leads to severe morbidity. In this study, we investigated the sensitivity of motor unit number estimate (MUNE) to detect early motor axon dysfunction in streptozotocin (STZ)-treated mice. We compared the findings with in vitro changes in the morphology and electrophysiology of the neuromuscular junction. Adult Thy1-YFP and Swiss Webster mice were made diabetic following three interdaily intraperitoneal STZ injections. Splay testing and rotarod performance assessed motor activity for 6 wk. Electromyography was carried out in the same time course, and compound muscle action potential (CMAP) amplitude, latency, and MUNE were estimated. Two-electrode voltage clamp was used to calculate quantal content (QC) of evoked transmitter release. We found that an early reduction in MUNE was evident before a detectable decline of motor activity. CMAP amplitude was not altered. MUNE decrease accompanied a drop of end-plate current amplitude and QC. We also observed small axonal loss, sprouting of nerve endings, and fragmentation of acetylcholine receptor clusters at the motor end plate. Our results suggest an early remodeling of motor units through the course of diabetic neuropathy, which can be readily detected by the MUNE technique. The early detection of MUNE anomalies is significant because it suggests that molecular changes associated with pathology and leading to neurodegeneration might already be occurring at this stage. Therefore, trials of interventions to prevent motor axon dysfunction in diabetic neuropathy should be administered at early stages of the disorder.
Oxidative stress and dysregulation of the taurine transporter in high-glucose-exposed human Schwann cells: implications for pathogenesis of diabetic neuropathy
Authors: Askwith Trevor , Zeng Wei , Eggo Margaret C. , Stevens Martin J.
Published: July 2009

In human Schwann cells, the role of taurine in regulating glucose-induced changes in antioxidant defense systems has been examined. Treatment with high glucose for 7 days induced reactive oxygen species, increased 4-hydroxynoneal adducts (20 ± 5%, P < 0.05) and poly(ADP-ribosyl)ated proteins (40 ± 13%, P < 0.05). Increases in these markers of oxidative stress were reversed by simultaneous incubation in 0.25 mM taurine. Both high glucose and taurine independently increased superoxide dismutase and catalase activity and decreased glutathione levels, but their effects were not additive. Glucose reduced taurine transporter (TauT) mRNA and protein in a dose-dependent manner with maximal decreases of 66 ± 6 and 63 ± 12%, respectively ( P < 0.05 both). The Vmaxfor taurine uptake was decreased in 30 mM glucose from 61 ± 5 to 42 ± 3 pmol·min−1·mg protein−1( P < 0.001). Glucose-induced TauT downregulation could be reversed by inhibition of aldose reductase, a pathway that depletes NADPH and increases osmotic stress and protein glycation. TauT protein was increased more than threefold, and the Vmaxfor taurine uptake doubled ( P < 0.05 both) by prooxidants. TauT downregulation was reversed both by treatment with the antioxidant α-lipoic acid, which increased TauT mRNA by 60% and Vmaxby 50% ( P < 0.05 both), and by the aldose reductase inhibitor sorbinil, which increased TauT mRNA 380% and Vmaxby 98% ( P < 0.01 both). These data highlight the potential therapeutic benefits of taurine supplementation in diabetic complications and provide mechanisms whereby taurine restoration could be achieved in order to prevent or reverse diabetic complications.
Role of iduronate-2-sulfatase in glucose-stimulated insulin secretion by activation of exocytosis
Authors: Piquer S. , Casas S. , Quesada I. , Nadal A. , Julià M. , Novials A. , Gomis R.
Published: July 2009

Iduronate-2-sulfatase (IDS) is a lysosomal enzyme expressed in pancreatic islets responsible for the degradation of proteoglycans such as perlecan and dermatan sulfate. Previous findings of our group demonstrated the involvement of IDS in the normal pathway of lysosomal degradation of secretory peptides, suggesting a role of this enzyme in β-cell secretory functionality. The present study was undertaken to characterize the effect of IDS overexpression on insulin release. INS1E cells were transiently transfected with a construct encoding human IDS (hIDS). hIDS overexpression was associated with a gain of function detected by a reduction in heparan sulfate content. hIDS potentiated the glucose-stimulated insulin secretory response compared with controls (61%) with no changes in insulin mRNA levels or insulin peptide content. Results on quantification of the exocytotic process showed a significant increase in hIDS-transfected cells compared with controls. Furthermore, ultramorphological analysis demonstrated an increase in the number of granules in the immediate vicinity of the plasma membrane in hIDS-transfected cells and a decrease in total vesicles per square micrometer. hIDS overexpression induced phosphorylation of protein kinase C (PKC) α and its newly myristoylated alanine-rich C kinase substrate, MARCKS. We conclude that IDS has a role in glucose-stimulated insulin secretion via a mechanism that involves the activation of exocytosis through phosphorylation of PKCα and MARCKS.
Opposite responses to lidocaine between intrapulmonary mechanical and chemical sensors
Authors: Li Huafeng , Du Lei , Otmishi Peyman , He Yuwen , Guardiola Juan , Yu Jerry
Published: July 2009

We attempted to determine whether intrapulmonary sensory receptors are nourished by the pulmonary or the systemic circulation. Single-unit activity from the cervical vagus nerve was recorded in anesthetized, open chest, mechanically ventilated rabbits, comparing responses to right or left ventricular injection of 2% lidocaine (at 4 mg/kg). Airway mechanosenors [slowly adapting receptor (SARs) and rapidly adapting receptors] were inhibited by lidocaine, whereas chemosensors (C-fiber receptors and high-threshold Aδ-receptors) were stimulated. Furthermore, all types of airway sensors were perfused preferentially by the pulmonary circulation. For example, 14 of the 15 tested SARs ceased discharge at 4.1 ± 0.6 s after lidocaine injection into the right ventricle. The blocking effect lasted 35 ± 6.2 s. In contrast, none of the 15 SARs ceased their activity after lidocaine injection into the left ventricle. Our data show that intrapulmonary sensors are mainly nourished by the pulmonary circulation. Their very short latency indicates that these sensors receive ample blood supply. Thus, intrapulmonary sensors rely on the pulmonary circulation to detect bioactive agents in the blood.
The timing of “catch-up growth” affects metabolism and appetite regulation in male rats born with intrauterine growth restriction
Authors: Coupé Bérengère , Grit Isabelle , Darmaun Dominique , Parnet Patricia
Published: July 2009

Epidemiological studies demonstrated a relationship between low birth weight mainly caused by intrauterine growth restriction (IUGR) and adult metabolic disorders. The concept of metabolic programming centers on the idea that nutritional and hormonal status during the key period of development determines the long-term control of energy balance by programming future feeding behavior and energy expenditure. The present study examined the consequence of early or late “catch-up growth” after IUGR on feeding behavior and metabolic cues of male offspring of rat dams exposed to protein restriction during gestation and/or lactation. Our results suggest that early catch-up growth may be favorable for fasting metabolic parameters at weaning, as no differences were observed on plasma leptin, triglyceride, glucose, and insulin levels compared with controls. In contrast, if pups remained malnourished until weaning, low insulin concentration was detected and was accompanied by hyperphagia associated with a large increase in hypothalamic NPY and AgRP mRNA expression. At adult age, on a regular chow diet, only the meal structure was modified by fetal programming. The two IUGR groups demonstrated a reduced meal duration that enhanced the speed of food ingestion and consequently increased the rest period associated to the satiety state without changes in the hypothalamic expression of appetite neuropeptides. Our findings demonstrate that in IUGR, regardless of postnatal growth magnitude, metabolic programming occurred in utero and was responsible for both feeding behavior alteration and postprandial higher insulin level in adults. Additionally, catch-up growth immediately after early malnutrition could be a key point for the programming of postprandial hyperleptinemia.
Metabolic phenotyping of a model of adipocyte differentiation
Authors: Roberts Lee D. , Virtue Sam , Vidal-Puig Antonio , Nicholls Andrew W. , Griffin Julian L.
Published: July 2009

The 3T3-L1 murine cell line is a robust and widely used model for the study of adipogenesis and processes occurring in mature adipocytes. The fibroblastic like cells can be induced by hormones to differentiate into mature adipocytes. In this study, the metabolic phenotype associated with differentiation of the 3T3-L1 cell line has been studied using gas chromatography-mass spectrometry,1H nuclear magnetic resonance spectroscopy, liquid chromatography-mass spectrometry, direct infusion-mass spectrometry, and13C substrate labeling in conjunction with multivariate statistics. The changes in metabolite concentrations at distinct periods during differentiation have been defined including alterations in the TCA cycle, glycolysis, the production of odd chain fatty acids by α-oxidation, fatty acid synthesis, fatty acid desaturation, polyamine biosynthesis, and trans-esterification to produce complex lipids. The metabolic changes induced during differentiation of the 3T3-L1 cell line were then compared with the metabolic differences between pre- and postdifferentiation primary adipocytes. These metabolic alterations reflect the changing role of the 3T3-L1 cells during differentiation, as well as possibly providing metabolic triggers to stimulate the processes which occur during differentiation.
Robust Stabilization Approach andH∞Performance via Static Output Feedback for a Class of Nonlinear Systems
Authors: Bedioui Neila , Salhi Salah , Ksouri Mekki
Published: July 2009

This paper deals with the stability and stabilization problems for a class of discrete‐time nonlinear systems. The systems are composed of a linear constant part perturbated by an additive nonlinear function which satisfies a quadratic constraint. A new approach to design a static output feedback controller is proposed. A sufficient condition, formulated as an LMI optimization convex problem, is developed. In fact, the approach is based on a family of LMI parameterized by a scalar, offering an additional degree of freedom. The problem of performance taking into account anH∞criterion is also investigated. Numerical examples are provided to illustrate the effectiveness of the proposed conditions.
On the Low‐Temperature Response of Semiconductor Gas Sensors
Authors: Helwig A. , Müller G. , Sberveglieri G. , Eickhoff M.
Published: July 2009

The present paper compares three different kinds of semiconductor gas sensing
materials: metal oxides (MOX), hydrogen‐terminated diamond (HD), and hydrogenated
amorphous silicon (a‐Si:H). Whereas in MOX materials oxygen is the chemically reactive
surface species, HD and a‐Si:H are covalently bonded semiconductors with hydrogenterminated
surfaces. We demonstrate that these dissimilar semiconductor materials exhibit
the same kind of low‐temperature gas response. This low‐temperature response‐mechanism
is mediated by a thin layer of adsorbed water with the semiconductor materials themselves
acting as pH sensors. In this adsorbate‐limited state the gas sensitivity is limited to
molecular species that can easily dissolve in H2O and subsequently undergo electrolytic
dissociation. At higher temperatures, where a closed layer of adsorbed water can no longer
exist, the gas response is limited by direct molecule‐semiconductor interactions. In this
latter mode of operation, MOX gas sensors respond to adsorbed gases according to their
different oxidising or reducing properties. Hydrogenated amorphous silicon (a‐Si:H), on the
other hand, exhibits a significantly different cross sensitivity profile, revealing that gas‐surface
interactions may largely be restricted to analyte molecules with lone‐pair and
electron‐deficient three‐centre orbitals.
Epsilon Haemoglobin Specific Antibodies with Applications in Noninvasive Prenatal Diagnosis
Authors: Sørensen Morten Dræby , Gonzalez Dosal Regina , Jensen Kim Bak , Christensen Britta , Kølvraa Steen , Jensen Uffe Birk , Kristensen Peter
Published: July 2009

Invasive procedures for prenatal diagnosis are associated with increased risk of abortion; thus, development of noninvasive procedures would be beneficial. Based on the observation that embryonic nucleated red blood cell (NRBC) crosses the placenta and enters the circulation of pregnant women, the ability to identify such cell would allow development of such procedures. Identification of NRBCs in blood samples would be possible provided that specific antibodies are available. Here we have isolated recombinant antibodies using phage display. From the panel of antibody fragments specifically recognising ε‐Hb, one was chosen for further characterization, DAb1. DAb1 binds to ε‐Hb both in Western blots and immunocytochemistry. Several ε‐Hb positive cells were detected in a blood sample taken as postchorionic villus sampling (CVS). To evaluate the sensitivity of the method, K562 cells (which express ε‐Hb) were spiked in a blood sample followed by staining in solution and FACS analysis.
Anaplasma phagocytophilumandAnaplasma marginaleElicit Different Gene Expression Responses in Cultured Tick Cells
Authors: Zivkovic Zorica , Blouin Edmour F. , Manzano-Roman Raúl , Almazán Consuelo , Naranjo Victoria , Massung Robert F. , Jongejan Frans , Kocan Katherine M. , de la Fuente José
Published: July 2009

The genusAnaplasma(Rickettsiales: Anaplasmataceae) includes obligate tick-transmitted intracellular organisms,Anaplasma phagocytophilumandAnaplasma marginalethat multiply in both vertebrate and tick host cells. Recently, we showed thatA. marginaleaffects the expression of tick genes that are involved in tick survival and pathogen infection and multiplication. However, the gene expression profile inA. phagocytophilum-infected tick cells is currently poorly characterized. The objectives of this study were to characterize tick gene expression profile inIxodes scapularisticks and cultured ISE6 cells in response to infection withA. phagocypthilumand to compare tick gene expression responses inA. phagocytophilum- andA. marginale-infected tick cells by microarray and real-time RT-PCR analyses. The results of these studies demonstrated modulation of tick gene expression byA. phagocytophilumand provided evidence of different gene expression responses in tick cells infected withA. phagocytophilumandA. marginale. These differences inAnaplasma-tick interactions may reflect differences in pathogen life cycle in the tick cells.
Immune Reactions Against Elongation Factor 2 Kinase: Specific Pathogenesis of Gastric Ulcer fromHelicobacter pyloriInfection
Authors: Ayada Kiyoshi , Yokota Kenji , Kawahara Yoshiro , Yamamoto Yumiko , Hirai Kazuyuki , Inaba Tomoki , Kita Masahide , Okada Hiroyuki , Yamamoto Kazuhide , Oguma Keiji
Published: July 2009

Helicobacter pylori(H. pylori) infection is a definite causative factor for gastric ulcers (GUs). In the present study we detected a specific antigen of gastric epithelial cells (HGC-27) using cell ELISA, which was recognized by the sera of GU patients (n=20) but not in patients with chronic gastritis (CG;n=20) or in healthy volunteers (HC;n=10). This antigen was over-expressed by a stressful (heat-stressed) environment, and was identified as elongation factor 2 kinase (EF-2K) by western blotting. The GU patients' lymphocytes stimulated byH. pylorispecifically disrupted heat-stressed HGC-27 cells in a cytotoxic assay. In flow cytometry, the effector cells (lymphocytes) from GU patients were significantly differentiated to T helper type 1 lymphocyte (Th1) and cytotoxic T lymphocyte (CTL) as opposed to those from CG patients. The target cells (HGC-27) expressed EF-2K and MHC-class I together with costimulatory molecules from heat stress. This antigen specific immune mechanism could have a prominent role in the pathogenesis of GU.
Improving Response Rates to EGFR-Targeted Therapies for Head and Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment with Src Inhibitors
Authors: Egloff Ann Marie , Grandis Jennifer Rubin
Published: July 2009

The epidermal growth factor receptor- (EGFR-) directed antibody, cetuximab, was FDA-approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 2006. Additional EGFR-targeting agents in clinical development for SCCHN include other EGFR-directed antibodies, tyrosine kinase inhibitors and antisense DNA. Although the majority of SCCHN overexpress EGFR, SCCHN clinical responses to EGFR-targeting agents have been modest. Molecular predictors for SCCHN response to EGFR-targeted therapies have not been identified. However, molecular correlate studies in lung cancer and colon cancer, which have EGFR-targeted therapeutics FDA-approved for treatment, may provide insights. We describe candidate predictive markers for SCCHN response to EGFR-targeted therapies and their prevalence in SCCHN. Clinical response will likely be improved by targeted therapy combination treatments. Src family kinases mediate EGFR-dependent and -independent tumor progression pathways in many cancers including SCCHN. Several Src-targeting agents are in clinical development for solid malignancies. Molecular correlate studies for Src-targeting therapies are few and biomarkers correlated with patient response are limited. Identifying SCCHN patients who will respond to combined EGFR- and Src-targeting will require further characterization of molecular correlates. We discuss rationale for EGFR and Src co-targeting for SCCHN treatment and describe recent clinical trials implementing combined Src- and EGFR-targeted therapeutics.
Functional Equations Related to Inner Product Spaces
Authors: Park Choonkil , Park Won-Gil , Najati Abbas
Published: July 2009

Let V, W be real vector spaces. It is shown that an odd mapping
f : V → W satisfies for all x1, …, x2n ∈ V if and only if the odd mapping f : V → W is Cauchy additive. Furthermore, we prove the generalized Hyers‐Ulam stability of the above functional equation
in real Banach spaces.
The Cell Fate Determination Factor DACH1 Is Expressed in Estrogen Receptor-α–Positive Breast Cancer and Represses Estrogen Receptor-α Signaling
Authors: Popov Vladimir M. , Zhou Jie , Shirley L. Andrew , Quong Judy , Yeow Wen-Shuz , Wright Jennifer A. , Wu Kongming , Rui Hallgeir , Vadlamudi Ratna K. , Jiang Jie , Kumar Rakesh , Wang Chenguang , Pestell Richard G.
Published: July 2009

The Dachshund (dac) gene, initially cloned as a dominant inhibitor of the Drosophila hyperactive EGFR mutant ellipse, encodes a key component of the cell fate determination pathway involved in Drosophila eye development. Analysis of more than 2,200 breast cancer samples showed improved survival by some 40 months in patients whose tumors expressed DACH1. Herein, DACH1 and estrogen receptor-α (ERα) expressions were inversely correlated in human breast cancer. DACH1 bound and inhibited ERα function. Nuclear DACH1 expression inhibited estradiol (E2)-induced DNA synthesis and cellular proliferation. DACH1 bound ERα in immunoprecipitation-Western blotting, associated with ERα in chromatin immunoprecipitation, and inhibited ERα transcriptional activity, requiring a conserved DS domain. Proteomic analysis identified proline, glutamic acid, and leucine rich protein 1 (PELP1) as a DACH1-binding protein. The DACH1 COOH terminus was required for binding to PELP1. DACH1 inhibited induction of ERα signaling. E2 recruited ERα and disengaged corepressors from DACH1 at an endogenous ER response element, allowing PELP1 to serve as an ERα coactivator. DACH1 expression, which is lost in poor prognosis human breast cancer, functions as an endogenous inhibitor of ERα function. [Cancer Res 2009;69(14):5752–60]
Targeted In vivo Imaging of Integrin αvβ6 with an Improved Radiotracer and Its Relevance in a Pancreatic Tumor Model
Authors: Hausner Sven H. , Abbey Craig K. , Bold Richard J. , Gagnon M. Karen , Marik Jan , Marshall John F. , Stanecki Cathy E. , Sutcliffe Julie L.
Published: July 2009

The cell surface receptor αvβ6 is epithelial specific, and its expression is tightly regulated; it is low or undetectable in adult tissues but has been shown to be increased in many different cancers, including pancreatic, cervical, lung, and colon cancers. Studies have described αvβ6 as a prognostic biomarker linked to poor survival. We have recently shown the feasibility of imaging αvβ6 in vivo by positron emission tomography (PET) using the peptide [18F]FBA-A20FMDV2. Here, we describe improved αvβ6 imaging agents and test their efficacy in a mouse model with endogenous αvβ6 expression. The modified compounds maintained high affinity for αvβ6 and >1,000-fold selectivity over related integrins (by ELISA) and showed significantly improved αvβ6-dependent binding in cell-based assays (>60% binding versus <10% for [18F]FBA-A20FMDV2). In vivo studies using either a melanoma cell line (transduced αvβ6 expression) or the BxPC-3 human pancreatic carcinoma cell line (endogenous αvβ6 expression) revealed that the modified compounds showed significantly improved tumor retention. This, along with good clearance of nonspecifically bound activity, particularly for the new radiotracer [18F]FBA-PEG28-A20FMDV2, resulted in improved PET imaging. Tumor/pancreas and tumor/blood biodistribution ratios of >23:1 and >47:1, respectively, were achieved at 4 hours. Significantly, [18F]FBA-PEG28-A20FMDV2 was superior to 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) in imaging the BxPC-3 tumors. Pancreatic ductal adenocarcinoma is highly metastatic and current preoperative evaluation of resectability using noninvasive imaging has limited success, with most patients having metastases at time of surgery. The fact that these tumors express αvβ6 suggests that this probe has significant potential for the in vivo detection of this malignancy, thus having important implications for patient care and therapy. [Cancer Res 2009;69(14):5843–50]
Overexpression of DPAGT1 Leads to Aberrant N-Glycosylation of E-Cadherin and Cellular Discohesion in Oral Cancer
Authors: Nita-Lazar Mihai , Noonan Vikki , Rebustini Ivan , Walker Janice , Menko A. Sue , Kukuruzinska Maria A.
Published: July 2009

Cancer cells are frequently characterized by aberrant increases in protein N-glycosylation and by disruption of E-cadherin–mediated adherens junctions. The relationship between altered N-glycosylation and loss of E-cadherin adhesion in cancer, however, remains unclear. Previously, we reported that complex N-glycans on the extracellular domains of E-cadherin inhibited the formation of mature adherens junctions. Here, we examined whether dysregulated N-glycosylation was one of the underlying causes for cellular discohesion in oral cancer. We show that dense cultures of human salivary epidermoid carcinoma A253 cells exhibited elevated expression of DPAGT1, the gene that initiates protein N-glycosylation. Overexpression of DPAGT1 correlated with the production of E-cadherin–bearing complex N-glycans in nascent adherens junctions. Partial inhibition of DPAGT1 with small interfering RNA reduced the complex N-glycans of E-cadherin and increased the abundance of α-catenin and stabilizing proteins in adherens junctions. This was associated with the assembly of functional tight junctions. The inverse relationship between DPAGT1 expression and intercellular adhesion was a feature of oral squamous cell carcinoma. Oral squamous cell carcinomas displayed overexpression of DPAGT1 that correlated with diminished localization of E-cadherin and α-catenin at the sites of adherens junctions. Our studies show for the first time that DPAGT1 is an upstream regulator of E-cadherin N-glycosylation status and adherens junction composition and suggest that dysregulation of DPAGT1 causes disturbances in intercellular adhesion in oral cancer. [Cancer Res 2009;69(14):5673–80]
MUC1, a New Hypoxia Inducible Factor Target Gene, Is an Actor in Clear Renal Cell Carcinoma Tumor Progression
Authors: Aubert Sébastien , Fauquette Valérie , Hémon Brigitte , Lepoivre Réjane , Briez Nicolas , Bernard David , Van Seuningen Isabelle , Leroy Xavier , Perrais Michaël
Published: July 2009

The hypoxia inducible factor (HIF) signaling pathway is known as the main renal carcinogenetic pathway. MUC1, an O-glycoprotein membrane-bound mucin, is overexpressed in clear renal cell carcinomas (cRCC) with correlation to two major prognostic factors: tumor-node-metastasis stage and nuclear Fürhman grade. We questioned whether there is a direct link between the HIF pathway and MUC1 overexpression in renal tumors. Interestingly, we observed concomitant increase of HIF-1α and MUC1 in metastatic cRCC group versus nonmetastatic cRCC group. Using different renal cell models and small interfering RNA assays targeting either HIF-1α or YC-1, a HIF-1 pharmacologic inhibitor, we showed induction of MUC1 expression under hypoxia by a HIF-dependent mechanism. Chromatin immunoprecipitation assay showed a direct binding of HIF-1α at the MUC1 promoter. In addition, combined site-directed mutagenesis and gel shift assay allowed the identification of two functional putative hypoxia responsive elements at −1488/−1485 and at −1510/−1507 in the promoter. Using a rat kidney model of ischemia/reperfusion, we confirmed in vivo that clamping renal pedicle for 1 hour followed by 2 hours of reperfusion induced increased MUC1 expression. Furthermore, MUC1 knockdown induced significant reduction of invasive and migration properties of renal cancer cells under hypoxia. Altogether, these results show that MUC1 is directly regulated by HIF-1α and affects the invasive and migration properties of renal cancer cells. Thus, MUC1 could serve as a potential therapeutic target in cRCC. [Cancer Res 2009;69(14):5707–15]
Xenoestrogen-Induced Epigenetic Repression of microRNA-9-3 in Breast Epithelial Cells
Authors: Hsu Pei-Yin , Deatherage Daniel E. , Rodriguez Benjamin A.T. , Liyanarachchi Sandya , Weng Yu-I , Zuo Tao , Liu Joseph , Cheng Alfred S.L. , Huang Tim H-M.
Published: July 2009

Early exposure to xenoestrogens may predispose to breast cancer risk later in adult life. It is likely that long-lived, self-regenerating epithelial progenitor cells are more susceptible to these exposure injuries over time and transmit the injured memory through epigenetic mechanisms to their differentiated progeny. Here, we used progenitor-containing mammospheres as an in vitro exposure model to study this epigenetic effect. Expression profiling identified that, relative to control cells, 9.1% of microRNAs (82 of 898 loci) were altered in epithelial progeny derived from mammospheres exposed to a synthetic estrogen, diethylstilbestrol. Repressive chromatin marks, trimethyl Lys27 of histone H3 (H3K27me3) and dimethyl Lys9 of histone H3 (H3K9me2), were found at a down-regulated locus, miR-9-3, in epithelial cells preexposed to diethylstilbestrol. This was accompanied by recruitment of DNA methyltransferase 1 that caused an aberrant increase in DNA methylation of its promoter CpG island in mammosphere-derived epithelial cells on diethylstilbestrol preexposure. Functional analyses suggest that miR-9-3 plays a role in the p53-related apoptotic pathway. Epigenetic silencing of this gene, therefore, reduces this cellular function and promotes the proliferation of breast cancer cells. Promoter hypermethylation of this microRNA may be a hallmark for early breast cancer development, and restoration of its expression by epigenetic and microRNA-based therapies is another viable option for future treatment of this disease. [Cancer Res 2009;69(14):5936–45]