bluuebunny/crossref_metadata_2025 huggingface dataset:
PHANTOM ENERGY FROM GRADED ALGEBRAS
Authors: CHAVES MAX , SINGLETON DOUGLAS
Published: January 2007

We construct a model of phantom energy using the graded Lie algebra SU(2/1). The negative kinetic energy of the phantom field emerges naturally from the graded Lie algebra, resulting in an equation of state with w < -1. The model also contains ordinary scalar fields and anticommuting (Grassmann) vector fields which can be taken as two-component dark matter. A potential term is generated for both the phantom fields and the ordinary scalar fields via a postulated condensate of the Grassmann vector fields. Since the phantom energy and dark matter arise from the same Lagrangian, the phantom energy and dark matter of this model are coupled via the Grassmann vector fields. In the model presented here phantom energy and dark matter come from a gauge principle rather than being introduced in an ad hoc manner.
ANOMALY AND ANOMALY-FREE TREATMENT OF QFT's BASED ON SYMMETRY-PRESERVING LOOP REGULARIZATION
Authors: MA YONG-LIANG , WU YUE-LIANG
Published: January 2007

The triangle anomaly in massless and massive QED is investigated by adopting the symmetry-preserving loop regularization method proposed recently in Refs. 1 and 2. The method is realized in the initial dimension of theory without modifying the original Lagrangian, it preserves symmetries under non-Abelian gauge and Poincaré transformations in spite of the existence of two intrinsic mass scales Mc and μs which actually play the roles of UV- and IR-cutoff respectively. The axial-vector–vector-vector (AVV) triangle diagrams in massless and massive QED are evaluated explicitly by using the loop regularization. It is shown that when the momentum k of external state is soft with [Formula: see text], m2 (m is the mass of loop fermions) and Mc → ∞, both massless and massive QED become anomaly free. The triangle anomaly is found to appear as quantum corrections in the case that m2, [Formula: see text] and Mc → ∞. Especially, it is justified that in the massless QED with μs = 0 and Mc → ∞, the triangle anomaly naturally exists as quantum effects in the axial-vector current when the ambiguity caused by the trace of gamma matrices with γ5 is eliminated by simply using the definition of γ5. It is explicitly demonstrated how the Ward identity anomaly of currents depends on the treatment for the trace of gamma matrices, which enables us to make a clarification whether the ambiguity of triangle anomaly is caused by the regularization scheme in the perturbation calculations or by the trace of gamma matrices with γ5. For comparison, an explicit calculation based on the Pauli–Villars regularization and dimensional regularization is carried out and the possible ambiguities of Ward identity anomalies caused from these two regularization schemes are carefully discussed, which include the ambiguities induced by the treatment of the trace of gamma matrices with γ5 and the action of the external momentum on the amplitude before the direct calculation of the AVV diagram.
THE PUZZLE OF GRAVITATION
Authors: SIDHARTH B. G.
Published: January 2007

We consider a model in which the Universe has an underpinning of oscillators in the quantum vacuum (or dark energy) at the Planck scale and deduce a number of otherwise inexplicable large number relations which have been considered to be empirical accidents. The analysis shows that the gravitational energy is the residual energy of the Planck oscillators constituting the Universe at large on the one hand, and elementary particles on the other. This explains a mysterious puzzle first pointed out by Weinberg several years ago, in a formula relating the pion mass to the Hubble constant, a puzzle which has remained unexplained ever since.
THEORY OF QUANTUM FIRST TIME OF ARRIVAL VIA SPATIAL CONFINEMENT I: CONFINED TIME OF ARRIVAL OPERATORS FOR CONTINUOUS POTENTIALS
Authors: GALAPON ERIC A.
Published: January 2007

The constructions of two classes of self-adjoint and compact first time of arrival operators for confined systems under arbitrary, everywhere continuous potential are detailed, extending in the interacting case the concept of confined quantum time of arrival operators first developed for the free particle. One class is the quantized confined time of arrival operators and another is the class of algebra preserving confined time of arrival operators. The former is the projection of the quantization of the classical time of arrival, and is constructed by solving the quantization problem of the multiple-valued and non-everywhere-real-valued classical time of arrival for arbitrary potential. The later arises to address the nonconjugacy with the Hamiltonian of the entire class of the quantized confined time of arrival operators, and is constructed by solving the obstruction to quantization present in Euclidean space. These two sets of operators coincide for linear systems; but differ for nonlinear systems, with the former as the leading term of the latter. The confined time of arrival operators for potentials representative of linear and nonlinear systems are numerically investigated and demonstrated to have the same dynamical behaviors as those of the free confined time of arrival operators. In particular, the eigenfunctions evolve according to Schrödinger equation such that the corresponding probabilities of locating the quantum particle in the neighborhood of the arrival point are maximum at their respective eigenvalues.
ARITHMETIC SPACE–TIME GEOMETRY FROM STRING THEORY
Authors: SCHIMMRIGK ROLF
Published: January 2007

An arithmetic framework for string compactification is described. The approach is exemplified by formulating a strategy that allows to construct geometric compactifications from exactly solvable theories at c = 3. It is shown that the conformal field theoretic characters can be derived from the geometry of space–time, and that the geometry is uniquely determined by the two-dimensional field theory on the worldsheet. The modular forms that appear in these constructions admit complex multiplication, and allow an interpretation as generalized McKay–Thompson series associated to the Mathieu and Conway groups. This leads to a string motivated notion of arithmetic moonshine.
ARTIFICIALLY INDUCED POSITRONIUM OSCILLATIONS IN A TWO-SHEETED SPACE–TIME: CONSEQUENCES ON THE OBSERVED DECAY PROCESSES
Authors: SARRAZIN MICHAËL , PETIT FABRICE
Published: January 2007

Following recent theoretical results, it is suggested that positronium (Ps) might undergo spontaneous oscillations between two 4D space–time sheets whenever subjected to constant irrotational magnetic vector potentials. We show that these oscillations that would come together with o-Ps/p-Ps oscillations should have important consequences on Ps decay rates. Experimental setup and conditions are also suggested for demonstrating in nonaccelerator experiments this new invisible decay mode.
SPIN-CHARGE SEPARATION FOR THE SU(3) GAUGE THEORY
Authors: DZHUNUSHALIEV VLADIMIR
Published: January 2007

The idea of a spin-charge separation of the SU(2) gauge potential is extended to the SU(3) case. It is shown that in this case there exist different nonperturbative ground states characterized by different gauge condensate [Formula: see text].
A MEASUREMENT INSTRUMENT FOR TQM IMPLEMENTATION IN THE THAI MANUFACTURING INDUSTRY
Authors: DAS ANUPAM , PAUL HIMANGSHU , SWIERCZEK FREDRIC W. , LAOSIRIHONGTHONG TRITOS
Published: January 2007

It is particularly important for developing countries to define useful TQM constructs to measure these principles, and their effect on improvement of performance. This research is aimed at measuring TQM constructs in the Thai manufacturing industry and Thai culture. The research identifies nine TQM implementation constructs and one outcome construct. A measurement instrument is developed based on a survey of some 275 ISO 9000 certified manufacturing companies in Thailand. A stepwise regression model is then used to identify the primary implementation construct regressors that significantly influence the outcome construct. The results show that customer focus, continuous improvement, top management commitment, employee involvement and product innovation are significantly and positively related to product quality. The findings are useful for practitioners and academia in developing countries.
THE RELATIONSHIP BETWEEN INTELLECTUAL CAPITAL AND NEW VENTURE PERFORMANCE: AN EMPIRICAL INVESTIGATION OF THE MODERATING ROLE OF THE ENVIRONMENT
Authors: JUMA NORMA , McGEE JEFFREY
Published: January 2007

Many organizations today view intellectual capital (IC) as their most valuable asset. New ventures, in particular, can leverage their IC to attain and sustain a competitive advantage. This study investigates whether IC has a direct impact on venture performance. We also seek to determine if this relationship is moderated by environmental dimensions. Our findings suggest that human capital is the most critical component of IC when predicting operating performance of high-tech ventures, while intellectual property is the crucial component when predicting market-based performance. Our findings also suggest that the relationship between IC and venture performance is influenced by the environment.
New Approaches in the Therapy of Cardiomyopathy in Muscular Dystrophy
Authors: McNally Elizabeth M.
Published: January 2007

Cardiomyopathy is a frequent occurrence in muscular dystrophy, and heart disease in muscular dystrophy can contribute to both morbidity and mortality. A number of novel therapies are being developed for muscular dystrophy, and the efficacy of these therapies for heart disease is unknown. The most common X-linked recessive disease is Duchenne muscular dystrophy (DMD), which arises from defects in the dystrophin gene. Therapy specifically aimed at DMD is reviewed in the context of its projected effect on cardiomyopathy associated with DMD. Additionally, novel therapies are being pursued to treat specifically the cardiomyopathy of DMD. There is substantial genetic heterogeneity underlying the muscular dystrophies, and not all muscular dystrophy patients develop cardiomyopathy. A subset of muscular dystrophies may place patients at significantly greater risk of developing cardiomyopathy and cardiac rhythm disturbances. These disorders are discussed, highlighting recent studies and recommendations for therapy.
Acute Ischemic Stroke: Overview of Recent Therapeutic Developments
Authors: Suwanwela Nijasri , Koroshetz Walter J.
Published: January 2007

Stroke, a disorder encompassing all cerebrovascular accidents, is a public health problem of immense proportions across the globe. Therapeutic efforts are directed at three aspects: prevention, acute treatment, and rehabilitation. Preventative measures, which in many instances mirror those for cardiovascular disease, can achieve the greatest public health impact. Measures that enhance the recovery of neurologic function and reduce neurologic disability after stroke can also affect a large population of handicapped stroke survivors. In the past 10 years, the greatest changes have occurred in the field of acute stroke treatment. Ultra-early-stage therapies with the potential to dramatically reverse severe neurologic deficits, or halt their progression, have caused a restructuring of the emergency care of neurologic patients. The parallels with the evolution of emergency treatment of acute coronary syndromes after 1970 are striking. This review focuses on aspects of stroke therapy that are either just entering, or soon to enter, current practice.
New Therapeutic Approaches for Multiple Sclerosis
Authors: De Jager Philip L. , Hafler David A.
Published: January 2007

Although several therapies exist for multiple sclerosis (MS), the most common inflammatory demyelinating disease of the central nervous system (CNS), there remains a large unmet clinical need for more effective immunomodulatory treatments in this category of diseases and for interventions that address their neurodegenerative component, which is currently untreated. Progress in our understanding of the immunology of MS over the past 30 years has recently synergized with novel computational methods and emerging high-throughput technologies that characterize variations in DNA, RNA, proteins, and metabolites to usher in a period of intense pathophysiologic investigation. These efforts are beginning to define subsets of patients with different forms of demyelinating disease. This partitioning of patients will prove valuable as we begin to tailor immunotherapy to the underlying pathophysiologic processes of individual patients using current therapies, emerging treatments, and rational combinations of all of these treatments. Preventing the entry of lymphocytes into the CNS and modifying the nature of the immune response are treatment approaches that work in the inflammatory component of MS but have little or no effect on neurodegeneration. Two challenges confront us: to develop cocktails of therapies that shift the immune homeostasis of patients with MS toward a healthy profile, and to identify and modulate the activity of targets within the neurodegenerative component of MS.
Cytokine Therapy for Crohn's Disease: Advances in Translational Research
Authors: Pizarro Theresa T. , Cominelli Fabio
Published: January 2007

Crohn's disease (CD) and ulcerative colitis (UC), the two idiopathic inflammatory bowel diseases (IBDs), affect almost two million individuals in North America and several million worldwide. Cytokines are important in the pathogenesis of CD, and their manipulation has successfully reduced disease severity and maintained remission. Following the discovery of novel cytokines and the role they may play in gut mucosal immunity, as well as the emergence of new concepts and changing paradigms in CD pathogenesis, the roles of several cytokines have been elucidated and tested in both preclinical animal models and clinical trials of patients with IBD. Complementary to this, proof of concept for new cytokine targets is rapidly developing, with the possibility of future cytokine-based therapies that may offer greater specificity and decreased toxicity for the treatment of CD. This review discusses novel concepts in CD pathogenesis and the roles of cytokines in the initiation and perpetuation of disease. In addition, we review applications of cytokine-based therapies in human clinical trials and preclinical animal studies. Finally, we discuss novel cytokine targets not yet investigated in vivo and describe their potential contribution to CD pathogenesis.
Osmotic regulation of betaine homocysteine-S-methyltransferase expression in H4IIE rat hepatoma cells
Authors: Schäfer Christine , Hoffmann Lars , Heldt Katrin , Lornejad-Schäfer Mohammad Reza , Brauers Gernot , Gehrmann Thor , Garrow Timothy A. , Häussinger Dieter , Mayatepek Ertan , Schwahn Bernd C. , Schliess Freimut
Published: January 2007

Cell hydration changes critically affect liver metabolism and gene expression. In the course of gene expression studies using nylon cDNA-arrays we found that hyperosmolarity (405 mosmol/l) suppressed the betaine-homocysteine methyltransferase ( Bhmt) mRNA expression in H4IIE rat hepatoma cells. This was confirmed by Northern blot and real-time quantitative RT-PCR analysis, which in addition unraveled a pronounced induction of Bhmt mRNA expression by hypoosmotic (205 mosmol/l) swelling. Osmotic regulation of Bhmt mRNA expression was largely paralleled at the levels of Bhmt protein and enzymatic activity. Like hyperosmotic NaCl, hyperosmotic raffinose but not hyperosmotic urea suppressed Bhmt mRNA expression, suggesting that cell shrinkage rather than increased ionic strength or hyperosmolarity per se is the trigger. Hypoosmolarity increased the expression of a reporter gene driven by the entire human BHMT promoter, whereas destabilization of BHMT mRNA was observed under hyperosmotic conditions. Osmosensitivity of Bhmt mRNA expression was impaired by inhibitors of tyrosine kinases and cyclic nucleotide-dependent kinases. The osmotic regulation of BHMT may be part of a cell volume-regulatory response and additionally lead to metabolic alterations that depend on the availability of betaine-derived methyl groups.
Increased gastric expression of MMP-7 in hypergastrinemia and significance for epithelial-mesenchymal signaling
Authors: Varro Andrea , Kenny Susan , Hemers Elaine , McCaig Catherine , Przemeck Sabine , Wang Timothy. C. , Bodger Keith , Pritchard D. Mark
Published: January 2007

Chronic hypergastrinemia is associated with enterochromaffin-like (ECL) cell hyperplasia, which may progress to gastric carcinoid tumors. The latter consists of epithelial cells and stroma, and both compartments usually regress after normalization of hypergastrinemia. We previously showed that matrix metalloproteinase (MMP)-7 in gastric epithelial cells was upregulated by Heliobacter pylori and described MMP-7-dependent reciprocal signaling between the epithelium and a key stromal cell type, the myofibroblast. Here, we describe the regulation of gastric MMP-7 by gastrin and the potential significance for recruiting and maintaining myofibroblast populations. Biopsies of the gastric corpus and ECL cell carcinoid tumors were obtained from hypergastrinemic patients. Western blot analysis, ELISA, immunohistochemistry, and promoter-luciferase (luc) reporter assays were used to study MMP-7 expression. Gastric myofibroblasts were identified by α-smooth muscle actin (α-SMA) expression, and the effects of MMP-7 on myofibroblast proliferation were investigated. In hypergastrinemic patients, there was an increased abundance of MMP-7 and α-SMA in gastric corpus biopsies and ECL cell carcinoid tumors. In the latter, MMP-7 was localized to ECL cells but not stromal cells, which were nevertheless well represented. Gastrin stimulated MMP-7-luc expression in both AGS-GR and primary human gastric epithelial cells. Conditioned medium from gastrin-treated human gastric glands stimulated myofibroblast proliferation, which was inhibited by neutralizing antibodies to MMP-7. MMP-7 increased the proliferation of myofibroblasts via the MAPK and phosphatidylinositol 3-kinase (PI3K) pathways. In conclusion, stimulation of gastric MMP-7 by elevated plasma gastrin may activate epithelial-mesenchymal signaling pathways regulating myofibroblast function via MAPK and PI3K pathways and contribute to stromal deposition in ECL cell carcinoid tumors.
Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats
Authors: Kajiya Masahito , Hirota Masanori , Inai Yousuke , Kiyooka Takahiko , Morimoto Taro , Iwasaki Tatsuo , Endo Kousuke , Mohri Satoshi , Shimizu Juichiro , Yada Toyotaka , Ogasawara Yasuo , Naruse Keiji , Ohe Tohru , Kajiya Fumihiko
Published: January 2007

Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline ( n = 126) to induce PH or with saline as controls ( n = 114). After 3 wk, coronary arterioles (diameter = 30–100 μm) and small arteries (diameter = 100–200 μm) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of Nω-nitro-l-arginine methyl ester (l-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without l-NAME, and in the presence of SOD. The degree of suppression in vasodilation by l-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small aretries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels.
Leptin induces elongation of cardiac myocytes and causes eccentric left ventricular dilatation with compensation
Authors: Abe Yukiko , Ono Koh , Kawamura Teruhisa , Wada Hiromichi , Kita Toru , Shimatsu Akira , Hasegawa Koji
Published: January 2007

One of the major manifestations of obesity is an increased production of the adipocyte-derived 16-kDa peptide leptin, which acts mainly on hypothalamic leptin receptors. Leptin receptors are widely distributed in various tissues, including the heart. Whereas increased plasma leptin levels have been reported in patients with congestive heart failure, systemic alterations induced by obesity can affect cardiac hypertrophy, and the direct effects of leptin on cardiac structure and function still remain to be determined. We first exposed primary cardiac myocytes from neonatal rats to leptin for 48 h. This resulted in a significant increase in myocyte long-axis length ( P < 0.05 at 50 ng/ml) but not in the short-axis width. Leptin induced the rapid phosphorylation of STAT3 and its DNA binding in cardiac myocytes. Administration of a JAK2 inhibitor, AG-490, completely inhibited all of these effects by leptin. Furthermore, we examined the effect of continuous infusion of leptin for 4 wk following myocardial infarction in mice. Echocardiography demonstrated that left ventricular fractional shortening in the leptin-infused group (28.4 ± 2.8%) was significantly higher than that in the PBS-infused group (18.4 ± 2.2%) following myocardial infarction. Interestingly, left ventricular diastolic dimension in the leptin-infused group (4.56 ± 0.12 mm) was also higher than that in the PBS-infused group (4.13 ± 0.09 mm). These results demonstrate that leptin induces the elongation of cardiac myocytes via a JAK/STAT pathway and chronic leptin infusion causes eccentric dilatation with augmented systolic function after myocardial infarction.
The alcoholic lung: epidemiology, pathophysiology, and potential therapies
Authors: Joshi Pratibha C. , Guidot David M.
Published: January 2007

Epidemiological evidence gathered only in the past decade reveals that alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome by as much as three- to fourfold. Experimental models and clinical studies are beginning to elucidate the mechanisms underlying this previously unrecognized association and are revealing for the first time that chronic alcohol abuse causes discrete changes, particularly within the alveolar epithelium, that render the lung susceptible to acute edematous injury in response to sepsis, trauma, and other inflammatory insults. Recent studies in relevant animal models as well as in human subjects are identifying common mechanisms by which alcohol abuse targets both the alveolar epithelium and the alveolar macrophage, such that the risks for acute lung injury and pulmonary infections are inextricably linked. Specifically, chronic alcohol ingestion decreases the levels of the antioxidant glutathione within the alveolar space by as much as 80–90%, and, as a consequence, impairs alveolar epithelial surfactant production and barrier integrity, decreases alveolar macrophage function, and renders the lung susceptible to oxidant-mediated injury. These changes are often subclinical and may not manifest as detectable lung impairment until challenged by an acute insult such as sepsis or trauma. However, even otherwise healthy alcoholics have evidence of severe oxidant stress in the alveolar space that correlates with alveolar epithelial and macrophage dysfunction. This review focuses on the epidemiology and the pathophysiology of alcohol-induced lung dysfunction and discusses potential new treatments suggested by recent experimental findings.
Regulation of interleukin-8 via an airway epithelial signaling cascade
Authors: Nakanaga Takashi , Nadel Jay A. , Ueki Iris F. , Koff Jonathan L. , Shao Matt X. G.
Published: January 2007

Airways function as an innate immune organ against airborne bacteria that are inhaled and deposited in airways. One of the mechanisms of host defense is to recruit neutrophils into airways to clear the invaders. Airway epithelial cells produce neutrophil chemoattractant interleukin (IL)-8 in response to invading bacteria. In this study we show a signaling pathway on the plasma surface of human airway epithelial NCI-H292 cells that regulate IL-8 production in response to a model inflammatory stimulus, phorbol 12-myristate 13-acetate, and a pathophysiological stimulus, gram-negative bacterial lipopolysaccharide. First, we show that EGF receptor (EGFR) and MAP kinase ERK1/2 are involved in IL-8 expression by these stimuli. Second, we show that EGFR ligand transforming growth factor (TGF)-α mediates IL-8 production. Third, we show that tumor necrosis factor-α-converting enzyme (TACE) is required for IL-8 production by cleaving EGFR proligand proTGF-α into soluble TGF-α, activating EGFR. Last, we show that dual oxidase 1 (Duox1), a homolog of NADPH oxidase in airways, mediates TACE activation and IL-8 expression via generation of reactive oxygen species. In summary, we describe a signaling pathway, Duox1-TACE-TGF-α-EGFR, on the surface of airway epithelial (NCI-H292) cells that mediates airway epithelial defense against bacterial infection by producing IL-8. This pathway, which also regulates mucin production in human airways, provides mechanisms for killing foreign organisms and for their clearance.
Estimating the rate of oxygen consumption during submersion from the heart rate of diving animals
Authors: Green J. A. , Halsey L. G , Butler P. J. , Holder R. L.
Published: January 2007

How animals manage their oxygen stores during diving and other breath-hold activities has been a topic of debate among physiologists for decades. Specifically, while the behavior of free-ranging diving animals suggests that metabolism during submersion must be primarily aerobic in nature, no studies have been able to determine their rate of oxygen consumption during submersion (V̇o2d) and hence prove that this is the case. In the present study, we combine two previously used techniques and develop a new model to estimate V̇o2d accurately and plausibly in a free-ranging animal and apply it to data for macaroni penguins ( Eudyptes chrysolophus) as an example. For macaroni penguins at least, V̇o2d can be predicted by measuring heart rate during the dive cycle and the subsequent surface interval duration. Including maximum depth of the dive improves the accuracy of these predictions. This suggests that energetically demanding locomotion events within the dive combine with the differing buoyancy and locomotion costs associated with traveling to depth to influence its cost in terms of oxygen use. This will in turn effect the duration of the dive and the duration of the subsequent recovery period. In the present study, V̇o2d ranged from 4 to 28 ml·min−1·kg−1, indicating that, at least as far as aerobic metabolism was concerned, macaroni penguins were often hypometabolic, with rates of oxygen consumption usually below that for this species resting in water (25.6 ml·min−1·kg−1) and occasionally lower than that while resting in air (10.3 ml·min−1·kg−1).
Presynaptic α-adrenoceptors in median preoptic nucleus modulate inhibitory neurotransmission from subfornical organ and organum vasculosum lamina terminalis
Authors: Kolaj Miloslav , Renaud Leo P.
Published: January 2007

The median preoptic nucleus (MnPO) in the lamina terminalis receives a prominent catecholaminergic innervation from the dorsomedial and ventrolateral medulla. The present investigation used whole cell patch-clamp recordings in rat brain slice preparations to evaluate the hypothesis that presynaptic adrenoceptors could modulate GABAergic inputs to MnPO neurons. Bath applications of norepinephrine (NE; 20–50 μM) induced a prolonged and reversible suppression of inhibitory postsynaptic currents (IPSCs) and reduced paired-pulse depression evoked by stimulation in the subfornical organ and organum vasculosum lamina terminalis. These events were not correlated with any observed changes in membrane conductance arising from NE activity at postsynaptic α1- or α2-adrenoceptors. Consistent with a role for presynaptic α2-adrenoceptors, responses were selectively mimicked by an α2-adrenoceptor agonist (UK-14304) and blockable with an α2-adrenoceptor antagonist (idazoxan). Although the α1-adrenoceptor agonist cirazoline and the α1-adrenoceptor antagonist prazosin were without effect on these evoked IPSCs, NE was noted to increase (via α1-adrenoceptors) or decrease (via α2-adrenoceptors) the frequency of spontaneous and tetrodotoxin-resistant miniature IPSCs. Collectively, these observations imply that both presynaptic and postsynaptic α1- and α2-adrenoceptors in MnPO are capable of selective modulation of rapid GABAA receptor-mediated inhibitory synaptic transmission along the lamina terminalis and therefore likely to exert a prominent influence in regulating cell excitability within the MnPO.
Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure
Authors: Yao Xing-Hai , Grégoire Nyomba B. L.
Published: January 2007

Adverse events during pregnancy, including prenatal ethanol (EtOH) exposure, are associated with insulin-resistant diabetes in male rat offspring, but it is unclear whether this is true for female offspring. We investigated whether prenatal EtOH exposure alters glucose metabolism in adult female rat offspring and whether this is associated with reduced in vivo insulin signaling in skeletal muscle. Female Sprague-Dawley rats were given EtOH, 4 g·kg−1·day−1by gavage throughout pregnancy. Glucose tolerance test and hyperinsulinemic euglycemic clamp were performed, and insulin signaling was investigated in skeletal muscle, in adult female offspring. We gave insulin intravenously to these rats and determined the association of glucose transporter-4 with plasma membranes, as well as the phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKCζ. Although EtOH offspring had normal birth weight, they were overweight as adults and had fasting hyperglycemia, hyperinsulinemia, and reduced insulin-stimulated glucose uptake. After insulin treatment, EtOH-exposed rats had decreased membrane glucose transporter-4, PDK1, Akt, and PKCζ in the gastrocnemius muscle, compared with control rats. Insulin stimulation of PDK1, Akt, and PKCζ phosphorylation was also reduced. In addition, the expression of the protein tribbles-3 and the phosphatase enzyme activity of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which prevent Akt activation, were increased in muscle from EtOH-exposed rats. Female rat offspring exposed to EtOH in utero develop insulin-resistant diabetes in association with excessive PTEN and tribbles-3 signaling downstream of the phosphatidylinositol 3-kinase pathway in skeletal muscle, which may be a mechanism for the abnormal glucose tolerance.
Novel technology for the provision of power to implantable physiological devices
Authors: Budgett David M. , Hu Aiguo Patrick , Si Ping , Pallas Wayne T. , Donnelly Mark G. , Broad Jared W. T. , Barrett Carolyn J. , Guild Sarah-Jane , Malpas Simon C.
Published: January 2007

We report the development of a novel technology that enables the wireless transmission of sufficient amounts of power to implantable physiological devices. The system involves a primary unit generating the magnetic field and a secondary pickup unit deriving power from the magnetic field and a power conditioner. The inductively coupled system was able to supply a minimum of 20 mW at all locations and pickup orientations across a rat cage, although much higher power of up to 10 W could be achieved. We hypothesized that it would be possible to use this technology to record a high-fidelity ECG signal in a conscious rat. A device was constructed in which power was utilized to recharge a battery contained within a telemetry device recording ECG signal sampled at 2,000 Hz in conscious rats (200–350 g) living in their home cage. Attributes of the ECG signal (QT, QRS, and PR interval) could be obtained with a high degree of accuracy (<1 ms). ECG and heart rate changes in response to treatment with the beta blocker propranolol and the proarrhythmic alkaloid aconitine were measured. Transmitters were implanted for up to 4 mo, and the characteristic circadian variation in heart rate was recorded. Such technology allows potentially lifetime monitoring without the need for implant refurbishment. The ability to provide suitable power levels to implanted devices without concern to the orientation of the device and without causing heating provides the basis for the development of new devices to record or influence physiological signals in animals or humans over significantly longer time periods than can currently be accommodated.
Variation in senescent-dependent lung changes in inbred mouse strains
Authors: Huang Kewu , Mitzner Wayne , Rabold Richard , Schofield Brian , Lee Hannah , Biswal Shyam , Tankersley Clarke G.
Published: January 2007

Previous studies from our laboratories showed lung development differences between inbred strains of mice. In the present study, the C57BL/6J (B6) and DBA/2J (D2) strains were examined for senescent-dependent differences with respect to the lung structure and function. Specifically, we hypothesize that senescent changes in lung vary between strains due to identifiable gene expression differences. Quasi-static pressure-volume curves and respiratory impedance measurements were performed on 2- and 20-mo-old B6 and D2 mice. Lung volume at 30 cmH2O (V30) pressure was significantly ( P < 0.01) increased with age in both strains, but the increase was proportionally greater in D2 (68%) than in B6 (40%) mice. In addition, decreased elastic recoil pressure at 50% of V30 and a reduction in airway resistance as a function of positive end-expiratory pressure were observed in 20-mo-old D2 mice but not in B6 mice. Morphometric analysis of lung parenchyma showed significant decreases in elastic fiber content with age in both strains, but the collagen content was significantly ( P < 0.01) increased with age in D2 but not B6 mice at 20 mo. Furthermore, using quantitative RT-PCR methods, gene expression differences between strains suggested that D2 mice significantly ( P < 0.05) downregulated the expressions of elastin ( Eln) and procollagen I, III, and VI ( Col1a1, Col3a1, and Col6a3) in lung tissue at 20 mo of age. These age-dependent changes were accompanied by an increased gene expression in matrix metalloproteinase 9 ( Mmp9) in D2 and an increase in tissue inhibitor of matrix metalloproteinase ( Timp1 and Timp4) in B6 mice. In conclusion, the results from the present study demonstrate that lung mechanics of both strains show significant age-dependent changes. However, changes in D2 mice are accelerated relative to B6 mice. Moreover, gene expression differences appear to be involved in the strain-specific changes of lung mechanic properties.
Use of motor cortex stimulation to measure simultaneously the changes in dynamic muscle properties and voluntary activation in human muscles
Authors: Todd Gabrielle , Taylor Janet L. , Butler Jane E. , Martin Peter G. , Gorman Robert B. , Gandevia Simon C.
Published: January 2007

Force responses to transcranial magnetic stimulation of motor cortex (TMS) during exercise provide information about voluntary activation and contractile properties of the muscle. Here, TMS-generated twitches and muscle relaxation during the TMS-evoked silent period were measured in fresh, heated, and fatigued muscle. Subjects performed isometric contractions of elbow flexors in two studies. Torque and EMG were recorded from elbow flexor and extensor muscles. One study ( n = 6) measured muscle contraction times and relaxation rates during brief maximal and submaximal contractions in fresh and fatigued muscle. Another study ( n = 7) aimed to 1) assess the reproducibility of muscle contractile properties during brief voluntary contractions in fresh muscle, 2) validate the technique for contractile properties in passively heated muscle, and 3) apply the technique to study contractile properties during sustained maximal voluntary contractions. In both studies, muscle contractile properties during voluntary contractions were compared with the resting twitch evoked by motor nerve stimulation. Measurement of muscle contractile properties during voluntary contractions is reproducible in fresh muscle and reveals faster and slower muscle relaxation rates in heated and fatigued muscle, respectively. The technique is more sensitive to altered muscle state than the traditional motor nerve resting twitch. Use of TMS during sustained maximal contractions reveals slowing of muscle contraction and relaxation with different time courses and a decline in voluntary activation. Voluntary output from the motor cortex becomes insufficient to maintain complete activation of muscle, although slowing of muscle contraction and relaxation indicates that lower motor unit firing rates are required for fusion of force.
Residence at 3,800-m altitude for 5 mo in growing dogs enhances lung diffusing capacity for oxygen that persists at least 2.5 years
Authors: Hsia Connie C. W. , Johnson Robert L. , McDonough Paul , Dane D. Merrill , Hurst Myresa D. , Fehmel Jennifer L. , Wagner Harrieth E. , Wagner Peter D.
Published: January 2007

Mammals native to high altitude (HA) exhibit larger lung volumes than their lowland counterparts. To test the hypothesis that adaptation induced by HA residence during somatic maturation improves pulmonary gas exchange in adulthood, male foxhounds born at sea level (SL) were raised at HA (3,800 m) from 2.5 to 7.5 mo of age and then returned to SL prior to somatic maturity while their littermates were simultaneously raised at SL. Following return to SL, all animals were trained to run on a treadmill; gas exchange and hemodynamics were measured 2.5 years later at rest and during exercise while breathing 21% and 13% O2. The multiple inert gas elimination technique was employed to estimate ventilation-perfusion (V̇a/Q̇) distributions and lung diffusing capacity for O2 (DlO2). There were no significant intergroup differences during exercise breathing 21% O2. During exercise breathing 13% O2, peak O2 uptake and V̇a/Q̇ distributions were similar between groups but arterial pH, base excess, and O2 saturation were higher while peak lactate concentration was lower in animals raised at HA than at SL. At a given exercise intensity, alveolar-arterial O2 tension gradient (A-aDo2) attributable to diffusion limitation was lower while Dlo2 was 12–25% higher in HA-raised animals. Mean systemic arterial blood pressure was also lower in HA-raised animals; mean pulmonary arterial pressures were similar. We conclude that 5 mo of HA residence during maturation enhances long-term gas exchange efficiency and DlO2 without impacting V̇a/Q̇ inequality during hypoxic exercise at SL.
Simulated microgravity effects on the rat carotid and femoral arteries: role of contractile protein expression and mechanical properties of the vessel wall
Authors: Hwang Sunup , Shelkovnikov Stanislav A. , Purdy Ralph E.
Published: January 2007

The goal of this study was to determine the effects of microgravity on myofilament protein expression and both passive and active length-force relationships in carotid and femoral arteries. Microgravity was simulated by 20-day hindlimb unweighting (HU) in Wistar male rats, and carotid and femoral artery segments were isolated from both HU and control (CTL) rats for Western blot and length-force analysis. Western blots revealed that HU significantly decreased myosin light chain-20 (MLC-20) protein levels in both carotid and femoral arteries and decreased myosin heavy chain (MHC) in femoral artery. α-Actin levels were not altered by HU treatment in either artery. Length-force analysis demonstrated that HU did not change either passive or active length-force relationships in the femoral artery. HU-treated arterial rings developed significantly less force to 100 mM K+than CTL, but optimal lengths were identical. In the carotid artery, length-active force curves were identical for both CTL and HU; however the length-passive force curve for HU-treated rings exhibited a steeper slope than CTL, suggesting decreased compliance of the artery wall. In conclusion, our data suggest that the HU-induced decreases in both MLC-20 and MHC in femoral artery are responsible for the decreased contraction to 100 mM K+in HU-treated femoral artery rings. In the carotid artery, the HU-induced decrease in vessel wall compliance may counter any decrease in contractility caused by the decreased MLC-20 levels.
Detection of Aminophenylnorharman, a Possible Endogenous Mutagenic and Carcinogenic Compound, in Human Urine Samples
Authors: Nishigaki Rena , Totsuka Yukari , Kataoka Hiroyuki , Ushiyama Hirohumi , Goto Sumio , Akasu Takayuki , Watanabe Tetsushi , Sugimura Takashi , Wakabayashi Keiji
Published: January 2007

Mutagenic/carcinogenic 9-(4′-aminophenyl)-9H-pyrido[3,4-b]indole [aminophenylnorharman (APNH)] is formed from norharman and aniline in the presence of cytochrome P450 3A4/1A2. Because both precursors are widely distributed in the environment, human exposure is unavoidable. To clarify APNH formation in the human body, amounts of the compound in 24-h human urine collected from smokers and nonsmokers, eating a normal diet, were analyzed by liquid chromatography/electrospray ionization tandem mass spectrometry. In addition, norharman and aniline were also analyzed by high-performance liquid chromatography and gas chromatography, respectively. APNH could be detected in all urine samples at levels 49 to 449 pg for smokers and 21 to 594 pg for nonsmokers per 24-h urine, respectively. The amounts of norharman and aniline were 46 to 185 ng and 0.70 to 8.10 μg for smokers and 52 to 447 ng and 0.49 to 5.72 μg for nonsmokers, respectively, per 24-h urine (none of the levels differing significantly between smokers and nonsmokers). To exclude exogenous exposure to norharman and aniline, we analyzed the levels of APNH, norharman, and aniline in urine samples collected from inpatients receiving parenteral alimentation. Similar to the healthy volunteers, all urine samples contained 12 to 338 pg of APNH, 6 to 75 ng of norharman, and 0.33 to 1.86 μg of aniline per 24-h urine. These results suggest that APNH should be considered as a novel endogenous mutagen/carcinogen; thus, it is very important to determine the biological significance of this carcinogen for human cancer development. (Cancer Epidemiol Biomarkers Prev 2007;16(1):151–6)
Common Melanocytic Nevi in 7-Year-Old Schoolchildren Residing at Different Latitudes in Sweden
Authors: Rodvall Ylva , Wahlgren Carl-Fredrik , Ullén Henrik , Wiklund Kerstin
Published: January 2007

Background: Current epidemiologic research shows consistently that increased number of acquired common melanocytic nevi (CMN) is an important risk factor for cutaneous malignant melanoma. The purpose of this study was to investigate the number of CMN in relation to tanning habits and complexion among 7-year-old children residing at different latitudes in Sweden.

Methods: Two municipalities were chosen at latitude 65°N to 68°N in the north of Sweden and two at latitude 57°N in the south. Children born in 1994 and registered in the municipalities were to be included (N = 1,676). A questionnaire was sent to their parents asking about the child's tanning habits. A body examination of CMN of size ≥2 mm was done by the same trained nurse in 1,380 (82.3%) of the children.

Results: CMN was significantly less prevalent among children living in the north with a prevalence of 5.6 [95% confidence interval (95% CI), 4.8-6.5] inland and 6.2 (95% CI, 5.3-7.2) coastal compared with the south with a prevalence of 9.5 (95% CI, 8.2-11.0) inland and 10.4 (95% CI, 8.9-12.0) coastal. In addition, blond hair, blue/gray/green eyes, holidays at seaside resorts abroad, more frequent sunburns, and parents fancying tanning were significant predictors of higher prevalence of CMN.

Conclusions: These findings support previous evidence that the development of CMN is related to the level of sun exposure in childhood expressed as latitude of residence, holidays at seaside resort abroad, and number of sunburns. To reduce the incidence of cutaneous malignant melanoma, a change in attitude and behavior must start with young children and their parents. (Cancer Epidemiol Biomarkers Prev 2007;16(1):122–7)
Role of GSTM3 Polymorphism in the Risk of Developing Esophageal Cancer
Authors: Jain Meenu , Kumar Shaleen , Lal Punita , Tiwari Anu , Ghoshal Uday C. , Mittal Balraj
Published: January 2007

GSTM3 is involved in detoxification of carcinogens and may be important in modulating cancer susceptibility. GSTM3 genotype frequencies were determined in peripheral blood DNA of 149 esophageal cancer patients and 200 nonmalignant controls using the PCR followed by PAGE. Patients who were heterozygous carriers of GSTM3 AB genotype had an enhanced risk for developing esophageal cancer [odds ratio (OR), 2.1; 95% confidence interval (95% CI), 1.1-3.7; P = 0.01]. In males, the risk due to GSTM3 AB genotype increased further (OR, 3.4; 95% CI, 1.7-6.8; P = 0.000). Interaction of GSTM3 AB + BB and GSTM1 null genotypes marginally modulated risk (OR, 2.3; 95% CI, 1.1-3.7; P = 0.01). Association with histology (adenocarcinoma: OR, 3.4; 95% CI, 1.1-10.9; P = 0.03) and tumor site (middle third location: OR, 2.2; 95% CI, 1.1-4.4; P = 0.01; lower third location: OR, 2.6; 95% CI, 1.2-5.6; P = 0.01) was also documented. Our results suggest that GSTM3 polymorphism may influence esophageal cancer susceptibility, in particular modulating the risk for adenocarcinoma histology and tumors of the mid and lower third region. (Cancer Epidemiol Biomarkers Prev 2007;16(1):178–81)
Polymorphisms of Catechol-O-Methyltransferase in Men with Renal Cell Cancer
Authors: Tanaka Yuichiro , Hirata Hiroshi , Chen Zhong , Kikuno Nobuyuki , Kawamoto Ken , Majid Shahana , Tokizane Takashi , Urakami Shinji , Shiina Hiroaki , Nakajima Koichi , Dhir Rajiv , Dahiya Rajvir
Published: January 2007

The estrogen metabolite, 4-hydroxy-estrogen, has been shown to play a role in malignant transformation of male kidneys. To counteract the effects of this catechol-estrogen, the catechol-O-methyltransferase (COMT) enzyme is capable of neutralizing the genotoxic effects of this compound. A polymorphic variant of COMT has been shown to have a reduced enzyme activity, and thus, we hypothesize that single nucleotide polymorphisms of the COMT gene can be a risk factor for renal cell cancer (RCC). To determine this hypothesis, a study of a Japanese male population was used and the genetic distributions of COMT polymorphisms at codons 62 (C→T), 72 (G→T), and 158 (G→A) were analyzed in 157 normal healthy subjects and 123 sporadic RCC (clear cell type) samples by using a sequence-specific PCR technique. These experiments show that the variant genotype (P = 0.025) and allele (P = 0.011) at codon 62 is a risk factor for RCC. The odds ratio and 95% confidence interval for cancer were 3.16 and 1.29 to 7.73, respectively, for the T/T genotype as compared with wild-type. No associations for renal cancer were found at either codons 72 or 158 in this Japanese male population. However, codons 62 and 158 were observed to be in linkage disequilibrium, and haplotype analysis shows the combined forms of T-A, T-G, and C-A to be associated with RCC as compared with C-G (P < 0.001). When evaluating the risk of COMT polymorphisms with grade of cancer, no associations were observed for any of the genotypes. This study is the first to report COMT polymorphism to be associated with RCC. These results are important in understanding the role of COMT polymorphisms in the pathogenesis of RCC. (Cancer Epidemiol Biomarkers Prev 2007;16(1):92–7)