bluuebunny/crossref_metadata_2025 huggingface dataset:
A20 is up‐regulated in primary mouse hepatocytes subjected to hypoxia and reperfusion
Authors: Sun Jiao , Sun Luning , Zhang Ning , Lu Xiaomei , Zhang Haipeng
Published: June 2012

Hepatic ischemia reperfusion–induced injury is a major medical concern, and it is important to characterize the adaptive mechanisms of hepatocytes to hypoxia and reoxygenation to sustain liver function. In this study, we reported a proteomic analysis of ischemia reperfusion–induced global responses in primary hepatocytes. The primary hepatocytes were isolated from mice and exposed to oxygen to mimic ischemia reperfusion. Total proteins were extracted from the cells and analyzed by two‐dimensional gel electrophoresis followed by matrix‐assisted laser desorption time‐of‐flight mass spectrometry. Zinc finger protein A20, mercaptopyruvate sulfur transferase, apolipoprotein E precursor and carbamoyl‐phosphate synthase mitochondrial precursor were identified as differentially expressed in differently exposed groups. Reverse transcriptase polymerase chain reaction and Western blot analysis validated that A20 was significantly up‐regulated in the hepatocytes subjected to hypoxia and reperfusion. In addition, the expression of peroxisome proliferator‐activated receptor α, an A20 target, was up‐regulated in the hepatocytes subjected to hypoxia and reperfusion. Our results on A20 provide new insight into the mechanism underlying the adaptation of hepatocytes to hypoxia and reperfusion. Because of its role in the up‐regulation of peroxisome proliferator‐activated receptor α expression to protect hepatocytes from reperfusion‐induced apoptosis, A20 is a potential target for the prevention and therapy of liver injury after ischemia reperfusion. Copyright © 2012 John Wiley & Sons, Ltd.
Identifying and Characterizing Binding Sites on the Irreversible Inhibition of Human Glutathione S‐Transferase P1‐1 by S‐Thiocarbamoylation
Authors: Quesada‐Soriano Indalecio , Primavera Alessandra , Casas‐Solvas Juan M. , Téllez‐Sanz Ramiro , Barón Carmen , Vargas‐Berenguel Antonio , Lo Bello Mario , García‐Fuentes Luís
Published: June 2012

Human glutathione S‐transferase P1‐1 (hGST P1‐1) is involved in cell detoxification processes through the conjugation of its natural substrate, reduced glutathione (GSH), with xenobiotics. GSTs are known to be overexpressed in tumors, and naturally occurring isothiocyanates, such as benzyl isothiocyanate (BITC), are effective cancer chemopreventive compounds. To identify and characterize the potential inhibitory mechanisms of GST P1‐1 induced by isothiocyanate conjugates, we studied the binding of GST P1‐1 and some cysteine mutants to the BITC–SG conjugate as well as to the synthetic S‐(N‐benzylcarbamoylmethyl)glutathione conjugate (BC–SG). We report here the inactivation of GST P1‐1 through the covalent modification of two Cys47 residues per dimer and one Cys101. The evidence has been compiled by isothermal titration calorimetry (ITC) and electrospray ionization mass spectrometry (ESI‐MS). ITC experiments suggest that the BITC–SG conjugate generates adducts with Cys47 and Cys101 at physiological temperatures through a corresponding kinetic process, in which the BITC moiety is covalently bound to these enzyme cysteines through an S‐thiocarbamoylation reaction. ESI‐MS analysis of the BITC–SG incubated enzymes indicates that although the Cys47 in each subunit is covalently attached to the BITC ligand moiety, only one of the Cys101 residues in the dimer is so attached. A plausible mechanism is given for the emergence of inactivation through the kinetic processes with both cysteines. Likewise, our molecular docking simulations suggest that steric hindrance is the reason why only one Cys101 per dimer is covalently modified by BITC–SG. No covalent inactivation of GST P1‐1 with the BC–SG inhibitor has been observed. The affinities and inhibitory potencies for both conjugates are high and very similar, but slightly lower for BC–SG. Thus, we conclude that the presence of the sulfur atom from the isothiocyanate moiety in BITC–SG is crucial for its irreversible inhibition of GST P1‐1.
Synthesis and Characterization of a Hypoxia‐Sensitive MRI Probe
Authors: Rojas‐Quijano Federico A. , Tircsó Gyula , Tircsóné Benyó Enikő , Baranyai Zsolt , Tran Hoang Huan , Kálmán Ferenc K. , Gulaka Praveen K. , Kodibagkar Vikram D. , Aime Silvio , Kovács Zoltán , Sherry A. Dean
Published: June 2012

Tissue hypoxia occurs in pathologic conditions, such as cancer, ischemic heart disease and stroke when oxygen demand is greater than oxygen supply. An imaging method that can differentiate hypoxic versus normoxic tissue could have an immediate impact on therapy choices. In this work, the gadolinium(III) complex of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) with a 2‐nitroimidazole attached to one carboxyl group via an amide linkage was prepared, characterized and tested as a hypoxia‐sensitive MRI agent. A control complex, Gd(DO3A‐monobutylamide), was also prepared in order to test whether the nitroimidazole side‐chain alters either the water proton T1 relaxivity or the thermodynamic stability of the complex. The stabilities of these complexes were lower than that of Gd(DOTA)− as expected for mono‐amide derivatives. The water proton T1 relaxivity (r1), bound water residence lifetime (τM) and rotational correlation time (τR) of both complexes was determined by relaxivity measurements, variable temperature 17O NMR spectroscopy and proton nuclear magnetic relaxation dispersion (NMRD) studies. The resulting parameters (r1=6.38 mM−1 s−1 at 20 MHz, τM=0.71 μs, τR=141 ps) determined for the nitroimidazole derivative closely parallel to those of other Gd(DO3A‐monoamide) complexes of similar molecular size. In vitro MR imaging experiments with 9L rat glioma cells maintained under nitrogen (hypoxic) versus oxygen (normoxic) gas showed that both agents enter cells but only the nitroimidazole derivative was trapped in cells maintained under N2 as evidenced by an approximately twofold decrease in T1 measured for hypoxic cells versus normoxic cells exposed to this agent. These results suggest that the nitroimidazole derivative might serve as a molecular reporter for discriminating hypoxic versus normoxic tissues by MRI.
Absolute Configuration Determination and Convenient Asymmetric Synthesis ofcis‐3‐(9‐Anthryl)cyclohexanol with Proline as a Catalyst
Authors: Wysocki Jędrzej , Kwit Marcin , Gawronski Jacek
Published: June 2012

cis‐(3R)‐(9‐anthryl) derivative of cyclohexanol was conveniently obtained in enantiomerically pure form from 2‐cyclohexenone using asymmetric Michael addition of anthrone catalyzed byl‐proline in a key step. The absolute configuration of the addition product was unequivocally determined by means of electronic circular dichroism measurements combined with calculation of the circular dichroism spectrum by using a density functional theory method.Chirality 24:833–839, 2012. © 2012 Wiley Periodicals, Inc.
Future Technologies – Times Changing for Inorganic Raw Materials Resources
Authors: Sextl Gerhard , Brämer Thilo , Gellermann Carsten , Reller Armin
Published: June 2012

Ähnlich wie beim Erdöl wird es bei vielen Metallen zukünftig eine Peak‐Problematik geben, denn mittlerweile sind selbst die ergiebigen Förderstätten vieler anorganischer Rohstoffe erschöpft. Auch bei den Primärrohstoffen ist der Metallgehalt der Erze inzwischen so gering, dass deren Ausbeute immer ressourcen‐ und energieaufwendiger wird. Anhand von Anwendungsbeispielen wird gezeigt, dass viele Rohstoffe, auch wenn sie nur einen geringen Anteil im Produkt ausmachen, trotzdem großen Einfluss auf unser tägliches Leben haben. Eine Wiederaufbereitung und Rückführung dieser wertvollen Ressourcen in die Wertstoffkreisläufe steht deshalb ganz oben auf der gesellschaftlichen Agenda der nächsten Jahrzehnte. Anhand ausgewählter Beispiele werden der Stand und die Entwicklung der gegenwärtigen Aufbereitungsprozesse beschrieben.
C‐X‐C chemokine receptor 7
Authors: Yates Travis J. , Knapp Judith , Gosalbez Miguel , Lokeshwar Soum D. , Gomez Christopher S. , Benitez Anaid , Ekwenna Obi O. , Young Ezekiel E. , Manoharan Murugesan , Lokeshwar Vinata B.
Published: June 2012

BACKGROUND:

C‐X‐C chemokine receptor 4 (CXCR4) and CXCR7 are 7‐transmembrane chemokine receptors of the stroma‐derived factor (SDF‐1). CXCR4, but not CXCR7, has been examined in bladder cancer (BCa). This study examined the functional and clinical significance of CXCR7 in BCa.

METHODS:

CXCR4 and CXCR7 levels were measured in BCa cell lines, tissues (normal = 25; BCa = 44), and urine specimens (n = 186) by quantitative polymerase chain reaction and/or immunohistochemistry. CXCR7 function in BCa cells were examined by transient transfections using a CXCR7 expression vector or small interfering RNA.

RESULTS:

In BCa cell lines, CXCR7 messenger RNA levels were 5‐ to 37‐fold higher than those for CXCR4. Transient overexpression of CXCR7 in BCa cell lines promoted growth and chemotactic motility. CXCR7 colocalized and formed a functional complex with epidermal growth factor receptor, phosphoinositide 3‐kinase/Akt, Erk, and src and induced their phosphorylation. CXCR7 also induced up‐regulation of cyclin‐D1 and bcl‐2. Suppression of CXCR7 expression reversed these effects and induced apoptosis. CXCR7 messenger RNA levels and CXCR7 staining scores were significantly (5‐ to 10‐fold) higher in BCa tissues than in normal tissues (P < .001). CXCR7 expression independently associated with metastasis (P = .019) and disease‐specific mortality (P = .03). CXCR7 was highly expressed in endothelial cells in high‐grade BCa tissues when compared to low‐grade BCa and normal bladder. CXCR7 levels were elevated in exfoliated urothelial cells from high‐grade BCa patients (P = .0001; 90% sensitivity; 75% specificity); CXCR4 levels were unaltered.

CONCLUSIONS:

CXCR7 promotes BCa cell proliferation and motility plausibly through epidermal growth factor receptor receptor and Akt signaling. CXCR7 expression is elevated in BCa tissues and exfoliated cells and is associated with high‐grade and metastasis. Cancer 2013. © 2012 American Cancer Society.
Number of primary melanomas is an independent predictor of survival in patients with metastatic melanoma
Authors: Murali Rajmohan , Brown Philip T. , Kefford Richard F. , Scolyer Richard A. , Thompson John F. , Atkins Michael B. , Long Georgina V.
Published: June 2012

BACKGROUND:

A history of multiple primary melanomas (PMs) has been associated with improved survival in patients with early stage melanoma, but whether it also is correlated with survival in patients with metastatic melanoma is unknown. The authors sought to address the latter question in the current study.

METHODS:

Patients with metastatic melanoma diagnosed at the Melanoma Institute Australia between 1983 and 2008 were identified. Overall survival (OS) was calculated from date of first distant metastasis. Survival analysis was performed using the Kaplan‐Meier method, log‐rank tests, and multivariate Cox proportional hazards models.

RESULTS:

Of 2942 patients with metastatic melanoma, 2634 (89.5%) had 1 PM and 308 (10.5%) had >1 PM. Factors that were associated independently with shorter OS were site of metastasis, including the brain (hazard ratio [HR], 2.41; 95% confidence interval [CI], 2.07‐2.81; P < .001) and nonlung viscera (HR, 1.92; 95% CI, 1.67‐2.22; P < .001, vs lymph node/subcutaneous/soft tissue), age >60 years (HR, 1.23; 95% CI, 1.12‐1.36; P < .001), shorter disease‐free interval from PM to first distant metastasis (≤12 months vs >36 months: HR, 1.62; 95% CI, 1.39‐1.89; P < .001), and fewer PMs (1 vs >1; HR, 1.26; 95% CI, 1.08‐1.47; P = .004).

CONCLUSIONS:

A history of multiple PM was an independent predictor of improved survival for patients with metastatic melanoma. The results indicate that a history of multiple PMs should be incorporated into multivariate analyses of prognostic factors and treatment outcomes. Cancer 2012. © 2012 American Cancer Society.
Enrichment of CD133‐expressing cells in rectal cancers treated with preoperative radiochemotherapy is an independent marker for metastasis and survival
Authors: Sprenger Thilo , Conradi Lena‐Christin , Beissbarth Tim , Ermert Heiko , Homayounfar Kia , Middel Peter , Rüschoff Josef , Wolff Hendrik A. , Schüler Philipp , Ghadimi B. Michael , Rödel Claus , Becker Heinz , Rödel Franz , Liersch Torsten
Published: June 2012

BACKGROUND:

The transmembrane glycoprotein CD133 (cluster of differentiation 133; also known as Prominin or PROM1) has been described as a potential stem cell marker in colorectal cancer and is associated with higher tumorigenic potential and resistance to radiochemotherapy (RCT). In this study, CD133 expression was evaluated in pre‐RCT tumor biopsies and the corresponding post‐RCT surgical specimens from patients with locally advanced rectal adenocarcinoma, and expression levels were correlated with histopathologic features and clinical follow‐up.

METHODS:

One hundred twenty‐six patients with International Union Against Cancer (UICC) stage II/III rectal cancer who received preoperative 5‐fluorouracil (5‐FU)‐based RCT within the German Rectal Cancer Trials were investigated. Pre‐RCT and post‐RCT CD133 expression levels were determined using immunohistochemistry and were correlated with histopathologic parameters, tumor regression grade, cancer recurrence, and patient survival.

RESULTS:

Compared with pre‐RCT biopsies, significantly higher CD133 expression was observed in tumor specimens (P = .01). However, no correlations were observed for either biopsies or tumor specimens between CD133 expression levels, histopathologic characteristics, or survival. In matched analyses of corresponding biopsy/tumor pairs, patients who had an increased fraction of CD133‐expressing (CD133+) cells after preoperative RCT had significantly higher residual tumor stages (P = .02) and lower histopathologic tumor regression (P < .01). Moreover, these patients had significantly reduced disease‐free survival and cancer‐specific overall survival in univariate analysis (P < .001 and P = .004, respectively) and multivariate analysis (P = .003 and P = .024, respectively).

CONCLUSIONS:

The enrichment of CD133+ cancer cells during preoperative RCT was correlated with minor local tumor response, increased distant cancer recurrence, and decreased survival. The current results indicate that the up‐regulation of intratumoral CD133 expression, in contrast to absolute pre‐RCT and post‐RCT CD133 levels, plays an important role in tumor progression and metastasis in patients with rectal cancer who are receiving neoadjuvant RCT. Cancer 2013. © 2012 American Cancer Society.
Calbindin expression in developing striatum of zebra finches and its relation to the formation of area X
Authors: Garcia‐Calero Elena , Scharff Constance
Published: June 2012

A sexually dimorphic network of brain regions controls learning and production of song in zebra finches. How this specialized song system evolved is unknown. To start addressing this question, we focused on developmental differences between the sexes, using the expression of the calcium‐binding protein calbindin (CB) during embryonic to adult stages to map out the early development of Area X, a male‐specific striatal structure. We related this pattern to the expression of three transcription factors, Pax6 and Islet1 to delineate the striatal radial domains, and Nkx2.1 as a marker for cells of pallidal origin. An incipient Area X‐CB+ domain became discernable at embryonic day 13 in the Islet1‐ventral striatal field. This region contained many Nkx2.1‐expressing cells with a morphology characteristic of migrating cells. Eight days after hatching (PHD) CB staining clearly delineated Area X. Another CB+ structure formed around PHD5 at the subpallial/pallial boundary. We call it the CB+striatal capsule (CB‐StC) and discuss its relation with the previously described striatal capsule in vertebrates. The CB cell population in both Area X and CB‐StC, but not in the surrounding striatum, colocalized with the striatal medium spiny neurons (MSNs) marker, D1‐receptor associated signaling protein dopamine‐and‐cAMP‐regulated phosphoprotein of 32 kDa, DARPP32. In females, CB‐positive cells were also present in the rostral striatum but did not coalesce into an Area X‐like structure. We discuss possible reasons for CB expression in MSNs in songbirds and mammals, but not described in chicken striatum. J. Comp. Neurol. 521:326–341, 2013. © 2012 Wiley Periodicals, Inc.
Distribution of glycinergic neurons in the brain of glycine transporter‐2 transgenic Tg(glyt2:Gfp) adult zebrafish: Relationship to brain–spinal descending systems
Authors: Barreiro‐Iglesias Antón , Mysiak Karolina Sandra , Adrio Fátima , Rodicio María Celina , Becker Catherina G. , Becker Thomas , Anadón Ramón
Published: June 2012

We used a Tg(glyt2:gfp) transgenic zebrafish expressing the green fluorescent protein (GFP) under control of the glycine transporter 2 (GLYT2) regulatory sequences to study for the first time the glycinergic neurons in the brain of an adult teleost. We also performed in situ hybridization using a GLYT2 probe and glycine immunohistochemistry. This study was combined with biocytin tract tracing from the spinal cord to reveal descending glycinergic pathways. A few groups of GFP+/GLYT2− cells were observed in the midbrain and forebrain, including numerous pinealocytes. Conversely, a small nucleus of the midbrain tegmentum was GLYT2+ but GFP−. Most of the GFP+ and GLYT2+ neurons were observed in the rhombencephalon and spinal cord, and a portion of these cells showed double GLYT2/GFP labeling. In the hindbrain, GFP/GLYT2+ populations were observed in the medial octavolateral nucleus; the secondary, magnocellular, and descending octaval nuclei; the viscerosensory lobes; and reticular populations distributed from trigeminal to vagal levels. No glycinergic cells were observed in the cerebellum. Tract tracing revealed three conspicuous pairs of GFP/GLYT2+ reticular neurons projecting to the spinal cord. In the spinal cord, GFP/GLYT2+ cells were observed in the dorsal and ventral horns. GFP+ fibers were observed from the olfactory bulbs to the spinal cord, although their density varied among regions. The Mauthner neurons received very rich GFP+ innervation, mainly around the axon cap. Comparison of the zebrafish glycinergic system with the glycinergic systems of other adult vertebrates reveals shared patterns but also divergent traits in the evolution of this system. J. Comp. Neurol. 521:389–425, 2013. © 2012 Wiley Periodicals, Inc.
Efficient Fractionation of Spruce by SO2‐Ethanol‐Water Treatment: Closed Mass Balances for Carbohydrates and Sulfur
Authors: Iakovlev Mikhail , van Heiningen Adriaan
Published: June 2012

SO2‐ethanol‐water (SEW) lignocellulosic fractionation has the potential to overcome the present techno‐economic barriers that hinder the commercial implementation of renewable transportation fuel production. In this study, SEW fractionation of spruce wood chips is examined for its ability to separate the main wood components, hemicelluloses, lignin, and cellulose, and the potential to recover SO2 and ethanol from the spent fractionation liquid. Therefore, overall sulfur and carbohydrate mass balances are established. 95–97 % of the charged SO2 remains in the liquid and can be fully recovered by distillation. During fractionation, hemicelluloses and lignin are effectively dissolved, whereas cellulose is preserved in the solid (fibre) phase. Hemicelluloses are hydrolysed, producing up to 50 % monomeric sugars, whereas dehydration and oxidation of carbohydrates are insignificant. The latter is proven by the closed carbohydrate material balances as well as by the near absence of corresponding by‐products (furfural, hydroxymethylfurfural (HMF) and aldonic acids). In addition, acid methanolysis/GC and acid hydrolysis/high performance anion exchange chromatography (HPAEC) methods for the carbohydrate determination are compared.
Catalytic Lignin Valorization Process for the Production of Aromatic Chemicals and Hydrogen
Authors: Zakzeski Joseph , Jongerius Anna L. , Bruijnincx Pieter C. A. , Weckhuysen Bert M.
Published: June 2012

With dwindling reserves of fossil feedstock as a resource for chemicals production, the fraction of chemicals and energy supplied by alternative, renewable resources, such as lignin, can be expected to increase in the foreseeable future. Here, we demonstrate a catalytic process to valorize lignin (exemplified with kraft, organosolv, and sugarcane bagasse lignin) using a mixture of cheap, bio‐renewable ethanol and water as solvent. Ethanol/water mixtures readily solubilize lignin under moderate temperatures and pressures with little residual solids. The molecular weight of the dissolved lignins was shown to be reduced by gel permeation chromatography and quantitative HSQC NMR methods. The use of liquid‐phase reforming of the solubilized lignin over a Pt/Al2O3 catalyst at 498 K and 58 bar is introduced to yield up to 17 % combined yield of monomeric aromatic oxygenates such as guaiacol and substituted guaiacols generating hydrogen as a useful by‐product. Reduction of the lignin dissolved in ethanol/water using a supported transition metal catalyst at 473 K and 30 bar hydrogen yields up to 6 % of cyclic hydrocarbons and aromatics.
Nonlinear Simulations of Peeling‐Ballooning Modes with Parallel Velocity Perturbation
Authors: Xia T. Y. , Xu X. Q. , Dudson B. D. , Li J.
Published: June 2012

The fast‐reconnection simulation of ELMs in high‐confinement mode tokamak discharges with non‐ideal physics effects has been reported by Xu, et al [1] with a minimum set of three‐field two‐fluid equations. Here we improve the simulation by adding the perturbed parallel velocity and Hall effect, then extend the model to a set of four‐field two‐fluid equations to describe the pedestal collapse with the BOUT++ simulation code. Compared to the previous results, we find that the perturbed parallel velocity can decrease the growth rate by 20.0%, and the ELM size is decreased by 12.1%. The Hall effect influences the linear growth rate effectively. Without perturbed parallel velocity, the Hall effect will increase the growth rate by 9.8%. It is increased by 19.1% if the parallel velocity is considered. These results are consistent with the qualitative theoretical analysis. In order to smooth the perturbed zigzags of the profiles of variables, we add the hyper‐diffusion terms in the equations. We use the hyper‐diffusion of pressure which does not affect the linear growth rate and the ELM structure obviously, but they can smooth the profiles effectively on grid scales. Last the effects of other differencing methods are discussed and we find that lower order method yeilds lower fluctuation level and smaller ELM size (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Simulation Study of L/H Transition with Self‐Consistent Integrated Modelling of Core and SOL/Divertor Transport
Authors: Yagi M. , Shimizu K. , Takizuka T. , Honda M. , Hayashi N. , Hoshino K. , Fukuyama A.
Published: June 2012

We have developed a self‐consistent integrated simulation model of core and scrape‐off‐layer (SOL)/divertor transport. This model enables the user to investigate operational scenarios with compatible high‐confinement core plasmas and detached divertor plasmas. A 1.5D core code TOPICS‐IB and a 2D divertor code SONIC are successfully coupled using a Multiple Program Multiple Data parallel computing system. This integrated code, which can include Monte‐Carlo models for neutrals and impurities, provides efficient plasma/neutral simulations. The dynamic simulation for the L/H transition in JT‐60SA is carried out by this integrated code using a current‐diffusive ballooning mode (CDBM) transport model that includes the E×B shearing effect. The impact of SOL/divertor transport on the L/H transition is studied (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Statistical Analysis of the Spatial Behavior of Plasma Blobs Around the Plasma Column in a Linear Plasma Device
Authors: Tanaka H. , Ohno N. , Tsuji Y. , Okazaki K. , Kajita S.
Published: June 2012

A new statistical analysis technique is applied to the spatial behavior of coherent plasma structures around the plasma column in the linear plasma device NAGDIS‐II. The two‐dimensional behavior of visible light emission is measured using a fast‐imaging camera, and the movie data shows that spiral shaped structures appear intermittently and rotate around the plasma column. The ejection position of the structures in the azimuthal direction is detected and then analyzed. To extract detailed statistics in the spatial domain, the effect of the global rotation is removed. By reconstructing the trajectory of a structure over a 360° range and using rescaled range (R/S) analysis, it is found that the trajectory is similar to a Brownian motion superimposed upon the global rotation. This result indicates that the process of generation of these structures is influenced by previous ejection events (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Impurity Seeding with Dust Injection in Tokamak Edge Plasmas
Authors: Smirnov R.D. , Krasheninnikov S.I. , Pigarov A.Yu. , Rognlien T.D. , Mansfield D.K. , Skinner C.H. , Roquemore A.L.
Published: June 2012

Impurity seeding of tokamak edge plasmas in the form of dust is modeled using the recently coupled DUSTT/UEDGE code. The effects on edge plasma performance due to lithium and carbon dust continuously injected at different poloidal locations in NSTX and ITER are modeled. Modeling demonstrates that dust injection into the edge plasma with rates of the order of several 10 mg · s–1 for NSTX and 1 g · s–1 for ITER can significantly increase radiation power losses leading to substantial reduction of the divertor heat load. The impact of different rates of dust injection on plasma operation and stability is discussed. The simulated edge plasma performance with injected dust is compared with the case of injection of an equivalent amount of dust material in the form of atomic vapor. It is shown that injection of dust in ITER can lead to better assimilation of impurities in the divertor plasma as compared to neutral gas injection (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On Recent Massively Parallelized PIC Simulations of the SOL
Authors: Tskhakaya D.
Published: June 2012

Recent results of massively parallel kinetic (PIC/MC) simulations of the tokamak scrape‐off layer are discussed. It is demonstrated that a number of well studied properties of the low‐recycling divertor plasma, such as the sound speed and the average energy of plasma particles impinging on the divertors, cannot be generalized to the high recycling case. A new analytical model for plasma boundary condition has been derived (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A maximum likelihood approach to generate hypotheses on the evolution and historical biogeography in the Lower Volga Valley regions (southwest Russia)
Authors: Mavrodiev Evgeny V. , Laktionov Alexy P. , Cellinese Nico
Published: June 2012

The evolution of the diverse flora in the Lower Volga Valley (LVV) (southwest Russia) is complex due to the composite geomorphology and tectonic history of the Caspian Sea and adjacent areas. In the absence of phylogenetic studies and temporal information, we implemented a maximum likelihood (ML) approach and stochastic character mapping reconstruction aiming at recovering historical signals from species occurrence data. A taxon‐area matrix of 13 floristic areas and 1018 extant species was constructed and analyzed with RAxML and Mesquite. Additionally, we simulated scenarios with numbers of hypothetical extinct taxa from an unknown palaeoflora that occupied the areas before the dramatic transgression and regression events that have occurred from the Pleistocene to the present day. The flora occurring strictly along the river valley and delta appear to be younger than that of adjacent steppes and desert‐like regions, regardless of the chronology of transgression and regression events that led to the geomorphological formation of the LVV. This result is also supported when hypothetical extinct taxa are included in the analyses. The history of each species was inferred by using a stochastic character mapping reconstruction method as implemented in Mesquite. Individual histories appear to be independent from one another and have been shaped by repeated dispersal and extinction events. These reconstructions provide testable hypotheses for more in‐depth investigations of their population structure and dynamics.
Cytotoxic T lymphocyte effector function is independent of nucleus–centrosome dissociation
Authors: Lui‐Roberts Winnie W. Y. , Stinchcombe Jane C. , Ritter Alex T. , Akhmanova Anna , Karakesisoglou Iakowos , Griffiths Gillian M.
Published: June 2012

Cytotoxic T lymphocytes (CTLs) kill tumorigenic and virally infected cells by targeted secretion of lytic granule contents. The precise point at which secretion occurs is directed by the centrosome docking at the immunological synapse (IS). The centrosome is highly dynamic in CTLs, lagging behind the nucleus in the uropod of migrating CTLs, but translocating across the entire length of the cell to dock at the IS when a target cell is recognized. While in most cell types, the centrosome is always closely associated with the nuclear membrane, in CTLs, it often appears to be dissociated from the nucleus, both in migrating cells and when forming an IS. We asked whether this dissociation is required for CTL killing, by expressing GFP‐BICD2‐NT‐nesprin‐3, which tethers the centrosome to the nucleus irreversibly. Immunofluorescence microscopy revealed that the centrosome polarized successfully to the central supramolecular activation complex (cSMAC) of the synapse in GFP‐BICD2‐NT‐nesprin‐3‐expressing CTLs, with the centrosome and nucleus migrating together to the IS. CTLs in which the centrosome was “glued” to the nucleus were able to dock and release granules at the IS as effectively as mock‐treated cells. These data demonstrate that CTL cytotoxicity is independent of centrosomal dissociation from the nuclear envelope.
Platinum(0) Complexes with Alkynylphosphane Ligands
Authors: Berenguer Jesús R. , Lalinde Elena , Moreno M. Teresa , Montaño Patricia
Published: June 2012

The reactivity of the Pt0 derivative [Pt2(dba)3] (dba = trans,trans‐dibenzylideneacetone) towards PPh2C≡CR [R = Ph, tolyl (Tol), C5H4N‐2] and PPh2C≡CPPh2 (dppa) has been explored. Treatment of [Pt2(dba)3] with PPh2C≡CR (8 equiv.) in THF gave the tetrahedral complexes [Pt(PPh2C≡CR)4] [R = Ph (1), Tol (3), C5H4N‐2 (5)], whereas reactions with a molar ratio of 1:4 afforded the binuclear derivatives [{Pt(PPh2C≡CR)(μ‐κP:η2‐PPh2C≡CR)}2] [R = Ph (2), Tol (4) X‐ray, C5H4N‐2 (6)], which were shown to be generated through the mononuclear complexes 1, 3 and 5 as intermediate species. An analogous reaction using 4 equiv. of PPh2C≡CPPh2 afforded [Pt2(PPh2C≡CPPh2)2(μ‐κ2PP′‐PPh2C≡CPPh2)3] (7), in which two “Pt(PPh2C≡CPPh2)” fragments are joined through three bridging dppa ligands (μ‐κ2PP′‐PPh2C≡CPPh2). Attempts to crystallize 7 at –30 °C afforded crystals of [Pt2{PPh2C≡CP(O)Ph2}2(μ‐κ2PP′‐PPh2C≡CPPh2)3] (8) by oxidation of the free end of the terminal dppa ligands. The compound was characterized by X‐ray diffraction.
Minimum required signal‐to‐noise ratio for optimal precision in HPLC and CE
Authors: Meyer Christoph , Seiler Patricia , Bies Celine , Cianciulli Claudia , Wätzig Hermann , Meyer Veronika R.
Published: June 2012

In a survey, results of more than 100 assay determinations of various analytes (active pharmaceutical ingredients, methylparabene, chlorthalidone, and proteins) at different concentration levels were collected with signal‐to‐noise ratio (S/N) levels between 2 and higher than 10 000. It must be concluded that without having a S/N of at least 50, repeatabilities (combination of injection, separation process, and integration) of 2% cannot be achieved, in contrast to the general assumption that a S/N of 10 is sufficient for analytical HPLC. These data now confirm an earlier assumption with a much broader fundamental of measurements. The empirical functions %RSD = 58/(S/N) + 0.30 (for HPLC data) and %RSD = 73/(S/N) + 1.07 (for CE data) could be derived. It was shown that a S/N of greater than 100 is necessary for optimal precision. Before optimizing HPLC or CE methods, for example, for sample pretreatment, S/N > 100 should be the prerequisite, else optimal precision will not be achieved. Only after the detection‐related scatter is sufficiently reduced, other sources of variation can be successfully tackled.
Instrumentation design for hydrodynamic sample injection in microchip electrophoresis: A review
Authors: Saito Renata M. , Coltro Wendell K. T. , de Jesus Dosil P.
Published: June 2012

Reproducible and representative sample injection in microchip electrophoresis has been a bottleneck for quantitative analytical applications. Electrokinetic sample injection is the most used because it is easy to perform. However, this injection method is usually affected by sample composition and the bias effect. On the other hand, these drawbacks are overcome by the hydrodynamic (HD) sample injection, although this injection mode requires HD flow control. This review gives an overview of the basic principles, the instrumentation designs, and the performance of HD sample injection systems for microchip electrophoresis.
Implementation of a genetically tuned neural platform in optimizing fluorescence from receptor–ligand binding interactions on microchips
Authors: Alvarado Judith , Hanrahan Grady , Nguyen Huong T. H. , Gomez Frank A.
Published: June 2012

This paper describes the use of a genetically tuned neural network platform to optimize the fluorescence realized upon binding 5‐carboxyfluorescein‐D‐Ala‐D‐Ala‐D‐Ala (5‐FAM‐(D‐Ala)3) (1) to the antibiotic teicoplanin from Actinoplanes teichomyceticus electrostatically attached to a microfluidic channel originally modified with 3‐aminopropyltriethoxysilane. Here, three parameters: (i) the length of time teicoplanin was in the microchannel; (ii) the length of time 1 was in the microchannel, thereby, in equilibrium with teicoplanin, and; (iii) the amount of time buffer was flushed through the microchannel to wash out any unbound 1 remaining in the channel, are examined at a constant concentration of 1, with neural network methodology applied to optimize fluorescence. Optimal neural structure provided a best fit model, both for the training set (r2 = 0.985) and testing set (r2 = 0.967) data. Simulated results were experimentally validated demonstrating efficiency of the neural network approach and proved superior to the use of multiple linear regression and neural networks using standard back propagation.
Microfabricated devices for biomolecule encapsulation
Authors: Desmarais Samantha M. , Haagsman Henk P. , Barron Annelise E.
Published: June 2012

Biomolecule encapsulation in droplets is important for miniaturizing biological assays to reduce reagent consumption, cost and time of analysis, and can be most effectively achieved by using microfabricated devices. Microfabricated fluidic devices can generate emulsified drops of uniform size with controlled dimensions and contents. Biological and chemical components such as cells, microgels, beads, hydrogel precursors, polymer initiators, and other droplets can be encapsulated within these drops. Encapsulated emulsions are appealing for a variety of applications since drops can be used as tiny reaction vessels to perform high‐throughput reactions at fast rates, consuming minimal sample and solvent amounts due to the small size (micron diameters) of the emulsion drops. Facile mixing and droplet coalescence allow for a diversity of assays to be performed on‐chip with tunable parameters. The simplicity of operation and speed of analysis with microencapsulated drops lends itself well to an array of quantitative biomolecular studies such as directed evolution, single‐molecule DNA amplification, single‐cell encapsulation, high‐throughput sequencing, enzyme kinetics, and microfluidic cell culture. This review highlights recent advances in the field of microfabricated encapsulating devices, emphasizing the development of emulsifying encapsulations, device design, and current assays that are performed using encapsulating droplets.
Microfluidic‐assisted synthesis of hemispherical and discoidal chitosan microparticles at an oil/water interface
Authors: Yang Chih‐Hui , Huang Keng‐Shiang , Wang Chih‐Yu , Hsu Yi‐Yao , Chang Fang‐Rong , Lin Yung‐Sheng
Published: June 2012

This study reports a facile method for the synthesis of hemispherical and discoidal chitosan microparticles by a combination of microfluidic technology and gelation strategy at an oil/water interface. Utilizing microfluidic emulsification in a cross‐junction channel, the formation of regular droplets was achieved. Following the ionic gelation procedure at the liquid–liquid interface of the gelling solution and oil solution in the reservoir pool, either hemispherical or discoidal chitosan microparticles were obtained. Special emphasis was put on the interface reaction of emulsion gelation parameters such as ionic crosslinkers, density modifiers, and surfactants, to tailor the morphologies of chitosan particles ranging from 160 to 750 μm. In addition, the proposed microfluidic device is capable of generating relatively uniform microparticles with a well‐controllable shape and size. Being a simple, low‐cost and high‐throughput process is an added advantage. The synthesized hemispherical and discoidal chitosan microparticles can be applied to many applications in the pharmaceutical and biomedical arena.
1,3‐propanediol production from glucose by mixed‐culture fermentation of Zygosacharomyces rouxii and Klebsiella pneumonia
Authors: Ma Zheng , Shentu Xuping , Bian Yalin , Yu Xiaoping
Published: June 2012

1,3‐propanediol is an important chemical widely used in polymer production. In this study, two strains, Zygosacharomyces rouxii JL2011 and Klebsiella pneumoniae S6, were used as a mixed culture for 1,3‐propanediol production directly from glucose. Two important parameters including inoculation time of K. pneumoniae S6 at stage of mixed culture and initial cell ratio of Z. rouxii JL2011 to K. pneumoniae S6 in mixed fermentation were optimized in culture flasks. In those experiments, the best results were obtained with a yield of 6.8 g/L 1,3‐propanediol from glucose when K. pneumoniae S6 was inoculated after 48 h in the culture of Z. rouxii JL2011 by mixed culture of Z. rouxii JL2011 and K. pneumoniae S6 with initial cell ratio of 1:200. In a 7‐L bioreactor, the maximum 1,3‐propanediol production could reach up to 15.2 g/L. Thus, this study presents an effective process for 1,3‐propanediol microbial production from glucose by using mixed culture of Z. rouxii JL2011 and K. pneumoniae S6. This work does not only demonstrate a new way to produce 1,3‐propanediol from a low‐cost feedstock, but may also make a valuable contribution to the development of a cost‐effective fermentation based on renewable resources.
Study on spontaneous ignition of stored food waste to be used for recycling
Authors: Murasawa Naoharu , Koseki Hiroshi , Iwata Yusaku , Gao Lijing
Published: June 2012

Although stored at near room temperature, a large amount of stored industrial food waste or their recycled material gradually heats up and then ignites. To understand this phenomenon, soy sauce squeezing residue produced from the soy sauce brewing process and fish meal residue from processing fish were examined. We used a thermo gravimetric/differential thermal analysis system, a highly sensitive heat flux calorimeter (C80) and a spontaneous ignition tester to study their thermal properties. We applied Frank–Kamenetskii's thermal ignition theory to obtain the critical ignition temperature (Tc) and the relationship between Tc and the pile height. Copyright © 2012 John Wiley & Sons, Ltd.
Genistein induces growth arrest and suppresses telomerase activity in brain tumor cells
Authors: Khaw Aik Kia , Yong Jacklyn Wei Yan , Kalthur Guruprasad , Hande M. Prakash
Published: June 2012

Genistein, a soy isoflavone, has been reported to exhibit multiple effects, such as inducing cell cycle arrest, triggering apoptosis, inhibiting the activation of NFKB and inactivating several signaling cascades in human cancer cells. In vivo studies demonstrating antiangiogenesis and antimetastatic effects of genistein have also been reported. Here, we demonstrate that genistein inhibits the growth of glioblastoma multiforme and medulloblastoma cells with different TP53 mutations and radio‐responses by arresting the cells at G2/M phase of the cell cycle. The cell cycle arrest was found to be independent of DNA damage and such an arrest was sustainable for at least 10 days even after drug removal. Annexin V staining revealed absence of apoptotic or necrotic cell populations after genistein treatment. This supports the observation that genistein induces insignificant DNA damage and indicates that the cell cycle arrest triggered does not lead to cell death. Gene and protein expression studies reveal similar changes in the same pathways following treatment in the cell types tested. Genistein was also able to inhibit telomerase activity resulting in telomere shortening. Thus, we demonstrate, for the first time, that genistein induces growth arrest in association with telomerase inhibition in brain tumor cells via the suppression of TR‐ and TERT mRNA. By elucidating the mechanisms of anticancer effects after genistein treatment in brain tumor cells, there will be a premise for the incorporation of genistein dietary sources to complement radiotherapy in brain tumor patients. © 2012 Wiley Periodicals, Inc.
Oligodendroglia are limited in type I interferon induction and responsiveness in vivo
Authors: Kapil Parul , Butchi Niranjan B. , Stohlman Stephen A. , Bergmann Cornelia C.
Published: June 2012

Type I interferons (IFNα/β) provide a primary defense against infection. Nevertheless, the dynamics of IFNα/β induction and responsiveness by central nervous system (CNS) resident cells in vivo in response to viral infections are poorly understood. Mice were infected with a neurotropic coronavirus with tropism for oligodendroglia and microglia to probe innate antiviral responses during acute encephalomyelitis. Expression of genes associated with the IFNα/β pathways was monitored in microglia and oligodendroglia purified from naïve and infected mice by fluorescent activated cell sorting. Compared with microglia, oligodendroglia were characterized by low basal expression of mRNA encoding viral RNA sensing pattern recognition receptors (PRRs), IFNα/β receptor chains, interferon sensitive genes (ISG), as well as kinases and transcription factors critical in IFNα/β signaling. Although PRRs and ISGs were upregulated by infection in both cell types, the repertoire and absolute mRNA levels were more limited in oligodendroglia. Furthermore, although oligodendroglia harbored higher levels of viral RNA compared with microglia, Ifnα/β was only induced in microglia. Stimulation with the double stranded RNA analogue poly I:C also failed to induce Ifnα/β in oligodendroglia, and resulted in reduced and delayed induction of ISGs compared with microglia. The limited antiviral response by oligodendroglia was associated with a high threshold for upregulation of Ikkε and Irf7 transcripts, both central to amplifying IFNα/β responses. Overall, these data reveal that oligodendroglia from the adult CNS are poor sensors of viral infection and suggest they require exogenous IFNα/β to establish an antiviral state. © 2012 Wiley Periodicals, Inc.
The balance of forward and backward hippocampal sequences shifts across behavioral states
Authors: Wikenheiser Andrew M. , Redish A. David
Published: June 2012

Place cell firing patterns in the rat hippocampus are often organized as sequences. Sequences falling within cycles of the theta (6–10 Hz) local field potential (LFP) oscillation represent segments of ongoing behavioral trajectories. Sequences expressed during sharp wave ripple (SWR) complexes represent spatial trajectories through the environment, in both the same direction as actual trajectories (forward sequences) and in an ordering opposite that of behavior (backward sequences). Although hippocampal sequences could fulfill unique functional roles depending on the direction of the sequence and the animal's state when the sequence occurs, quantitative comparisons of sequence direction across behavioral and physiological states within the same experiment, employing consistent methodology, are lacking. Here, we used cross‐correlation and Bayesian decoding to measure the direction of hippocampal sequences in rats during active behavior, awake rest and slow‐wave sleep. During pretask sleep, few sequences were detected in either direction. Sequences within theta cycles during active behavior were overwhelmingly forward. Sequences during quiescent moments of behavior were both forward and backward, in equal proportion. During postbehavior sleep, sequences were again expressed in both directions, but significantly more forward than backward sequences were detected. The shift in the balance of sequence direction could reflect changing functional demands on the hippocampal network across behavioral and physiological states. © 2012 Wiley Periodicals, Inc.
A polymer coating applied to Salmonella prevents the binding of Salmonella‐specific antibodies
Authors: Lee Che‐Hsin , Lin Yu‐Hsin , Hsieh Jeng‐Long , Chen Man‐Chin , Kuo Wan‐Lin
Published: June 2012

The use of Salmonella as a potential antitumor agent has been investigated, but innate immunity against this bacterium reduces the efficacy of its tumor‐targeting and antitumor activities. The purpose of this study was to investigate the modulation of the tumor‐targeting efficiency of Salmonella enterica serovar choleraesuis by modifying the immune response to these bacteria by coating them with poly(allylamine hydrochloride) (PAH), designated PAH‐S.C. To evaluate this modulation, we used naïve mice and mice immunized with Salmonella to study the role of the preexisting immune response to the antitumor activity of PAH‐S.C. When anti‐Salmonella antibodies were present, the invasion activity, cytotoxicity, and gene transfer of Salmonella was significantly decreased, both in vitro and in vivo. Treatment with PAH‐S.C. resulted in delayed tumor growth and enhanced survival in immunized mice. Furthermore, immunohistochemical studies of the tumors revealed the infiltration of neutrophils and macrophages in immunized mice treated with PAH‐S.C. These results indicate that Salmonella encapsulation effectively circumvented the Salmonella‐specific immune response.