bluuebunny/crossref_metadata_2025 huggingface dataset:
Application and evaluation of electromagnetic methods for imaging saltwater intrusion in coastal aquifers: Seaside Groundwater Basin, California
Authors: Nenna Vanessa , Herckenrath Daan , Knight Rosemary , Odlum Nick , McPhee Darcy
Published: February 2013

Developing effective resource management strategies to limit or prevent saltwater intrusion as a result of increasing demands on coastal groundwater resources requires reliable information about the geologic structure and hydrologic state of an aquifer system. A common strategy for acquiring such information is to drill sentinel wells near the coast to monitor changes in water salinity with time. However, installation and operation of sentinel wells is costly and provides limited spatial coverage. We studied the use of noninvasive electromagnetic (EM) geophysical methods as an alternative to installation of monitoring wells for characterizing coastal aquifers. We tested the feasibility of using EM methods at a field site in northern California to identify the potential for and/or presence of hydraulic communication between an unconfined saline aquifer and a confined freshwater aquifer. One-dimensional soundings were acquired using the time-domain electromagnetic (TDEM) and audiomagnetotelluric (AMT) methods. We compared inverted resistivity models of TDEM and AMT data obtained from several inversion algorithms. We found that multiple interpretations of inverted models can be supported by the same data set, but that there were consistencies between all data sets and inversion algorithms. Results from all collected data sets suggested that EM methods are capable of reliably identifying a saltwater-saturated zone in the unconfined aquifer. Geophysical data indicated that the impermeable clay between aquifers may be more continuous than is supported by current models.
3D stochastic gravity inversion using nonstationary covariances
Authors: Shamsipour Pejman , Marcotte Denis , Chouteau Michel , Rivest Martine , Bouchedda Abderrezak
Published: February 2013

The flexibility of geostatistical inversions in geophysics is limited by the use of stationary covariances, which, implicitly and mostly for mathematical convenience, assumes statistical homogeneity of the studied field. For fields showing sharp contrasts due, for example, to faults or folds, an approach based on the use of nonstationary covariances for cokriging inversion was developed. The approach was tested on two synthetic cases and one real data set. Inversion results based on the nonstationary covariance were compared to the results from the stationary covariance for two synthetic models. The nonstationary covariance better recovered the known synthetic models. With the real data set, the nonstationary assumption resulted in a better match with the known surface geology.
Scattering versus intrinsic attenuation in the vadose zone: A VSP experiment
Authors: Mangriotis Maria-Daphne , Rector James W. , Herkenhoff E. Frederic , Neu John C.
Published: February 2013

We studied scattering versus intrinsic attenuation estimates in the vadose zone from a shallow VSP experiment conducted in the Lawrence Livermore National Laboratory (LLNL) facility. Using permanent downhole geophones and a vertical impact source, we estimated effective attenuation of the downgoing transmitted P-wave. We compared theoretical scattering attenuation estimates and finite-difference synthetics to the measured field [Formula: see text] values ([Formula: see text] being a measure of attenuation). Using a selected range of impedance profiles of variance typical for a sedimentary basin, our estimates of [Formula: see text] are in the order of 20–85. Given the short propagation pathlengths involved ([Formula: see text]), we show that attenuation due to lateral heterogeneity is not significant. We analyzed additional distorting factors, including near-field presence, local impedance effects, and interference from reflections originating beneath receivers, and found that they may significantly impact attenuation measurement in near-surface studies, and result in biased [Formula: see text] values. From a comparison of the analyzed ranges of [Formula: see text] to the measured [Formula: see text] values, we deduced [Formula: see text], which is consistently low, but whose inferred frequency dependence depends strongly on the scattering model assumed. The ranges for the [Formula: see text] factor resulting from scattering and distorting factors, and the intrinsic [Formula: see text] value were estimated as, respectively, 4–7, and 7–4. We identified two potential mechanisms which could lead to low [Formula: see text] values in the vadose zone: patchy saturation and squirt flow. We found through viscoelastic 3D synthetic modeling using a standard linear solid (SLS), that the field [Formula: see text] frequency dependence can be reproduced, although nonuniquely, for the studied range of impedance variance.
Wavefield extrapolation in pseudodepth domain
Authors: Ma Xuxin , Alkhalifah Tariq
Published: February 2013

Wavefields are commonly computed in the Cartesian coordinate frame. Its efficiency is inherently limited due to spatial oversampling in deep layers, where the velocity is high and wavelengths are long. To alleviate this computational waste due to uneven wavelength sampling, we convert the vertical axis of the conventional domain from depth to vertical time or pseudodepth. This creates a nonorthognal Riemannian coordinate system. Isotropic and anisotropic wavefields can be extrapolated in the new coordinate frame with improved efficiency and good consistency with Cartesian domain extrapolation results. Prestack depth migrations are also evaluated based on the wavefield extrapolation in the pseudodepth domain.
When the drugs don't work: the potential of glutamatergic antipsychotics in schizophrenia
Authors: Papanastasiou Evangelos , Stone James M. , Shergill Sukhi
Published: February 2013

Currently available antipsychotic drugs target dopaminergic neurotransmission. Many patients do not respond fully to these treatments, and there has been considerable effort to investigate alternative targets. Here we summarise the rationale and recent evidence supporting efforts to develop glutamatergic antipsychotic drugs.
Effectiveness of cognitive analytic therapy for personality disorders
Authors: Mulder Roger , Chanen Andrew M.
Published: February 2013

Personality disorders affect up to 50% of psychiatric out-patients. Most treatment studies have been performed in patients with borderline personality disorder. Structured psychosocial interventions for people with borderline personality disorders appear to have similar efficacy. There is some evidence that non-structured, non-specialised treatments offered by psychiatric general services might be ineffective and possibly harmful in patients with personality disorders. Cognitive analytic therapy is a time-limited, integrative psychotherapy, which appears to be effective for a range of personality disorders and superior to treatment as usual. Its practical nature and relatively short time limit may make it suitable for front-line clinical services.
Use of liothyronine in preventing electroconvulsive therapy-induced memory impairment: evaluation
Authors: Masoudzadeh Abbas , Yahyavi Seyyed Taha , Rashidi Hooman , Mohammadpour Reza Ali , Kiani Reza
Published: February 2013

Aims and method

To evaluate the effect of liothyronine administration on the cognitive side-effects of electroconvulsive therapy (ECT), 30 participants with major depressive disorder that were suitable candidates for ECT were randomly allocated to either a liothyronine or a placebo group. Participants in the liothyronine group received a daily 50 μg dose for the whole period of receiving ECT starting the day before ECT, whereas the other group received a placebo. The Hamilton Rating Scale for Depression (HRSD) and the Wechsler Memory Scale – revised (WMS-R) were used for evaluating mood and memory before the first ECT session and after the sixth session (the HRSD was also used after the third session).

Results

The results indicated that after the sixth ECT session, participants that received liothyronine achieved significantly better scores on the HRSD and WMS-R.

Clinical implications

Further studies with a larger number of participants, through multicentre research projects, are indicated to obtain adequate data for meta-analysis and systematic review.
How to run a psychiatry summer school
Authors: Greening Jayne , Tarn Mark , Purkis Judy
Published: February 2013

Graduates in the UK are not choosing a career in psychiatry. This paper sets out to do three related things: review the factors that attract and deter medical students from a career in psychiatry, describe the provision of current summer schools and special programmes in psychiatry, and provide detail of how initiatives such as summer schools may be set up, run and evaluated locally to potentially address some of those issues identified in the first section.
Proposed changes for substance use and gambling disorders in DSM-5: impact on assessment and treatment in the UK
Authors: Petry Nancy M. , Bowden-Jones Henrietta , George Sanju
Published: February 2013

In the USA, DSM-5 is scheduled for publication in 2013. It is likely to include some substantial changes to the diagnosis of substance use disorders and pathological gambling. This paper reviews the proposed changes to these diagnoses and their potential impact on diagnosis, treatment and research of these disorders in the UK.
Community treatment orders – principles and attitudes
Authors: Sharma Vimal Kumar
Published: February 2013

The community treatment order (CTO) was implemented in 2008 as part of the 2007 amendments to the Mental Health Act 1983. Initially, health professionals and patient groups were sceptical about the successful implementation of CTOs. However, as more than the expected number of patients has been subjected to CTOs in the past 3 years in England and Wales, the professionals' views are shifting in favour of CTOs. More needs to be done to improve the approach and attitude of care providers so that CTOs are used in the most appropriate and effective way for the patients.
Involuntary out-patient commitment: 2-year follow-up
Authors: Castells-Aulet Laura , Hernández-Viadel Miguel , Asensio-Pascual Pedro , Cañete-Nicolás Carlos , Bellido-Rodríguez Carmen , Lera-Calatayud Guillem , Calabuig-Crespo Roman
Published: February 2013

Aims and method

To evaluate the impact of involuntary out-patient commitment (OPC) in patients with severe mental disorder who use hospital services. This is a retrospective–observational study in a population of 91 patients under OPC. The psychiatric diagnosis, sociodemographic variables, who requested the court order and for what motive were studied. The study also looked at the use of the available health services (emergency room visits, admissions, average length of hospital stay) for the period beginning 2 years before and ending 2 years after the initiation of the OPC.

Results

The number of emergency room visits, admissions and the length of hospitalisation diminished in the 2 years following the initiation of the OPC. In terms of diagnosis, the OPC has the most impact on individuals with schizophrenia and delusional disorder.

Clinical implications

The OPC can be useful for certain patients with severe mental disorder, particularly individuals with schizophrenia and delusional disorder.
Roles of Chemokine Ligand-2 (CXCL2) and Neutrophils in Influencing Endothelial Cell Function and Inflammation of Human Adipose Tissue
Authors: Rouault Christine , Pellegrinelli Vanessa , Schilch Raphaela , Cotillard Aurélie , Poitou Christine , Tordjman Joan , Sell Henrike , Clément Karine , Lacasa Danièle
Published: February 2013

The hypertrophied white adipose tissue (WAT) during human obesity produces inflammatory mediators, including cytokines (IL-6 and TNFα) and chemokines ([C-C motif] chemokine ligand 2 and IL-8). These inflammatory factors are preferentially produced by the nonadipose cells, particularly the adipose tissue infiltrating macrophages. We identified the chemokine (C-X-C motif) ligand 2 (CXCL2) by a transcriptomic approach. Because CXCL2 could represent a WAT-produced chemokine, we explored its role in obesity-associated inflammation. CXCL2 levels in serum and mRNA in WAT were higher in obese subjects compared with lean ones. CXCL2 secretions were higher in sc and visceral (vis) WAT from obese compared with lean subjects. In vis WAT, CXCL2 mRNA expression was higher in macrophages compared with other WAT cells and positively correlated with the inflammatory macrophage markers TNFα and IL-6. CXCL2 triggered the in vitro adhesion of the neutrophils, its selective cell targets, to endothelial cells (ECs) of vis WAT (vis WAT-ECs). Immunohistological analysis indicated that activated neutrophils were adherent to the endothelium of vis WAT from human obese subjects. Blood neutrophils from obese subjects released high levels of proinflammatory mediators (IL-8, chemokine motif ligand 2 [CCL2], matrix metalloproteinase [MMP] 9, and myeloperoxidase [MPO]). Visceral WAT-ECs, treated by neutrophil-conditioned media prepared from obese subjects, displayed an increase of the expression of inflammatory molecules associated with senescence and angiogenic capacities. To conclude, CXCL2, a WAT-produced chemokine being up-regulated in obesity, stimulates neutrophil adhesion to vis WAT-ECs. Activated neutrophils in obesity may influence vis WAT-ECs functions and contribute to WAT inflammation.
Peptide Hormone Release Monitored From Single Vesicles in “Membrane Lawns” of Differentiated Male Pituitary Cells: SNAREs and Fusion Pore Widening
Authors: Stenovec Matjaž , Gonçalves Paula P. , Zorec Robert
Published: February 2013

In this study we used live-cell immunocytochemistry and confocal microscopy to study the release from a single vesicle in a simplified system called membrane lawns. The lawns were prepared by exposing differentiated pituitary prolactin (PRL)-secreting cells to a hypoosmotic shear stress. The density of the immunolabeled ternary soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) complexes that bind complexin was approximately 10 times lower than the PRL-positive, lawn-resident vesicles; this indicates that some but not all vesicles are associated with ternary SNARE complexes. However, lawn-resident PRL vesicles colocalized relatively well with particular SNARE proteins: synaptobrevin 2 (35%), syntaxin 1 (22%), and 25-kDa synaptosome associated protein (6%). To study vesicle discharge, we prepared lawn-resident vesicles, derived from atrial natriuretic peptide tagged with emerald fluorescent protein (ANP.emd)-transfected cells, which label vesicles. These maintained the structural passage to the exterior because approximately 40% of ANP.emd-loaded vesicles were labeled by extracellular PRL antibodies. Cargo release from the lawn-resident vesicles, monitored by the decline in the ANP.emd fluorescence intensity, was similar to that in intact cells. It is likely that SNARE proteins are required for calcium-dependent release from these vesicles. This is because the expression of the dominant-negative SNARE peptide, which interferes with SNARE complex formation, reduced the number of PRL-positive spots per cell (PRL antibodies placed extracellularly) significantly, from 58 ± 9 to 4 ± 2. In dominant-negative SNARE-treated cells, the PRL-positive area was reduced from 0.259 ± 0.013 to 0.123 ± 0.014 μm2, which is consistent with a hindered vesicle luminal access for extracellular PRL antibodies. These results indicate that vesicle discharge is regulated by SNARE-mediated fusion pore widening.
Dopamine Mediates Testosterone-Induced Social Reward in Male Syrian Hamsters
Authors: Bell Margaret R. , Sisk Cheryl L.
Published: February 2013

Adolescent maturation of responses to social stimuli is essential for adult-typical sociosexual behavior. Naturally occurring developmental changes in male Syrian hamster responses to a salient social cue, female hamster vaginal secretions (VS), provide a good model system for investigating neuroendocrine mechanisms of adolescent change in social reward. Sexually naïve adult, but not juvenile, males show a conditioned place preference (CPP) to VS, indicating that VS is not rewarding before puberty. In this series of experiments, the authors examined the roles of testosterone and dopamine receptor activation in mediating the adolescent gain in positive valence of VS. Experiment 1 showed that testosterone replacement is necessary for gonadectomized adult hamsters to form a CPP to VS. Experiment 2 showed that testosterone treatment is sufficient for juvenile hamsters to form a CPP to VS, and that the dopamine receptor antagonist haloperidol blocks formation of a CPP to VS in these animals. Experiments 3 and 4 demonstrated that the disruption of VS CPP with low doses of haloperidol is the result of a reduction in the attractive properties of VS and not attributable to aversive properties of haloperidol. Together, these studies demonstrate that the unconditioned rewarding properties of a social cue necessary for successful adult sociosexual interactions come about as the result of the pubertal increase in circulating testosterone in male hamsters. Furthermore, this social reward can be prevented by dopamine receptor antagonism, indicating that hypothalamic and/or mesocorticolimbic dopaminergic circuits are targets for hormonal activation of social reward.
From ‘Blade Runner’ to ‘Stem-Cell Player’ and beyond
Authors: Saw K-Y. , Jee C. S-Y.
Published: February 2013

Modern athletes are constantly susceptible to performance-threatening injury as they push their bodies to greater limits and endure higher physical stresses. Loss of performance and training time can adversely and permanently affect a sportsperson’s career. Now more than ever with advancing medical technology the answer may lie in biologic therapy. We have been using peripheral blood stem cells (PBSC) clinically and have been able to demonstrate that stem cells differentiate into target cells to enable regenerative repair. The potential of this technique as a regenerative agent can be seen in three broad applications: 1) articular cartilage, 2) bone and 3) soft tissue. This article highlights the successful cases, among many, in all three of these applications.
On maximal curves of Fermat type
Authors: Tafazolian Saeed , Torres Fernando
Published: February 2013

The aim of this paper is to give a characterization of a maximal curve given by the equation xn + ym = 1 over a finite field Fq
2.
G-Fano threefolds, I
Authors: Prokhorov Yuri
Published: February 2013

We classify Fano threefolds with only terminal singularities whose canonical class is Cartier and divisible by 2 with the additional assumption that the G-invariant part of the Weil divisor class group is of rank 1 with respect to an action of some group G. In particular, we find a lot of examples of Fano 3-folds with “many” symmetries.
G-Fano threefolds, II
Authors: Prokhorov Yuri
Published: February 2013

We classify Fano threefolds with only Gorenstein terminal singularities and Picard number greater than 1, satisfying the additional assumption that the G-invariant part of the Weil divisor class group is of rank 1 with respect to an action of some group G.
The importance of induced aberrations in the correction of secondary color
Authors: Rogers John R.
Published: February 2013

Much publicity has been given to the art and science of choosing glass types for the reduction of secondary color, particularly for systems (such as achromats) in which all the elements are in contact. Although it has long been recognized that airspaces between elements can influence chromatic aberration and can even be used to reduce or correct secondary color, comparatively, little emphasis has been placed on this in the published literature. This tutorial is intended to call attention to the induced component of secondary color and suggests methods for improving color correction.
Influence of partial unfolding and aggregation of human stefin B (cystatin B) EPM1 mutants G50E and Q71P on selective cleavages by cathepsins B and S
Authors: Polajnar Mira , Vidmar Robert , Vizovišek Matej , Fonović Marko , Kopitar-Jerala Nataša , Žerovnik Eva
Published: February 2013

Human stefins and cystatins are physiologically important cysteine proteinase inhibitors, acting as a first line of defense against undesirable proteolysis. Mutations in the cystatin B gene cause a rare form of epilepsy EPM1. Its two missense mutants, G50E and Q71P, lack the inhibitory activity and are partially unfolded, which leads to changes in their aggregation behavior, both in vitro and in the cell. SDS-PAGE and MALDI-TOF mass spectrometry were used to follow the hydrolysis of human stefin B wild type, G50E and Q71P, by cathepsins B and S in vitro. Cathepsin S was found to degrade both mutants, with Q71P being degraded faster. This correlates with the openness of the protein structure, Q71P having more exposed hydrophobic surfaces. Cathepsin B acted more selectively, degrading G50E into smaller fragments, while still leaving a portion of the full-length protein intact. Q71P was cleaved only at the exposed N-terminal end. The co-localization of stefin B wild type and EPM1 mutants with cathepsins showed that cathepsins accumulate around the aggregates formed by the EPM1 mutants. We hypothesize that the aggregation of both full-length mutants prevents the cathepsin molecule from accessing the substrate protein’s core, whereas the cleaved fragments would be expected to aggregate stronger.
Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist
Authors: Savard Martin , Labonté Julie , Dubuc Céléna , Neugebauer Witold , D’Orléans-Juste Pedro , Gobeil Fernand
Published: February 2013

We recently identified a novel human B2 receptor (B2R) agonist [Hyp3,Thi5,NChg7,Thi8]-bradykinin (NG291) with greater in vitro and in vivo potency and duration of action than natural bradykinin (BK). Here, we further examined its stability and selectivity toward B2R. The hypotensive, antithrombotic, and profibrinolytic functions of NG291 relative to BK and its analogue ([Hyp3,Thi5,(4-Me)Tyr8(ΨCH2NH)Arg9]-BK) (RMP-7) were also tested. Contraction assays using isolated mouse stomachs (containing kinin B1R, B2R, and kininase I- and II-like activities) showed that NG291 is a more potent contractant than BK and is inhibited by HOE-140 (B2R antagonist) but unaffected by R954 (B1R antagonist), whereas both decreased the potency of BK. In stomach tissues from B2R knockout mice, BK maintained its activity via B1R, whereas NG291 had no contractile effect, indicating that it was selective for B2R. Unlike BK, NG291 was not degraded by rabbit lung ACE. Comparing intravenously administered BK and NG291 revealed that NG291 exhibited more potent and prolonged hypotensive action and greater antithrombotic and profibrinolytic activities. These effects were of comparable magnitude to RMP-7 and were absent in B2R knockout mice. We concluded that NG291 is a novel biostable B2R-selective agonist that may prove suitable for investigating the (pre)clinical cardioprotective efficacy of B2R activation.
Plasma kallikrein-kinin system and diabetic retinopathy
Authors: Liu Jia , Feener Edward P.
Published: February 2013

Diabetic retinopathy (DR) occurs, to some extent, in most people with at least 20 years’ duration of diabetes mellitus. The progression of DR to its sight-threatening stages is usually associated with the worsening of underlying retinal vascular dysfunction and disease. The plasma kallikrein-kinin system (KKS) is activated during vascular injury, where it mediates important functions in innate inflammation, blood flow, and coagulation. Recent findings from human vitreous proteomics and experimental studies on diabetic animal models have implicated the KKS in contributing to DR. Vitreous fluid from people with advanced stages of DR contains increased levels of plasma KKS components, including plasma kallikrein (PK), coagulation factor XII, and high-molecular-weight kininogen. Both bradykinin B1 and B2 receptor isoforms (B1R and B2R, respectively) are expressed in human retina, and retinal B1R levels are increased in diabetic rodents. The activation of the intraocular KKS induces retinal vascular permeability, vasodilation, and retinal thickening, and these responses are exacerbated in diabetic rats. Preclinical studies have shown that the administration of PK inhibitors and B1R antagonists to diabetic rats ameliorates retinal vascular hyperpermeability and inflammation. These findings suggest that components of plasma KKS are potential therapeutic targets for diabetic macular edema.
Deciphering the emerging role of SUMO conjugation in the hypoxia-signaling cascade
Authors: Núñez-O’Mara Analía , Berra Edurne
Published: February 2013

By driving the primary transcriptional response, the hypoxia inducible factor (HIF) is a master player of the hypoxia-signaling cascade, activation of which is essential to maintain oxygen homeostasis. HIF is formed by the interaction of a constitutive HIF-1β subunit with a HIF-α subunit tightly regulated through the concerted action of the prolyl hydroxylase domain containing proteins (PHDs) and factor inhibiting HIF. In well-oxygenated cells, HIF-α prolyl-hydroxylation by PHDs is the recognition signal for the binding of the ubiquitin E3 ligase pVHL, allowing protein poly-ubiquitination and degradation by the proteasome. Factor inhibiting HIF-mediated asparaginyl hydroxylation prevents interaction with the CBP/p300 coactivator and hence reduces HIF-dependent transcriptional activity. Upon low oxygen availability, HIF-α hydroxylation is blocked, resulting in protein stabilization and HIF complex activation. Post-translational modifications other than hydroxylation appear to be important in the cellular response to hypoxia. Small ubiquitin-like modifier (SUMO) is a 10 kDa protein readily conjugated to the lysine (K) residues of numerous cellular substrates in a sequential process termed SUMOylation. Recent data support the idea that a fine balance in SUMOylation/deSUMOylation is required for the adequate activation of the hypoxia-signaling cascade. In the present review, we will concentrate on the mechanisms of SUMOylation and its consequences in the cellular response to hypoxia.
Role of hypoxia inducible factor-1α for interferon synthesis in mouse dendritic cells
Authors: Wobben Regina , Hüsecken Yvonne , Lodewick Claudia , Gibbert Kathrin , Fandrey Joachim , Winning Sandra
Published: February 2013

Dendritic cells (DCs) are an important link between innate and adaptive immunity. DCs get activated in inflamed tissues where oxygen tension is usually low, which requires the transcription factor hypoxia inducible factor (HIF)-1 for cellular adaptation. To investigate whether the HIF-1 transcriptional complex plays a pivotal role in the function of DCs, we compared the effects of exogenous inflammatory stimuli and hypoxia on HIF-1α in bone marrow-derived DCs from wild type and myeloid-specific HIF-1α knock-out mice. We showed that the Toll-like receptor ligands lipopolysaccharides and cytosine-phosphatidyl-guanines significantly induce HIF-1α mRNA and protein, leading to elevated HIF-1 target gene expression of vascular endothelial growth factor. In contrast, polyinosinic:polycytidylic acid did not show comparable effects. Furthermore the potential to up-regulate inflammatory cytokines critically influences DC function. Our data demonstrate that HIF-1α protein is needed for adequate production of interferon-α and -β. In co-cultures of DCs and cytotoxic T cells, we observed that DCs lacking active HIF-1α protein induce significantly less CD278 and granzyme B mRNA in T cells. We conclude that HIF-1α plays a crucial role in DC interferon production and T cell activation, linking the innate and adaptive immune system.
Hydroxynonenal-stimulated activity of the uncoupling protein in Acanthamoeba castellanii mitochondria under phosphorylating conditions
Authors: Woyda-Ploszczyca Andrzej , Jarmuszkiewicz Wieslawa
Published: February 2013

The influence of 4-hydroxy-2-nonenal (HNE), a lipid peroxidation end product, on the activity of the amoeba Acanthamoeba castellanii uncoupling protein (AcUCP) in isolated phosphorylating mitochondria was studied. Under phosphorylating conditions, exogenously added HNE induced GTP-sensitive AcUCP-mediated mitochondrial uncoupling. The HNE-induced proton leak decreased the yield of oxidative phosphorylation in an HNE concentration-dependent manner. The present study describes how the contributions of ATP synthase and HNE-induced AcUCP in phosphorylating respiration vary when the rate of succinate oxidation is decreased by limiting succinate uptake or inhibiting complex III activity within the range of a constant membrane potential. In phosphorylating mitochondria, at a given HNE concentration (100 μm), the efficiency of AcUCP in mitochondrial uncoupling increased as the respiratory rate decreased because the AcUCP contribution remained constant while the ATP synthase contribution decreased with the respiratory rate. HNE-induced uncoupling can be inhibited by GTP only when ubiquinone is sufficiently oxidized, indicating that in phosphorylating A. castellanii mitochondria, the sensitivity of AcUCP activity to GTP depends on the redox state of the membranous ubiquinone.
Hydroxylase-dependent regulation of the NF-κB pathway
Authors: Scholz Carsten C. , Taylor Cormac T.
Published: February 2013

Hypoxia is associated with a diverse range of physiological and pathophysiological processes, including development, wound healing, inflammation, vascular disease and cancer. The requirement that eukaryotic cells have for molecular oxygen as the terminal electron acceptor for the electron transport chain means that the maintenance of oxygen delivery is key for bioenergetic homeostasis. Metazoans have evolved an effective way to adapt to hypoxic stress at the molecular level through a transcription factor termed the hypoxia inducible factor. A family of oxygen-sensing hydroxylases utilizes molecular oxygen as a co-substrate for the hydroxylation of hypoxia inducible factor α subunits, thereby reducing its expression and transcriptional activity when oxygen is available. Recent studies have indicated that other hypoxia-responsive transcriptional pathways may also be hydroxylase-dependent. In this review, we will discuss the role of hydroxylases in the regulation of NF-κB, a key regulator of immunity and inflammation. Developing our understanding of the role of hydroxylases in hypoxic inflammation may identify novel therapeutic approaches in chronic inflammatory disease.
The human Ah receptor: hints from dioxin toxicities to deregulated target genes and physiological functions
Authors: Bock Karl Walter
Published: February 2013

Marked species differences of dioxin toxicity prompted the review of three well-studied human dioxin toxicities (chloracne, inflammation and cancer) and deregulated Ah receptor (AhR) target genes to obtain hints as to the physiological functions of this receptor. Dioxin here stands for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Microarray analysis of dermal cysts from a dioxin-poisoned patient revealed, in addition to induced CYP1A1, increased expression of gremlin, an antagonist of bone morphogenetic proteins. Dioxin-mediated skin and intestinal inflammation is associated with deregulated T cell differentiation. In the supernatant of CD4+ T cells obtained from the dioxin-poisoned patient, increased interleukin-22 was detected, a cytokine that may be controlled in part by AhR-regulated Notch. Cancer is one of the long-term consequences of chronic inflammation. In line with dioxin-sensitive lymphoid tissue, enhanced death of lymphoid cancer was observed in the dioxin-exposed Seveso population 25 years after poisoning. Accumulating evidence suggests that endogenous AhR ligands, notably the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole, in contrast to TCDD, is rapidly metabolized by AhR-induced CYP1A1. The feedback loop between 6-formylindolo[3,2-b]carbazole, AhR and CYP1A1 guarantees transient activation that, in contrast to sustained activation by TCDD, may be essential for a putative role of the AhR in stem/progenitor cell homeostasis.
Recent advances in the electrochemistry and spectroelectrochemistry of membrane proteins
Authors: Melin Frederic , Hellwig Petra
Published: February 2013

Integral membrane proteins are encountered in fundamental natural processes, such as photosynthesis and respiration. The relation between the structure of the proteins and their function and dynamics are still not clear in most cases. Once fully understood, these processes could ultimately help researchers to develop alternative methods for producing energy, either from light or biomass. They could also lead to more efficient antibiotics, which would selectively inhibit a specific membrane protein of pathogenic bacteria. Since the chemical reactions involved in both photosynthesis and respiration are redox reactions, electrochemical methods can play a considerable role in uncovering their mechanisms. The electrochemical characterization of membrane proteins is, however, quite challenging. An overview on the techniques used for the characterization of membrane proteins, including classical approaches such as voltammetry and spectroelectrochemistry, and recent developments, such as their combination with surface-enhanced techniques is given.
Cannabinoid hyperemesis syndrome: a specific cause of cyclical vomiting
Authors: Morris Reshmi , Fisher Martin
Published: February 2013

Cyclical vomiting syndrome (CVS) is a disorder that occurs mostly in children, adolescents and young adults in which episodes of nausea and vomiting occur up to six to 12 times per year. In the past decade, one specific cause of cyclical vomiting syndrome, referred to as cannabinoid hyperemesis syndrome (CHS), has been described in a subset of patients who report chronic marijuana use. Of interest, almost all of these patients report compulsive bathing in hot water as part of the syndrome. In this report, we present the case of a 20-year-old female with CHS, review the issues generally encountered in CVS and discuss the known details of CHS. This is an important syndrome that needs to be considered as a potential diagnosis when patients present with cyclical vomiting.
Experiences of returning to elite alpine skiing after ACL injury and ACL reconstruction
Authors: Nordahl Birgitta , Sjöström Rita , Westin Maria , Werner Suzanne , Alricsson Marie
Published: February 2013

Aim:To explore the experiences of alpine skiing at the elite level after anterior cruciate ligament (ACL) injury and reconstruction.

Design:A qualitative approach where semi-structured interviews were conducted, and an analysis of the manifest content was performed.

Participants:Five ski high school students, two male and three female skiers, who had suffered ACL injuries and undergone ACL reconstructions.

Results: Seven categories were identified. The participants described their perceived opportunities with regard to returning to alpine skiing after ACL injury and reconstruction as something positive to do with self-belief, being mentally and physically prepared, regaining confidence in their own ability, being given time and using active strategies. In contrast, perceived barriers to a return to elite alpine skiing gave rise to negative feelings, for example, fear, disheartenment, a total lack of or ambivalent confidence in their own ability and the use of passive strategies.

Conclusion:The two male skiers returned to alpine skiing. They reported confidence in their own ability, active strategies and support on all levels, as well as enhanced physical ability. The female skiers did not return to their pre-injury level of competitive alpine skiing. They stated a lack of support on all levels, deterioration in their physical ability and two out of three reported passive strategies and no or ambivalent confidence in their own ability. The most important factors were family support, support on all levels, access to a physiotherapist and time given.
Why is the nanoscale special (or not)? Fundamental properties and how it relates to the design of nano-enabled drug delivery systems
Authors: Otto Daniel P. , de Villiers Melgardt M.
Published: February 2013

Nanoscience studies describe natural phenomena at the submicron scale. Below a critical nanoscale limit, the physical, chemical, and biological properties of materials show a marked departure in their behavior compared to the bulk. At the nanoscale, energy conversion is dominated by phonons, whereas at larger scales, electrons determine the process. The surface-to-volume ratio at the nanoscale is immense, and interfacial interactions are markedly more important than at the macroscopic level, where the majority of the material is shielded from the surface. These properties render the nanoparticles to be significantly different from their larger counterparts. Nano-enabled drug delivery systems have resulted from multidisciplinary cooperation aimed at improving drug delivery. Significant improvements in the thermodynamic and delivery properties are seen due to nanotechnology. Hybrid nanodelivery systems, i.e., membranes with nanopores that can gate stimuli-responsive drug release could be a future development. Nanotechnology will improve current drug delivery and create novel future delivery systems. The fundamental properties and challenges of nanodelivery systems are discussed in this review.
Learning the core ideas of scanning probe microscopy by toy model inquiries
Authors: Lindell Anssi , Kähkönen Anna-Leena
Published: February 2013

Atomic force microscopy has developed from an atomic level imaging technique to a large family of nanoscientific research setups called scanning probe microscopy. Following this trend, we also need to develop our education from instructions to use the instrument for imaging into an approach of deeper understanding of the science behind the technologies. In this article, we describe our new university level scanning probe microscopy laboratory unit to learn the main scientific principles and applications of the instruments. Three inquiries using toy models were designed to cover the core ideas of scanning probe microscopy. Learning outcomes were analyzed and categorized into levels from the research reports of nine students. We found that practically every student learned atomic force imaging basics: scanning and essential properties of the topography image. One-third of the students showed good understanding in image artifacts and probe calibration, but just one of the students reached the level beyond the topography images to scanning force microscopy and combined force and topography techniques in his report. Also, the connection between scanning probe techniques and human senses was considered an important objective in design of this laboratory unit, although with modest success in learning so far.
Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches
Authors: Le Trequesser Quentin , Seznec Hervé , Delville Marie-Hélène
Published: February 2013

The successful development of nanomaterials illustrates the considerable interest in the development of new molecular probes for medical diagnosis and imaging. Substantial progress was made in the synthesis protocol and characterization of these materials, whereas toxicological issues are sometimes incomplete. Nanoparticle-based contrast agents (CAs) tend to become efficient tools for enhancing medical diagnostics and surgery for a wide range of imaging modalities. The multimodal nanoparticles (NPs) are much more efficient than the conventional molecular-scale CAs. They provide new abilities for in vivo detection and enhanced targeting efficiencies through longer circulation times, designed clearance pathways, and multiple binding capacities. Properly protected, they can safely be used for the fabrication of various functional systems with targeting properties, reduced toxicity, and proper removal from the body. This review mainly describes the advances in the development of mono- to multimodal NPs and their in vitro and in vivo relevant biomedical applications ranging from imaging and tracking to cancer treatment. Besides the specific applications for classical imaging (magnetic resonance imaging, positron emission tomography, computed tomography, ultrasound, and photoacoustic imaging), the less common imaging techniques such as terahertz molecular imaging (THMI) or ion beam analysis (IBA) are mentioned. The perspectives on the multimodal theranostic NPs and their potential for clinical advances are also mentioned.
Bioorthogonal chemistries for nanomaterial conjugation and targeting
Authors: Rahim Maha K. , Kota Rajesh , Lee Sumi , Haun Jered B.
Published: February 2013

Bioorthogonal chemistries are covalent reaction pairs that proceed in the presence of biological components with complete specificity. A suite of reactions has been described to date that provides scientists and engineers with diverse operational characteristics for different applications. Nanomaterials in particular have benefitted from these new capabilities, resulting in improved coupling efficiencies and multifunctionality. In this review, we will discuss the application of bioorthogonal chemistries to different nanomaterial systems, highlighting the advantages and limitations for use in bioconjugation. We will also describe how recent improvements in the reaction speed of catalyst-free bioorthogonal chemistries have enabled the successful coupling of nanomaterials directly to live cells. Using a recently developed reaction pair, tetrazine and trans-cyclooctene, the direct covalent coupling to cells has been shown to occur on time-scales that are relevant for biological studies and diagnostic applications and can even amplify nanomaterial binding greater than tenfold relative to traditional immunoconjugates. This powerful technique still maintains exquisite specificity, however, yielding robust results in clinical diagnostic applications using human tissue and blood samples. Future work will likely focus on further advancement of the in situ amplification technique, such as increasing nanomaterial binding, enabling multiplexed detection through the use of orthogonal reaction systems and extension to applications in vivo.
Nanoscience and nanotechnology: where are we heading?
Authors: Jin Rongchao
Published: February 2013

No abstract available.
Mechanical and wear behavior of vinyl ester-carbon/cement by-pass dust particulate filled homogeneous and their functionally graded composites
Authors: Gangil Brijesh , Patnaik Amar , Kumar Anoop
Published: February 2013

The paper presents the processing, mechanical and sliding wear characterization of particulate filled cement by-pass dust and carbon fiber (fixed) reinforced homogeneous and functionally graded vinyl ester composites. Homogeneous and graded composites are fabricated by simple mechanical stirring and vertical centrifugal casting technique, respectively. Among the physical and mechanical properties, void content, hardness and impact strength are found to increase with increase in filler content in case of functionally graded materials (FGMs), whereas tensile strength and flexural strength are found to deteriorate for both FGMs and homogeneous composites as compared to the neat composites. Sliding wear characteristics are studied with the help of pin-on-disc test employing the design of experiments approach based on Taguchi’s orthogonal arrays. The present study reveals that graded composites exhibit good mechanical and wear characteristics compared to homogeneous composites. Scanning electron microscopy confirms the dispersion of carbon fiber in the matrix in graded composites.
Reactor Dosimetry and RPV Life Management
Authors: Belousov S. , Ilieva K. , Mitev M.
Published: February 2013

Reactor dosimetry (RD) is a tool that provides data for neutron fluence accumulated over the reactor pressure vessel (RPV) during the reactor operation. This information, however, is not sufficient for RPV lifetime assessment. The life management of RPV is a multidisciplinary task. To assess whether the RPV steel properties at the current stage (for actual accumulated neutron fluence) of reactor operation are still “safe enough,” the dependence of material properties on the fluence must be known; this is a task for material science (MS). Moreover, the mechanical loading over the RPV during normal operation and accidences have to be known, as well, for evaluation, if the RPV material integrity in this loading condition and existing cracks is provided. The crack loading path in terms of stress intensity factor is carried out by structural analyses (SA). Pressure and temperature distribution over RPV used in these analyses are obtained from a thermal hydraulic (TH) calculation. The conjunction of RD and other disciplines in RPV integrity assessment is analyzed in accordance with the FFP (fitness for purpose) approach. It could help to improve the efficiency in multi-disciplinary tasks solutions.
Korean Standard Nuclear Plant Ex-Vessel Neutron Dosimetry Program Ulchin 4
Authors: Duo J. I. , Chen J. , Kulesza J. A. , Fero A. H. , Yoo C. S. , Kim B. C.
Published: February 2013

A comprehensive ex-vessel neutron dosimetry (EVND) surveil-lance program has been deployed in 16 pressurized water reactors (PWR) in South Korea and EVND dosimetry sets have already been installed and analyzed in Westinghouse reactor designs. In this paper, the unique features of the design, training, and installation in the Korean standard nuclear plant (KSNP) Ulchin Unit 4 are presented. Ulchin Unit 4 Cycle 9 represents the first dosimetry analyzed from the EVND design deployed in KSNP plants: Yongg-wang Units 3 through 6 and Ulchin Units 3 through 6. KSNP's cavity configuration precludes a conventional installation from the cavity floor. The solution, requiring the installation crew to access the cavity at an elevation of the active core, places a premium on rapid installation due to high area dose rates. Numerous geometrical features warranted the use of a detailed design in true 3D mechanical design software to control interferences. A full-size training mockup maximized the crew ability to correctly install the instrument in minimum time. The analysis of the first dosimetry set shows good agreements between measurement and calculation within the associated uncertainties. A complete EVND system has been successfully designed, installed, and analyzed for a KNSP plant. Current and future EVND analyses will continue supporting the successful operation of PWR units in South Korea.
Comparison of Attenuation Coefficients for VVER-440 and VVER-1000 Pressure Vessels
Authors: Marek Milan , Rataj Jan , Vandlik Stanislav
Published: February 2013

The paper summarizes the attenuation coefficient of the neutron fluence with E > 0.5 MeV through a reactor pressure vessel for vodo-vodyanoi energetichesky reactor (VVER) reactor types measured and/or calculated for mock-up experiments, as well as for operated nuclear power plant (NPP) units. The attenuation coefficient is possible to evaluate directly only by using the retro-dosimetry, based on a combination of the measured activities from the weld sample and concurrent ex-vessel measurement. The available neutron fluence attenuation coefficients (E > 0.5 MeV), calculated and measured at a mock-up experiment simulating the VVER-440-unit conditions, vary from 3.5 to 6.15. A similar situation is used for the calculations and mock-up experiment measurements for the VVER-1000 RPV, where the attenuation coefficient of the neutron fluence varies from 5.99 to 8.85. Because of the difference in calculations for the real units and the mock-up experiments, the necessity to design and perform calculation benchmarks both for VVER-440 and VVER-1000 would be meaningful if the calculation model is designed adequately to a given unit.