bluuebunny/crossref_metadata_2025 huggingface dataset:
Ca2+-dependent permeability transition regulation in rat brain mitochondria by 2′,3′-cyclic nucleotides and 2′,3′-cyclic nucleotide 3′-phosphodiesterase
Authors: Azarashvili Tamara , Krestinina Olga , Galvita Anastasia , Grachev Dmitry , Baburina Yulia , Stricker Rolf , Evtodienko Yuri , Reiser Georg
Published: April 2009

Recent evidence indicates that 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP), a marker enzyme of myelin and oligodendrocytes, is also present in neural and nonneural mitochondria. However, its role in mitochondria is still completely unclear. We found CNP in rat brain mitochondria and studied the effects of CNP substrates, 2′,3′-cyclic nucleotides, on functional parameters of rat brain mitochondria. 2′,3′-cAMP and 2′,3′-cNADP stimulated Ca2+ overload-induced Ca2+ release from mitochondrial matrix. This Ca2+ release under threshold Ca2+ load correlated with membrane potential dissipation and mitochondrial swelling. The effects of 2′,3′-cyclic nucleotides were suppressed by cyclosporin A, a potent inhibitor of permeability transition (PT). PT development is a key stage in initiation of apoptotic mitochondria-induced cell death. 2′,3′-cAMP effects were observed on the functions of rat brain mitochondria only when PT was developed. This demonstrates involvement of 2′,3′-cAMP in PT regulation in rat brain mitochondria. We also discovered that, under PT development, the specific enzymatic activity of CNP was reduced. Thus we hypothesize that suppression of CNP activity under threshold Ca2+ load leads to elevation of 2′,3′-cAMP levels that, in turn, promote PT development in rat brain mitochondria. Similar effects of 2′,3′-cyclic nucleotides were observed in rat liver mitochondria. Involvement of CNP in PT regulation was confirmed in experiments using mitochondria from CNP-knockdown oligodendrocytes (OLN93 cells). CNP reduction in these mitochondria correlated with lowering the threshold for Ca2+ overload-induced Ca2+ release. Thus our results reveal a new function for CNP and 2′,3′-cAMP in mitochondria, being a regulator/promotor of mitochondrial PT.
Kv2.1 and silent Kv subunits underlie the delayed rectifier K+ current in cultured small mouse DRG neurons
Authors: Bocksteins Elke , Raes Adam L. , Van de Vijver Gerda , Bruyns Tine , Van Bogaert Pierre-Paul , Snyders Dirk J.
Published: April 2009

Silent voltage-gated K+ (Kv) subunits interact with Kv2 subunits and primarily modulate the voltage dependence of inactivation of these heterotetrameric channels. Both Kv2 and silent Kv subunits are expressed in the mammalian nervous system, but little is known about their expression and function in sensory neurons. This study reports the presence of Kv2.1, Kv2.2, and silent subunit Kv6.1, Kv8.1, Kv9.1, Kv9.2, and Kv9.3 mRNA in mouse dorsal root ganglia (DRG). Immunocytochemistry confirmed the protein expression of Kv2.x and Kv9.x subunits in cultured small DRG neurons. To investigate if Kv2 and silent Kv subunits are underlying the delayed rectifier K+ current ( IK) in these neurons, Kv2-mediated currents were isolated by the extracellular application of rStromatoxin-1 (ScTx) or by the intracellular application of Kv2 antibodies. Both ScTx- and anti-Kv2.1-sensitive currents displayed two components in their voltage dependence of inactivation. Together, both components accounted for approximately two-thirds of IK. A comparison with results obtained in heterologous expression systems suggests that one component reflects homotetrameric Kv2.1 channels, whereas the other component represents heterotetrameric Kv2.1/silent Kv channels. These observations support a physiological role for silent Kv subunits in small DRG neurons.
Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size
Authors: Trendelenburg Anne Ulrike , Meyer Angelika , Rohner Daisy , Boyle Joseph , Hatakeyama Shinji , Glass David J.
Published: April 2009

Myostatin is a negative regulator of skeletal muscle size, previously shown to inhibit muscle cell differentiation. Myostatin requires both Smad2 and Smad3 downstream of the activin receptor II (ActRII)/activin receptor-like kinase (ALK) receptor complex. Other transforming growth factor-β (TGF-β)-like molecules can also block differentiation, including TGF-β1, growth differentiation factor 11 (GDF-11), activins, bone morphogenetic protein 2 (BMP-2) and BMP-7. Myostatin inhibits activation of the Akt/mammalian target of rapamycin (mTOR)/p70S6 protein synthesis pathway, which mediates both differentiation in myoblasts and hypertrophy in myotubes. Blockade of the Akt/mTOR pathway, using small interfering RNA to regulatory-associated protein of mTOR (RAPTOR), a component of TOR signaling complex 1 (TORC1), increases myostatin-induced phosphorylation of Smad2, establishing a myostatin signaling-amplification role for blockade of Akt. Blockade of RAPTOR also facilitates myostatin's inhibition of muscle differentiation. Inhibition of TORC2, via rapamycin-insensitive companion of mTOR (RICTOR), is sufficient to inhibit differentiation on its own. Furthermore, myostatin decreases the diameter of postdifferentiated myotubes. However, rather than causing upregulation of the E3 ubiquitin ligases muscle RING-finger 1 ( MuRF1) and muscle atrophy F-box ( MAFbx), previously shown to mediate skeletal muscle atrophy, myostatin decreases expression of these atrophy markers in differentiated myotubes, as well as other genes normally upregulated during differentiation. These findings demonstrate that myostatin signaling acts by blocking genes induced during differentiation, even in a myotube, as opposed to activating the distinct “atrophy program.” In vivo, inhibition of myostatin increases muscle creatine kinase activity, coincident with an increase in muscle size, demonstrating that this in vitro differentiation measure is also upregulated in vivo.
Lipoxin A4 inhibits IL-1β-induced IL-8 and ICAM-1 expression in 1321N1 human astrocytoma cells
Authors: Decker Yann , McBean Gethin , Godson Catherine
Published: April 2009

There is a growing appreciation that endogenously produced mediators may actively promote the resolution of inflammation. Lipoxins (LX) are a group of recently discovered lipid mediators that have been shown to exert anti-inflammatory and proresolution effects on cells of myeloid and nonmyeloid origin. LXs mediate a number of processes, including regression of pro-inflammatory cytokine production, inhibition of cell proliferation, and stimulation of phagocytosis of apoptotic leukocytes by macrophages. Lipoxin A4 (LXA4) is one of the principal LXs formed by mammalian cells. Recently, a G protein-coupled receptor that binds LXA4, the lipoxin A4 receptor, was identified in astrocytes and microglia, suggesting that these cells may be a target for LX action in the brain. In this study, we have investigated the potential of LXA4 to modify inflammatory responses of astrocytes, using the 1321N1 human astrocytoma cell line as a model system. As shown by quantitative RT-PCR, LXA4 (10 nM) significantly inhibited ( P < 0.05) the IL-1β-induced stimulation of IL-8 and ICAM-1 expression in these cells. Furthermore, LXA4 (10 nM) decreased the expression of IL-1β-induced IL-8 protein levels ( P < 0.05). LXA4 (10 nM) was found to inhibit IL-1β-induced degradation of IκBα ( P < 0.05), and the activation of an NFκB regulated reporter gene construct ( P < 0.05). Overall, these data suggest that LXA4 exerts anti-inflammatory effects in 1321N1 astrocytoma cells at least in part via an NFκB-dependent mechanism. It is concluded that LXA4 may represent a potentially novel therapeutic approach to acute or chronic inflammation in the brain.
Comparative assessment of the quadriceps and the diaphragm in patients with COPD
Authors: Caron Marc-André , Debigaré Richard , Dekhuijzen P. N. Richard , Maltais François
Published: April 2009

Chronic obstructive pulmonary disease (COPD) and other chronic diseases such as heart failure are accompanied by skeletal muscle alterations that further enhance morbidity and mortality in affected individuals. Several studies have highlighted important structural and biochemical modifications in limb and respiratory muscles in COPD. Reviewing the similarities and differences between the two most studied muscles in COPD, the quadriceps and the diaphragm, may be helpful in providing important clues about the mechanisms underlying muscle changes associated with this disease. Although oxidative stress is present in both muscles, other muscle alterations are clearly distinct between the quadriceps and the diaphragm. For example, the oxidative metabolism varies in opposite directions, the diaphragm exhibiting increased resistance to fatigue while the quadriceps in COPD is characterized by premature fatigability. Differences in muscle phenotypic expression between the diaphragm and the quadriceps indicate that, in addition to systemic factors, the local microenvironment must participate in the reorganization seen in these two skeletal muscles in COPD.
Visuospatial Working Memory Capacity Predicts the Organization of Acquired Explicit Motor Sequences
Authors: Bo J. , Seidler R. D.
Published: April 2009

Studies have suggested that cognitive processes such as working memory and temporal control contribute to motor sequence learning. These processes engage overlapping brain regions with sequence learning, but concrete evidence has been lacking. In this study, we determined whether limits in visuospatial working memory capacity and temporal control abilities affect the temporal organization of explicitly acquired motor sequences. Participants performed an explicit sequence learning task, a visuospatial working memory task, and a continuous tapping timing task. We found that visuospatial working memory capacity, but not the CV from the timing task, correlated with the rate of motor sequence learning and the chunking pattern observed in the learned sequence. These results show that individual differences in short-term visuospatial working memory capacity, but not temporal control, predict the temporal structure of explicitly acquired motor sequences.
Stress-Induced Changes in Nucleus Accumbens Glutamate Synaptic Plasticity
Authors: Campioni Matthew R. , Xu Ming , McGehee Daniel S.
Published: April 2009

Stress hormones released in the CNS following exposure to unavoidable, aversive stimuli have been shown to alter the physiology of neurons in multiple brain regions including hippocampus, amygdala, prefrontal cortex, and ventral tegmental area. The nucleus accumbens (NAc), a motor-limbic interface linked to motivation and reward, receives inputs from each of these stress-affected brain regions, raising the possibility that its function might also be altered in response to stress. To assess potential stress-induced plasticity in the NAc, we exposed adult mice to daily cold water forced swim for 2 consecutive days and conducted electrophysiological experiments assessing glutamate receptor function in brain slices taken 18–24 h following the second swim. We found that AMPA receptor (AMPAR)/ N-methyl-d-aspartate receptor (NMDAR) ratios, a measure of synaptic strength, were increased in the NAc shell but not core medium spiny neurons (MSNs) in stressed animals relative to controls. This effect was blocked by preadministration of glucocorticoid receptor (GR) antagonist RU486, suggesting that the observed changes are dependent on corticosteroid signaling. The role of corticosterone (CORT) in the observed plasticity was confirmed, because exogenous administration of 10 mg/kg CORT also enhanced AMPAR/NMDAR ratios in the NAc shell. The synaptic changes in NAc shell MSNs reflect an enhancement of AMPAR-mediated currents, as we observed increased AMPAR miniature postsynaptic current (mEPSC) amplitude following stress but no change in NMDAR mEPSCs. We hypothesize that altered information processing via plasticity of excitatory inputs might contribute to reward-related behaviors such as stress-induced reinstatement of drug seeking in animals and relapse in humans.
The Role of Visuohaptic Experience in Visually Perceived Depth
Authors: Ho Yun-Xian , Serwe Sascha , Trommershäuser Julia , Maloney Laurence T. , Landy Michael S.
Published: April 2009

Berkeley suggested that “touch educates vision,” that is, haptic input may be used to calibrate visual cues to improve visual estimation of properties of the world. Here, we test whether haptic input may be used to “miseducate” vision, causing observers to rely more heavily on misleading visual cues. Human subjects compared the depth of two cylindrical bumps illuminated by light sources located at different positions relative to the surface. As in previous work using judgments of surface roughness, we find that observers judge bumps to have greater depth when the light source is located eccentric to the surface normal (i.e., when shadows are more salient). Following several sessions of visual judgments of depth, subjects then underwent visuohaptic training in which haptic feedback was artificially correlated with the “pseudocue” of shadow size and artificially decorrelated with disparity and texture. Although there were large individual differences, almost all observers demonstrated integration of haptic cues during visuohaptic training. For some observers, subsequent visual judgments of bump depth were unaffected by the training. However, for 5 of 12 observers, training significantly increased the weight given to pseudocues, causing subsequent visual estimates of shape to be less veridical. We conclude that haptic information can be used to reweight visual cues, putting more weight on misleading pseudocues, even when more trustworthy visual cues are available in the scene.
Auditory Streaming of Amplitude-Modulated Sounds in the Songbird Forebrain
Authors: Itatani Naoya , Klump Georg M.
Published: April 2009

Streaming in auditory scene analysis refers to the perceptual grouping of multiple interleaved sounds having similar characteristics while sounds with different characteristics are segregated. In human perception, auditory streaming occurs on the basis of temporal features of sounds such as the rate of amplitude modulation. We present results from multiunit recordings in the auditory forebrain of awake European starlings ( Sturnus vulgaris) on the representation of sinusoidally amplitude modulated (SAM) tones to investigate the effect of temporal envelope structure on neural stream segregation. Different types of rate modulation transfer functions in response to SAM tones were observed. The strongest responses were found for modulation frequencies (fmod) <160 Hz. The streaming stimulus consisted of sequences of alternating SAM tones with the same carrier frequency but differing in fmod (ABA-ABA-ABA-…). A signals had a modulation frequency evoking a large excitation, whereas the fmod of B signals was ≤4 octaves higher. Synchrony of B signal responses to the modulation decreased as fmod increased. Spike rate in response to B signals dropped as fmod increased. Faster signal repetition resulted in fewer spikes, suggesting the contribution of forward suppression to the response that may be due to both signals having similar spectral energy and that is not related to the temporal pattern of modulation. These two effects are additive and may provide the basis for a more separated representation of A and B signals by two populations of neurons that can be viewed as a neuronal correlate of segregated streams.
Effects of Human Arm Impedance on Dynamics Learning and Generalization
Authors: Darainy Mohammad , Mattar Andrew A. G. , Ostry David J.
Published: April 2009

Previous studies have demonstrated anisotropic patterns of hand impedance under static conditions and during movement. Here we show that the pattern of kinematic error observed in studies of dynamics learning is associated with this anisotropic impedance pattern. We also show that the magnitude of kinematic error associated with this anisotropy dictates the amount of motor learning and, consequently, the extent to which dynamics learning generalizes. Subjects were trained to reach to visual targets while holding a robotic device that applied forces during movement. On infrequent trials, the load was removed and the resulting kinematic error was measured. We found a strong correlation between the pattern of kinematic error and the anisotropic pattern of hand stiffness. In a second experiment subjects were trained under force-field conditions to move in two directions: one in which the dynamic perturbation was in the direction of maximum arm impedance and the associated kinematic error was low and another in which the perturbation was in the direction of low impedance where kinematic error was high. Generalization of learning was assessed in a reference direction that lay intermediate to the two training directions. We found that transfer of learning was greater when training occurred in the direction associated with the larger kinematic error. This suggests that the anisotropic patterns of impedance and kinematic error determine the magnitude of dynamics learning and the extent to which it generalizes.
Identification of Induction Motor Parameters in Industrial Drives with Artificial Neural Networks
Authors: Karanayil Baburaj , Rahman Muhammed Fazlur , Grantham Colin
Published: April 2009

This paper presents a new method of online estimation of the stator and rotor resistance of the induction motor in the indirect vector‐controlled drive, with artificial neural networks. The back propagation algorithm is used for training of the neural networks. The error between the rotor flux linkages based on a neural network model and a voltage model is back propagated to adjust the weights of the neural network model for the rotor resistance estimation. For the stator resistance estimation, the error between the measured stator current and the estimated stator current using neural network is back propagated to adjust the weights of the neural network. The performance of the stator and rotor resistance estimators and torque and flux responses of the drive, together with these estimators, is investigated with the help of simulations for variations in the stator and rotor resistance from their nominal values. Both types of resistance are estimated experimentally, using the proposed neural network in a vector‐controlled induction motor drive. Data on tracking performances of these estimators are presented. With this approach, the rotor resistance estimation was found to be insensitive to the stator resistance variations both in simulation and experiment.
The Incidence, Management, and Outcome of Penetrating Bladder Injuries in Civilians Resultant from Armed Conflict in Baghdad 2005-2006
Authors: Petros Firas G. , Santucci Richard A. , Al-Saigh Naimet K.
Published: April 2009

The purpose of this paper is to review the diagnosis, treatment, and outcomes of penetrating bladder injuries suffered by civilians in the Iraqi war zone.Materials and Methods.All civilian trauma cases received alive at Al-Yarmouk Teaching Hospital from January 2005 to August 2006 were reviewed for the presence of bladder injury.Results.533 cases of penetrating abdominal trauma were identified, of which 177 (33%) involved the genitourinary (GU) system and 64 (12%) involved the bladder. Most (70%) were young males, and most (55%) had grade IV injuries. Associated injuries occurred in 63/64 (98%) of patients. 3 patients had missed bladder injuries, and all of these had complications related to their missed injury. Bladder-related complications occurred in 11% of cases, and mortality in 13%, all due to extravesical injuries.Conclusions.Penetrating bladder injury among civilians in Baghdad war zone resulted in 64 cases in 18 months. The initial detection rate is very high (98%), and after primary repair, lasting complications are rare. Morbidities from missed injuries were severe hematuria and vesicorectal fistula. However, (3%) of vesicorectal fistulae healed spontaneously with prolonged bladder drainage. Associated injuries are the rule in penetrating bladder injury patients, and must be diligently investigated and treated.
Adaptive Maximums of Random Variables for Network Simulations
Authors: Chiou Rong Nan , Shyi Chia-Nian
Published: April 2009

In order to enhance the precision of network simulations, the paper proposes an approach to adaptively decide the maximum of random variables that create the discrete probabilities to generate nodal traffic on simulated networks.
In this paper, a statistical model is first suggested to manifest the bound of statistical errors. Then, according to the minimum probability that generates nodal traffic, a formula is proposed to decide the maximum. In the formula, a precision parameter is used to present the degree of simulative accuracy. Meanwhile, the maximum adaptively varies with the traffic distribution among nodes because the decision depends on the minimum probability generating nodal traffic. In order to verify the effect of the adaptive maximum on simulative precision, an optical network is introduced. After simulating the optical network, the theoretic average waiting time of nodes on the optical network is exploited to validate the exactness of the simulation. The proposed formula deciding the adaptive maximum can be generally exploited in the simulations of various networks. Based on the precision parameter K, a recursive procedure will be developed to automatically produce the adaptive maximum for network simulations in the future.
Effect of Lower Extremity Bypass Surgery on Inflammatory Reaction and Endothelial Dysfunction in Type 2 Diabetic Patients
Authors: Tsai Pei-Hsuan , Liu Jun-Jen , Chou Szu-Yuan , Chang Yao-Chung , Yeh Sung-Ling
Published: April 2009

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia and dyslipidemia. The abnormalities in nutrient metabolism and elevated inflammatory mediators resulting from DM lead to impairment of wound healing and vulnerability to infection and foot ulcers. Diabetic lower limb ischemia often leads to limb necrosis. Lower extremity bypass surgery (LEBS) is indicated to prevent limb loss in patients with critical leg ischemia. This study investigated the alteration of inflammatory and endothelium dysfunction markers before and after LEBS in DM patients. Twenty one type 2 DM patients with LEBS were included. Blood was drawn before and at 1 day and 7 days after surgery in the patients. Plasma soluble cellular adhesion molecule levels and blood leukocyte integrin expressions were measured. Also, plasma concentrations of endothelin-1 and nitric oxide were analyzed to evaluate the vascular endothelial function. The results showed that there were no significant differences in plasma cellular adhesion molecules, endothelin-1 and nitric oxide levels, nor did any differences in leukocyte integrin expressions before and after the operation. These results suggest that the efficacy of LEBS on alleviating inflammatory reaction and improving endothelial function in DM patients was not obvious.
Paleopathology of Human Tuberculosis and the Potential Role of Climate
Authors: Nerlich Andreas G. , Lösch Sandra
Published: April 2009

Both origin and evolution of tuberculosis and its pathogens (Mycobacterium tuberculosiscomplex) are not fully understood. The paleopathological investigation of human remains offers a unique insight into the molecular evolution and spread including correlative data of the environment. The molecular analysis of material from Egypt (3000–500 BC), Sudan (200–600 AD), Hungary (600–1700 AD), Latvia (1200–1600 AD), and South Germany (1400–1800 AD) urprisingly revealed constantly high frequencies of tuberculosis in all different time periods excluding significant environmental influence on tuberculosis spread. The typing of various mycobacteria strains provides evidence for ancestralM. tuberculosisstrains in Pre- to early Egyptian dynastic material (3500–2650 BC), while typicalM. africanumsignatures were detected in a Middle Kingdom tomb (2050–1650 BC). Samples from the New Kingdom to Late Period (1500–500 BC) indicated modernM. tuberculosisstrains. No evidence was seen forM. bovisin Egyptian material whileM. bovissignatures were first identified in Siberian biomaterial dating 2000 years before present. These results contraindicates the theory thatM. tuberculosisevolved fromM. bovisduring early domestication in the region of the “Fertile Crescent,” but supports the scenario thatM. tuberculosisprobably derived from an ancestral progenitor strain. The environmental influence of this evolutionary scenario deserves continuing intense evaluation.
Association of Plasma Circulatory Markers,Chlamydia pneumoniae, and High Sensitive C-Reactive Protein in Coronary Artery Disease Patients of India
Authors: Jha Hem Chandra , Srivastava Pragya , Sarkar Rakesh , Prasad Jagdish , Mittal Aruna Singh
Published: April 2009

Plasma inflammatory markers have been shown to be predictors for cardiovascular risk, however, there is no study where the levels of plasma circulatory markers have been evaluated in coronary artery disease patients (CAD pts) positive forC. pneumoniaeIgA and high sensitive C-reactive protein (hsCRP) which may help in better understanding of disease pathogenesis. A total of 192 patients and 192 controls attending the Cardiology Outpatient Department of Safdarjung Hospital were enrolled. The levels of plasma circulatory inflammatory markers were evaluated by ELISA. The levels of circulatory plasma markers (IL-4, IL-8, IL-13, ICAM-1, and VCAM-1) were significantly higher, whereas, levels of IL-10 and IFN-γwere significantly lower in CAD pts compared to healthy controls. The levels of IL-4, IL-8, and ICAM-1 (P=.007, .015, and .048) were significantly higher, however, IL-10 and IFN-γwere significantly lower (P<.001,<.001) inC. pneumoniaeIgA positive CAD pts. The levels of IL-4, IL-8, IL-13, ICAM-1, and VCAM-1 were higher but not significant and levels of IL-10 and IFN-γwere significantly (P<.001,<.001) lower in hsCRP positive CAD pts. Our study suggested that circulatory cytokines, namely, IL-4, IL-8, and adhesive molecules like ICAM-1 were enhanced after infection withC. pneumoniaewhereas in contrast to this IL-10 and IFN-λwere lowered. Suggesting the important role of these cytokines in progression of CAD.
Influence of Different Cations of N3 Dyes on Their Photovoltaic Performance and Stability
Authors: Andrade Luísa , Zakeeruddin Shaik M. , Nazeeruddin Mohammad K. , Ribeiro Helena Aguilar , Mendes Adélio , Graetzel Michael
Published: April 2009

The N3 dye was modified by substituting two of its protons by potassium or sodium cations. The performance and stability of dye-sensitized solar cells incorporating the new dyes were evaluated under light soaking(1000 W⋅m-2)at50∘C. Photocurrent measurements demonstrated that proton substitution by potassium cations rends the system more stable. Further characterization of the potassium-based devices was performed by electrochemical impedance spectroscopy to investigate the charge-transfer phenomena occurring at the different interfaces of the cells.
Discrete Analysis of Portfolio Selection with Optimal Stopping Time
Authors: Liang Jianfeng
Published: April 2009

Most of the investments in practice are carried out without certain horizons. There are many factors to drive investment to a stop. In this paper, we consider a portfolio selection policy with market-related stopping time. Particularly, we assume that the investor exits the market once his wealth reaches a given investment target or falls below a bankruptcy threshold. Our objective is to minimize the expected time when the investment target is obtained, at the same time, we guarantee the probability that bankruptcy happens is no larger than a given level. We formulate the problem as a mix integer linear programming model and make analysis of the model by using a numerical example.
Surface Enamel Remineralization: Biomimetic Apatite Nanocrystals and Fluoride Ions Different Effects
Authors: Roveri Norberto , Battistella Elisa , Bianchi Claudia Letizia , Foltran Ismaela , Foresti Elisabetta , Iafisco Michele , Lelli Marco , Naldoni Alberto , Palazzo Barbara , Rimondini Lia
Published: April 2009

A new method for altered enamel surface remineralization has been proposed . To this aim carbonate‐hydroxyapatite nanocrystals which mimic for composition, structure, nanodimensions, and morphology dentine apatite crystals and resemble closely natural apatite chemical‐physical properties have been used. The results underline the differences induced by the use of fluoride ions and hydroxyapatite nanocrystals in contrasting the mechanical abrasions and acid attacks to which tooth enamel is exposed. Fluoride ions generate a surface modification of the natural enamel apatite crystals increasing their crystallinity degree and relative mechanical and acid resistance. On the other hand, the remineralization produced by carbonate‐hydroxyapatite consists in a deposition of a new apatitic mineral into the eroded enamel surface scratches. A new biomimetic mineral coating, which progressively fills and shadows surface scratches, covers and safeguards the enamel structure by contrasting the acid and bacteria attacks.
Machinable Cu-40Zn Composites Containing Graphite Particles by Powder Metallurgy Process
Authors: Kondoh Katsuyoshi , Imai Hisashi , Kosaka Yoshiharu , Kojima Akimichi , Umeda Junko
Published: April 2009

Advanced Cu-40mass%Zn alloys with a high tensile strength and excellent machinability have been developed via a powder metallurgy (P/M) process. They are environmentally benign because fine graphite particles are included instead of lead (Pb) to improve their machinability. The effect of the content and particle size of the graphite on the mechanical properties and machinability are investigated in this paper. When applying a conventional P/M process consisting of the cold compaction and hot extrusion to consolidate elementally premixed mixture of Cu-40mass%Zn and graphite powder, the addition of 1 mass% graphite particles with  m in diameter is suitable to obtain a high tensile strength and good machinability at the same time.
Epitope specificity of anti-factor VIII antibodies from inhibitor positive acquired and congenital haemophilia A patients using synthetic peptides spanning A and C domains
Authors: Gharagozlou Soheila , Sharifian Ramazan , Khoshnoodi Jalal , Karimi Katayoon , Milani Monica , Okita David , Conti-Fine Bianca , Shokri Fazel
Published: April 2009

Development of antibodies (Ab) that either block the function of coagulation factor VIII (FVIII) (inhibitors) or clear it from circulation, seriously complicate the treatment of haemophilia A patients with FVIII products. Autoantibodies which develop in subjects without congenital FVIII defects, cause acquired haemophilia, a rare but life-threatening coagulopathy. Identification of the FVIII epitopes to which inhibitor Abs bind will help understanding the mechanisms of inhibitor activity, and perhaps development of new therapies. Here, we examined the FVIII peptide sequence regions recognised by anti-FVIII Ab in the plasma of six congenital and one acquired haemophilia patients with high inhibitor titers (24.4–2000 BU/ml). We used indirect ELISA and overlapping synthetic peptides, 20 residues long, spanning the sequence of the A and C FVIII domains. None of the plasma samples reacted with A1, A3 or C1 domain peptides. Six plasmas reacted with A2 and/or C2 peptides. Peptides spanning residues A2–521–690 and C2–2251–2332 were recognised most frequently and strongly. They include residues that contribute to the binding sites for activated factor IX and phosphatidyl serine/ von Willebrand factor. These results suggest that anti-FVIII Abs share a pattern of antigen specificity in our panel of patients, and that exposed regions of the FVIII molecule that form functionally important binding sites elicit an intense Ab response.
Variants in the coagulation factor 2 receptor (F2R) gene influence the risk of myocardial infarction in men through an interaction with interleukin 6 serum levels
Authors: Vikström Max , Meuzelaar Linda Strömqvist , Chernogubova Ekaterina , Silveira Angela , van’t Hooft Ferdinand , Hamsten Anders , Faire Ulf de , Gigante Bruna
Published: April 2009

Thrombin-activated factor 2 receptor (F2R) links thrombosis to inflammation modulating interleukin (IL)6 synthesis. We have investigated the role of F2R genetic variants and their interaction with IL6 serum levels in the occurrence of myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP). Seven SNPs –1738 G/A, –506-/GGCCGCGGGAAGC (D/I), 2860 G/A, 2930 T/C, 9113 C/A, 9333 C/T and 120813 T/C within F2R locus were genotyped in the SHEEP (n=2,774). The C allele at position 2930 was associated with a slight reduction in MI risk in men. IL6 serum levels were higher in male cases carrying genotypes AA at the –1738 (p= 0.01) and GG at the 2860 loci (p= 0.03) and both alleles were found to differentially modulate IL6 serum levels in the context of selective haplotypes. High IL6 serum levels (>75th percentile), were independently associated with an increased risk of MI in men with an odds ratio (OR) (95% confidence interval [CI]) of 2.44 (1.72–3.46), (p=0.0016), but not in women ( OR 0.83 [95%CI 0.50–1.36], p=0.64). In the presence of high IL6 serum levels, the –1738A allele increased and the 2860A allele reduced the risk of MI (all p≤0.02). Consistently, the AG diplotype increased MI risk (OR 1.71 [95%CI 1.17–2.51], p=0.005). The –1738 and 2860 loci association with IL6 serum levels was replicated in men in the Stockholm Coronary Artery Risk Factor (SCARF) study (both p≤0.04). In the pooled data from the two populations, the A and G allele modulated the risk of MI in men with high IL6 serum levels (p≤0.03). Our results demonstrate that in men F2R genetic variants influence the risk of MI mainly through an interaction with IL6 serum levels.
Tissue factor procoagulant activity of plasma microparticles is increased in patients with early-stage prostate cancer
Authors: Spath Brigitte , Friedrich Martin , Chun Felix Kyoung-Hwan , Marx Guy , Amirkhosravi Ali , Francis John , Bokemeyer Carsten , Eifrig Barbara , Haubold Katja , Rink Michael , Langer Florian
Published: April 2009

Tissue factor (TF) plays a critical role in tumour growth and metastasis, and its enhanced release into plasma in association with cellular microparticles (MPs) has recently been associated with pathological cancer progression. We have previously demonstrated significantly elevated levels of plasma TF antigen as well as systemic coagulation and platelet activation in patients with localised prostate cancer. In this prospective study, we used a highly sensitive one-stage clotting assay to measure preoperative TF-specific procoagulant activity (PCA) of plasma MPs in 68 consecutive patients with early-stage prostate cancer to further explore the relevance of circulating TF in this tumour entity. Automated calibrated thrombography was used to monitor thrombin generation in cell-free plasma samples in the absence of exogenous TF or phospholipids. Compared to healthy male controls (n=20), patients had significantly increased levels of both D-dimer and TF-specific PCA of plasma MPs (p<0.001). Furthermore, MP-associated TF PCA was higher in patients with (n=29) than in those without (n=39) laboratory evidence of an acute-phase reaction (p=0.004) and decreased to normal levels within one week after radical prostatectomy. Overall, we found a significant correlation between TF-specific PCA of plasma MPs and plasma D-dimer (p=0.002), suggesting that plasma MPs contributed to in-vivo coagulation activation in a TF-dependent manner. Thrombin generation in plasma was also significantly increased in patients compared to controls (p<0.01). Collectively, our findings suggest that TF-specific PCA of plasma MPs contributes to intravascular coagulation activation in patients with early-stage prostate cancer and may represent a potential link between hypercoagulability, inflammation, and disease progression.
Single-chain antibodies as diagnostic tools and therapeutic agents
Authors: Muhlen Constantin von zur , Elverfeldt Dominik von , Peter Karlheinz , Hagemeyer Christoph
Published: April 2009

Over three decades after the generation of the first mouse monoclonal antibodies by Kohler and Milstein, recombinant antibodies are the fastest growing class of therapeutic proteins. Furthermore, antibodies are key detection reagents in research and diagnostics. Technology improvements have provided several approaches to manufacturing human antibodies with high affinity for biologically relevant targets. Approximately 300 development programs for therapeutic antibodies have been reported in industrial and academic laboratories, and this clearly demonstrates the expectations towards antibody technology. Antibody fragments are a subclass with growing clinical importance. This review focuses on single-chain antibodies as one of the smallest possible format for recombinant antibodies and their use as diagnostic tools and therapeutic agents. We describe the structure, selection and production of single-chain antibodies. Furthermore, we review current applications of antibody fragments focusing on thrombus targeting using fibrin- and platelet-specific single-chain antibodies as well as describing novel noninvasive imaging approaches for the diagnosis of thrombosis and inflammation.
Common Coding Variants of the
HNF1A
Gene Are Associated With Multiple Cardiovascular Risk Phenotypes in Community-Based Samples of Younger and Older European-American Adults
Authors: Reiner Alexander P. , Gross Myron D. , Carlson Christopher S. , Bielinski Suzette J. , Lange Leslie A. , Fornage Myriam , Jenny Nancy S. , Walston Jeremy , Tracy Russell P. , Williams O. Dale , Jacobs David R. , Nickerson Deborah A.
Published: April 2009

Background—

The transcription factor hepatocyte nuclear factor (HNF)-1α regulates the activity of a number of genes involved in innate immunity, blood coagulation, lipid and glucose transport and metabolism, and cellular detoxification. Common polymorphisms of the HNF-1α gene (
HNF1A
) were recently associated with plasma C-reactive protein and γ-glutamyl transferase concentration in middle-aged to older European Americans (EA).

Methods and Results—

We assessed whether common variants of
HNF1A
are associated with C-reactive protein, γ-glutamyl transferase, and other atherosclerotic and metabolic risk factors, in the large, population-based Coronary Artery Risk Development in Young Adults Study of healthy young EA (n=2154) and African American (AA; n=2083) adults. The minor alleles of Ile27Leu (
rs
1169288) and Ser486Asn (
rs
2464196) were associated with 0.10 to 0.15 standard deviation units lower C-reactive protein and γ-glutamyl transferase levels in EA. The same
HNF1A
coding variants were associated with higher low-density lipoprotein cholesterol, apolipoprotein B, creatinine, and fibrinogen in EA. We replicated the associations between
HNF1A
coding variants and C-reactive protein, fibrinogen, low-density lipoprotein cholesterol, and renal function in a second population-based sample of EA adults 65 years and older from the Cardiovascular Health Study. The
HNF1A
Ser486Asn and/or Ile27Leu variants were also associated with increased risk of subclinical coronary atherosclerosis in Coronary Artery Risk Development in Young Adults and with incident coronary heart disease in Cardiovascular Health Study. The Ile27Leu and Ser486Asn variants were 3-fold less common in AA than in EA. There was little evidence of association between
HNF1A
genotype and atherosclerosis-related phenotypes in AA.

Conclusions—

Common polymorphisms of
HNF1A
seem to influence multiple phenotypes related to cardiovascular risk in the general population of younger and older EA adults.
Rapamycin-Eluting Stents in the Arterial Duct
Authors: Lee Kyong-Jin , Hinek Aleksander , Chaturvedi Rajiv R. , Almeida Claudia L. , Honjo Osami , Koren Gideon , Benson Leland N.
Published: April 2009

Background—

Maintaining arterial duct patency by stent implantation may be advantageous in congenital heart disease management algorithms. Rapamycin, an immunosuppressant drug that demonstrates antiproliferative properties and inhibits smooth muscle cell migration, may deter the intimal hyperplasia that occurs during spontaneous closure and after-stent implantation of the arterial duct.

Methods and Results—

Twenty-eight Yorkshire piglets (7 to 11 days old; weight, 2.2 to 4.9 kg) underwent stent implantation of the arterial duct (rapamycin-eluting (n=14) or bare metal (n=14) stents, 3.5-mm diameter) and were euthanized at 2, 4, and 6 weeks. Dissected arterial ducts were analyzed for lumen diameter, smooth muscle cell, and extracellular matrix components. Isolated arterial duct–derived smooth muscle cells were cultured in the presence or absence of rapamycin. Cellular proliferation rates were assessed by Ki-67 detection and [
3
H]-thymidine incorporation. No significant neointimal proliferation was present in either stent type at 2 weeks. At 4 weeks, the median luminal diameters of the bare metal stents were 87% (
P
=0.009), 54% (
P
=0.004), and 77% (
P
=0.004) that of the drug-eluting stents at the middle and aortic and pulmonary artery ends, respectively. At 6 weeks, the median luminal diameters of the bare metal stents were 0% (
P
=0.18), 5% (
P
=0.25), and 61% (
P
=0.13) that of the drug-eluting stents at the same respective levels. Complete histological occlusion was found in at least 1 level of the lumen in 9 pigs: 1 (17%) in the BMS group at 4 weeks, 5 (83%) in the BMS group at 6 weeks, and 3 (50%) in the DES group at 6 weeks. In vitro studies demonstrated 50%-lower proliferation rates in rapamycin-treated cultures of duct-derived smooth muscle cell cultures (
P
<0.001).

Conclusions—

Rapamycin has antiproliferative actions on the arterial duct. Drug-eluting stents may be a more efficient tool than current palliative options for maintaining patency in critically duct-dependent states, but there may be a finite time-related benefit.
Importance of the First Link
Authors: Berdowski Jocelyn , Beekhuis Freerk , Zwinderman Aeilko H. , Tijssen Jan G.P. , Koster Rudolph W.
Published: April 2009

Background—

The content of emergency calls for suspected cardiac arrest is rarely analyzed. This study investigated the recognition of a cardiac arrest by dispatchers and its influence on survival rates.

Methods and Results—

During 8 months, voice recordings of 14 800 consecutive emergency calls were collected to audit content and cardiac arrest recognition. The presence of cardiac arrest during the call was assessed from the ambulance crew report. Included calls were placed by laypersons on site and did not involve trauma. Prevalence of cardiac arrest was 3.0%. Of the 285 cardiac arrests, 82 (29%) were not recognized during the call, and 64 of 267 suspected calls (24%) were not cardiac arrest. We analyzed a random sample (n=506) of 9230 control calls. Three-month survival was 5% when a cardiac arrest was not recognized versus 14% when it was recognized (
P
=0.04). If the dispatcher did not recognize the cardiac arrest, the ambulance was dispatched a mean of 0.94 minute later (
P
<0.001) and arrived 1.40 minutes later on scene (
P
=0.01) compared with recognized calls. The main reason for not recognizing the cardiac arrest was not asking if the patient was breathing (42 of 82) and not asking to describe the type of breathing (16 of 82). Normal breathing was never mentioned in true cardiac arrest calls. A logistic regression model identified spontaneous trigger words like facial color that could contribute to cardiac arrest recognition (odds ratio, 7.8 to 9.7).

Conclusions—

Not recognizing a cardiac arrest during emergency calls decreases survival. Spontaneous words that the caller uses to describe the patient may aid in faster and better recognition of a cardiac arrest.
Long Time Coming: Prospects for Democracy in Iraq
Authors: Moon Bruce E.
Published: April 2009

Prospects for democracy in Iraq should be assessed in light of the historical precedents of nations with comparable political experiences. Saddam Hussein's Iraq was an unusually extreme autocracy, which lasted an unusually long time. Since the end of the nineteenth century, only thirty nations have experienced an autocracy as extreme as Iraq's for a period exceeding two decades. The subsequent political experience of those nations offers a pessimistic forecast for Iraq and similar nations. Only seven of the thirty are now democratic, and only two of them have become established democracies; the democratic experiments in the other five are still in progress. Among the seven, the average time required to transit the path from extreme autocracy to coherent, albeit precarious, democracy has been fifty years, and only two have managed this transition in fewer than twenty-five years. Even this sober assessment is probably too optimistic, because Iraq lacks the structural conditions that theory and evidence indicate have been necessary for successful democratic transitions in the past. Thus, the odds of Iraq achieving democracy in the next quarter century are close to zero, at best about two in thirty, but probably far less.
The Social Market Roots of Democratic Peace
Authors: Mousseau Michael
Published: April 2009

Democracy does not cause peace among nations. Rather, domestic conditions cause both democracy and peace. From 1961 to 2001, democratic nations engaged in numerous fatal conflicts with each other, including at least one war, yet not a single fatal militarized incident occurred between nations with contract-intensive economies—those where most people have the opportunity to participate in the market. In contract-intensive economies, individuals learn to respect the choices of others and value equal application of the law. They demand liberal democracy at home and perceive it in their interest to respect the rights of nations and international law abroad. The consequences involve more than just peace: the contract-intensive democracies are in natural alliance against any actor—state or nonstate—that seeks to challenge Westphalian law and order. Because China and Russia lack contractualist economies, the economic divide will define great power politics in the coming decade. To address the challenges posed by China and Russia, preserve the Westphalian order, and secure their citizens from terrorism, the contract-intensive powers should focus their efforts on supporting global economic opportunity, rather than on promoting democracy.
Bridge over Troubled Water? Envisioning a China-Taiwan Peace Agreement
Authors: Saunders Phillip C. , Kastner Scott L.
Published: April 2009

In Taiwan's 2008 presidential election, both candidates advocated signing a peace agreement with China, and Chinese leaders have also expressed interest in reaching such an agreement. Although substantial obstacles remain in the way of a cross-strait peace agreement, this increased interest on both sides of the Taiwan Strait suggests that a closer examination of an agreement's possible dimensions and consequences is warranted. This analysis considers what an agreement might look like, whether and how it might be effective in reducing the possibility of cross-strait military conflict, the relevant barriers to an agreement, and whether an agreement—if reached—would be likely to endure.
Reflections on Power and the Post-Colonial Context: Tales from the Field
Authors: Pintchman Tracy
Published: April 2009

The history of ethnographic practice in anthropology is inseparable from histories of colonialism—including racist assumptions and exploitative interests. This essay comments on concerns about power and ethnographic work from a different point of view, considering the relative powerlessness of the ethnographer in the context of a relationship that developed in the field. The essay argues that power relations in the practice of ethnography are in fact quite variegated, dependent on multiple factors, and too complex and richly textured to be captured in a single, simple “first world/third world” kind of dichotomous mapping.