bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of the human Na+-dependent glucose cotransporter hSGLT2
Authors: Ghezzi Chiara , Wright Ernest M.
Published: June 2012

The human Na+-glucose cotransporter SGLT2 is expressed mainly in the kidney proximal convoluted tubule where it is considered to be responsible for the bulk of glucose reabsorption. Phosphorylation profiling has revealed that SGLT2 exists in a phosphorylated state in the rat renal proximal tubule cortex, so we decided to investigate the regulation of human SGLT2 (hSGLT2) by protein kinases. hSGLT2 was expressed in human embryonic kidney (HEK) 293T cells, and the activity of the protein was measured using radiotracer and whole cell patch-clamp electrophysiology assays before and after activation of protein kinases. 8-Bromo-adenosine cAMP (8-Br-cAMP) was used to activate protein kinase A, and sn-1,2-dioctanoylglycerol (DOG) was used to activate protein kinase C (PKC). 8-Br-cAMP stimulated d-[α- methyl-14C]glucopyranoside ([14C]α-MDG) uptake and Na+-glucose currents by 200% and DOG increased [14C]α-MDG uptake and Na+-glucose currents by 50%. In both cases the increase in SGLT2 activity was marked by an increase in the maximum rate of transport with no change in glucose affinity. These effects were completely negated by mutation of serine 624 to alanine. Insulin induced a 250% increase in Na+-glucose transport by wild-type but not S624A SGLT2. Parallel studies confirmed that the activity of hSGLT1 was regulated by PKA and PKC due to changes in the number of transporters in the cell membrane. hSGLT1 was relatively insensitive to insulin. We conclude that hSGLT1 and hSGLT2 are regulated by different mechanisms and suggest that insulin is an SGLT2 agonist in vivo.
Kv3 channels contribute to the delayed rectifier current in small cultured mouse dorsal root ganglion neurons
Authors: Bocksteins Elke , Van de Vijver Gerda , Van Bogaert Pierre-Paul , Snyders Dirk J.
Published: June 2012

Delayed rectifier voltage-gated K+ (KV) channels are important determinants of neuronal excitability. However, the large number of KV subunits poses a major challenge to establish the molecular composition of the native neuronal K+ currents. A large part (∼60%) of the delayed rectifier current ( IK) in small mouse dorsal root ganglion (DRG) neurons has been shown to be carried by both homotetrameric KV2.1 and heterotetrameric channels of KV2 subunits with silent KV subunits (KVS), while a contribution of KV1 channels has also been demonstrated. Because KV3 subunits also generate delayed rectifier currents, we investigated the contribution of KV3 subunits to IK in small mouse DRG neurons. After stromatoxin (ScTx) pretreatment to block the KV2-containing component, application of 1 mM TEA caused significant additional block, indicating that the ScTx-insensitive part of IK could include KV1, KV3, and/or M-current channels (KCNQ2/3). Combining ScTx and dendrotoxin confirmed a relevant contribution of KV2 and KV2/KVS, and KV1 subunits to IK in small mouse DRG neurons. After application of these toxins, a significant TEA-sensitive current (∼19% of total IK) remained with biophysical properties that corresponded to those of KV3 currents obtained in expression systems. Using RT-PCR, we detected KV3.1–3 mRNA in DRG neurons. Furthermore, Western blot and immunocytochemistry using KV3.1-specific antibodies confirmed the presence of KV3.1 in cultured DRG neurons. These biophysical, pharmacological, and molecular results demonstrate a relevant contribution (∼19%) of KV3-containing channels to IK in small mouse DRG neurons, supporting a substantial role for KV3 subunits in these neurons.
Inflammation alters regional mitochondrial Ca2+ in human airway smooth muscle cells
Authors: Delmotte Philippe , Yang Binxia , Thompson Michael A. , Pabelick Christina M. , Prakash Y. S. , Sieck Gary C.
Published: June 2012

Regulation of cytosolic Ca2+ concentration ([Ca2+]cyt) in airway smooth muscle (ASM) is a key aspect of airway contractility and can be modulated by inflammation. Mitochondria have tremendous potential for buffering [Ca2+]cyt, helping prevent Ca2+ overload, and modulating other intracellular events. Here, compartmentalization of mitochondria to different cellular regions may subserve different roles. In the present study, we examined the role of Ca2+ buffering by mitochondria and mitochondrial Ca2+ transport mechanisms in the regulation of [Ca2+]cyt in enzymatically dissociated human ASM cells upon exposure to the proinflammatory cytokines TNF-α and IL-13. Cells were loaded simultaneously with fluo-3 AM and rhod-2 AM, and [Ca2+]cyt and mitochondrial Ca2+ concentration ([Ca2+]mito) were measured, respectively, using real-time two-color fluorescence microscopy in both the perinuclear and distal, perimembranous regions of cells. Histamine induced a rapid increase in both [Ca2+]cyt and [Ca2+]mito, with a significant delay in the mitochondrial response. Inhibition of the mitochondrial Na+/Ca2+ exchanger (1 μM CGP-37157) increased [Ca2+]mito responses in perinuclear mitochondria but not distal mitochondria. Inhibition of the mitochondrial uniporter (1 μM Ru360) decreased [Ca2+]mito responses in perinuclear and distal mitochondria. CGP-37157 and Ru360 significantly enhanced histamine-induced [Ca2+]cyt. TNF-α and IL-13 both increased [Ca2+]cyt, which was associated with decreased [Ca2+]mito in the case of TNF-α but not IL-13. The effects of TNF-α on both [Ca2+]cyt and [Ca2+]mito were affected by CGP-37157 but not by Ru360. Overall, these data demonstrate that in human ASM cells, mitochondria buffer [Ca2+]cyt after agonist stimulation and its enhancement by inflammation. The differential regulation of [Ca2+]mito in different parts of ASM cells may serve to locally regulate Ca2+ fluxes from intracellular sources versus the plasma membrane as well as respond to differential energy demands at these sites. We propose that such differential mitochondrial regulation, and its disruption, may play a role in airway hyperreactivity in diseases such as asthma, where [Ca2+]cyt is increased.
Denervation-induced mitochondrial dysfunction and autophagy in skeletal muscle of apoptosis-deficient animals
Authors: O′Leary Michael F. N. , Vainshtein Anna , Carter Heather N. , Zhang Yuan , Hood David A.
Published: June 2012

Skeletal muscle undergoes remarkable adaptations in response to chronic decreases in contractile activity, such as a loss of muscle mass, decreases in both mitochondrial content and function, as well as the activation of apoptosis. Although these adaptations are well known, questions remain regarding the signaling pathways that mediated these changes. Autophagy is an organelle turnover pathway that could contribute to these adaptations. The purpose of this study was to determine whether denervation-induced muscle disuse would result in the activation of autophagy gene expression in both wild-type (WT) and Bax/Bak double knockout (DKO) animals, which display an attenuated apoptotic response. Denervation caused a reduction in muscle mass for WT and DKO animals; however, there was a 40% attenuation in muscle atrophy in DKO animals. Mitochondrial state 3 respiration was significantly reduced, and reactive oxygen species production was increased by two- to threefold in both WT and DKO animals. Apoptotic markers, including cytosolic AIF and DNA fragmentation, were elevated in WT, but not in DKO animals following denervation. Autophagy proteins including LC3II, ULK1, ATG7, p62, and Beclin1 were increased similarly following denervation for both WT and DKO. Interestingly, denervation markedly increased the localization of LC3II to subsarcolemmal mitochondria, and this was more pronounced in the DKO animals. Thus denervation-induced muscle disuse activates both apoptotic and autophagic signaling pathways in muscle, and autophagic protein expression does not exhibit a compensatory increase in the presence of attenuated apoptosis. However, the absence of Bax and Bak may represent a potential signal to trigger mitophagy in muscle.
Disruption of muscle renin-angiotensin system in AT1a−/−mice enhances muscle function despite reducing muscle mass but compromises repair after injury
Authors: Murphy Kate T. , Allen Andrew M. , Chee Annabel , Naim Timur , Lynch Gordon S.
Published: June 2012

The role of the renin-angiotensin system (RAS) in vasoregulation is well established, but a localized RAS exists in multiple tissues and exerts diverse functions including autonomic control and thermogenesis. The role of the RAS in the maintenance and function of skeletal muscle is not well understood, especially the role of angiotensin peptides, which appear to contribute to muscle atrophy. We tested the hypothesis that mice lacking the angiotensin type 1A receptor (AT1A−/−) would exhibit enhanced whole body and skeletal muscle function and improved regeneration after severe injury. Despite 18- to 20-wk-old AT1A−/−mice exhibiting reduced muscle mass compared with controls ( P < 0.05), the tibialis anterior (TA) muscles produced a 25% higher maximum specific (normalized) force ( P < 0.05). Average fiber cross-sectional area (CSA) and fiber oxidative capacity was not different between groups, but TA muscles from AT1A−/−mice had a reduced number of muscle fibers as well as a higher proportion of type IIx/b fibers and a lower proportion of type IIa fibers ( P < 0.05). Measures of whole body function (grip strength, rotarod performance, locomotor activity) were all improved in AT1A−/−mice ( P < 0.05). Surprisingly, the recovery of muscle mass and fiber CSA following myotoxic injury was impaired in AT1A−/−mice, in part by impaired myoblast fusion, prolonged collagen infiltration and inflammation, and delayed expression of myogenic regulatory factors. The findings support the therapeutic potential of RAS inhibition for enhancing whole body and skeletal muscle function, but they also reveal the importance of RAS signaling in the maintenance of muscle mass and for normal fiber repair after injury.
Protein kinase C-α activation promotes recovery of mitochondrial function and cell survival following oxidant injury in renal cells
Authors: Nowak Grazyna , Bakajsova Diana
Published: June 2012

We demonstrated that nonselective PKC activation promotes mitochondrial function in renal proximal tubular cells (RPTC) following toxicant injury. However, the specific PKC isozyme mediating this effect is unknown. This study investigated the role of PKC-α in the recovery of mitochondrial functions in oxidant-injured RPTC. Wild-type PKC-α (wtPKC-α) and inactive PKC-α mutants were overexpressed in RPTC to selectively increase or block PKC-α activation. Oxidant ( tert-butyl hydroperoxidel; TBHP) exposure activated PKC-α in RPTC but decreased PKC-α levels in mitochondria following treatment. Uncoupled and state 3 respirations and activities of complexes I and IV in TBHP-injured cells decreased to 55, 44, 49, and 65% of controls, respectively. F0F1-ATPase activity and ATP content in injured RPTC decreased to 59 and 60% of controls, respectively. Oxidant exposure increased reactive oxygen species (ROS) production by 210% and induced mitochondrial fragmentation and 52% RPTC lysis. Overexpressing wtPKC-α did not block TBHP-induced ROS production but improved respiration and complex I activity, restored complex IV and F0F1-ATPase activities, promoted recovery of ATP content, blocked mitochondrial fragmentation, and reduced RPTC lysis to 14%. In contrast, inhibiting PKC-α 1) induced mitochondrial hyperpolarization and fragmentation; 2) blocked increases in ROS production; 3) prevented recovery of respiratory complexes and F0F1-ATPase activities, respiration, and ATP content; and 4) exacerbated TBHP-induced RPTC lysis. We conclude that 1) activation of PKC-α prevents mitochondrial hyperpolarization and fragmentation, decreases cell death, and promotes recovery of mitochondrial respiration and ATP content following oxidant injury in RPTC; and 2) respiratory complexes I and IV and F0F1-ATPase are targets of active PKC-α.
Nebivolol-induced vasodilation of renal afferent arterioles involves β3-adrenergic receptor and nitric oxide synthase activation
Authors: Feng Ming-Guo , Prieto Minolfa C. , Navar L. Gabriel
Published: June 2012

Nebivolol is a β1-adrenergic blocker that also elicits renal vasodilation and increases the glomerular filtration rate (GFR). However, its direct actions on the renal microvasculature and vasodilator mechanism have not been established. We used the in vitro blood-perfused juxtamedullary nephron technique to determine the vasodilator effects of nebivolol and to test the hypothesis that nebivolol induces vasodilation of renal afferent arterioles via an nitric oxide synthase (NOS)/nitric oxide (NO)/soluble guanylate cyclase (sGC)/cGMP pathway and the afferent arteriolar vasodilation effect may be mediated through the release of NO by activation of NOS via a β3-adrenoceptor-dependent mechanism. Juxtamedullary nephrons were superfused with nebivolol either alone or combined with the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or the NOS inhibitor Nω-nitro-l-arginine (l-NNA) or the β-blockers metoprolol (β1), butoxamine (β2), and SR59230A (β3). Nebivolol (100 μmol/l) markedly increased afferent and efferent arteriolar diameters by 18.9 ± 3.0 and 15.8 ± 1.8%. Pretreatment with l-NNA (1,000 μmol/l) or ODQ (10 μmol/l) decreased afferent vasodilator diameters and prevented the vasodilator effects of nebivolol (2.0 ± 0.2 and 2.4 ± 0.6%). Metoprolol did not elicit significant changes in afferent vasodilator diameters and did not prevent the effects of nebivolol to vasodilate afferent arterioles. However, treatment with SR59230A, but not butoxamine, markedly attenuated the vasodilation responses to nebivolol. Using a monoclonal antibody to β3-receptors revealed predominant immunostaining on vascular and glomerular endothelial cells. These data indicate that nebivolol vasodilates both afferent and efferent arterioles and that the afferent vasodilator effect is via a mechanism that is independent of β1-receptors but is predominantly mediated via a NOS/NO/sGC/cGMP-dependent mechanisms initiated by activation of endothelial β3-receptors.
A point process framework for modeling electrical stimulation of the auditory nerve
Authors: Goldwyn Joshua H. , Rubinstein Jay T. , Shea-Brown Eric
Published: June 2012

Model-based studies of responses of auditory nerve fibers to electrical stimulation can provide insight into the functioning of cochlear implants. Ideally, these studies can identify limitations in sound processing strategies and lead to improved methods for providing sound information to cochlear implant users. To accomplish this, models must accurately describe spiking activity while avoiding excessive complexity that would preclude large-scale simulations of populations of auditory nerve fibers and obscure insight into the mechanisms that influence neural encoding of sound information. In this spirit, we develop a point process model of individual auditory nerve fibers that provides a compact and accurate description of neural responses to electric stimulation. Inspired by the framework of generalized linear models, the proposed model consists of a cascade of linear and nonlinear stages. We show how each of these stages can be associated with biophysical mechanisms and related to models of neuronal dynamics. Moreover, we derive a semianalytical procedure that uniquely determines each parameter in the model on the basis of fundamental statistics from recordings of single fiber responses to electric stimulation, including threshold, relative spread, jitter, and chronaxie. The model also accounts for refractory and summation effects that influence the responses of auditory nerve fibers to high pulse rate stimulation. Throughout, we compare model predictions to published physiological data of response to high and low pulse rate stimulation. We find that the model, although constructed to fit data from single and paired pulse experiments, can accurately predict responses to unmodulated and modulated pulse train stimuli. We close by performing an ideal observer analysis of simulated spike trains in response to sinusoidally amplitude modulated stimuli and find that carrier pulse rate does not affect modulation detection thresholds.
Motion-defined contour processing in the early visual cortex
Authors: Gharat Amol , Baker Curtis L.
Published: June 2012

From our daily experience, it is very clear that relative motion cues can contribute to correctly identifying object boundaries and perceiving depth. Motion-defined contours are not only generated by the motion of objects in a scene but also by the movement of an observer's head and body (motion parallax). However, the neural mechanism involved in detecting these contours is still unknown. To explore this mechanism, we extracellularly recorded visual responses of area 18 neurons in anesthetized and paralyzed cats. The goal of this study was to determine if motion-defined contours could be detected by neurons that have been previously shown to detect luminance-, texture-, and contrast-defined contours cue invariantly. Motion-defined contour stimuli were generated by modulating the velocity of high spatial frequency sinusoidal luminance gratings (carrier gratings) by a moving squarewave envelope. The carrier gratings were outside the luminance passband of a neuron, such that presence of the carrier alone within the receptive field did not elicit a response. Most neurons that responded to contrast-defined contours also responded to motion-defined contours. The orientation and direction selectivity of these neurons for motion-defined contours was similar to that of luminance gratings. A given neuron also exhibited similar selectivity for the spatial frequency of the carrier gratings of contrast- and motion-defined contours. These results suggest that different second-order contours are detected in a form-cue invariant manner, through a common neural mechanism in area 18.
Heterostructures for Realizing Magnon-Induced Spin Transfer Torque
Authors: Jayathilaka P. B. , Monti M. C. , Markert J. T. , Miller Casey W.
Published: June 2012

This work reports efforts fabricating heterostructures of different materials relevant for the realization of magnon-induced spin transfer torques. We find the growth of high-quality magnetite on MgO substrates to be straightforward, while using transition metal buffer layers of Fe, Cr, Mo, and Nb can alter the structural and magnetic properties of the magnetite. Additionally, we successfully fabricated and characterized Py/Cr/Fe3O4and Fe3O4/Cr/Fe3O4spin valve structures. For both, we observe a relatively small giant magnetoresistance and confirm an inverse dependence on spacer layer thickness. Thus, we have shown certain materials combinations that may form the heterostructures that are the building blocks necessary to achieve magnon-induced spin transfer torque devices.
CD28 Family and Chronic Rejection: “To Belatacept...and Beyond!”
Authors: Silva Marcos V. , Machado Juliana R. , Rocha Laura P. , Castellano Lúcio R. , Reis Marlene A. , Corrêa Rosana R. M.
Published: June 2012

Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.
6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest
Authors: Lin Ching-Bin , Lin Chun-Che , Tsay Gregory J.
Published: June 2012

6-Gingerol, a natural component of ginger, has been widely reported to possess antiinflammatory and antitumorigenic activities. Despite its potential efficacy against cancer, the anti-tumor mechanisms of 6-gingerol are complicated and remain sketchy. In the present study, we aimed to investigate the anti-tumor effects of 6-gingerol on colon cancer cells. Our results revealed that 6-gingerol treatment significantly reduced the cell viability of human colon cancer cell, LoVo, in a dose-dependent manner. Further flow cytometric analysis showed that 6-gingerol induced significant G2/M phase arrest and had slight influence on sub-G1 phase in LoVo cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs), and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, cyclin B1, and CDK1 were diminished; in contrast, levels of the negative cell cycle regulators p27Kip1and p21Cip1were increased in response to 6-gingerol treatment. In addition, 6-gingerol treatment elevated intracellular reactive oxygen species (ROS) and phosphorylation level of p53. These findings indicate that exposure of 6-gingerol may induce intracellular ROS and upregulate p53, p27Kip1, and p21Cip1levels leading to consequent decrease of CDK1, cyclin A, and cyclin B1 as result of cell cycle arrest in LoVo cells. It would be suggested that 6-gingerol should be beneficial to treatment of colon cancer.
Robust Speed Tracking of Networked PMSM Servo Systems with Uncertain Feedback Delay and Load Torque Disturbance
Authors: Ling Qiang , Li Jing , Deng Haojiang
Published: June 2012

This paper considers a class of networked Permanent Magnet Synchronous Motors (PMSMs), whose feedback loops are closed over a shared data network. Although the installation and maintenance cost of the networked PMSM system can be lowered by replacing the conventional point‐to‐point feedback cables with a network, the network packet dropouts and transmission delay may degrade the system’s performance and even destabilize it. The load torque disturbance is another source to deteriorate the PMSM system’s performance. To investigate the effects of the data network and the torque disturbance on the speed tracking of a PMSM system is one major task of this paper. In particular, we derive a sufficient stability condition for this system in an LMI (linear matrix inequality) form and provides a way to bound the system’s H∞ performance. Moreover, we adopt an iterative LMI method to design the speed controller of the PMSM system, which can robustly guarantee stability and performance against
the network‐induced delays, packet dropouts, and the torque disturbance. Simulations are done to verify the effectiveness of the obtained results.
Properties of the Photometric Components of Lenticular Galaxies
Authors: Aguerri J. Alfonso L.
Published: June 2012

After almost one century since their definition, the origin of lenticular galaxies is still a matter of debate. Several formation processes have been proposed in order to explain the wide variety of their observational properties. These properties could indicate that the class of lenticulars is a family formed by galaxies with different formations and evolutions. Here I review the main observational properties of the photometric components of lenticular galaxies reported in recent decades. I revise the main processes proposed in order to explain their origin and evolution. I also explain the different properties of the lenticular galaxies that have evolved through each of these formation processes. A unique opportunity for understanding the origin of S0 galaxies will shortly be forthcoming. This is due to the morphological classifications of large galaxy samples that have recently been published. These classifications have given us our first ever opportunity to study large samples of lenticulars within a wide range of masses and located in a great variety of environments. These large samples will provide us with a real census of nearby lenticular galaxies and could be crucial in finally helping us to understand the origin and evolution of these galaxies.
Telemonitoring in Chronic Heart Failure: A Systematic Review
Authors: Giamouzis Gregory , Mastrogiannis Dimos , Koutrakis Konstantinos , Karayannis George , Parisis Charalambos , Rountas Chris , Adreanides Elias , Dafoulas George E. , Stafylas Panagiotis C. , Skoularigis John , Giacomelli Sara , Olivari Zoran , Triposkiadis Filippos
Published: June 2012

Heart failure (HF) is a growing epidemic with the annual number of hospitalizations constantly increasing over the last decades for HF as a primary or secondary diagnosis. Despite the emergence of novel therapeutic approached that can prolong life and shorten hospital stay, HF patients will be needing rehospitalization and will often have a poor prognosis. Telemonitoring is a novel diagnostic modality that has been suggested to be beneficial for HF patients. Telemonitoring is viewed as a means of recording physiological data, such as body weight, heart rate, arterial blood pressure, and electrocardiogram recordings, by portable devices and transmitting these data remotely (via a telephone line, a mobile phone or a computer) to a server where they can be stored, reviewed and analyzed by the research team. In this systematic review of all randomized clinical trials evaluating telemonitoring in chronic HF, we aim to assess whether telemonitoring provides any substantial benefit in this patient population.
Water Quality andAnopheles gambiaeLarval Tolerance to Pyrethroids in the Cities of Douala and Yaoundé (Cameroon)
Authors: Tene Fossog Billy , Kopya Edmond , Ndo Cyrille , Menze-Djantio Benjamin , Costantini Carlo , Njiokou Flaubert , Awono-Ambene Parfait , Antonio-Nkondjio Christophe
Published: June 2012

The poor management of the urban environment in sub-Saharan Africa is affectingAnopheles gambiaesusceptibility to insecticides. A study was undertaken to assess the influence of breeding sites physicochemical parameters on malaria vectors population tolerance to insecticides. A total of 18, 262 larvae collected from 104 breeding sites were exposed to diagnostic concentrations of permethrin and deltamethrin. Larvae originating from cultivated sites were more tolerant than larvae from polluted or nonpolluted sites. No significant difference was observed between polluted and nonpolluted sites. Field larvae were 142 to 325 times and 6.08 to 9.57 times more tolerant to deltamethrin and permethrin, respectively, than larvae of theA. gambiaeKisumu strain used as control. A low but significant correlation was detected between physicochemical parameters and larval insecticide tolerance. Cultivated sites were negatively and significantly correlated to larval tolerance to both deltamethrin (r=−0.421;P<0.0001) and permethrin (r=−0.392;P<0.0001). Dissolved oxygen (r=+0.466;P<0.0001) and ammonia (r=−0.205;P=0.04) appeared significantly correlated to larval tolerance to deltamethrin. The data suggest a direct correlation between some characteristics from the breeding sites and larval tolerance to pyrethroids.
Unsupervised Neural Techniques Applied to MR Brain Image Segmentation
Authors: Ortiz A. , Gorriz J. M. , Ramirez J. , Salas-Gonzalez D.
Published: June 2012

The primary goal of brain image segmentation is to partition a given brain image into different regions representing anatomical structures. Magnetic resonance image (MRI) segmentation is especially interesting, since accurate segmentation in white matter, grey matter and cerebrospinal fluid provides a way to identify many brain disorders such as dementia, schizophrenia or Alzheimer’s disease (AD). Then, image segmentation results in a very interesting tool for neuroanatomical analyses. In this paper we show three alternatives to MR brain image segmentation algorithms, with the Self-Organizing Map (SOM) as the core of the algorithms. The procedures devised do not use any a priori knowledge about voxel class assignment, and results in fully-unsupervised methods for MRI segmentation, making it possible to automatically discover different tissue classes. Our algorithm has been tested using the images from the Internet Brain Image Repository (IBSR) outperforming existing methods, providing values for the average overlap metric of 0.7 for the white and grey matter and 0.45 for the cerebrospinal fluid. Furthermore, it also provides good results for high-resolution MR images provided by the Nuclear Medicine Service of the “Virgen de las Nieves” Hospital (Granada, Spain).
The Effect of Polyvinylpyrrolidone on the Optical Properties of the Ni‐Doped ZnS Nanocrystalline Thin Films Synthesized by Chemical Method
Authors: Thi Tran Minh , Tinh Le Van , Van Bui Hong , Ben Pham Van , Trung Vu Quoc
Published: June 2012

We report the optical properties of polyvinyl‐pyrrolidone (PVP) and the influence of PVP concentration on the photoluminescence spectra of the PVP (PL) coated ZnS : Ni nanocrystalline thin films synthesized by the wet chemical method and spin‐coating. PL spectra of samples were clearly showed that the 520 nm luminescence peak position of samples remains unchanged, but their peak intensity changes with PVP concentration. The PVP polymer is emissive with peak maximum at 394 nm with the exciting wavelength of 325 nm. The photoluminescence exciting (PLE) spectrum of PVP recorded at 394 nm emission shows peak maximum at 332 nm. This excitation band is attributed to the electronic transitions in PVP molecular orbitals. The absorption edges of the PVP‐coated ZnS : Ni0.3% samples that were shifted towards shorter wavelength with increasing of PVP concentration can be explained by the absorption of PVP in range of 350 nm to 400 nm. While the PVP coating does not affect the microstructure of ZnS : Ni nanomaterial, the analyzed results of the PL, PLE, and time‐resolved PL spectra and luminescence decay curves of the PVP and PVP‐coated ZnS : Ni samples allow to explain the energy transition process from surface PVP molecules to the Ni2+ centers that occurs via hot ZnS.
Cortical GABAergic Interneurons in Cross-Modal Plasticity following Early Blindness
Authors: Desgent Sébastien , Ptito Maurice
Published: June 2012

Early loss of a given sensory input in mammals causes anatomical and functional modifications in the brain via a process called cross-modal plasticity. In the past four decades, several animal models have illuminated our understanding of the biological substrates involved in cross-modal plasticity. Progressively, studies are now starting to emphasise on cell-specific mechanisms that may be responsible for this intermodal sensory plasticity. Inhibitory interneurons expressing γ-aminobutyric acid (GABA) play an important role in maintaining the appropriate dynamic range of cortical excitation, in critical periods of developmental plasticity, in receptive field refinement, and in treatment of sensory information reaching the cerebral cortex. The diverse interneuron population is very sensitive to sensory experience during development. GABAergic neurons are therefore well suited to act as a gate for mediating cross-modal plasticity. This paper attempts to highlight the links between early sensory deprivation, cortical GABAergic interneuron alterations, and cross-modal plasticity, discuss its implications, and further provide insights for future research in the field.
Mesenchymal Stem Cells for Cardiac Regeneration: Translation to Bedside Reality
Authors: Elnakish Mohammad T. , Hassan Fatemat , Dakhlallah Duaa , Marsh Clay B. , Alhaider Ibrahim A. , Khan Mahmood
Published: June 2012

Cardiovascular disease (CVD) is the leading cause of death worldwide. According to the World Health Organization (WHO), an estimate of 17.3 million people died from CVDs in 2008 and by 2030, the number of deaths is estimated to reach almost 23.6 million. Despite the development of a variety of treatment options, heart failure management has failed to inhibit myocardial scar formation and replace the lost cardiomyocyte mass with new functional contractile cells. This shortage is complicated by the limited ability of the heart for self-regeneration. Accordingly, novel management approaches have been introduced into the field of cardiovascular research, leading to the evolution of gene- and cell-based therapies. Stem cell-based therapy (aka, cardiomyoplasty) is a rapidly growing alternative for regenerating the damaged myocardium and attenuating ischemic heart disease. However, the optimal cell type to achieve this goal has not been established yet, even after a decade of cardiovascular stem cell research. Mesenchymal stem cells (MSCs) in particular have been extensively investigated as a potential therapeutic approach for cardiac regeneration, due to their distinctive characteristics. In this paper, we focus on the therapeutic applications of MSCs and their transition from the experimental benchside to the clinical bedside.
Semi‐Slant Warped Product Submanifolds of a Kenmotsu Manifold
Authors: Al-Solamy Falleh R. , Khan Meraj Ali
Published: June 2012

We study semi‐slant warped product submanifolds of a Kenmotsu manifold. We obtain a characterization for warped product submanifolds in terms of warping function and shape operator and finally proved an inequality for squared norm of second fundamental form.
Numerical Model for Cavitational Flow in Hydraulic Poppet Valves
Authors: Bernad Sandor I. , Susan-Resiga Romeo
Published: June 2012

The paper presents a numerical simulation and analysis of the flow inside a poppet valve. First, the single-phase (liquid) flow is investigated, and an original model is introduced for quantitatively describing the vortex flow. Since an atmospheric outlet pressure produces large negative absolute pressure regions, a two-phase (cavitating) flow analysis is also performed. Both pressure and density distributions inside the cavity are presented, and a comparison with the liquid flow results is performed. It is found that if one defines the cavity radius such that up to this radius the pressure is no larger than the vaporization pressure, then both liquid and cavitating flow models predict the cavity extent. The current effort is based on the application of the recently developed full cavitation model that utilizes the modified Rayleigh-Plesset equations for bubble dynamics.
General Form of Model-Free Control Law and Convergence Analyzing
Authors: Li Xiuying , Wang Guanghui , Han Zhigang
Published: June 2012

The general form of model-free control law is introduced, and its convergence is analyzed. Firstly, the necessity to improve the basic form of model free control law is explained, and the functional combination method as the approach of improvement is presented. Then, a series of sufficient conditions of convergence are given. The analysis denotes that these conditions can be satisfied easily in the engineering practice.
The Components ofFlemingia macrophyllaAttenuate Amyloidβ-Protein Accumulation by Regulating Amyloidβ-Protein Metabolic Pathway
Authors: Lin Yun-Lian , Tsay Huey-Jen , Liao Yung-Feng , Wu Mine-Fong , Wang Chuen-Neu , Shiao Young-Ji
Published: June 2012

Flemingia macrophylla(Leguminosae) is a popular traditional remedy used in Taiwan as anti-inflammatory, promoting blood circulation and antidiabetes agent. Recent study also suggested its neuroprotective activity against Alzheimer's disease. Therefore, the effects ofF. macrophyllaon Aβproduction and degradation were studied. The effect ofF. macrophyllaon Aβmetabolism was detected using the cultured mouse neuroblastoma cells N2a transfected with human Swedish mutant APP (swAPP-N2a cells). The effects on Aβdegradation were evaluated on a cell-free system. An ELISA assay was applied to detect the level of Aβ1-40 and Aβ1-42. Western blots assay was employed to measure the levels of soluble amyloid precursor protein and insulin degrading enzyme (IDE). Three fractions ofF. macrophyllamodified Aβaccumulation by both inhibitingβ-secretase and activating IDE. Three flavonoids modified Aβaccumulation by activating IDE. The activated IDE pool by the flavonoids was distinctly regulated by bacitracin (an IDE inhibitor). Furthermore, flavonoid 94-18-13 also modulates Aβaccumulation by enhancing IDE expression. In conclusion, the components ofF. macrophyllapossess the potential for developing new therapeutic drugs for Alzheimer's disease.
A Chaotic Pulse‐Time Modulation Method for Digital Communication
Authors: Xuan Quyen Nguyen , Van Yem Vu , Manh Hoang Thang
Published: June 2012

We present and investigate a method of chaotic pulse‐time modulation (PTM) named chaotic pulse‐width‐position modulation (CPWPM) which is the combination of pulse‐position‐modulation (PPM) and pulse‐width modulation (PWM) with the inclusion of chaos
technique for digital communications. CPWPM signal is in the pulse train format, in which binary information is modulated onto
chaotically‐varied intervals of position and width of pulses, and therefore two bits are encoded on a single pulse. The operation of the
method is described and the theoretical evaluation of bit‐error rate (BER) performance in the presence of additive white Gaussian noise
(AWGN) is provided. In addition, the chaotic behavior with tent map and its effect on average parameters of the system are investigated.
Theoretical estimation and numerical simulation of a CPWPM system with specific parameters are carried out in order to verify the
performance of the proposed method.
The Effects of TLR Activation on T-Cell Development and Differentiation
Authors: Jin Bo , Sun Tao , Yu Xiao-Hong , Yang Ying-Xiang , Yeo Anthony E. T.
Published: June 2012

Invading pathogens have unique molecular signatures that are recognized by Toll-like receptors (TLRs) resulting in either activation of antigen-presenting cells (APCs) and/or costimulation of T cells inducing both innate and adaptive immunity. TLRs are also involved in T-cell development and can reprogram Treg cells to become helper cells. T cells consist of various subsets, that is, Th1, Th2, Th17, T follicular helper (Tfh), cytotoxic T lymphocytes (CTLs), regulatory T cells (Treg) and these originate from thymic progenitor thymocytes. T-cell receptor (TCR) activation in distinct T-cell subsets with different TLRs results in differing outcomes, for example, activation of TLR4 expressed in T cells promotes suppressive function of regulatory T cells (Treg), while activation of TLR6 expressed in T cells abrogates Treg function. The current state of knowledge of regarding TLR-mediated T-cell development and differentiation is reviewed.
Positive Solutions of an Initial Value Problem for Nonlinear Fractional Differential Equations
Authors: Baleanu D. , Mohammadi H. , Rezapour Sh.
Published: June 2012

We investigate the existence and multiplicity of positive solutions for the nonlinear fractional differential equation initial value problem u(0) = 0, 0 < t < 1, where is the standard Riemann‐Liouville differentiation and f : [0,1] × [0, ∞) → [0, ∞) is continuous. By using some fixed‐point results on cones, some existence and multiplicity results of positive solutions are obtained.
Aqueous Two‐Phase Systems: A New Approach for the Determination of Brilliant Blue FCF in Water and Food Samples
Authors: Shiri Sabah , Khezeli Tahere , Lotfi Shahram , Shiri Sina
Published: June 2012

A novel, simple, and more sensitive spectrophotometric procedure has been developed for the determination of brilliant blue FCF in water and food samples by an aqueous two‐phase system (ATPS). In this method, adequate amount of polyethylene glycol/ sodium carbonate (PEG‐4000/Na2CO3) was added to aqueous solution for formation of a homogeneous solution. To the mixture solution, suitable amount of Na2CO3 was added, the mixture solution was shaken until the salt was dissolved, and then it was separated into two clear phases easily and rapidly. The target analyte in the water sample was extracted into the polyethylene glycol phase. After extraction, measuring the absorbance at 634 nm was done. The effects of different parameters such as polyethylene glycol (type and concentration), pH, salt (type and amount), centrifuge time, and temperature on the ATPS of dye was investigated and optimum conditions were established. Linear calibration curves were obtained in the range of 0.25–750 ng/mL for brilliant blue FCF under optimum conditions. Detection limit based on three times the standard deviation of the blank (3Sb) was 0.12 ng/mL. The relative standard deviation (RSD) for 400 ng/mL was 3.14%. The method was successfully applied to the determination of brilliant blue FCF in spiked samples with satisfactory results. The relative recovery was between 96.0 and 102.2%.
Cure Models as a Useful Statistical Tool for Analyzing Survival
Authors: Othus Megan , Barlogie Bart , LeBlanc Michael L. , Crowley John J.
Published: June 2012

Cure models are a popular topic within statistical literature but are not as widely known in the clinical literature. Many patients with cancer can be long-term survivors of their disease, and cure models can be a useful tool to analyze and describe cancer survival data. The goal of this article is to review what a cure model is, explain when cure models can be used, and use cure models to describe multiple myeloma survival trends. Multiple myeloma is generally considered an incurable disease, and this article shows that by using cure models, rather than the standard Cox proportional hazards model, we can evaluate whether there is evidence that therapies at the University of Arkansas for Medical Sciences induce a proportion of patients to be long-term survivors. Clin Cancer Res; 18(14); 3731–6. ©2012 AACR.
Functional Analysis of the ATM-p53-p21 Pathway in the LRF CLL4 Trial: Blockade at the Level of p21 Is Associated with Short Response Duration
Authors: Lin Ke , Adamson Janet , Johnson Gillian G. , Carter Anthony , Oates Melanie , Wade Rachel , Richards Sue , Gonzalez David , Matutes Estella , Dearden Claire , Oscier David G. , Catovsky Daniel , Pettitt Andrew R.
Published: June 2012

Purpose: This study sought to establish whether functional analysis of the ATM-p53-p21 pathway adds to the information provided by currently available prognostic factors in patients with chronic lymphocytic leukemia (CLL) requiring frontline chemotherapy.

Experimental Design: Cryopreserved blood mononuclear cells from 278 patients entering the LRF CLL4 trial comparing chlorambucil, fludarabine, and fludarabine plus cyclophosphamide were analyzed for ATM-p53-p21 pathway defects using an ex vivo functional assay that uses ionizing radiation to activate ATM and flow cytometry to measure upregulation of p53 and p21 proteins. Clinical endpoints were compared between groups of patients defined by their pathway status.

Results: ATM-p53-p21 pathway defects of four different types (A, B, C, and D) were identified in 194 of 278 (70%) samples. The type A defect (high constitutive p53 expression combined with impaired p21 upregulation) and the type C defect (impaired p21 upregulation despite an intact p53 response) were each associated with short progression-free survival. The type A defect was associated with chemoresistance, whereas the type C defect was associated with early relapse. As expected, the type A defect was strongly associated with TP53 deletion/mutation. In contrast, the type C defect was not associated with any of the other prognostic factors examined, including TP53/ATM deletion, TP53 mutation, and IGHV mutational status. Detection of the type C defect added to the prognostic information provided by TP53/ATM deletion, TP53 mutation, and IGHV status.

Conclusion: Our findings implicate blockade of the ATM-p53-p21 pathway at the level of p21 as a hitherto unrecognized determinant of early disease recurrence following successful cytoreduction. Clin Cancer Res; 18(15); 4191–200. ©2012 AACR.
Progenitor-like Traits Contribute to Patient Survival and Prognosis in Oligodendroglial Tumors
Authors: Ng Felicia Soo-Lee , Toh Tan Boon , Ting Esther Hui-Ling , Koh Geraldene Rong-Hui , Sandanaraj Edwin , Phong Mark , Wong Swee Seong , Leong Siew Hong , Kon Oi Lian , Tucker-Kellogg Greg , Ng Wai Hoe , Ng Ivan , Tang Carol , Ang Beng Ti
Published: June 2012

Purpose: Patient-derived glioma-propagating cells (GPC) contain karyotypic and gene expression profiles that are found in the primary tumor. However, their clinical relevance is unclear. We ask whether GPCs contribute to disease progression and survival outcome in patients with glioma by analyzing gene expression profiles.

Experimental Design: We tapped into public sources of GPC gene expression data and derived a gene signature distinguishing oligodendroglial from glioblastoma multiforme (GBM) GPCs. By adapting a method in glioma biology, the Connectivity Map, we interrogated its strength of association in public clinical databases. We validated the top-ranking signaling pathways Wnt, Notch, and TGFβ, in GPCs and primary tumor specimens.

Results: We observed that patients with better prognosis correlated with oligodendroglial GPC features and lower tumor grade, and this was independent of the current clinical indicator, 1p/19q status. Patients with better prognosis had proneural tumors whereas the poorly surviving cohort had mesenchymal tumors. In addition, oligodendroglial GPCs were more sensitive to Wnt and Notch inhibition whereas GBM GPCs responded to TGFβR1 inhibition.

Conclusions: We provide evidence that GPCs are clinically relevant. In addition, the more favorable prognosis of oligodendroglial tumors over GBM could be recapitulated transcriptomically at the GPC level, underscoring the relevance of this cellular model. Our gene signature detects molecular heterogeneity in oligodendroglial tumors that cannot be accounted for by the 1p/19q status alone, indicating that stem-like traits contribute to clinical status. Collectively, these data highlight the limitation of morphology-based histologic analyses in tumor classification, consequently impacting on treatment decisions. Clin Cancer Res; 18(15); 4122–35. ©2012 AACR.