bluuebunny/crossref_metadata_2025 huggingface dataset:
Anandamide inhibits transport-related oxygen consumption in the loop of Henle by activating CB1 receptors
Authors: Silva Guillermo B. , Atchison Douglas K. , Juncos Luis I. , García Néstor H.
Published: December 2012

The energy required for active Na chloride reabsorption in the thick ascending limb (TAL) depends on oxygen consumption and oxidative phosphorylation (OXP). In other cells, Na transport is inhibited by the endogenous cannabinoid anandamide through the activation of the cannabinoid receptors (CB) type 1 and 2. However, it is unclear whether anandamide alters TAL transport and the mechanisms that could be involved. We hypothesized that anandamide inhibits TAL transport via activation of CB1 receptors and NO. For this, we measured oxygen consumption (QO2) in TAL suspensions to monitor the anandamide effects on transport and OXP. Anandamide reduced QO2 in a concentration-dependent manner. During Na-K-2Cl cotransport and Na/H exchange inhibition, anandamide did not inhibit TAL QO2. To test the role of the cannabinoid receptors, we used specific agonists and antagonists of CB1 and CB2 receptors. The CB1-selective agonist WIN55212–2 reduced QO2 in a concentration-dependent manner. Also, the CB1 receptor antagonist rimonabant blocked the effect of anandamide on QO2. In contrast, the CB2-selective agonist JHW-133 had no effect on QO2, while the CB2 receptor antagonist AM-630 failed to block the anandamide effects on QO2. To confirm these results, we measured CB1 and CB2 receptor expression and only CB1 expression was detected. Because CB1 receptors are strong nitric oxide synthase (NOS) stimulators and NO inhibits transport in TALs, we evaluated the role of NO. Anandamide stimulated NO production and the NOS inhibitor NG-nitro-l-arginine methyl ester blocked the anandamide effects on QO2. We conclude that anandamide inhibits TAL Na transport-related QO2 via activation of CB1 receptor and NOS.
Juxtaglomerular cell CaSR stimulation decreases renin release via activation of the PLC/IP3pathway and the ryanodine receptor
Authors: Ortiz-Capisano M. Cecilia , Reddy Mahendranath , Mendez Mariela , Garvin Jeffrey L. , Beierwaltes William H.
Published: December 2012

The calcium-sensing receptor (CaSR) is a G-coupled protein expressed in renal juxtaglomerular (JG) cells. Its activation stimulates calcium-mediated decreases in cAMP content and inhibits renin release. The postreceptor pathway for the CaSR in JG cells is unknown. In parathyroids, CaSR acts through Gqand/or Gi. Activation of Gqstimulates phospholipase C (PLC), and inositol 1,4,5-trisphosphate (IP3), releasing calcium from intracellular stores. Gistimulation inhibits cAMP formation. In afferent arterioles, the ryanodine receptor (RyR) enhances release of stored calcium. We hypothesized JG cell CaSR activation inhibits renin via the PLC/IP3and also RyR activation, increasing intracellular calcium, suppressing cAMP formation, and inhibiting renin release. Renin release from primary cultures of isolated mouse JG cells ( n = 10) was measured. The CaSR agonist cinacalcet decreased renin release 56 ± 7% of control ( P < 0.001), while the PLC inhibitor U73122 reversed cinacalcet inhibition of renin (104 ± 11% of control). The IP3inhibitor 2-APB also reversed inhibition of renin from 56 ± 6 to 104 ± 11% of control ( P < 0.001). JG cells were positively labeled for RyR, and blocking RyR reversed CaSR-mediated inhibition of renin from 61 ± 8 to 118 ± 22% of control ( P < 0.01). Combining inhibition of IP3and RyR was not additive. Giinhibition with pertussis toxin plus cinacalcet did not reverse renin inhibition (65 ± 12 to 41 ± 8% of control, P < 0.001). We conclude stimulating JG cell CaSR activates Gq, initiating the PLC/IP3pathway, activating RyR, increasing intracellular calcium, and resulting in calcium-mediated renin inhibition.
On the feasibility of concurrent human TMS-EEG-fMRI measurements
Authors: Peters Judith C. , Reithler Joel , Schuhmann Teresa , de Graaf Tom , Uludağ Kâmil , Goebel Rainer , Sack Alexander T.
Published: December 2012

Simultaneously combining the complementary assets of EEG, functional MRI (fMRI), and transcranial magnetic stimulation (TMS) within one experimental session provides synergetic results, offering insights into brain function that go beyond the scope of each method when used in isolation. The steady increase of concurrent EEG-fMRI, TMS-EEG, and TMS-fMRI studies further underlines the added value of such multimodal imaging approaches. Whereas concurrent EEG-fMRI enables monitoring of brain-wide network dynamics with high temporal and spatial resolution, the combination with TMS provides insights in causal interactions within these networks. Thus the simultaneous use of all three methods would allow studying fast, spatially accurate, and distributed causal interactions in the perturbed system and its functional relevance for intact behavior. Concurrent EEG-fMRI, TMS-EEG, and TMS-fMRI experiments are already technically challenging, and the three-way combination of TMS-EEG-fMRI might yield additional difficulties in terms of hardware strain or signal quality. The present study explored the feasibility of concurrent TMS-EEG-fMRI studies by performing safety and quality assurance tests based on phantom and human data combining existing commercially available hardware. Results revealed that combined TMS-EEG-fMRI measurements were technically feasible, safe in terms of induced temperature changes, allowed functional MRI acquisition with comparable image quality as during concurrent EEG-fMRI or TMS-fMRI, and provided artifact-free EEG before and from 300 ms after TMS pulse application. Based on these empirical findings, we discuss the conceptual benefits of this novel complementary approach to investigate the working human brain and list a number of precautions and caveats to be heeded when setting up such multimodal imaging facilities with current hardware.
Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD
Authors: He Qionger , Titley Heather , Grasselli Giorgio , Piochon Claire , Hansel Christian
Published: December 2012

Ethanol profoundly influences cerebellar circuit function and motor control. It has recently been demonstrated that functional N-methyl-d-aspartate (NMDA) receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in the adult cerebellum. Using whole cell patch-clamp recordings from mouse cerebellar slices, we examined whether ethanol can affect NMDA receptor signaling in mature Purkinje cells. NMDA receptor-mediated currents were isolated by bath application of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzol[f]quinoxaline (NBQX). The remaining d-2-amino-5-phosphonovaleric acid (d-APV)-sensitive current was reduced by ethanol at concentrations as low as 10 mM. At a concentration of 50 mM ethanol, the blockade of d-APV-sensitive CF-excitatory postsynaptic currents was significantly stronger. Ethanol also altered the waveform of CF-evoked complex spikes by reducing the afterdepolarization. This effect was not seen when NMDA receptors were blocked by d-APV before ethanol wash-in. In contrast to CF synaptic transmission, parallel fiber (PF) synaptic inputs were not affected by ethanol. Finally, ethanol (10 mM) impaired long-term depression (LTD) at PF to Purkinje cell synapses as induced under control conditions by paired PF and CF activity. However, LTD induced by pairing PF stimulation with depolarizing voltage steps (substituting for CF activation) was not blocked by ethanol. These observations suggest that the sensitivity of cerebellar circuit function and plasticity to low concentrations of ethanol may be caused by an ethanol-mediated impairment of NMDA receptor signaling at CF synapses onto cerebellar Purkinje cells.
Age-dependent actions of dopamine on inhibitory synaptic transmission in superficial layers of mouse prefrontal cortex
Authors: Paul Kush , Cox Charles L.
Published: December 2012

Numerous developmental changes in the nervous system occur during the first several weeks of the rodent lifespan. Therefore, many characteristics of neuronal function described at the cellular level from in vitro slice experiments conducted during this early time period may not generalize to adult ages. We investigated the effect of dopamine (DA) on inhibitory synaptic transmission in superficial layers of the medial prefrontal cortex (PFC) in prepubertal [postnatal age (P; days) 12–20], periadolescent (P30–48), and adult (P70–100) mice. The PFC is associated with higher-level cognitive functions, such as working memory, and is associated with initiation, planning, and execution of actions, as well as motivation and cognition. It is innervated by DA-releasing fibers that arise from the ventral tegmental area. In slices from prepubertal mice, DA produced a biphasic modulation of inhibitory postsynaptic currents (IPSCs) recorded in layer II/ III pyramidal neurons. Activation of D2-like receptors leads to an early suppression of the evoked IPSC, which was followed by a longer-lasting facilitation of the IPSC mediated by D1-like DA receptors. In periadolescent mice, the D2 receptor-mediated early suppression was significantly smaller compared with the prepubertal animals and absent in adult animals. Furthermore, we found significant differences in the DA-mediated lasting enhancement of the inhibitory response among the developmental groups. Our findings suggest that behavioral paradigms that elicit dopaminergic release in the PFC differentially modulate inhibition of excitatory pyramidal neuron output in prepuberty compared with periadolescence and adulthood in the superficial layers (II/III) of the cortex.
Reduction of spinal sensory transmission by facilitation of 5-HT1B/D receptors in noninjured and spinal cord-injured humans
Authors: D'Amico Jessica M. , Li Yaqing , Bennett David J. , Gorassini Monica A.
Published: December 2012

Activation of receptors by serotonin (5-HT1) and norepinephrine (α2) on primary afferent terminals and excitatory interneurons reduces transmission in spinal sensory pathways. Loss or reduction of descending sources of serotonin and norepinephrine after spinal cord injury (SCI) and the subsequent reduction of 5-HT1/α2 receptor activity contributes, in part, to the emergence of excessive motoneuron activation from sensory afferent pathways and the uncontrolled triggering of persistent inward currents that depolarize motoneurons during muscle spasms. We tested in a double-blind, placebo-controlled study whether facilitating 5-HT1B/D receptors with the agonist zolmitriptan reduces the sensory activation of motoneurons during an H-reflex in both noninjured control and spinal cord-injured participants. In both groups zolmitriptan, but not placebo, reduced the size of the maximum soleus H-reflex with a peak decrease to 59% (noninjured) and 62% (SCI) of predrug values. In SCI participants we also examined the effects of zolmitriptan on the cutaneomuscular reflex evoked in tibialis anterior from stimulation to the medial arch of the foot. Zolmitriptan, but not placebo, reduced the long-latency, polysynaptic component of the cutaneomuscular reflex (first 200 ms of reflex) by ∼50%. This ultimately reduced the triggering of the long-lasting component of the reflex (500 ms poststimulation to end of reflex) known to be mediated by persistent inward currents in the motoneuron. These results demonstrate that facilitation of 5-HT1B/D receptors reduces sensory transmission in both monosynaptic and polysynaptic reflex pathways to ultimately reduce long-lasting reflexes (spasms) after SCI.
Monitoring spike train synchrony
Authors: Kreuz Thomas , Chicharro Daniel , Houghton Conor , Andrzejak Ralph G. , Mormann Florian
Published: December 2012

Recently, the SPIKE-distance has been proposed as a parameter-free and timescale-independent measure of spike train synchrony. This measure is time resolved since it relies on instantaneous estimates of spike train dissimilarity. However, its original definition led to spuriously high instantaneous values for eventlike firing patterns. Here we present a substantial improvement of this measure that eliminates this shortcoming. The reliability gained allows us to track changes in instantaneous clustering, i.e., time-localized patterns of (dis)similarity among multiple spike trains. Additional new features include selective and triggered temporal averaging as well as the instantaneous comparison of spike train groups. In a second step, a causal SPIKE-distance is defined such that the instantaneous values of dissimilarity rely on past information only so that time-resolved spike train synchrony can be estimated in real time. We demonstrate that these methods are capable of extracting valuable information from field data by monitoring the synchrony between neuronal spike trains during an epileptic seizure. Finally, the applicability of both the regular and the real-time SPIKE-distance to continuous data is illustrated on model electroencephalographic (EEG) recordings.
BCI Could Make Old Two-Player Games Even More Fun: A Proof of Concept with “Connect Four”
Authors: Maby Emmanuel , Perrin Margaux , Bertrand Olivier , Sanchez Gaëtan , Mattout Jérémie
Published: December 2012

We present a brain-computer interface (BCI) version of the famous “Connect Four”. Target selection is based on brain event-related responses measured with nine EEG sensors. Two players compete against each other using their brain activity only. Importantly, we turned the general difficulty of producing a reliable BCI command into an advantage, by extending the game play and rules, in a way that adds fun to the game and might well prove to trigger up motivation in future studies. The principle of this new BCI is directly inspired from our own implementation of the classical P300 Speller (Maby et al. 2010, Perrin et al. 2011). We here establish a proof of principle that the same electrophysiological markers can be used to design an efficient two-player game. Experimental evaluation on two competing healthy subjects yielded an average accuracy of 82%, which is in line with our previous results on many participants and demonstrates that the BCI “Connect Four” can effectively be controlled. Interestingly, the duration of the game is not significantly affected by the usual slowness of BCI commands. This suggests that this kind of BCI games could be of interest to healthy players as well as to disabled people who cannot play with classical games.
Metastatic Basal Cell Carcinoma: A Biological Continuum of Basal Cell Carcinoma?
Authors: Mehta Karaninder S. , Mahajan Vikram K. , Chauhan Pushpinder S. , Sharma Anju Lath , Sharma Vikas , Abhinav C. , Khatri Gayatri , Prabha Neel , Sharma Saurabh , Negi Muninder
Published: December 2012

Basal cell carcinoma (BCC) accounts for 80% of all nonmelanoma skin cancers. Its metastasis is extremely rare, ranging between 0.0028 and 0.55 of all BCC cases. The usual metastasis to lymph nodes, lungs, bones, or skin is from the primary tumor situated in the head and neck region in nearly 85% cases. A 69-year-old male developed progressively increasing multiple, fleshy, indurated, and at places pigmented noduloulcerative plaques over back, chest, and left axillary area 4 years after wide surgical excision of a pathologically diagnosed basal cell carcinoma. The recurrence was diagnosed as infiltrative BCC and found metastasizing to skin, soft tissue and muscles, and pretracheal and axillary lymph nodes. Three cycles of chemotherapy comprising intravenouscisplatin (50 mg) and 5-florouracil (5-FU, 750 mg) on 2 consecutive days and repeated at every 21 days were effective. As it remains unclear whether metastatic BCC is itself a separate subset of basal cell carcinoma, we feel that early BCC localized at any site perhaps constitutes a biological continuum that may ultimately manifest with metastasis in some individuals and should be evaluated as such. Long-standing BCC is itself potentially at risk of recurrence/dissemination; it is imperative to diagnose and appropriately treat all BCC lesions at the earliest.
Application of Statistical Design for the Production of Cellulase by Trichoderma reesei Using Mango Peel
Authors: Saravanan P. , Muthuvelayudham R. , Viruthagiri T.
Published: December 2012

Optimization of the culture medium for cellulase production using Trichoderma reesei was carried out. The optimization of cellulase production using mango peel as substrate was performed with statistical methodology based on experimental designs. The screening of nine nutrients for their influence on cellulase production is achieved using Plackett-Burman design. Avicel, soybean cake flour, KH2PO4, and CoCl2·6H2O were selected based on their positive influence on cellulase production. The composition of the selected components was optimized using Response Surface Methodology (RSM). The optimum conditions are as follows: Avicel: 25.30 g/L, Soybean cake flour: 23.53 g/L, KH2PO4: 4.90 g/L, and CoCl2·6H2O: 0.95 g/L. These conditions are validated experimentally which revealed an enhanced Cellulase activity of 7.8 IU/mL.
Celiac Artery Stenting to Facilitate Hepatic Yttrium-90 Radioembolization Therapy
Authors: Chamarthy Murthy R. , Hughes Terence W. , Gupta Mohit , Vossen Josephina A. , Velasco Noel B. , Zinn Kenneth M.
Published: December 2012

Radioembolization offers a novel way to treat the nonresectable, liver predominant hepatic malignancies with better tumor response and overall progression-free survival rates. Transarterial catheter-based radioembolization procedure involves the hepatic arterial administration of glass- or resin-based beta emitting Yttirum-90 microspheres. Safe delivery of the tumoricidal radiation dose requires careful angiogram planning and coil embolization to quantify lung shunting and prevent systemic toxicity, respectively. Diagnostic pretreatment angiogram also serves to identify the hepatic arterial variant anatomy and other coexisting pathologies that might require a different or alternative approach. We describe a complex case of celiac artery stenosis with tortuous pancreaticoduodenal arterial arcade precluding access to the right hepatic artery for performing radioembolization. Celiac artery stenting of the stenosis was performed to facilitate subsequent safe and successful Yttrium-90 microsphere radioembolization.
Knee Osteoarthritis Treatment with the KineSpring Knee Implant System: A Report of Two Cases
Authors: Hayes David A. , Miller Larry E. , Block Jon E.
Published: December 2012

Osteoarthritis (OA) is a leading cause of disability in middle-aged and older adults with the prevalence expected to increase by 40% by 2025. This dramatic projected increase in OA reflects, in large part, the alarming obesity epidemic. Indeed, it is now well understood that abnormal loading across the knee joint due to malalignment and/or excessive weight gain is responsible for accelerating OA progression. Consequently, there is a therapeutic need for alternative knee OA treatments that directly address joint overload to fill the gap between ineffective conservative care and invasive joint-modifying surgical procedures. We describe two cases that presented with bilateral knee OA resistant to conservative treatments, each with one knee previously and unsuccessfully treated with high tibial osteotomy to improve alignment and the contralateral knee successfully treated with a joint-preserving, load-absorbing implant (KineSpring Knee Implant System).
University-School Collaborative Networks: A Strategy to Improve the Professional Skills of Future Teachers
Authors: Mérida Serrano Rosario , Olivares García María de los Ángeles , González Alfaya Elena
Published: December 2012

This paper presents an experiment in teaching innovation developed at the University of Cordoba's Faculty of Education (Spain), in the second year of the Infant Education Teacher Training course, within the subject of general didactics. The innovative approach taken focused on setting up a collaborative network between infants' schools and the university. Taking Project Work as the central axis, a learning network has been built with the participation of sixteen Infant Education teachers, three hundred twenty children from this stage, seven university teachers, eighty-five trainee teachers, and two Infant Education advisers from a continuing professional development centre for teachers. The theoretical foundations that support this experiment are described along with their different stages, evaluating the benefits of each of them in facilitating the acquisition of professional competences among university students.
On the Fuzzy Number Space with the Level Convergence Topology
Authors: Font J. J. , Miralles A. , Sanchis M.
Published: December 2012

We characterize compact sets of𝔼1endowed with the level convergence topologyτℓ. We also describe the completion(𝔼1̂,𝒰̂)of𝔼1with respect to its natural uniformity, that is, the pointwise uniformity𝒰, and show other topological properties of𝔼1̂, as separability. We apply these results to give an Arzela-Ascoli theorem for the space of(𝔼1,τℓ)-valued continuous functions on a locally compact topological space equipped with the compact-open topology.
Analysis of the Nonlinear Structural‐Acoustic Resonant Frequencies of a Rectangular Tube with a Flexible End Using Harmonic Balance and Homotopy Perturbation Methods
Authors: Lee Y. Y.
Published: December 2012

The structural acoustic problem considered in this study is the nonlinear resonant frequencies of a rectangular tube with one open end, one flexible end, and four rigid side walls A multiacoustic single structural modal formulation is derived from two coupled partial differential equations which represent the large amplitude structural vibration of the flexible end and acoustic pressure induced within the tube. The results obtained from the harmonic balance and homotopy perturbation approaches verified each other. The effects of vibration amplitude, aspect ratio, the numbers of acoustic modes and harmonic terms, and so forth, on the first two resonant natural frequencies, are examined.
Applications of Hyperbolic Metamaterial Substrates
Authors: Guo Yu , Newman Ward , Cortes Cristian L. , Jacob Zubin
Published: December 2012

We review the properties of hyperbolic metamaterials and show that they are promising candidates as substrates for nanoimaging, nanosensing, fluorescence engineering, and controlling thermal emission. Hyperbolic metamaterials can support unique bulk modes, tunable surface plasmon polaritons, and surface hyperbolic states (Dyakonov plasmons) that can be used for a variety of applications. We compare the effective medium predictions with practical realizations of hyperbolic metamaterials to show their potential for radiative decay engineering, bioimaging, subsurface sensing, metaplasmonics, and super-Planckian thermal emission.
Corrosion Behaviour of AZ and ZA Magnesium Alloys in Alkaline Chloride Media
Authors: Öteyaka Mustafa Ö. , Ghali Edward , Tremblay Réal
Published: December 2012

Corrosion behaviour of AZ and ZA magnesium alloys in untreated, aerated, and deaerated chloride media was investigated. The influence of impurity, alloying element, and oxygen on corrosion potential, rate, and pitting was examined in alkaline media saturated with Mg(OH)2at pH 9 and 25°C. After 8 h immersion, slightly less active corrosion potentials were generally observed in deaerated than oxygen containing solutions. AZ91D and ZA104 alloys recorded much lower corrosion rates in deaerated medium as compared to AZ91E, ZAC 10403 (0.3Ca), and ZACS1040305 (0.3Ca+ 0.5Sr). Generally, ZAC alloy showed the highest corrosion rate, followed by ZACS alloy, and both showed a constant value in the three media with or without oxygen. The effect of oxygen is then dependent on the alloy properties and is not a simple acceleration of the cathodic reaction but could cause also inhibition and/or passivation. Pit depth and distribution were influenced by alloy composition. The pits were found deeper and more localized on AZ and more uniformly dispersed on ZA alloy surfaces.
DoloTest in General Practice Study: Sensitivity and Specificity Screening for Depression
Authors: Kristiansen Kim , Lyngholm-Kjaerby Pernille , Moe Claus
Published: December 2012

Background. Coexistence of pain and depression has significant impact on the patient’s quality of life and treatment outcome. DoloTest is a pain and HRQoL assessment tool developed to provide shared understanding between the clinician and the patient of the condition by a visual profile. Aim. To find the sensitivity and specificity of DoloTest as a screening tool for depression for patients in primary care. Methods. All patients coming to a primary care clinic were asked to fill in a DoloTest and a Major Depression Inventory. Results. 715 (68.5%) of 1044 patients entered the study. 34.4% came due to pain. 16.1% met depression criteria, and 26.8% of patients coming due to pain met criteria for depression. 65.6% of the men and 54.2% of the women meeting the criteria for depression came due to pain. Depressed patients had statistically significant higher scores on all DoloTest domains. Selecting the cutoff value for the domain “low spirits” to be “65” (0–100) for depression gave a sensitivity of 78% (70–85%) and a specificity of 95% (93–96%) for meeting depression criteria. Conclusion. DoloTest can with a high sensitivity and specificity identify persons meeting criteria for depression and is an easy-to-use screening tool to identify patients with the coexistence of pain and depression.
Synthesis of a Novel Family of Polysilsesquioxanes Having Oligothiophenes with Well-Defined Structures
Authors: Imae Ichiro , Takayama Shotaro , Tokita Daisuke , Ooyama Yousuke , Komaguchi Kenji , Ohshita Joji , Harima Yutaka
Published: December 2012

Our recent results on the synthesis and properties of a novel family of polysilsesquioxanes having oligothiophenes were reviewed. The polymers anchored on SiO2or ITO substrates showed excellent mechanical hardness due to the formation of a three-dimensional siloxane network structure and chemical linkage between polymer and the surface of metal-oxide substrates. Optical, electrochemical, and electrical properties of polymers were also investigated.
The Clinical Significance of the Dense Fine Speckled Immunofluorescence Pattern on HEp-2 Cells for the Diagnosis of Systemic Autoimmune Diseases
Authors: Mahler Michael , Fritzler Marvin J.
Published: December 2012

Antinuclear antibodies (ANAs) are a serological hallmark in the diagnosis of systemic autoimmune rheumatic diseases (SARD). The indirect immunofluorescence (IIF) assay on HEp-2 cells is a commonly used test for the detection of ANA and has been recently recommended as the screening test of choice by a task force of the American College of Rheumatology. However, up to 20% of apparently healthy individuals (HI) have been reported to have a positive IIF ANA test, primarily related to autoantibodies that target the dense fine speckles 70 (DFS70) antigen. Even more important, the DFS IIF pattern has been reported in up to 33% of ANA positive HI, but not in ANA positive SARD sera. Since the intended use of the ANA HEp-2 test is to aid in the diagnosis and classification of SARD, the detection and reporting of anti-DFS70 antibodies and their associated pattern (DFS) as a positive test significantly reduce the specificity and the positive likelihood of the ANA test. This has significant implications for medical management and diagnostic algorithms involving the detection of ANA. Recently, a novel immunoadsorption method has been developed that specifically blocks anti-DFS70 antibodies and, therefore, significantly increases the specificity of the ANA test for SARD. This immunoadsorption method has the potential to overcome a significant limitation of the ANA HEp-2 assay. The present paper summarizes the current knowledge about anti-DFS70 antibodies and their clinical impact on ANA testing.
Parallel Mesh Adaptive Techniques for Complex Flow Simulation: Geometry Conservation
Authors: Casagrande Angelo , Leyland Pénélope , Formaggia Luca
Published: December 2012

Dynamic mesh adaptation on unstructured grids, by localised refinement and derefinement, is a very efficient tool for enhancing solution accuracy and optimising computational time. One of the major drawbacks, however, resides in the projection of the new nodes created, during the refinement process, onto the boundary surfaces. This can be addressed by the introduction of a library capable of handling geometric properties given by a CAD (computer-aided design) description. This is of particular interest also to enhance the adaptation module when the mesh is being smoothed, and hence moved, to then reproject it onto the surface of the exact geometry.
Neutrino Mass from Cosmology
Authors: Lesgourgues Julien , Pastor Sergio
Published: December 2012

Neutrinos can play an important role in the evolution of the universe, modifying some of the cosmological observables. In this contribution we summarize the main aspects of cosmological relic neutrinos, and we describe how the precision of present cosmological data can be used to learn about neutrino properties, in particular their mass, providing complementary information to beta decay and neutrinoless double-beta decay experiments. We show how the analysis of current cosmological observations, such as the anisotropies of the cosmic microwave background or the distribution of large-scale structure, provides an upper bound on the sum of neutrino masses of order 1 eV or less, with very good perspectives from future cosmological measurements which are expected to be sensitive to neutrino masses well into the sub-eV range.
Fuzzy Investment Portfolio Selection Models Based on Interval Analysis Approach
Authors: Guo Haifeng , Sun BaiQing , Karimi Hamid Reza , Ge Yuanjing , Jin Weiquan
Published: December 2012

This paper employs fuzzy set theory to solve the unintuitive problem of the Markowitz mean‐variance (MV) portfolio model and extend it to a fuzzy investment portfolio selection model. Our model establishes intervals for expected returns and risk preference, which can take into account investors′ different investment appetite and thus can find the optimal resolution for each interval. In the empirical part, we test this model in Chinese stocks investment and find that this model can fulfill different kinds of investors’ objectives. Finally, investment risk can be decreased when we add investment limit to each stock in the portfolio, which indicates our model is useful in practice.
Global Synchronization of Neutral‐Type Stochastic Delayed Complex Networks
Authors: Zhang Ya , Song Bo , Park Ju H. , Wu Zheng-Guang
Published: December 2012

This paper is concerned with the delay‐dependent synchronization criterion for neutral‐type stochastic delayed complex networks. Firstly, expectations of stochastic crossterms containing the Itô integral are investigated. In fact, for stochastic delay systems, if we want to obtain the delay‐dependent condition with less conservatism, how to deal with expectations of stochastic cross terms properly is of vital importance, and many existing results did not deal with expectations of these stochastic cross terms correctly. Then, based on this, this paper establishes a novel delay‐dependent synchronization criterion for neutral‐type stochastic delayed complex networks. In the derivation process, the mathematical development avoids bounding stochastic cross terms. Thus, this method shows less conservatism. Finally, a numerical example is provided to demonstrate the effectiveness of the proposed approach.
Matter Instability in Theories with Modified Induced Gravity
Authors: Nozari Kourosh , Kiani Faeze
Published: December 2012

Matter stability is a necessary condition to have a cosmologically viable model. Modified gravity in the spirit off(R)theories suffers from matter instability in some subdomains of the model parameter space. It has been shown recently that the late-time cosmic speedup can be explained through anf(R)-modified induced gravity program. In this paper, we study the issue of matter instability in a braneworld setup with modified induced gravity.
Nontrivial Solution of Fractional Differential System Involving Riemann‐Stieltjes Integral Condition
Authors: Yang Ge-Feng
Published: December 2012

We study the existence and uniqueness of nontrivial solutions for a class of fractional
differential system involving the Riemann‐Stieltjes integral condition, by using the Leray‐Schauder nonlinear alternative and the Banach contraction mapping principle, some sufficient conditions of the existence and uniqueness of a nontrivial solution of a system are obtained.
Traffic Behavior in CA Model of Vehicular Traffic through a Series of Signals
Authors: Tobita Kazuhiro , Nagatani Takashi
Published: December 2012

We study the traffic states and fundamental diagram of vehicular traffic controlled by a series of traffic lights using a deterministic cellular automaton (CA) model. The CA model is not described by a set of rules but is given by a difference equation. The vehicular traffic varies highly with both signal’s characteristics and vehicular density. The dependence of fundamental diagram on the signal’s characteristics is derived. At a low value of cycle time, the fundamental diagram displays the typical trapezoid, while it shows a triangle at a high value of cycle time. The dynamic transitions among distinct traffic states depend greatly on the signal’s characteristics. The dependence of the transition points on the cycle time split and offset time is found.
Antidiabetic Properties of Germinated Brown Rice: A Systematic Review
Authors: Imam Mustapha Umar , Azmi Nur Hanisah , Bhanger Muhammad Iqbal , Ismail Norsharina , Ismail Maznah
Published: December 2012

Diet is an important variable in the course of type 2 diabetes, which has generated interest in dietary options like germinated brown rice (GBR) for effective management of the disease among rice-consuming populations.In vitrodata and animal experiments show that GBR has potentials as a functional diet for managing this disease, and short-term clinical studies indicate encouraging results. Mechanisms for antidiabetic effects of GBR due to bioactive compounds likeγ-aminobutyric acid (GABA),γ-oryzanol, dietary fibre, phenolics, vitamins, acylated sterylβ-glucoside, and minerals include antihyperglycemia, low insulin index, antioxidative effect, antithrombosis, antihypertensive effect, hypocholesterolemia, and neuroprotective effects. The evidence so far suggests that there may be enormous benefits for diabetics in rice-consuming populations if white rice is replaced with GBR. However, long-term clinical studies are still needed to verify these findings on antidiabetic effects of GBR. Thus, we present a review on the antidiabetic properties of GBR from relevant preclinical and clinical studies, in order to provide detailed information on this subject for researchers to review the potential of GBR in combating this disease.
Severe Eosinophilic Syndrome Associated with the Use of Probiotic Supplements: A New Entity?
Authors: Mendoza Fabian A. , Purohit Shivani , Kenyon Lawrence , Jimenez Sergio A.
Published: December 2012

Severe eosinophilic syndromes related to the administration or use of unsuspected immunogenic substances have been described previously. Many of these diseases presented initially as clusters or isolated cases. The spanish toxic oil syndrome, the eosinophilia myalgia syndrome, and nephrogenic systemic fibrosis are examples of such diseases. We describe 2 cases of a severe eosinophilic syndrome characterized by marked peripheral blood eosinophilia (>15,000 cells/ml), mononeuritis multiplex, and necrotizing vasculitis which developed in a close temporal association with the recent onset use of nonprescription probiotics. There was no history of a prior autoimmune disease. Although both cases had prompt response to immunosuppression with rapid resolution of peripheral blood eosinophilia and accompanying constitutional symptoms, they remained with permanent neurological deficits.
Regulation of Hypoxia-Induced Cell Death in Human Tenocytes
Authors: Liang Min , Cornell Hannah R. , Zargar Baboldashti Nasim , Thompson Mark S. , Carr Andrew J. , Hulley Philippa A.
Published: December 2012

Degenerate shoulder tendons display evidence of hypoxia. However tendons are relatively avascular and not considered to have high oxygen requirements and the vulnerability of tendon cells to hypoxia is unclear. Cultured human tenocytes were exposed to hypoxia and the cellular response detected using QPCR, Western blotting, viability, and ELISA assays. We find that tenocytes respond to hypoxiain vitroby activating classical HIF-1α-driven pathways. Total hypoxia caused significant tenocyte apoptosis. Transcription factors typically involved in hypoxic response, HIF-1αand FOXO3A, were upregulated. Hypoxia caused sustained upregulation of several proapoptotic proteins known to mediate hypoxia-induced apoptosis, such as Bnip3 and Nix, but others were unchanged although they were reportedly hypoxia-sensitive in other cell types. Antiapoptotic proteins Bcl2 and Bcl-xL were unchanged by hypoxia. Normal human tenocytes expressed all isoforms of the hypoxia-induced vascular growth factor VEGF except VEGF-D. Hypoxia markedly upregulated VEGF-A mRNA, followed by increased VEGF protein secretion. However treatment with VEGF did not improve tenocyte survival. As a protective strategy for tenocytes at risk of hypoxic death we added prosurvival growth factors insulin or platelet rich plasma (PRP). Both agents strongly protected tenocytes from hypoxia-induced death over 48 h, suggesting possible efficacy in the acute postrupture tendon or integrating graft.
Significance of Visual Evoked Potentials in the Assessment of Visual Field Defects in Primary Open-Angle Glaucoma: A Review
Authors: Kothari Ruchi , Bokariya Pradeep , Singh Smita , Singh Ramji
Published: December 2012

Visual evoked potentials is an important visual electrophysiological tool which has been used for the evaluation of visual field defects in primary open-angle glaucoma and is an appropriate objective measure of optic nerve function. Significant correlations between the magnitude of the VEP parameters and MD of Humphrey static perimetry suggest that the impaired visual cortical responses observed in glaucoma patients can be revealed by both electrophysiological and psychophysical methods. In addition, the severity of global glaucomatous damage evidenced by reduction in MD could depend on the delay in neural conduction from retina to the visual cortex as revealed by the significant correlation between VEP latencies and MD which also supports the validity of the VEP testing in progression of glaucoma.
Targeting Tumor-Infiltrating Macrophages Decreases Tumor-Initiating Cells, Relieves Immunosuppression, and Improves Chemotherapeutic Responses
Authors: Mitchem Jonathan B. , Brennan Donal J. , Knolhoff Brett L. , Belt Brian A. , Zhu Yu , Sanford Dominic E. , Belaygorod Larisa , Carpenter Danielle , Collins Lynne , Piwnica-Worms David , Hewitt Stephen , Udupi Girish Mallya , Gallagher William M. , Wegner Craig , West Brian L. , Wang-Gillam Andrea , Goedegebuure Peter , Linehan David C. , DeNardo David G.
Published: December 2012

Tumor-infiltrating immune cells can promote chemoresistance and metastatic spread in aggressive tumors. Consequently, the type and quality of immune responses present in the neoplastic stroma are highly predictive of patient outcome in several cancer types. In addition to host immune responses, intrinsic tumor cell activities that mimic stem cell properties have been linked to chemoresistance, metastatic dissemination, and the induction of immune suppression. Cancer stem cells are far from a static cell population; rather, their presence seems to be controlled by highly dynamic processes that are dependent on cues from the tumor stroma. However, the impact immune responses have on tumor stem cell differentiation or expansion is not well understood. In this study, we show that targeting tumor-infiltrating macrophages (TAM) and inflammatory monocytes by inhibiting either the myeloid cell receptors colony-stimulating factor-1 receptor (CSF1R) or chemokine (C–C motif) receptor 2 (CCR2) decreases the number of tumor-initiating cells (TIC) in pancreatic tumors. Targeting CCR2 or CSF1R improves chemotherapeutic efficacy, inhibits metastasis, and increases antitumor T-cell responses. Tumor-educated macrophages also directly enhanced the tumor-initiating capacity of pancreatic tumor cells by activating the transcription factor STAT3, thereby facilitating macrophage-mediated suppression of CD8+ T lymphocytes. Together, our findings show how targeting TAMs can effectively overcome therapeutic resistance mediated by TICs. Cancer Res; 73(3); 1128–41. ©2012 AACR.
Tumor Suppressor Function of the Plasma Glutathione Peroxidase Gpx3 in Colitis-Associated Carcinoma
Authors: Barrett Caitlyn W. , Ning Wei , Chen Xi , Smith Jesse Joshua , Washington Mary K. , Hill Kristina E. , Coburn Lori A. , Peek Richard M. , Chaturvedi Rupesh , Wilson Keith T. , Burk Raymond F. , Williams Christopher S.
Published: December 2012

The glutathione peroxidases, a family of selenocysteine-containing redox enzymes, play pivotal roles in balancing the signaling, immunomodulatory, and deleterious effects of reactive oxygen species (ROS). The glutathione peroxidase GPX3 is the only extracellular member of this family, suggesting it may defend cells against ROS in the extracellular environment. Notably, GPX3 hypermethylation and underexpression occur commonly in prostate, gastric, cervical, thyroid, and colon cancers. We took a reverse genetics approach to investigate whether GPX3 would augment inflammatory colonic tumorigenesis, a process characterized by oxidative stress and inflammation, comparing Gpx3−/− mice in an established two-stage model of inflammatory colon carcinogenesis. Gpx3-deficient mice exhibited an increased tumor number, though not size, along with a higher degree of dysplasia. In addition, they exhibited increased inflammation with redistribution toward protumorigenic M2 macrophage subsets, increased proliferation, hyperactive WNT signaling, and increased DNA damage. To determine the impact of acute gene loss in an established colon cancer line, we silenced GPX3 in human Caco2 cells, resulting in increased ROS production, DNA damage and apoptosis in response to oxidative stress, combined with decreased contact-independent growth. Taken together, our results suggested an immunomodulatory role for GPX3 that limits the development of colitis-associated carcinoma. Cancer Res; 73(3); 1245–55. ©2012 AACR.
Polymorphisms in Inflammation Pathway Genes and Endometrial Cancer Risk
Authors: Delahanty Ryan J. , Xiang Yong-Bing , Spurdle Amanda , Beeghly-Fadiel Alicia , Long Jirong , Thompson Deborah , Tomlinson Ian , Yu Herbert , Lambrechts Diether , Dörk Thilo , Goodman Marc T. , Zheng Ying , Salvesen Helga B. , Bao Ping-Ping , Amant Frederic , Beckmann Matthias W. , Coenegrachts Lieve , Coosemans An , Dubrowinskaja Natalia , Dunning Alison , Runnebaum Ingo B. , Easton Douglas , Ekici Arif B. , Fasching Peter A. , Halle Mari K. , Hein Alexander , Howarth Kimberly , Gorman Maggie , Kaydarova Dylyara , Krakstad Camilla , Lose Felicity , Lu Lingeng , Lurie Galina , O'Mara Tracy , Matsuno Rayna K. , Pharoah Paul , Risch Harvey , Corssen Madeleine , Trovik Jone , Turmanov Nurzhan , Wen Wanqing , Lu Wei , Cai Qiuyin , Zheng Wei , Shu Xiao-Ou
Published: December 2012

Background: Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis.

Methods: To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P < 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls.

Results: Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85–0.99); CXCL3, 1.16 (1.05–1.29); IL6, 1.08 (1.00–1.17); MSR1, 0.90 (0.82–0.98); and MMP9, 0.91 (0.87–0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples.

Conclusions: These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer.

Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(2); 216–23. ©2012 AACR.
Tumoral Lymphocytic Infiltration and Expression of the Chemokine CXCL10 in Breast Cancers from the Ontario Familial Breast Cancer Registry
Authors: Mulligan Anna Marie , Raitman Irene , Feeley Linda , Pinnaduwage Dushanthi , Nguyen Linh T. , O'Malley Frances P. , Ohashi Pamela S. , Andrulis Irene L.
Published: December 2012

Purpose: Breast carcinomas, including basal and hereditary cases, often present with a prominent tumoral lymphocytic infiltrate. Chemokines could play a role in attracting these cells and contribute to tumor progression. We explored tumoral expression of CXCL10 and determined the relationship between CXCL10 and lymphocytic infiltrate in a cohort of breast cancers.

Experimental Design: Using tissue microarrays of 364 breast tumors, we evaluated expression of CXCL10 and its receptor, CXCR3, in relation to histopathologic features, biomarkers, and lymphocyte markers. In addition, we overexpressed CXCL10 and CXCR3 in MCF7 breast cancer cells and monitored T-lymphocyte migration and invasion.

Results: Forty-five percent of tumors expressed CXCL10, and a significant association was found with CXCR3 and lymphocytic infiltrate. Further characterization of the lymphocytic infiltrate revealed an association with CXCL10 expression for peritumoral CD4+ and CD8+ lymphocytes. CD8+ intratumoral lymphocytes, FOXP3+ regulatory T cells (Tregs), and T-BET+ TH1 cells were associated with BRCA1 and basal tumors. Conditioned media from MCF7 cells overexpressing both CXCL10 and CXCR3 increased T-lymphocyte migration and invasion.

Conclusions: Our findings suggest that CXCL10 may act in a paracrine manner, affecting the tumor microenvironment, and in an autocrine manner, acting on the tumor cells themselves and may play a role in tumor invasiveness and progression. The CXCL10-CXCR3 axis can serve as a potential target in BRCA1 and basal breast cancers, which present with a prominent lymphocytic infiltrate and a poor prognosis. Clin Cancer Res; 19(2); 336–46. ©2012 AACR.