bluuebunny/crossref_metadata_2025 huggingface dataset:
Short‐term Training Effects on Diastolic Function in Obese Persons With the Metabolic Syndrome
Authors: Baynard Tracy , Carhart Robert L. , Ploutz‐Snyder Lori L. , Weinstock Ruth S. , Kanaley Jill A.
Published: April 2008

The aim of this study was to determine the effects of a short‐term high‐intensity exercise program on diastolic function and glucose tolerance in obese individuals with and without metabolic syndrome (MetSyn). Obese men and women (BMI > 30 kg/m2; 39–60 years) with and without the MetSyn (MetSyn 13; non‐MetSyn 18) underwent exercise training consisting of 10 consecutive days of treadmill walking for 1 h/day at 70–75% of peak aerobic capacity. Subjects performed pre‐ and post‐training testing for aerobic capacity, glucose tolerance (2‐h meal test), and standard echocardiography. Aerobic capacity improved for both groups (non‐MetSyn 24.0 ± 1.6 ml/kg/min vs. 25.1 ± 1.5 ml/kg/min; MetSyn 25.2 ± 1.8 ml/kg/min vs. 26.2 ± 1.7 ml/kg/min, P < 0.05). Glucose area under the curve (AUC) improved in the MetSyn group (1,017 ± 58 pmol/l/min vs. 883 ± 75 pmol/l/min, P < 0.05) with no change for the non‐MetSyn group (685 ± 54 pmol/l/min vs. 695 ± 70 pmol/l/min). Isovolumic relaxation time (IVRT) improved in the MetSyn group (97 ± 6 ms vs. 80 ± 5 ms, P < 0.05), and remained normal in the non‐MetSyn group (82 ± 6 ms vs. 86 ± 5 ms). No changes in other diastolic parameters were observed. The overall reduction in IVRT was correlated with a decrease in diastolic blood pressure (DBP) (r = 0.45, P < 0.05), but not with changes in glucose tolerance. Body weight did not change with training in either group. A 10‐day high‐intensity exercise program improved diastolic function and glucose tolerance in the group with MetSyn. The reduction in IVRT in MetSyn was associated with a fall in blood pressure. These data suggest that it may be possible to reverse early parameters of diastolic dysfunction in MetSyn with a high‐intensity exercise program.
Vibrational dynamics of amorphous beryllium hydride and lithium beryllium hydrides
Authors: Sampath Sujatha , Kolesnikov Alexander I. , Lantzky Kristina M. , Yarger Jeffery L.
Published: April 2008

The vibrational density of states of amorphous beryllium hydride (a-BeH2) and lithium beryllium hydrides have been studied using inelastic neutron scattering, infrared, and Raman spectroscopies. The positions of the symmetrical (120–180meV) and antisymmetrical (200–260meV) Be–H stretching modes and those of the H–Be–H bending mode (50–120meV) have been determined and the results discussed and compared with recent theoretical calculations. With the addition of lithium to the beryllium hydride network, the vibrational bands are shifted to lower energies, indicating a less rigid network.
Dye reorientation as a probe of stress-induced mobility in polymer glasses
Authors: Lee Hau-Nan , Paeng Keewook , Swallen Stephen F. , Ediger M. D.
Published: April 2008

The reorientation of dye molecules can be used to monitor the segmental dynamics of a polymer melt. We utilize this technique to measure stress-induced mobility in a lightly cross-linked poly(methyl methacrylate) (PMMA) glass during tensile creep deformation. At 377K (18K below the glass transition temperature Tg), the mobility increased by a factor of 100 during deformation with a stress of 20MPa. Generally, the mobility increased as the stress, strain, and strain rate increased. After removing the stress, we observed that the enhanced mobility slowly disappeared during strain recovery. At 377K, when the stress is lower than 11MPa, almost no mobility enhancement was observed. Once the stress crossed this threshold value, the mobility dramatically increased.
On the corresponding states law of the Yukawa fluid
Authors: Orea Pedro , Duda Yurko
Published: April 2008

We have analyzed the currently available simulation results as well as performed some additional Monte Carlo simulation for the hard-core attractive Yukawa fluid in order to study its corresponding state behavior. We show that the values of reduced surface tension map onto the master curve and a universal equation of state can be obtained in the wide range of the attractive Yukawa tail length after a certain rescaling of the number density. Some comparisons with other nonconformal potentials are presented and discussed.
The vanishing limit of the square-well fluid: The adhesive hard-sphere model as a reference system
Authors: Largo J. , Miller M. A. , Sciortino F.
Published: April 2008

We report a simulation study of the gas-liquid critical point for the square-well potential, for values of well width δ as small as 0.005 times the particle diameter σ. For small δ, the reduced second virial coefficient at the critical point B2*c is found to depend linearly on δ. The observed weak linear dependence is not sufficient to produce any significant observable effect if the critical temperature Tc is estimated via a constant B2*c assumption, due to the highly nonlinear transformation between B2*c and Tc. This explains the previously observed validity of the law of corresponding states. The critical density ρc is also found to be constant when measured in units of the cube of the average distance between two bonded particles (1+0.5δ)σ. The possibility of describing the δ→0 dependence with precise functional forms provides improved accurate estimates of the critical parameters of the adhesive hard-sphere model.
Model study for large deformation of physical polymeric gels
Authors: Kawai Shinnosuke , Nitta Yoko , Nishinari Katsuyoshi
Published: April 2008

A model for large deformation of polymer gels with physical cross-linking is developed and shown to be in good agreement with experimental stress-strain curves which show strain hardening in intermediate strains followed by strain softening in large deformations near the yield strain. The model takes into account the coil-helix transition equilibrium and allows for the distribution of the end-to-end distance. The gel is considered to be formed by long flexible chains and crystalline zones acting as junctions of the chains. The number of segments contained in a flexible chain is variable due to the equilibrium between the two regions. As the end-to-end distance increases due to the deformation, more and more segments are reeled out from the junction zone. Finally, one end of the chain is librated from the junction and the chain becomes dangling. The appearance of dangling chains causes the strain softening because they cease to contribute to the elasticity. From the parameter dependence of the stress-strain relations, it was found that the yield behavior depends strongly on the distribution of end-to-end distance. The yield strain is approximately given by the ratio of the upper limit of the number of segments and the average end-to-end distance. The standard deviation of the end-to-end distance affects significantly the width of the peak in the stress-strain curve, thus determining the degree of strain softening.
Imaging with a 90frames∕s microbolometer focal plane array and high-power terahertz free electron laser
Authors: Dem’yanenko M. A. , Esaev D. G. , Knyazev B. A. , Kulipanov G. N. , Vinokurov N. A.
Published: April 2008

An uncooled microbolometer focal plane array (FPA) has been developed and used for imaging of objects illuminated by monochromatic coherent radiation of a free electron laser tunable in the range of 1.25–2.5THz. A sensitivity threshold of 1.3×10−3W∕cm2 was obtained for the FPA with a homemade absolute interferometric power meter. Videos up to 90frames∕s were recorded in both transmission and reflection/scattering modes. When objects were illuminated by laser radiation scattered by a rough metal surface, speckled images were observed. Good quality terahertz images were achieved through the fast rotation of the scatterer.
An investigation of electrical current induced phase transformations in the NiPtSi/polysilicon system
Authors: Kim Deok-kee , Domenicucci Anthony , Iyer Subramanian S.
Published: April 2008

We studied phase transformations and microstructural changes of NiPtSi/polysilicon fuses programmed with three different current densities (under, optimal, and over programming). Electromigration of NiPt toward the anode occurred in all three cases studied. Achieving high resistance after the fuse programming strongly depends on the kinetics of the electromigration and dopant diffusion processes which operate during the fuse blow. A thick silicide region was formed after electrically programmable fuse programming by the reaction of the electromigrated NiPt with the polysilicon layer underneath. The low tails of the underprogrammed fuses seemed to result from the incomplete electromigration and the incomplete dopant depletion due to the insufficient programming current density, while the depletion of the implanted dopants due to the sufficiently elevated temperature seemed to make the postresistance of the optimally programmed fuse higher. In the overprogrammed fuse, the newly formed silicide seemed to have further electromigrated due to the sufficiently high temperature during programming, which caused voids and hillocks. The high temperature caused melting of the polysilicon and the surrounding nitride layer, and their reaction as well. The conduction paths created by the unremoved silicide in fuse link caused the postprogramming resistance of the overprogrammed fuse to be low.
A conductivity study and calorimetric analysis of dried poly(sodium 4-styrene sulfonate)/poly(diallyldimethylammonium chloride) polyelectrolyte complexes
Authors: Imre Árpád W. , Schönhoff Monika , Cramer Cornelia
Published: April 2008

Ionically cross-linked polyelectrolyte complexes (PECs) of anionic poly(sodium 4-styrene sulfonate) (PSS) and cationic poly(diallyldimethylammonium chloride) (PDADMAC), xPSS⋅(1−x)PDADMAC, with molar fractions x ranging from 0.30 to 0.70, were prepared and subsequently dried. The PEC samples were analyzed by differential scanning calorimetry, and the ionic conductivity σdc of the samples was measured as a function of temperature by means of impedance spectroscopy. The thermograms display an endothermic peak in the temperature range of 90–143°C, which is attributed to a glass transition of the PEC. The glass transition temperature Tg has a symmetric x dependence with a minimum at x=0.50. The temperature dependence of σdcT is not affected by the glass transition. The ionic conductivity of the samples before drying is three orders of magnitude larger than σdc after drying; nevertheless, their activation enthalpies are identical. Arrhenius parameters obtained from the systematic study of several PEC compositions are discussed. The ionic conductivity of the PSS-rich samples is significantly higher than σdc of PDADMAC-rich samples. This implies a relatively high Na+ mobility as compared to Cl− mobility in PEC. In contrast to the symmetric x dependence of Tg, the conductivity of PEC increases and the activation enthalpy decreases with increasing x in the investigated composition range. A strong x dependence of σdc is observed for PSS-rich PEC, which is attributed to a significant variation in the mobility of the charge carriers.
Magnetic and magneto-optical anisotropies of ytterbium gallium garnet in high magnetic fields
Authors: Wang Wei , Qi Xin , Liu Gongqiang
Published: April 2008

A theoretical investigation on the anisotropic magnetization and Faraday rotation of paramagnetic ytterbium gallium garnet (YbGaG) is presented when the external magnetic fields are parallel to the [100], [110], and [111] crystallographic directions at above 4.2K. Here, only considering the crystal field effect, we demonstrate that the anisotropies of magnetization M become more obvious with the increase of the applied magnetic fields. Meanwhile, at 4.2K, M approaches saturation when the applied magnetic field He is up to 300kOe in YbGaG. Particularly, this paper further confirms that the Yb–Yb exchange interaction greatly affects on the magnetic and magneto-optical properties in paramagnetic YbGaG. Moreover, it is suggested that the exchange interaction show an obvious isotropy and temperature dependence. The theoretical explanation of magnetic and magneto-optical anisotropy in YbGaG to the available experimental results is obtained.
Infrared resonances of self-assembled Pb nanorods
Authors: Klevenz M. , Neubrech F. , Lovrincic R. , Jałochowski M. , Pucci A.
Published: April 2008

The formation of self-assembled Pb nanorods on a vicinal Si(335)/Au surface at 305K was monitored in situ with polarization dependent infrared spectroscopy. The rods have formed from Pb evaporated on a single domain Au-stabilized Si(335) surface under ultrahigh vacuum conditions and reached lengths of about 1μm. As the rods are aligned almost parallel, a large optical anisotropy of the transmitted infrared light was detected. A plasmonic antennalike resonance appeared in the spectra. Since such resonance frequencies are mainly determined by the length of the rods, the growth process was directly monitored via the shift of the resonance frequency. The estimated extinction cross section at resonance frequency indicates field enhancement similar to that observed for gold nanorods.
Trap densities in amorphous-InGaZnO4 thin-film transistors
Authors: Kimura Mutsumi , Nakanishi Takashi , Nomura Kenji , Kamiya Toshio , Hosono Hideo
Published: April 2008

Trap densities in amorphous-InGaZnO4 (α-IGZO) are extracted directly from the capacitance-voltage characteristics of thin-film transistors at low frequencies. It is found that the trap densities are flat in the energy gap, and are 1.7×1016cm−3eV−1 in the deep energy far from the conduction band edge (Ec), but become larger near Ec. Moreover, postannealing reduces the trap density near Ec, which is associated with the reduction of the hysteresis in the current-voltage characteristics. The annealed α-IGZO does not have a Gaussian-type state and has fewer tail states than amorphous Si.
Single impact crater functions for ion bombardment of silicon
Authors: Kalyanasundaram N. , Ghazisaeidi M. , Freund J. B. , Johnson H. T.
Published: April 2008

The average effect of a single 500eV incident argon ion on a silicon surface is studied using molecular dynamics simulations. More than 103 ion impacts at random surface points are averaged for each of seven incidence angles, from 0° to 28° off normal, to determine a local surface height change function, or a crater function. The crater shapes are mostly determined by mass rearrangement; sputtering has a relatively small effect. Analytical fitting functions are provided for several cases, and may serve as input into kinetic Monte Carlo calculations or stability analyses for surfaces subjected to ion bombardment.
On the dynamic fragmentation of laser shock-melted tin
Authors: de Rességuier T. , Signor L. , Dragon A. , Boustie M. , Berthe L.
Published: April 2008

Dynamic fragmentation in liquid metals is an issue of increasing interest in shock physics, both for basic and applied scientific motivations. In a recent paper, we have reported an exploratory study of liquid spall in tin samples melted upon laser-driven shocks. The need for further experiments and analyses to answer some questions raised by that work had been pointed out. Thus, we present here some complementary results, including specific recovery tests as well as high speed transverse shadowgraphy to visualize both the expanding cloud of fast droplets and the late motion of large fragments that had been inferred from postshock observations.
Low roll-off power efficiency organic light-emitting diodes consisted of nondoped ultrathin phosphorescent layer
Authors: Wang Jun , Yu Junsheng , Li Lu , Wang Tao , Yuan Kai , Jiang Yadong
Published: April 2008

Low roll-off power efficiency (ηp) organic light-emitting diodes at high current density were fabricated using a nondoped ultrathin bis[2-(4-tertbutylphenyl)benzothiazolato-N,C2′] iridium (acetylacetonate) phosphorescent layer and thin N,N′-di(naphthalene-2-yl)-N,N′-diphenyl-benzidine separate layer. A maximum ηp of 8.48lm∕W and luminance efficiency of 20.26cd∕A at 2014cd∕m2 were obtained from the device. The ηp roll-off percentage of ultrathin phosphor layer device was reduced to 20% at a current density of 20mA∕cm2, which is about 40% for conventional phosphorescent device. The low roll off of efficiency was attributed to the direct carrier trapping and confining emission zone function of the ultrathin phosphor layer.
Continuity or Change in Business Representation in Britain? An Assessment of the Heseltine Initiatives of the 1990s
Authors: Greaves Justin
Published: April 2008

Britain has a fragmented, overlapping, and underresourced system of business representation. Attempts at reform, however, have proved difficult and largely unsuccessful. A coherent and logical system is relevant, in terms of both an effective dialogue between government and business, and the promotion of competitiveness and productivity. Through interviews and archival evidence, I look at how government has attempted to reform business associations. The main focus is the Heseltine initiatives of the 1990s: I outline the various initiatives taken, reveal the extent to which policy represented continuity or change, and consider whether the initiatives were effective. I show that they had a degree of success but that they would have made greater impact if they had been sustained over a longer period of time. A consideration of the historical context, moreover, suggests there may be limits to the role of government intervention in business association reform.
A Description and Exploration of Recent State-Led Smart-Growth Efforts
Authors: Howell-Moroney Michael
Published: April 2008

I provide a systematic analysis of smart-growth activity across the fifty US states from 1998 to 2001, summarizing their efforts across more than twenty policy areas. My analysis then turns to a set of nonlinear regression models for predicting state adoption of smart-growth policy. The empirical results from a variety of models suggest that the rate of per capita housing-start growth, and to a lesser extent, political liberalism, and the percentage of state land devoted to urban uses are all consistent predictors of state smart-growth-policy adoption. In addition, analyses of associations between policy areas reveals positive associative adoption patterns between urban revitalization and land-preservation policy. Positive associations were also found between growth control and housing-affordability policies.
Broadening of Activity with Flow across Neural Structures
Authors: Lytton William W , Orman Rena , Stewart Mark
Published: April 2008

Synfire chains have long been suggested as a substrate for perception and information processing in the nervous system. However, embedding activation chains in a densely connected nervous matrix risks spread of signal that will obscure or obliterate the message. We used computer modeling and physiological measurements in rat hippocampus to assess this problem of activity broadening. We simulated a series of neural modules with feedforward propagation and random connectivity within each module and from one module to the next. We found that activity broadened as it propagated from one module to the next. This occurred over a wide array of parameters with greater broadening seen with increasing excitatory – excitatory synaptic strength. Activity broadening correlated positively with propagation velocity. Multi-electrode measurements of activity propagation in disinhibited CA1 slice demonstrated broadening of about 50% over 1 mm. Such broadening is a problem for information transfer that must be dealt with in a fully functioning nervous system.
Neural Enhancement and Pre-Emptive Perception: The Genesis of Attention and the Attentional Maintenance of the Cortical Salience Map
Authors: Gee Angela L , Ipata Anna E , Gottlieb Jacqueline , Bisley James W , Goldberg Michael E
Published: April 2008

One of the stable hypotheses in systems neuroscience is the relationship between attention and the enhancement of visual responses when an animal attends to the stimulus in its receptive field (Goldberg and Wurtz, 1972 Journal of Neurophysiology35 560 – 574). This was first discovered in the superior colliculus of the monkey: neurons in the superficial layers of the superior colliculus responded more intensely to the onset of a stimulus during blocks of trials in which the monkey had to make a saccade to it than they did during blocks of trials in which the monkey had to continue fixating a central point and not respond to the stimulus. This enhancement has been found in many brain regions, including prefrontal cortex (Boch and Goldberg, 1987 Investigative Ophthalmology28 Supplement, 124), V4 (Moran and Desimone, 1985 Science229 782 – 784), and lateral intraparietal area (Colby et al, 1996 Journal of Neurophysiology76 2841 – 2852; Colby and Goldberg, 1999 Annual Review of Neuroscience22 319 – 349), and even V1 (Lamme et al, 2000 Vision Research40 1507 – 1521). In these studies the assumption has been that the monkey attended to the stimulus because the stimulus evoked an enhanced response. In the experiments described here we show that for abruptly appearing stimuli, attention is not related to the initial response evoked by the stimulus, but by the activity present on the salience map in the parietal cortex when the stimulus appears. Attention to the stimulus may subsequently, by a top – down signal, sustain the map, but stimuli can as easily be suppressed by top – down features as they can be enhanced.
Action Rules: Why the Visual Control of Reaching and Grasping is Not Always Influenced by Perceptual Illusions
Authors: Goodale Melvyn A , Gonzalez Claudia L R , Króliczak Grzegorz
Published: April 2008

It is generally accepted that vision first evolved for the distal control of movement and that perception or ‘representational’ vision emerged much later. Vision-for-action operates in real time and uses egocentric frames of reference and the real metrics of the world. Vision-for-perception can operate over longer time scales and is much more scene-based in its computations. These differences in the timing and metrics of the two systems have been examined in experiments that have looked at the way in which each system deals with visual illusions. Although controversial, the consensus is that actions such as grasping and reaching are often unaffected by high-level pictorial illusions, which by definition affect perception. However, recent experiments have shown that, for actions to escape the effects of such illusions, they must be highly practiced actions, preferably with the right hand, and must be directed in real time at visible targets. This latter finding suggests that some of the critical components of the encapsulated (bottom – up) systems that mediate the visual control of skilled reaching and grasping movements are lateralised to the left hemisphere.
Action in Perception? Empirical and Philosophical Arguments against the Enactive Approach to Perception
Authors: Schumacher Ralph
Published: April 2008

This paper focuses on the epistemic conditions of visual perception, ie it concentrates on the question of what kind of knowledge is required for us in order to be able to see colours and shapes as spatial properties of things. According to contemporary theories of sensory perception that follow the tradition of George Berkeley, like Alva Noe's so-called enactive approach to perception, this type of visual perception requires a certain kind of implicit practical knowledge, namely implicit sensorimotor knowledge of the way sensory stimulation varies as the perceiver moves. Two objections are presented against this central claim of the enactive approach. First, empirical evidence from psychological research on children's cognitive and motor development suggests that visual content is entirely independent of sensorimotor knowledge. Second, the enactive approach gets involved in the characteristic problems of classical sense – datum theories by introducing the extremely problematic claim that the recognition of appearances is the epistemic starting point for the perception of things and their properties.
Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in
BACE1
-null mice
Authors: Savonenko A. V. , Melnikova T. , Laird F. M. , Stewart K.-A. , Price D. L. , Wong P. C.
Published: April 2008

β-Site APP-cleaving enzyme 1 (BACE1) is required for the penultimate cleavage of the amyloid-β precursor protein (APP) leading to the generation of amyloid-β peptides that is central to the pathogenesis of Alzheimer's disease. In addition to its role in endoproteolysis of APP, BACE1 participates in the proteolytic processing of neuregulin 1 (NRG1) and influences the myelination of central and peripheral axons. Although
NRG1
has been genetically linked to schizophrenia and
NRG1
+/−
mice exhibit a number of schizophrenia-like behavioral traits, it is not known whether altered BACE1-dependent NRG1 signaling can cause similar behavioral abnormalities. To test this hypothesis, we analyze the behaviors considered to be rodent analogs of clinical features of schizophrenia in
BACE1
−/−
mice with impaired processing of NRG1. We demonstrate that
BACE1
−/−
mice exhibit deficits in prepulse inhibition, novelty-induced hyperactivity, hypersensitivity to a glutamatergic psychostimulant (MK-801), cognitive impairments, and deficits in social recognition. Importantly, some of these manifestations were responsive to treatment with clozapine, an atypical antipsychotic drug. Moreover, although the total amount of ErbB4, a receptor for NRG1 was not changed, binding of ErbB4 with postsynaptic density protein 95 (PSD95) was significantly reduced in the brains of
BACE1
−/−
mice. Consistent with the role of ErbB4 in spine morphology and synaptic function,
BACE1
−/−
mice displayed reduced spine density in hippocampal pyramidal neurons. Collectively, our findings suggest that alterations in BACE1-dependent NRG1/ErbB4 signaling may participate in the pathogenesis of schizophrenia and related psychiatric disorders.
Purported nanobacteria in human blood as calcium carbonate nanoparticles
Authors: Martel Jan , Young John Ding-E
Published: April 2008

Recent evidence suggests a role for nanobacteria in a growing number of human diseases, including renal stone formation, cardiovascular diseases, and cancer. This large body of research studies promotes the view that nanobacteria are not only alive but that they are associated with disease pathogenesis. However, it is still unclear whether they represent novel life forms, overlooked nanometer-size bacteria, or some other primitive self-replicating microorganisms. Here, we report that CaCO
3
precipitates prepared
in vitro
are remarkably similar to purported nanobacteria in terms of their uniformly sized, membrane-delineated vesicular shapes, with cellular division-like formations and aggregations in the form of colonies. The gradual appearance of nanobacteria-like particles in incubated human serum as well as the changes seen with their size and shape can be influenced and explained by introducing varying levels of CO
2
and NaHCO
3
as well as other conditions known to influence the precipitation of CaCO
3
. Western blotting reveals that the monoclonal antibodies, claimed to be specific for nanobacteria, react in fact with serum albumin. Furthermore, nanobacteria-like particles obtained from human blood are able to withstand high doses of γ-irradiation up to 30 kGy, and no bacterial DNA is found by performing broad-range PCR amplifications. Collectively, our results provide a more plausible abiotic explanation for the unusual properties of purported nanobacteria.
Postendocytotic traffic of the galanin R1 receptor: A lysosomal signal motif on the cytoplasmic terminus
Authors: Xia Sheng , Dun Xing-Peng , Hu Ping-Sheng , Kjaer Svend , Zheng Kang , Qian Yu , Solén Christina , Xu Tao , Fredholm Bertil , Hökfelt Tomas , Xu Zhi-Qing David
Published: April 2008

The neuropeptide galanin R1 receptor (GalR1) was tagged at its C terminus with EGFP (GalR1–EGFP) to study receptor localization and trafficking. In PC12 and HEK293 cells, functional GalR1–EGFP was expressed on the plasma membrane and internalized into cytoplasmic vesicles after galanin stimulation. The internalization was blocked by 0.4 M sucrose and by silencing of clathrin with siRNA methodology. Internalized GalR1–EGFP and LysoTracker, a lysosomal marker, overlapped in intracellular vesicles after prolonged galanin stimulation. This colocalization was strongly reduced after site-directed mutagenesis of the motif YXXØ on the C terminus of GalR1 (where Ø is a bulky hydrophobic residue and X any amino acid). Taken together, these data suggest that GalR1 is internalized via the clathrin-dependent, endocytic pathway and then, to a large extent, delivered to lysosomes for degradation through the lysosome-targeting signal YXXØ.
Endothelin-1 Couples βPix to p66Shc: Role of βPix in Cell Proliferation through FOXO3a Phosphorylation and p27kip1Down-Regulation Independently of Akt
Authors: Chahdi Ahmed , Sorokin Andrey
Published: April 2008

The phosphorylation of forkhead transcription factor FOXO3a by Akt is critical regulator of cell proliferation induced by serum. We show that endothelin-1 (ET-1) stimulation of primary human mesangial cells (HMCs) induces βPix and p66Shc up-regulation, resulting in the formation of the βPix/p66Shc complex. In transformed HMCs, ET-1 induces a biphasic phosphorylation of p66Shc and FOXO3a. The second phase leads to p27kip1down-regulation independently of Akt. Depletion of βPix blocks the second phase of p66Shc and FOXO3a phosphorylation and prevents p27kip1down-regulation induced by ET-1. Depletion of either βPix or p66Shc inhibits ET-1–induced cell proliferation. The expression of β1Pix induces FOXO3a phosphorylation through activation of Rac1, ERK1/2, and p66Shc. Using either p66Shc- or Akt-depleted cells; we show that β1Pix-induced FOXO3a phosphorylation requires p66Shc but not Akt. β1Pix-induced p27kip1down-regulation was blocked by U0126 but not by wortmannin. Endogenous βPix and FOXO3a are constitutively associated with endogenous p66Shc. FOXO3a and p66Shc binding requires β1Pix homodimerization. Expression of β1Pix homodimerization deficient mutant abrogates β1Pix-induced p27kip1down-regulation and cell proliferation. Our results identify p66Shc and FOXO3a as novel partners of β1Pix and represent the first direct evidence of β1Pix in cell proliferation via Erk/p66Shc-dependent and Akt-independent mechanisms.
Novel Interactions of ESCRT-III with LIP5 and VPS4 and their Implications for ESCRT-III Disassembly
Authors: Shim Soomin , Merrill Samuel A. , Hanson Phyllis I.
Published: April 2008

The AAA+ ATPase VPS4 plays an essential role in multivesicular body biogenesis and is thought to act by disassembling ESCRT-III complexes. VPS4 oligomerization and ATPase activity are promoted by binding to LIP5. LIP5 also binds to the ESCRT-III like protein CHMP5/hVps60, but how this affects its function remains unclear. Here we confirm that LIP5 binds tightly to CHMP5, but also find that it binds well to additional ESCRT-III proteins including CHMP1B, CHMP2A/hVps2–1, and CHMP3/hVps24 but not CHMP4A/hSnf7–1 or CHMP6/hVps20. LIP5 binds to a different region within CHMP5 than within the other ESCRT-III proteins. In CHMP1B and CHMP2A, its binding site encompasses sequences at the proteins' extreme C-termini that overlap with “MIT interacting motifs” (MIMs) known to bind to VPS4. We find unexpected evidence of a second conserved binding site for VPS4 in CHMP2A and CHMP1B, suggesting that LIP5 and VPS4 may bind simultaneously to these proteins despite the overlap in their primary binding sites. Finally, LIP5 binds preferentially to soluble CHMP5 but instead to polymerized CHMP2A, suggesting that the newly defined interactions between LIP5 and ESCRT-III proteins may be regulated by ESCRT-III conformation. These studies point to a role for direct binding between LIP5 and ESCRT-III proteins that is likely to complement LIP5's previously described ability to regulate VPS4 activity.
Assessment of Suspected Cancer
Authors: Watson Max
Published: April 2008

Early detection of cancer is crucial to improve patients' chances of survival. Unfortunately, early signs of cancer are often easier to see with the benefit of hindsight than they are at the time of presentation. Although cancer is common, cancer diagnosis is a relatively rare occurrence for an individual GP and referral from primary to secondary care is often triggered by a GP's awareness of ‘alarm symptoms’ or ‘red flags’ that are considered to predict malignant disease. It is important to have a lower threshold for investigating cancer in people with recognized risk factors for the disease, such as smoking. Failure to respond to treatment as expected (for example, a chest infection that does not settle with antibiotics), or symptoms that are getting progressively worse should raise suspicion of a possible diagnosis of cancer in any patient.
Oncology Emergencies
Authors: Simon Chantal , Watson Max , Drake Anne , Fenton Audrey , McLoughlin Caroline
Published: April 2008

Although most oncology care takes place in secondary care, many patients are treated as outpatients. Oncology emergencies may occur when the patient is at home and the GP is often called. Therefore, it is important to know how to handle the common emergencies likely to arise. Remember that you are part of a team. For example, in many areas, there is a district or community nursing team available 24 hours a day who can be called upon to provide emergency nursing care, such as replacement dressings, or to attend to syringe drivers that have stopped functioning.
Alcohol and Primary Care
Authors: Bolland Will
Published: April 2008

In most countries and cultures of the world, alcohol consumption is tolerated and commonplace. In the UK, alcohol is an integral feature of many aspects of British culture. However, the consumption of alcohol is a major public health issue:

90% of the alcohol-related work in the NHS occurs in primary care—with 259 million alcohol-related consultations each year in the UK Alcohol misuse is associated with around 150 000 hospital admissions each year Around 70% of Accident and Emergency Department attendances between midnight and 5 am on weekend nights are alcohol related Between 15 000 and 22 000 deaths each year are associated with alcohol misuse, mainly resulting from stroke, cancer, liver disease, accidental injury or suicide 360 000 incidents of domestic violence are linked with alcohol misuse, around a third of all domestic violence Half of all violent crimes are alcohol related Up to 17 million days absent from work are alcohol-related.

The overall cost burden to the NHS from alcohol-related problems is calculated to be £1.7 billion, and the loss to the economy due to premature death from alcohol misuse is estimated to be ∼ £2.4 billion each year. However, the annual revenue to the Treasury in alcohol duties and VAT totals £13.3 billion.

In recent years, official statistics have shown a sharp rise in alcohol consumption, both in terms of overall per capita consumption and an increased prevalence of hazardous and harmful patterns of drinking, notably among women and young people. It was in response to this situation that the government published the Alcohol Harm Reduction Strategy for England in 2004.
Controlled Drugs: Regulations and Prescribing
Authors: Bolland Will , Simon Chantal
Published: April 2008

As a GP, it is important to know the regulations surrounding controlled drugs, both to be able to give patients advice and to enable you to prescribe controlled drugs safely. This article aims to outline the major pieces of legislation governing prescribing and usage of controlled drugs and to highlight good practice.
Overview of the GP Contract
Authors: Simon Chantal
Published: April 2008

Today, along with opticians, dentists and pharmacists, general practitioners (GPs) form the ‘front line’ of the NHS providing primary medical care and acting as ‘gatekeepers’ to the secondary care system. Around 97% of the British population is registered with a GP. Patients register with a practice of their choice in their area—whole families are often registered with the same practice. Once registered, patients stay with that practice for an average of 12 years.
Network of interacting synthetic molecules in steady state
Authors: Gelenbe Erol
Published: April 2008

In this paper, we study the steady-state behaviour of a reaction network of interacting molecules using the chemical master equation (CME). The model considers a set of base species from which further compounds are created via binary reactions, as well as by monomolecular and dissipation reactions. The model includes external arrivals of molecules into the reaction volume and assumes that the reaction rates are proportional to the number of molecules of the reactants that are present. We obtain an explicit expression for the solution of the CME in equilibrium under the assumption that the system obeys a mass conservation law for the overall rate of incoming and outgoing molecules. This closed-form solution shows that the joint probability distribution of the number of molecules of each species is in ‘product form’, i.e. it is the product of the marginal distributions for the number of molecules of each species. We also show that the steady-state distribution of the number of molecules of each base and synthesized species follows a Poisson distribution.
What helps when it hurts: children's views on pain relief
Authors: Franck L. S. , Sheikh A. , Oulton K.
Published: April 2008

Background  Previous studies have focused on children's views of sources of pain and only secondarily explored their views on pain‐relief strategies.

Methods  An exploratory cross‐sectional descriptive design and ‘draw and write’ technique were used to investigate what children think helps them when they have pain.

Results  The sample (n = 71) was comprised of 33% boys and 67% girls, with an age range of 4–16 years (mean ± SD: 9.25 ± 3.04). Four overarching themes were derived that were common to both the texts and drawings: ‘People who help’, ‘What I do that helps’, ‘What other people do that helps’ and ‘Things that help’. Children also described their emotional reactions to pain or pain relief. Multiple themes were represented in most of the texts and drawings. There were few differences in the themes present in the children's texts and drawings based on developmental age and no differences based on gender.

Conclusions  Children across the three developmental age groups view themselves as active agents in pain relief. Although less than half of the children described specific behaviours they had taken, almost all children indicated their active role as the central figure in relation to use of objects or the actions of others.
Serum testosterone and bioavailable testosterone correlate with age and body size in hypogonadal men treated with testosterone undecanoate (1000 mg IM – Nebido®)
Authors: Moisey Robert , Swinburne Julie , Orme Steve
Published: April 2008

Objective  To investigate the loading regimen for intramuscular (IM) testosterone undecanoate (Nebido®) to determine whether testosterone and bioavailable testosterone levels achieved correlate with age or body size of subjects studied.

Design  Retrospective observational study of testosterone naïve patients and patients previously treated with an alternative testosterone therapy.

Patients  51 hypogonadal men (35, 68·6% secondary hypogonadism). 8 (16%) had not previously received testosterone therapy.

Measurements  Patients received an IM injection of Nebido (1000 mg) at baseline and a second injection after 6 weeks. Serum was assayed at baseline and 18 weeks after commencing Nebido for total testosterone (TT) and SHBG. Bioavailable testosterone was calculated (cBioT) using TT and SHBG. Measurements were taken for weight, body mass index (BMI) and body surface area (BSA).

Results  Baseline TT (mean 11·5 nmol/l, range 0·3–54·8) increased by 50% after commencing Nebido (17·2 nmol/l (5·4–32·8), P = 0·0001). 75% of subjects had a TT within the reference range (8·0–25·0 nmol/l). Subjects with primary hypogonadism had a higher 18‐week TT [20·9 nmol/l (9·8–32·8) vs. 15·5 (5·4–32·6), P = 0·02] and SHBG [39·2 nmol/l (11–82) vs. 25·7 (9·0–60·0), P = 0·003] although the cBioT was not significantly different [4·9 nmol/l (2·9–7·3) vs. 4·2 (2·0–7·9), P = 0·12]. The 18‐week TT positively correlated with age (R = 0·36, P = 0·01) and negatively correlated with weight (R = –0·38, P = 0·006), BMI (R = –0·42, P = 0·002) and BSA (R =–0·38, P = 0·007). Similarly cBioT correlated with age (R = 0·28, P = 0·04), weight (R = –0·29, P = 0·03), BMI (R = –0·30, P = 0·03) and BSA (R = –0·27, P = 0·05). Age (t = 2·04, P = 0·05) and baseline testosterone (t = –9·26, P < 0·0001) were independent variables of the increase in TT at 18 weeks.

Conclusion  This starting regimen is simple and provides the majority of men with a TT within the reference range. Age and baseline TT are independent variables of the increase in TT with IM testosterone undecanoate. At week 18 age and body size correlated with the cBioT and TT and this may then be used to estimate dosing frequency for this therapy.
New mutation type in pseudohypoparathyroidism type Ia
Authors: Fernandez‐Rebollo Eduardo , Barrio Raquel , Pérez‐Nanclares Gustavo , Carcavilla Atilano , Garin Intza , Castaño Luis , De Nanclares Guiomar Pérez
Published: April 2008

Context  The GNAS gene encodes the α‐subunit of the stimulatory G proteins, which play a crucial role in intracellular signal transduction of peptide and neurotransmitter receptors. Heterozygous inactivating maternally inherited mutations of GNAS (including translation initiation mutations, amino acid substitutions, nonsense mutations, splice site mutations and small insertions or deletions) lead to a phenotype in which Albright hereditary osteodystrophy is associated with pseudohypoparathyroidism type Ia.

Objective  We sought to identify the molecular defect in a patient who was thought to have PHP‐Ia.

Methods and results  The GNAS gene of a 5‐year‐old boy with brachydactily, mental retardation, pseudohypoparathyroidism and congenital hypothyroidism was investigated. We found a heterozygous inversion of exon 2 and part of intron 1 of de novo origin. Molecular studies of cDNA from blood RNA demonstrated that both the normal and the mutant variants were stable and that new splice‐sites were generated.

Conclusion  This report demonstrates the first evidence for an inversion at the GNAS gene responsible of pseudohypoparathyroidism type Ia.
CD14 contributes to pulmonary inflammation and mortality during murine tuberculosis
Authors: Wieland Catharina W. , Van Der Windt Gerritje J. W. , Wiersinga W. Joost , Florquin Sandrine , Van Der Poll Tom
Published: April 2008

Toll‐like receptors play an essential role in the innate recognition of micro‐organisms by the host. CD14 is one of the extracellular adaptor proteins required for recognition of Gram‐negative bacteria and possibly also Mycobacterium tuberculosis. Therefore, we intranasally infected wild‐type (WT) and CD14 knock‐out (KO) mice with virulent M. tuberculosis H37Rv. We found no differences in bacterial load in the main target organ lung up to 32 weeks after infection. From 20 weeks onward 57% of WT mice succumbed, whereas all CD14 KO mice survived. The improved outcome of CD14 KO mice was accompanied by reduced pulmonary inflammation; lung cell counts and percentage of inflamed lung tissue were reduced in CD14 WT mice. These data suggest that during chronic infection CD14 KO mice are protected from lethality caused by lung tuberculosis because of a reduction of the inflammatory response.
Combining individual interviews and focus groups to enhance data richness
Authors: Lambert Sylvie D. , Loiselle Carmen G.
Published: April 2008

Title.  Combining individual interviews and focus groups to enhance data richness.

Aim.  This paper is a presentation of the critical reflection on the types of findings obtained from the combination of individual interviews and focus groups, and how such triangulation contributes to knowledge production and synthesis.

Background.  Increasingly, qualitative method triangulation is advocated as a strategy to achieve more comprehensive understandings of phenomena. Although ontological and epistemological issues pertaining to triangulation are a topic of debate, more practical discussions are needed on its potential contributions, such as enhanced data richness and depth of inquiry.

Method.  Data gathered through individual interviews and focus groups from a study on patterns of cancer information‐seeking behaviour are used to exemplify the added‐value but also the challenges of relying on methods combination.

Findings.  The integration of focus group and individual interview data made three main contributions: a productive iterative process whereby an initial model of the phenomenon guided the exploration of individual accounts and successive individual data further enriched the conceptualisation of the phenomenon; identification of the individual and contextual circumstances surrounding the phenomenon, which added to the interpretation of the structure of the phenomenon; and convergence of the central characteristics of the phenomenon across focus groups and individual interviews, which enhanced trustworthiness of findings.

Conclusion.  Although the use of triangulation is promising, more work is needed to identify the added‐value or various outcomes pertaining to method combination and data integration.
Governmentality, student autonomy and nurse education
Authors: Darbyshire Chris , Fleming Valerie E.M.
Published: April 2008

Title.  Governmentality, student autonomy and nurse education.

Aim.  This paper is a report of a study to explore how governmental practices operated in nurse education.

Background.  Since the 1980s nurse education internationally has been strongly influenced by educational theories that aim to promote student autonomy by encouraging self‐direction and critical thinking. Newer curriculum models advocate transformative approaches leading to greater emancipation, social equity and inclusion. Although these changes have been positively evaluated there had been limited critical research on how student behaviour is governed.

Method.  A discourse analytic study was conducted from 2000 to 2004 using interviews (n = 30) with a purposive sample students and teachers in one United Kingdom university. Data were also collated from the course curriculum and student handbook for the students’ programme. Data were analysed to identify how student behaviour is governed.

Findings.  Two governing practices are described: control and technologies of the self. These practices contribute to an overall system of governing student behaviour that creates tension between the avowed progressive empowerment discourse and taken for granted everyday educational practices. Students are subjected to a range of governmental and disciplinary strategies and, through a process of normalization, ultimately become their own supervisors within the system.

Conclusion.  The tensions between the demands of a professional outcome‐based nursing programme and notions of empowerment and student autonomy have not been resolved. Instead, present educational practice is characterized by normalizing discursive practices that aim to produce a specific version of a student subject as autonomous learner. Thus, discourses of both empowerment and professional behaviour govern students.