bluuebunny/crossref_metadata_2025 huggingface dataset:
A potential mechanism of energy‐metabolism oscillation in an aerobic chemostat culture of the yeast Saccharomyces cerevisiae
Authors: Xu Zhaojun , Tsurugi Kunio
Published: March 2006

The energy‐metabolism oscillation in aerobic chemostat cultures of yeast is a periodic change of the respiro‐fermentative and respiratory phase. In the respiro‐fermentative phase, the NADH level was kept high and respiration was suppressed, and glucose was anabolized into trehalose and glycogen at a rate comparable to that of catabolism. On the transition to the respiratory phase, cAMP levels increased triggering the breakdown of storage carbohydrates and the increased influx of glucose into the glycolytic pathway activated production of glycerol and ethanol consuming NADH. The resulting increase in the NAD+/NADH ratio stimulated respiration in combination with a decrease in the level of ATP, which was consumed mainly in the formation of biomass accompanying budding, and the accumulated ethanol and glycerol were gradually degraded by respiration via NAD+‐dependent oxidation to acetate and the respiratory phase ceased after the recovery of NADH and ATP levels. However, the mRNA levels of both synthetic and degradative enzymes of storage carbohydrates were increased around the early respiro‐fermentative phase, when storage carbohydrates are being synthesized, suggesting that the synthetic enzymes were expressed directly as active forms while the degradative enzymes were activated late by cAMP. In summary, the energy‐metabolism oscillation is basically regulated by a feedback loop of oxido‐reductive reactions of energy metabolism mediated by metabolites like NADH and ATP, and is modulated by metabolism of storage carbohydrates in combination of post‐translational and transcriptional regulation of the related enzymes. A potential mechanism of energy‐metabolism oscillation is proposed.
Role of gangliosides in the association of ErbB2 with lipid rafts in mammary epithelial HC11 cells
Authors: Sottocornola Elena , Misasi Roberta , Mattei Vincenzo , Ciarlo Laura , Gradini Roberto , Garofalo Tina , Berra Bruno , Colombo Irma , Sorice Maurizio
Published: March 2006

We analyzed the role of gangliosides in the association of the ErbB2 receptor tyrosine‐kinase (RTK) with lipid rafts in mammary epithelial HC11 cells. Scanning confocal microscopy experiments revealed a strict ErbB2–GM3 colocalization in wild‐type cells. In addition, analysis of membrane fractions obtained using a linear sucrose gradient showed that ErbB2, epidermal growth factor receptor (EGFR) and Shc‐p66 (proteins correlated with the ErbB2 signal transduction pathway) were preferentially enriched in lipid rafts together with gangliosides. Blocking of endogenous ganglioside synthesis by (+/–)‐threo‐1‐phenyl‐2‐decanoylamino‐3‐morpholino‐1‐propanol hydrochloride ([D]‐PDMP) induced a drastic cell‐surface redistribution of ErbB2, EGFR and Shc‐p66, within the Triton‐soluble fractions, as revealed by linear sucrose‐gradient analysis. This redistribution was partially reverted when exogenous GM3 was added to ganglioside‐depleted HC11 cells. The results point out the key role of ganglioside GM3 in retaining ErbB2 and signal‐transduction‐correlated proteins in lipid rafts.
Atypical PKCζ is involved in RhoA‐dependent mitogenic signaling by the P2Y12receptor in C6 cells
Authors: Van Kolen Kristof , Slegers Herman
Published: March 2006

When nucleotide hydrolysis is prevented, agonists of the P2Y12receptor enhance the proliferation of C6 glioma cells by RhoA‐dependent, protein kinase C (PKC)‐dependent activation of the extracellular signal‐regulated kinase (ERK) pathway [Claes P, Grobben B, Van Kolen K, Roymans D & Slegers H (2001)Br J Pharmacol134, 402–408; Grobben B, Claes P, Van Kolen K, Roymans D, Fransen P, Sys SU & Slegers H (2001)J Neurochem78, 1325–1338]. In this study, we show that ERK1/2 phosphorylation was not affected by transfection of the cells with the Gβγ‐subunit‐scavenging adrenergic receptor kinase peptide [βARK1‐(495–689)] or with Rap1GAPII, indicating that P2Y12receptor stimulation enhances ERK1/2 phosphorylation by Giα subunit‐mediated signaling independently of Rap1 activation. Inhibition of the RhoA downstream effector Rho‐associated coiled‐coil‐containing kinase (ROCK) with Y‐27632 did not affect the P2Y12receptor‐induced increase in ERK1/2 phosphorylation but abrogated the mitogenic response. Involvement of growth factor receptor transactivation in the signaling towards ERK phosphorylation could be ruled out by the lack of an effect of PP2, AG1024, AG1296 or SU1498, inhibitors of Src, insulin‐like growth factor receptor, platelet‐derived growth factor receptor and vascular endothelial growth factor receptor kinase activity, respectively. Experiments with bisindolylmaleimide I and IX indicated the requirement of PKC activity. Classical and novel PKC isoforms could be excluded by treatment of the cells with Gö6976 and calphostin C, whereas addition of a myristoylated PKCζ pseudosubstrate inhibitor completely abolished P2Y12receptor‐induced ERK1/2 activation. Moreover, coimmunoprecipitation experiments revealed PKCζ/Raf1 and PKCζ/ERK association, indicating the involvement of PKCζ. From the data presented, we can conclude that the P2Y12receptor enhances cell proliferation by a Giα‐dependent, RhoA‐dependent PKCζ/Raf1/MEK/ERK pathway that requires activation of ROCK, which is not involved in ERK1/2 signaling.
DOMESTIC VIOLENCE IN SAME‐GENDER RELATIONSHIPS
Authors: Rohrbaugh Joanna Bunker
Published: March 2006

Physical violence occurs in 11–12% of same‐gender couples, which suggests that domestic violence is an abuse of power that can happen in any type of intimate relationship, regardless of gender or sexual orientation. Although incidents of violence occur at the same rate in same‐gender couples and cross‐gender couples, the violence appears to be milder in same‐gender couples and it is unclear what percentage of same‐gender violence should be characterized as abuse or intimate terrorism. Same‐gender victims also suffer from the additional stress of severe isolation and the abuser's threats to expose the victim's sexual orientation in a hostile manner.
ALMOST, BUT NOT QUITE: THE FAILURE OF NEW YORK'S GET STATUTE
Authors: Glicksman Jeremy
Published: March 2006

The quandary of Jewish women unable to remarry because of their husbands’ refusal to grant them religious divorces is a real problem affecting real people. Husbands are wielding this lopsided power to “extort” money from their wives, obtain favorable child custody settlements, property settlements, and child support payments. The burgeoning divorce rate is certain to exacerbate this problem. Already, this situation has garnered international attention. In the wake of New York's legislative attempt to remedy this problem, countries, including the United Kingdom and Australia, have promulgated legislative solutions to this dilemma. New York is the only state in the United States to pass such a statute. Unfortunately, New York's statute is flawed because it is of limited applicability and still allows for situations in which the Jewish wife is civilly divorced but religiously married. This Note proposes amending New York's statute to make it applicable to any and all divorce proceedings and to any barrier to remarriage. This Note will further recommend that the proposed amended statute should be adopted worldwide.
Performance Evaluation of Innovative Micro-Traction-Drive-Utilized Angular-Contact Bearing
Authors: Tozaki Yasuyoshi , Umeda Akihiko , Sonobe Hiroyuki , Matsumoto Susumu , Yoshimi Takeshi , Shiotsu Isamu
Published: March 2006

Traction drive makes oil film between two rollers, and power is transmitted by oil film shearing. It has the following characteristics. (1) Traction drive can be operated at low level of vibration and noise, so they are more suitable at higher speed rotations than gear. (2) Traction drive can change continuously the distance from the contact point of the rotating part to the axis of rotation; it is useful in continuously variable transmission (CVT). Generally-fixed-reduction-ratio-type traction drive is developed for the purpose of use by high-speed rotation taking advantage of the feature of characteristic (1). On the other hand, the authors have developed a micro drive system for transmission; a micro-traction-drive based on the structure of an angular ball bearing is advantageous over geared speed reducers, for small scale equipment requiring high numbers of revolutions. A micro-traction-drive is easily manufactured by modifying angular bearings and tapered roller bearings for which preload inner race and outer race act as thrust force. The driving force is transmitted by the contact of the retainer with the rolling element in the rotating direction. The test of the experimental model of micro-traction-drive using an angular ball bearing of 10mm inner diameter, 30mm outer diameter, and 9mm width was carried out. Power-absorbing-type test equipment was made and the input and output torque, number of revolutions, temperature, noise, and state of lubrication were measured. With the same test equipment, the micro-traction-drive was compared to the equivalent type planetary gear with outer diameter of 32mm on the market. In comparison with commercially available speed reducers, the planetary gear system, the newly developed micro-traction was found to bear superior performance in terms of allowable transmission torque, efficiency, noise, and other characteristics.
The Use of System Identification Methods to Evaluate the Effects of Slider-Disk Contacts and Disk Micro-Waviness on the Flying Height Modulations
Authors: Deoras Saurabh K. , Talke Frank E.
Published: March 2006

System identification methods have been used to study the response of a magnetic recording slider during contact with a scratch on the disk surface. In addition, the slider response was studied taking into account the effect of disk micro-waviness at various disk rotational speeds. The simulated slider response was compared with the measured slider dynamic behavior. Very good agreement was found between simulated and measured data. The flying height modulation of the slider, due to disk micro-waviness, was found to depend on disk velocity.
Characteristics of Powder Lubricated Finite-Width Journal Bearings: A Hydrodynamic Analysis
Authors: Tsai Hung-Jung , Jeng Yeau-Ren
Published: March 2006

This paper analyzes the performance of hydrodynamic journal bearings by applying the control-volume method to solve the average lubrication equation for grain flow. The grain characteristics, including the particle size and the grain-grain collision elasticity are investigated. The nondimensional load, attitude angle, friction coefficient, and side flow are explored for different eccentricity and diameter-to-width ratios. The numerical results provide an understanding of the performance of powder lubricated journal bearings and are consistent with the experimental findings of Heshmat and Brewe.
An Efficient Algorithm for Fluid Force and its Jacobian Matrix in Journal Bearing
Authors: Xiao Zhonghui , Wang Liping , Zheng Tiesheng
Published: March 2006

Based on the theory of variational inequality, a rapid efficient algorithm for fluid force and its Jacobian matrix in journal bearing is presented in this paper. Primarily, to solve the fluid force is transformed to solve a set of linear algebraic equations with tri-diagonal coefficient matrices. Meanwhile, an amendatory direct-method is proposed to solve the united equations about fluid forces and their Jacobian matrices, rapidly and synchronously. The Reynolds boundary condition has to be satisfied automatically during the process. Secondly, the coefficient matrices, which are involved in the previous process, can be decomposed to an assembly of a part of relative with journal motion and a part of invariable matrix, which can be prepared in advance and be referred to later repeatedly. Through these measures, many redundant operations are avoided. The numerical examples show that, under the accuracy guaranteed, the algorithm in this paper can reduce computational time remarkably, which reveals that the current method has a good operational characteristic and practicability.
Thermohydrodynamic Behavior of a Slider Pocket Bearing
Authors: Dobrica Mihai B. , Fillon Michel
Published: March 2006

Pocket-pads or steps are often used in journal bearing design, allowing improvement of the latter’s dynamic behavior. Similar “discontinuous” geometries are used in designing thrust bearing pads. A literature review shows that, to date, only isoviscous and adiabatic studies of such geometries have been performed. The present paper addresses this gap, proposing a complete thermohydrodynamic (THD) steady model, adapted to three-dimensional (3D) discontinuous geometries. The model is applied to the well-known geometry of a slider pocket bearing, operating with an incompressible viscous lubricant. A model based on the generalized Reynolds equation, with concentrated inertia effects, is used to determine the 2D pressure distribution. On this basis, a 3D field of velocities is constructed which, in turn, allows the resolution of the 3D energy equation. Using a variable-size grid improves the accuracy in the discontinuity region, allowing an evaluation of the magnitude of error induced by Reynolds assumptions. The equations are solved using the finite volume method. This ensures good convergence even when a significant reverse flow is present. Heat evacuation through the pad is taken into account by solving the Laplace equation with convective boundary conditions that are realistic. The runner’s temperature, assumed constant, is determined by imposing a zero value for the global heat flux balance. The constructed model gives the pressure distribution and velocity fields in the fluid, as well as the temperature distribution across the fluid and solid pad. Results show important transversal temperature gradients in the fluid, especially in the areas of minimal film thickness. This further justifies the use of a complete THD model such as the one employed.
Optimization of the Cross Section of an Elastomeric Seal for Pneumatic Cylinders
Authors: Belforte Guido , Manuello Andrea , Mazza Luigi
Published: March 2006

The cross section of an elastomer seal for pneumatic actuator pistons was optimized to minimize the friction force exchanged with the cylinder bore. The new seal geometry was developed using a finite element numerical model which takes material nonlinearities and frictional contact with seat and cylinder bore surfaces into account. The friction force exchanged between the new seal and the pneumatic cylinder bore was measured experimentally using a suitable sensorized test bench.
In Vitro Study of Backside Wear Mechanisms on Mobile Knee-Bearing Components
Authors: Atwood S. A. , Kennedy F. E. , Currier J. H. , Van Citters D. W. , Collier J. P.
Published: March 2006

The long-term success of a total knee replacement depends on the wear performance of a polyethylene bearing that separates a metal femoral component from a metal tibial tray. Although fixed bearing designs secure the polyethylene bearing to the tibial tray, mobile bearing knees allow the polyethylene to move relative to the tibial tray. This study has evaluated the wear performance of an intended articulation on the inferior surface of the LCS®-Rotating Platform mobile bearing by conducting clinically relevant tribological testing and comparing results to retrieved knee bearings. A retrieval analysis leads to the conclusion that third-body particles in the contact produce curvilinear scratches longer than the expected rotation of the knee on both the polyethylene bearing and the CoCr tibial tray. Tribological testing shows that polymethylmethacrylate (PMMA) bone cement particles produce worn surfaces most similar to retrievals. Porous-coating beads and bone debris also have the ability to damage both surfaces. Worn polyethylene surfaces from pin-on-flat tests show scratches longer than the excursion length, and “skipping marks”—pits spaced at smaller rotation intervals along a scratch—as observed in retrievals. These wear features suggest that a ratcheting mechanism, which moves the third-body particles further along the scratch with each cycle, may be responsible for the observed wear.
Global Analysis Method of Friction Parameters in Strip-Drawing Tests
Authors: Pothier J.-M. , Roizard X. , Hihn J. Y. , Béteau J.-F. , Monteil G.
Published: March 2006

Numerous works have been recently carried out to describe friction and lubrication in the tool-sheet interface. This phenomenon is of great importance for all forming processes, particularly, in the deep drawing operations where the rapid progress in the field of computing requires the predictive knowledge of friction coefficient behaviors. The present paper considers the dynamical modeling by a global approach of the tangential force evolution. All measurements come from a tribometer equipped for strip-drawing tests on lubricated steel sheets and aluminum sheets, as a function of applied normal load. Models are obtained from serial, parallel, or closed-loop association structures for linear transfer functions. Numerical values of delays, time constants, and gain are identified for each test order; complexities and structures are determined with a double optimization. For all situations, a stop criterion is defined to achieve the optimal model, which is reached for the steel sheets.
Theoretical and Experimental Investigations Into Spacing Characteristics Between Roller and Three Types of Webs With Different Permeabilities
Authors: Hashimoto H. , Okajima M.
Published: March 2006

A new theoretical model for estimating the entrained air film thickness between a web and roller is presented for both impermeable and permeable webs. A simple curve fit formula for estimating the air film thickness, which considers the effects of air leakage from the web edges and air diffusion due to the permeability of web, was obtained based on a large number of simultaneous numerical solutions of the compressible Reynolds equation and the web equilibrium equation. The variation of air film thickness with roller velocity is measured for three typical webs: polyethylene terephthalate, coated paper, and newsprint. The effects of web permeability, web width, and web tension on the air film thickness are examined theoretically and experimentally for a wide range of roller velocity. Reasonable agreement is seen both quantitatively and qualitatively between the predicted and measured results. The validity of the formula for the first-order estimation of web-roller interface problems is verified experimentally.
A New Method for Elastic-Plastic Contact Analysis of a Deformable Sphere and a Rigid Flat
Authors: Lin Li Po , Lin Jen Fin
Published: March 2006

A new method is developed in the present study to determine the elastoplastic regime of a spherical asperity in terms of the interference of two contact surfaces. This method provides an efficient way to solve the problem of discontinuities often present in the reported solutions for the contact load and area or the gradients of these parameters obtained at either the inception or the end of the elastoplastic regime. The well-established solutions for the elastic regime and experimental data of metal materials using indentation tests are provided as the references to determine the errors of these contact parameters due to the use of the finite-element method. These numerical errors provide the basis to adjust the contact area and contact load of a rigid sphere in contact with a flat such that the dimensionless mean contact pressure Pave∕Y (Y: the yielding strength) and the dimensionless contact load Fpc∕Fec (Fec, Fpc: the contact loads corresponding to the inceptions of the elastoplastic and fully plastic regimes, respectively) reaches the criteria arising at the inception of the fully plastic regime, which are available from the reports of the indentation tests for metal materials. These two criteria are however not suitable for the present case of a rigid flat in contact with a deformable sphere. In the case of a rigid flat in contact with a deformable sphere, the proportions in the adjustments of these contact parameters are given individually the same as those arising in the indentation case. The elastoplastic regime for each of these two contact mechanisms can thus be determined independently. By assuming that the proportion of adjustment in the elastoplastic regime is a linear function, the discontinuities appearing in these contact parameters are absent from the two ends of the elastoplastic regime in the present study. These results are presented and compared with the published results.
Experimental Investigation of Fully Plastic Contact of a Sphere Against a Hard Flat
Authors: Jamari J. , Schipper D. J.
Published: March 2006

In this paper we report the experimental investigation to evaluate the published models for the contact of a deformable sphere against a hard flat in the fully plastic contact regime. A new measurement method has been used to measure the contact area. The behavior of the mean contact pressure and the contact area as a function of the contact load are presented. Substantial differences are found between the measurements and the model predictions. A constant value of the mean contact pressure as the load increases is observed, however, the value is lower than the hardness, as often reported. The contact area is found to be a simple truncation of the sphere by a hard flat.
Producing Ultrastrong Magnetic Fields in Neutron Star Mergers
Authors: Price D. J. , Rosswog S.
Published: March 2006

We report an extremely rapid mechanism for magnetic field amplification during the merger of a binary neutron star system. This has implications for the production of the short class of gamma-ray bursts, which recent observations suggest may originate in such mergers. In detailed magnetohydrodynamic simulations of the merger process, the fields are amplified by Kelvin-Helmholtz instabilities beyond magnetar field strength and may therefore represent the strongest magnetic fields in the universe. The amplification occurs in the shear layer that forms between the neutron stars and on a time scale of only 1 millisecond, that is, long before the remnant can collapse into a black hole.
Spin Coupling in Engineered Atomic Structures
Authors: Hirjibehedin Cyrus F. , Lutz Christopher P. , Heinrich Andreas J.
Published: March 2006

We used a scanning tunneling microscope to probe the interactions between spins in individual atomic-scale magnetic structures. Linear chains of 1 to 10 manganese atoms were assembled one atom at a time on a thin insulating layer, and the spin excitation spectra of these structures were measured with inelastic electron tunneling spectroscopy. We observed excitations of the coupled atomic spins that can change both the total spin and its orientation. Comparison with a model spin-interaction Hamiltonian yielded the collective spin configuration and the strength of the coupling between the atomic spins.
Retinoid Signaling Determines Germ Cell Fate in Mice
Authors: Bowles Josephine , Knight Deon , Smith Christopher , Wilhelm Dagmar , Richman Joy , Mamiya Satoru , Yashiro Kenta , Chawengsaksophak Kallayanee , Wilson Megan J. , Rossant Janet , Hamada Hiroshi , Koopman Peter
Published: March 2006

Germ cells in the mouse embryo can develop as oocytes or spermatogonia, depending on molecular cues that have not been identified. We found that retinoic acid, produced by mesonephroi of both sexes, causes germ cells in the ovary to enter meiosis and inititate oogenesis. Meiosis is retarded in the fetal testis by the action of the retinoid-degrading enzyme CYP26B1, ultimately leading to spermatogenesis. In testes of
Cyp26b1
-knockout mouse embryos, germ cells enter meiosis precociously, as if in a normal ovary. Thus, precise regulation of retinoid levels during fetal gonad development provides the molecular control mechanism that specifies germ cell fate.
Metallothionein isoform II expression in hyperplastic, dysplastic and neoplastic prostatic lesions
Authors: El Sharkawy S L , Abbas N F , Badawi M A , El Shaer M A
Published: March 2006

Background:Metallothionein is a low-molecular-weight cysteine-rich protein that has the ability to bind and sequestrate heavy metal ions. It is associated with metalloregulatory functions such as cell proliferation, growth and differentiation.

Aims:To investigate the expression of metallothionein in hyperplastic, dysplastic and neoplastic prostatic lesions and to correlate its expression with histological grade of prostatic carcinoma.

Method:The study was carried out on formalin-fixed and paraffin-wax-embedded tissue blocks from 8 patients with benign prostatic hyperplasia, 6 patients with prostatic intraepithelial neoplasia (PIN) and 30 patients with prostatic carcinoma, using the streptavidin–biotin technique. The histological grade was defined and the carcinomas were divided into low-grade (Gleason Score 2–4), 12 moderate grade (Gleason Score 5–6) and 10 high-grade (Gleason Score 7–10) carcinomas.

Results:Patchy metallothionein staining of epithelial cells was observed in normal and benign prostatic tissues. All cases of PIN and 20 of 30 patients with prostatic carcinoma showed positive staining for metallothionein. Metallothionein expression considerably increased from low-grade to high-grade tumours. The proportion of cells staining positively for metallothionein was directly correlated with histological grade of prostatic carcinoma. The epithelial cells lack uniformity in staining intensity, but the percentage of strongly positive cells increased with the histological grade of prostatic carcinoma.

Conclusions:The high incidence of metallothionein expression in PIN in our study suggests that it is associated with early prostate tumorigenesis. Also, metallothionein expression was directly correlated with the histological grade of prostatic carcinoma, suggesting that metallothionein may be a useful marker for predicting the prognosis of prostate cancer.
THE GENERALIZED UNCERTAINTY PRINCIPLE AND CORRECTIONS TO THE CARDY–VERLINDE FORMULA IN SAdS5 BLACK HOLES
Authors: SETARE M. R.
Published: March 2006

In this paper, we investigate a possible modification to the temperature and entropy of five-dimensional Schwarzschild anti-de Sitter black holes due to the incorporation of stringy corrections to the modified uncertainty principle. Then, we subsequently argue for corrections to the Cardy–Verlinde formula in order to account for the corrected entropy. Then, we show that one can taking into account the generalized uncertainty principle corrections of the Cardy–Verlinde entropy formula by just redefining the Virasoro operator L0 and the central charge c.
THEORETICAL DESCRIPTION OF DOUBLE BETA DECAY TRACKS IN A GERMANIUM DETECTOR AND OF THEIR DEPENDENCE ON PARTICLE AND NUCLEAR PHYSICS — A REVIEW
Authors: KLAPDOR-KLEINGROTHAUS H. V. , KRIVOSHEINA I. V. , TITKOVA I. V.
Published: March 2006

In this review for the first time a theoretical description of the tracks of events of nuclear double beta decay in a large Ge detector is presented. It is obvious that in principle the shapes and sizes of these tracks — and the corresponding time structure of pulses — depend on particle physics and nuclear physics parameters such as neutrino mass, right-handed current parameters, and nuclear matrix elements. The knowledge of this dependence is of importance, since the key to probe the existence of 0νββ decay beyond observation of a signal at the Q value of the process, Qββ, is the discrimination of ββ events from background γ events (or other events), in almost any double beta decay experiment (see Refs. 2 and 3). In this review Monte-Carlo simulations of tracks of neutrino-accompanied (2νββ) and neutrinoless double beta decay (0νββ) events, and of various kinds of background processes such as multiple and other γ interactions are reported for a large Ge detector. The time history of the evolution of the individual events is followed and the sizes of the events (volumes in the detector inside which the energy of the event is released) are investigated. Effects of the angular correlations of the two electrons in ββ decay, which again depend on the above nuclear and (for 0νββ decay) particle physics parameters, are taken into account and have been calculated for this purpose for the first time on basis of the experimental half-life of 76 Ge and of realistic nuclear matrix elements.

It is shown for ββ decay of 76 Ge , that 0νββ events are to a large extent separable from Compton scattering of γ events of the same energy, while double escape peaks of γ-lines show very similar behavior as 0νββ events, and in that sense can be useful for corresponding "calibration" of pulse shapes of the detector. The possibility to distinguish 0νββ events from γ events is found to be essentially independent of the particle physics parameters of the 0νββ process. A brief outlook is given on the potential of future experiments with respect to determination of the particle physics parameters 〈mν〉, 〈λ〉, 〈η〉. It is suggested, that the strategy in future 0νββ research should be, to combine confirmation of the HEIDELBERG-MOSCOW result with determination of the mechanism of the dominating decay, instead of repeating earlier experiments or ideas. The future experiment thus should not use 76 Ge or 136 Xe , but instead 124 Xe .
AN EMPIRICAL STUDY OF THE PROBABILITY DENSITY FUNCTION OF HF NOISE
Authors: GIESBRECHT J. , CLARKE R. , ABBOTT D.
Published: March 2006

To many, high-frequency (HF) radio communications is obsolete in this age of long-distance satellite communications and undersea optical fiber. Yet despite this, the HF band is used by defense agencies for backup communications and spectrum surveillance, and is monitored by spectrum management organizations to enforce licensing. Such activity usually requires systems capable of locating distant transmitters, separating valid signals from interference and noise, and recognizing signal modulation. Our research targets the latter issue. The ultimate aim is to develop robust algorithms for automatic modulation recognition of real HF signals. By real, we mean signals propagating by multiple ionospheric modes with co-channel signals and non-Gaussian noise. However, many researchers adopt Gaussian noise for their modulation recognition algorithms for the sake of convenience at the cost of accuracy. Furthermore, literature describing the probability density function (PDF) of HF noise does not abound. So we describe a simple empirical technique, not found in the literature, that supports our work by showing that the probability density function (PDF) for HF noise is generally not Gaussian. In fact, the probability density function varies with the time of day, electro-magnetic environment, and state of the ionosphere.
Suppressor of cytokine signaling-2 limits intestinal growth and enterotrophic actions of IGF-I in vivo
Authors: Michaylira Carmen Z. , Simmons James G. , Ramocki Nicole M. , Scull Brooks P. , McNaughton Kirk K. , Fuller C. Randall , Lund P. Kay
Published: March 2006

Suppressors of cytokine signaling (SOCS) typically limit cytokine receptor signaling via the JAK-STAT pathway. Considerable evidence demonstrates that SOCS2 limits growth hormone (GH) action on body and organ growth. Biochemical evidence that SOCS2 binds to the IGF-I receptor (IGF-IR) supports the novel possibility that SOCS2 limits IGF-I action. The current study tested the hypothesis that SOCS2 normally limits basal or IGF-I-induced intestinal growth and limits IGF-IR signaling in intestinal epithelial cells. Intestinal growth was assessed in mice homozygous for SOCS2 gene deletion (SOCS2 null) and wild-type (WT) littermates at different ages and in response to infused IGF-I or vehicle or EGF and vehicle. The effects of SOCS2 on IGF-IR signaling were examined in ex vivo cultures of SOCS2 null and WT intestine and Caco-2 cells. Compared with WT, SOCS2 null mice showed significantly enhanced small intestine and colon growth, mucosal mass, and crypt cell proliferation and decreases in radiation-induced crypt apoptosis in jejunum. SOCS2 null mice showed significantly greater growth responses to IGF-I in small intestine and colon. IGF-I-stimulated activation of IGF-IR and downstream signaling intermediates were enhanced in the intestine of SOCS2 null mice and were decreased by SOCS2 overexpression in Caco-2 cells. SOCS2 bound directly to the endogenous IGF-IR in Caco-2 cells. The intestine of SOCS2 null mice also showed enhanced growth responses to infused EGF. We conclude that SOCS2 normally limits basal and IGF-I- and EGF-induced intestinal growth in vivo and has novel inhibitory effects on the IGF-IR tyrosine kinase pathway in intestinal epithelial cells.
Mechanisms and pathophysiological implications of sinusoidal endothelial cell gap formation following treatment with galactosamine/endotoxin in mice
Authors: Ito Yoshiya , Abril Edward R. , Bethea Nancy W. , McCuskey Margaret K. , Cover Cathleen , Jaeschke Hartmut , McCuskey Robert S.
Published: March 2006

Neutrophil extravasation from sinusoids is a critical step for acute inflammatory tissue injury. However, the role of sinusoidal endothelial cells (SECs) in this process remains unclear. Matrix metalloproteinases (MMPs) have been shown to involve gap formation in SECs in several liver diseases. Therefore, the present study examined SEC modifications elicited by galactosamine (Gal)/endotoxin (ET). Treatment of male C3Heb/FeJ mice with Gal/ET or Gal/TNF caused the formation of numerous gaps in SECs at 4 h when no neutrophil extravasation occurred. Six hours after Gal/ET or Gal/TNF treatment, blood elements started to penetrate to the extrasinusoidal space through large gaps. Treatment with ET alone caused sinusoidal neutrophil accumulation but no gap formation, neutrophil extravasation, or hemorrhage. Gal/ET treatment increased hepatic MMP-2 and MMP-9 mRNA expression (6.7- and 11-fold, respectively). Pretreatment with 2-[(4-biphenylsulfonyl) amino]-3-phenyl-propionic acid, an MMP-2/MMP-9 inhibitor (5 mg/kg), minimized gap formation after Gal/ET and Gal/TNF treatment. The MMP inhibitor reduced injury only in the Gal/ET model mainly due to reduced TNF formation. The MMP inhibitor attenuated sinusoidal neutrophil accumulation at 6 h but failed to attenuate Gal/TNF-induced liver injury at 7 h due to excessive apoptosis. These results suggest that Gal/ET or Gal/TNF activates MMPs, which are responsible for SEC gap formation. Although the initial appearance of gap formation is independent of neutrophils, the gaps allow initial contact of neutrophils with damaged hepatocytes. In addition, MMP activation promotes neutrophil accumulation in sinusoids.
Chronic PKC-β2activation in HT-29 Cl.19a colonocytes prevents cAMP-mediated ion secretion by inhibiting apical membrane CFTR targeting
Authors: Broughman James R. , Sun Limin , Umar Shahid , Sellin Joseph H. , Morris Andrew P.
Published: March 2006

We investigated the effects of chronically applied PKC-stimulating phorbol esters on subcellular CFTR expression and localization in polarized HT-29 Cl.19A monolayers. Modulation of PKC activity with the PKC-β-specific agonist 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPA) or nonisoform-selective PMA altered monolayer CFTR immunofluorescence. A decrease in the CFTR signal within the luminal cellular pole was noted with both phorbol esters. Volumetric analysis of the intracellular CFTR signal revealed that both compounds promoted CFTR accumulation into punctate vesicle-like structures found adjacent to the cellular tight junction [labeled with zona occludens (ZO)-1 antibody], extending basally (DOPPA) into the cell. Puncta were more frequent with DOPPA and larger in size with PMA. DOPPA also promoted ZO-1 accumulation at tricellular corners associated with enhanced CFTR puncta number. The observed loss of CFTR immunofluorescence signal induced by low-dose PMA was related to CFTR sequestration into fewer cytoplasmic puncta and correlated with larger increases in PKC substrate phosphorylation. Both phorbol esters downregulated steady-state cellular CFTR mRNA levels by 70%. However, the effects of DOPPA and PMA were largely independent of CFTR biosynthesis: expression levels were 80–85% of control, and the glycosylation status of immunoprecipitated protein remained largely unchanged. Thus changes in cellular CFTR localization correlated with our companion study showing that PMA-induced inhibition of transcellular cAMP-dependent short-circuit current ( ISC) was accompanied by cytoplasmic PKC-β2accumulation and modest activation of PKC-β1and PKC-ε. The inhibitory effect of DOPPA on ISCwas related solely to increased cytoplasmic PKC-β2levels. Thus PKC-β2is hypothesized to participate in the regulation of CFTR apical plasma membrane targeting within the constitutive cellular biosynthetic pathway.
Prostaglandin-mediated inhibition of Na+/H+exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine
Authors: Moeser Adam J. , Nighot Prashant K. , Ryan Kathleen A. , Wooten Jenna G. , Blikslager Anthony T.
Published: March 2006

Prostaglandins stimulate repair of the ischemia-injured intestinal barrier in the porcine ileum through a mechanism involving cAMP-dependent Cl−secretion and inhibition of electroneutral Na+/H+exchanger (NHE) activity. In the present study, we focused on the role of individual NHE isoforms in the recovery of barrier function. Ischemia-injured porcine ileal mucosa was mounted on Ussing chambers. Short-circuit current ( Isc), transepithelial electrical resistance (TER), and isotopic fluxes of22Na were measured in response to PGE2and selective inhibitors of epithelial NHE isoforms. Immunoassays were used to assess the expression of NHE isoforms. Forty-five minutes of intestinal ischemia resulted in a 45% reduction in TER ( P < 0.01). Near-complete restitution occurred within 60 min. Inhibition of NHE2 with HOE-694 (25 μM) added to the mucosal surface of the injured ileum stimulated significant elevations in TER, independent of changes in Iscand histological evidence of restitution. Pharmacological inhibition of NHE3 or NHE1 with mucosal S-3226 (20 μM) or serosal cariporide (25 μM), respectively, had no effect. Ischemia-injured tissues treated with mucosal S-3226 or HOE-694 exhibited equivalent reductions in mucosal-to-serosal fluxes of22Na+(by ∼35%) compared with nontreated ischemia-injured control tissues ( P < 0.05). Intestinal ischemia resulted in increased expression of the cytoplasmic NHE regulatory factor EBP50 in NHE2 but not in NHE3 immunoprecipitates. Selective inhibition of NHE2, and not NHE3, induces recovery of barrier function in the ischemia-injured intestine.
Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium
Authors: Kimball Edward S. , Schneider Craig R. , Wallace Nathaniel H. , Hornby Pamela J.
Published: March 2006

Oil of mustard (OM) is a potent neuronal activator that is known to elicit visceral hyperalgesia when given intracolonically, but the full extent to which OM is also proinflammatory in the gastrointestinal tract is not known. We have previously shown that male CD-1 mice given a single administration of 0.5% OM develop a severe colitis that is maximum at day 3 and that gradually lessens until essentially absent by day 14. OM-induced neuronal stimulation is reported to be reduced by cannabinoid agonists, and cannabinoid receptor 1 (CB1R)−/−mice have exacerbated experimental colitis. Therefore, we examined the role of cannabinoids in this OM-induced 3-day model of colitis in CD-1 mice and in a 7-day dextran sulfate sodium (DSS) colitis model in BALB/c mice. In OM colitis, the CB1R-selective agonist ACEA and the CB2R-selective agonist JWH-133 reduced ( P < 0.05) colon weight gain (means ± SE; 82 ± 13% and 47 ± 15% inhibition, respectively), colon shrinkage (98 ± 24% and 42 ± 12%, respectively), colon inflammatory damage score (49 ± 11% and 40 ± 12%, respectively), and diarrhea (58 ± 12% and 43 ± 11%, respectively). Histological damage was similarly reduced by these treatments. Likewise, CBR agonists attenuated DSS colitis, albeit at higher doses; ACEA at 10 mg/kg, twice daily, inhibited ( P < 0.05) macroscopic and microscopic scores (46 ± 9% and 63 ± 7%, respectively); whereas 20 mg/kg, twice daily, of JWH-133 was required to diminish ( P < 0.05) macroscopic and microscopic scores (29 ± 7% and 43 ± 5%, respectively). CB1R and CB2R immunostaining of colon sections revealed that CB1R in enteric neurons was more intense in colitic vs. control mice; however, CB1R was also increased in the endothelial layer in OM colitis only. CB2R immunostaining was more marked in infiltrated immune cells in OM colitis. These findings validate the OM colitis model with respect to the DSS model and provide strong support to the emerging idea that cannabinoid receptor activation mediates protective mechanisms in experimental colitis. The demonstration of CB1R agonist effects in colitis support the neurogenic nature of the OM-induced colitis model and reinforce the importance of neuronal activation in intestinal inflammation.
Early activation of endoplasmic reticulum stress is associated with arginine-induced acute pancreatitis
Authors: Kubisch Constanze H. , Sans Maria Dolors , Arumugam Thiruvengadam , Ernst Stephen A. , Williams John A. , Logsdon Craig D.
Published: March 2006

Endoplasmic reticulum (ER) stress mechanisms have been found to play critical roles in a number of diseases states, such as diabetes mellitus and Alzheimer disease, but whether they are involved in acute pancreatitis is unknown. Here we show for the first time that all major ER stress sensing and signaling mechanisms are present in exocrine acini and are activated early in the arginine model of experimental acute pancreatitis. Pancreatitis was induced in rats by intraperitoneal injection of 4.0 g/kg body wt arginine. Pancreatitis severity was assessed by analysis of serum amylase, pancreatic trypsin activity, water content, and histology. ER stress-related molecules PERK, eIF2α, ATF6, XBP-1, BiP, CHOP, and caspase-12 were analyzed. Arginine treatment induced rapid and severe pancreatitis, as indicated by increased serum amylase, pancreatic tissue edema, and acinar cell damage within 4 h. Arginine treatment also caused an early activation of ER stress, as indicated by phosphorylation of PERK and its downstream target eIF2α, ATF6 translocation into the nucleus (within 1 h), and upregulation of BiP (within 4 h). XBP-1 splicing and CHOP expression were observed within 8 h. After 24 h, increased activation of the ER stress-related proapoptotic molecule caspase-12 was observed along with an increase in caspase-3 activity and TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labeling (TUNEL) staining in exocrine acini. These results indicate that ER stress is an important early acinar cell event that likely contributes to the development of acute pancreatitis in the arginine model.
FTY720 suppresses CD4+CD44highCD62L− effector memory T cell-mediated colitis
Authors: Fujii R. , Kanai T. , Nemoto Y. , Makita S. , Oshima S. , Okamoto R. , Tsuchiya K. , Totsuka T. , Watanabe M.
Published: March 2006

FTY720, a sphingosine-derived immunomodulator, causes immunosuppression via enhancement of lymphocyte sequestration into secondary lymphoid organs, thereby preventing their antigen-activated T cell egress to sites of inflammation. FTY720 is highly effective in inhibiting autoimmunity in various animal models. However, there is little known about how FTY720 controls the migration property of memory T cells. Here, we demonstrated that FTY720 prevents the development of colitis induced by the adoptive transfer of lamina propria (LP) colitogenic effector memory CD4+ T cells (TEM cells; CD45RBlowCD44highCD62L−) into severe combined immunodeficiency (SCID) mice and suppresses interferon-γ, interleukin-2, and tumor necrosis factor-α production by LP CD4+ T cells. The numbers of spleen, peripheral blood, mesenteric lymph node, and LP CD4+ T cells in FTY720-treated mice were significantly reduced compared with those in control mice. Notably, LP CD4+ TEM cells as well as splenic CD4+CD45RBhigh T cells expressed several spingosine-1-phosphate receptors that are targets for FTY720. Furthermore, FTY720 also prevented the development of colitis induced by the adoptive transfer of splenic CD4+CD45RBhigh T cells into SCID mice. Collectively, the present data indicate that FTY720 treatment may offer the potential not only to prevent the onset of disease but also to treat memory T cell-mediated autoimmune diseases including inflammatory bowel diseases.
Administration of r-VEGF-A prevents hepatic artery ligation-induced bile duct damage in bile duct ligated rats
Authors: Gaudio Eugenio , Barbaro Barbara , Alvaro Domenico , Glaser Shannon , Francis Heather , Franchitto Antonio , Onori Paolo , Ueno Yoshiyuki , Marzioni Marco , Fava Giammarco , Venter Julie , Reichenbach Ramona , Summers Ryun , Alpini Gianfranco
Published: March 2006

The hepatic artery, through the peribiliary plexus, nourishes the intrahepatic biliary tree. During obstructive cholestasis, the nutritional demands of intrahepatic bile ducts are increased as a consequence of enhanced proliferation; in fact, the peribiliary plexus (PBP) displays adaptive expansion. The effects of hepatic artery ligation (HAL) on cholangiocyte functions during cholestasis are unknown, although ischemic lesions of the biliary tree complicate the course of transplanted livers and are encountered in cholangiopathies. We evaluated the effects of HAL on cholangiocyte functions in experimental cholestasis induced by bile duct ligation (BDL). By using BDL and BDL + HAL rats or BDL + HAL rats treated with recombinant-vascular endothelial growth factor-A (r-VEGF-A) for 1 wk, we evaluated liver morphology, the degree of portal inflammation and periductular fibrosis, microcirculation, cholangiocyte apoptosis, proliferation, and secretion. Microcirculation was evaluated using a scanning electron microscopy vascular corrosion cast technique. HAL induced in BDL rats 1) the disappearance of the PBP, 2) increased apoptosis and impaired cholangiocyte proliferation and secretin-stimulated ductal secretion, and 3) decreased cholangiocyte VEGF secretion. The effects of HAL on the PBP and cholangiocyte functions were prevented by r-VEGF-A, which, by maintaining the integrity of the PBP and cholangiocyte proliferation, prevents damage of bile ducts following ischemic injury.
Hepcidin and hemojuvelin gene expression in rat liver damage: in vivo and in vitro studies
Authors: Sheikh Nadeem , Batusic Danko S. , Dudas Jozsef , Tron Kyrylo , Neubauer Katrin , Saile Bernhard , Ramadori Giuliano
Published: March 2006

In this work, we used two rat models, partial hepatectomy (PH) and CCl4administration, to study the changes in iron pathways in response to hepatic damage. Liver injury induced changes in the hepatic gene expression of hepcidin, hemojuvelin (Hjv), several other proteins of iron metabolism, and several cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ. Hepcidin gene expression was upregulated between 4 and 8 h with a maximum up to 16 h after surgery. However, Hjv gene expression was downregulated at the same time. An early upregulation of hepcidin (3 h) and downregulation of Hjv gene expression was found after CCl4administration. Transferrin receptor 1 and ferritin H gene expression was upregulated, whereas ferroportin 1 gene expression was downregulated. Hepatic IL-6 gene expression was upregulated early after PH and reached maximum 8 h after the PH. In CCl4-induced liver injury, IL-6, IL-1β, TNF-α, and IFN-γ upregulation were found at the maximum 12 h after the administration of the toxin. Treatment of isolated rat hepatocytes with IL-6 and, to a lesser extent, with IL-1β but not with TNF-α or IFN-γ dose dependently upregulated hepcidin and downregulated Hjv gene expression. In hepatic damage, changes of the hepatic gene expression of the main proteins involved in iron metabolism may be induced by locally synthesized mediators.