bluuebunny/crossref_metadata_2025 huggingface dataset:
Tri‐ and Pentacalix[4]pyrroles: Synthesis, Characterization and Their Use in the Extraction of Halide Salts
Authors: Aydogan Abdullah , Akar Ahmet
Published: January 2012

Calixpyrrole‐based oligomeric compounds were synthesized by “click chemistry” from the corresponding alkyne‐ and azide‐functionalized calix[4]pyrroles. Calix[4]pyrrole 3, possessing an alkyne functional group, was prepared through a mixed condensation of pyrrole with acetone and but‐3‐ynyl 4‐oxopentanoate. Another alkyne‐group‐containing calix[4]pyrrole 5 was obtained by treatment of 4′‐hydroxyphenyl‐functionalized calixpyrrole 4 with propargyl bromide. Tetrakis(azidopentyl)‐functionalized calix[4]pyrrole 7 was synthesized by reacting NaN3 with tetrabromopentyltetraethylcalix[4]pyrrole 6, which was prepared through a condensation reaction of pyrrole and 7‐bromohept‐2‐one. Oligomeric calixpyrrole compounds were found to be capable of extracting tetrabutylammonium chloride and fluoride salts from aqueous media. Extraction abilities of the oligomeric compounds were monitored by NMR and UV/Vis spectroscopy and thermogravimetric analysis.
Synthesis of Amphiphilic Azo‐Anion‐Radical Complexes of Chromium(III) and the Development of Ultrathin Redox‐Active Surfaces by the Langmuir–Schaefer Technique
Authors: Joy Sucheta , Pal Prabir , Mondal Tapan Kumar , Talapatra G. B. , Goswami Sreebrata
Published: January 2012

Neutral tris‐chelated chromium complex [Cr(La)3] (1 a), and its surfactant derivatives [Cr(Lb)3] (1 b), [Cr(Lc)3] (1 c), and [Cr(Ld)3] (1 d) (where La=2‐(4′‐methoxyphenylazo)pyridine, Lb=2‐(4′‐butyloxyphenylazo)pyridine, Lc=2‐(4′‐octyloxyphenylazo)pyridine, and Ld=2‐(4′‐dodecyloxyphenylazo)pyridine) were synthesized. The molecular structure of compound 1 a, determined by X‐ray diffraction, showed that the local geometry around the metal center is a distorted octahedral with meridional coordination of the ligands. The structural parameters, spectroscopic data, and density functional theory (DFT) calculations on representative complex 1 a suggest that ligand La is predominantly an azo‐anion‐radical‐type, and so the complex can be represented as [CrIII(La.−)3]. An assessment of their physicochemical and surface properties was performed with the aim of using these triple‐tailed metallosurfactants as precursors for redox‐responsive films. The surface‐pressure–molecular‐area isotherm measurement for compound 1 d shows that the complex forms a stable Langmuir film at the air/water interface. The monolayer and multilayers were successfully transferred onto the quartz substrate and the platinum working electrode at a surface pressure of 10 mN m−1 by the Langmuir–Schaefer (LS) technique. The LS films were studied by UV/Vis spectrometry, infrared spectroscopy, field‐emission scanning electron microscopy, and atomic force microscopy. A good linear relationship between the absorbance at 370 nm and the thickness of the layers against the number of deposited layers indicated the uniformity and reproducibility of this transfer process. Voltammograms for platinum‐surface‐bound LS film of compound 1 d showed that the redox response owing to the first oxidation is stable and reproducible after many cycles (>300 cycles). Spectroscopic studies and electrochemical measurements of compound 1 d on the LS films revealed that these complexes are potential candidates for molecular devices.
Different classes of input and output neurons reveal new features in microglomeruli of the adult Drosophila mushroom body calyx
Authors: Butcher Nancy J. , Friedrich Anja B. , Lu Zhiyuan , Tanimoto Hiromu , Meinertzhagen Ian A.
Published: January 2012

To investigate how sensory information is processed, transformed, and stored within an olfactory system, we examined the anatomy of the input region, the calyx, of the mushroom bodies of Drosophila melanogaster. These paired structures are important for various behaviors, including olfactory learning and memory. Cells in the input neuropil, the calyx, are organized into an array of microglomeruli each comprising the large synaptic bouton of a projection neuron (PN) from the antennal lobe surrounded by tiny postsynaptic neurites from intrinsic Kenyon cells. Extrinsic neurons of the mushroom body also contribute to the organization of microglomeruli. We employed a combination of genetic reporters to identify single cells in the Drosophila calyx by light microscopy and compared these with cell shapes, synapses, and circuits derived from serial‐section electron microscopy. We identified three morphological types of PN boutons, unilobed, clustered, and elongated; defined three ultrastructural types, with clear‐ or dense‐core vesicles and those with a dark cytoplasm having both; reconstructed diverse dendritic specializations of Kenyon cells; and identified Kenyon cell presynaptic sites upon extrinsic neurons. We also report new features of calyx synaptic organization, in particular extensive serial synapses that link calycal extrinsic neurons into a local network, and the numerical proportions of synaptic contacts between calycal neurons. All PN bouton types had more ribbon than nonribbon synapses, dark boutons particularly so, and ribbon synapses were larger and with more postsynaptic elements (2–14) than nonribbon (1–10). The numbers of elements were in direct proportion to presynaptic membrane area. Extrinsic neurons exclusively had ribbon synapses. J. Comp. Neurol. 520:2185–2201, 2012. © 2012 Wiley Periodicals, Inc.
Synaptic plasticity in the medial superior olive of hearing, deaf, and cochlear‐implanted cats
Authors: Tirko Natasha N. , Ryugo David K.
Published: January 2012

The medial superior olive (MSO) is a key auditory brainstem structure that receives binaural inputs and is implicated in processing interaural time disparities used for sound localization. The deaf white cat, a proven model of congenital deafness, was used to examine how deafness and cochlear implantation affected the synaptic organization at this binaural center in the ascending auditory pathway. The patterns of axosomatic and axodendritic organization were determined for principal neurons from the MSO of hearing, deaf, and deaf cats with cochlear implants. The nature of the synapses was evaluated through electron microscopy, ultrastructure analysis of the synaptic vesicles, and immunohistochemistry. The results show that the proportion of inhibitory axosomatic terminals was significantly smaller in deaf animals when compared with hearing animals. However, after a period of electrical stimulation via cochlear implants the proportion of inhibitory inputs resembled that of hearing animals. Additionally, the excitatory axodendritic boutons of hearing cats were found to be significantly larger than those of deaf cats. Boutons of stimulated cats were significantly larger than the boutons in deaf cats, although not as large as in the hearing cats, indicating a partial recovery of excitatory inputs to MSO dendrites after stimulation. These results exemplify dynamic plasticity in the auditory brainstem and reveal that electrical stimulation through cochlear implants has a restorative effect on synaptic organization in the MSO. J. Comp. Neurol. 520:2202–2217, 2012. © 2012 Wiley Periodicals, Inc.
Efferent projections of C3 adrenergic neurons in the rat central nervous system
Authors: Sevigny Charles P. , Bassi Jaspreet , Williams David A. , Anderson Colin R. , Thomas Walter G. , Allen Andrew M.
Published: January 2012

C3 neurons constitute one of three known adrenergic nuclei in the rat central nervous system (CNS). While the adrenergic C1 cell group has been extensively characterized both physiologically and anatomically, the C3 nucleus has remained relatively obscure. This study employed a lentiviral tracing technique that expresses green fluorescent protein behind a promoter selective to noradrenergic and adrenergic neurons. Microinjection of this virus into the C3 nucleus enabled the selective tracing of C3 efferents throughout the rat CNS, thus revealing the anatomical framework of C3 projections. C3 terminal fields were observed in over 40 different CNS nuclei, spanning all levels of the spinal cord, as well as various medullary, mesencephalic, hypothalamic, thalamic, and telencephalic nuclei. The highest densities of C3 axon varicosities were observed in Lamina X and the intermediolateral cell column of the thoracic spinal cord, as well as the dorsomedial medulla (both commissural and medial nuclei of the solitary tract, area postrema, and the dorsal motor nucleus of the vagus), ventrolateral periaqueductal gray, dorsal parabrachial nucleus, periventricular and rhomboid nuclei of the thalamus, and paraventricular and periventricular nuclei of the hypothalamus. In addition, moderate and sparse projections were observed in many catecholaminergic and serotonergic nuclei, as well as the area anterior and ventral to the third ventricle, Lamina X of the cervical, lumbar, and sacral spinal cord, and various hypothalamic and telencephalic nuclei. The anatomical map of C3 projections detailed in this survey hopes to lay the first steps toward developing a functional framework for this nucleus. J. Comp. Neurol. 520:2352–2368, 2012. © 2012 Wiley Periodicals Inc.
Lack of early pattern stimulation prevents normal development of the alpha (Y) retinal ganglion cell population in the cat
Authors: Burnat Kalina , Van Der Gucht Estelle , Waleszczyk Wioletta J. , Kossut Malgorzata , Arckens Lutgarde
Published: January 2012

Binocular deprivation of pattern vision (BD) early in life permanently impairs global motion perception. With the SMI‐32 antibody against neurofilament protein (NFP) as a marker of the motion‐sensitive Y‐cell pathway (Van der Gucht et al. [2001] Cereb. Cortex 17:2805–2819), we analyzed the impact of early BD on the retinal circuitry in adult, perceptually characterized cats (Burnat et al. [2005] Neuroreport 16:751–754). In controls, large retinal ganglion cells exhibited a strong NFP signal in the soma and in the proximal parts of the dendritic arbors. The NFP‐immunoreactive dendrites typically branched into sublamina a of the inner plexiform layer (IPL), i.e., the OFF inner plexiform sublamina. In the retina of adult BD cats, however, most of the NFP‐immunoreactive ganglion cell dendrites branched throughout the entire IPL. The NFP‐immunoreactive cell bodies were less regularly distributed, often appeared in pairs, and had a significantly larger diameter compared with NFP‐expressing cells in control retinas. These remarkable differences in the immunoreactivity pattern were typically observed in temporal retina. In conclusion, we show that the anatomical organization typical of premature Y‐type retinal ganglion cells persists into adulthood even if normal visual experience follows for years upon an initial 6‐month period of BD. Binocular pattern deprivation possibly induces a lifelong OFF functional domination, normally apparent only during development, putting early high‐quality vision forward as a premise for proper ON–OFF pathway segregation. These new observations for pattern‐deprived animals provide an anatomical basis for the well‐described motion perception deficits in congenital cataract patients. J. Comp. Neurol. 520:2414–2429, 2012. © 2012 Wiley Periodicals Inc.
Metabolic syndrome, physical activity and cardiac autonomic function
Authors: Soares‐Miranda Luisa , Sandercock Gavin , Vale Susana , Santos Rute , Abreu Sandra , Moreira Carla , Mota Jorge
Published: January 2012

Background

Our primary aim was to investigate the associations that components of metabolic syndrome and physical activity have with cardiac autonomic nervous system activity as estimated by heart rate variability (HRV) in young adults free of metabolic abnormalities. We also aimed to identify predictors of 3‐year changes in HRV.

Methods

Physical activity was assessed annually in 163 healthy participants over 3 years (2008–2010). Components of metabolic syndrome measured annually were; waist circumference, systolic blood pressure, high‐density lipoprotein, triglycerides, glucose, and C‐reactive protein. A linear mixed regression model was used to assess associations between HRV, metabolic syndrome components and physical activity. Linear regression was used to identify predictors of changes in HRV.

Results

 Metabolic syndrome components were negatively associated with HRV indices and higher heart rate, while physical activity was associated with higher HRV and lower heart rate. Physical activity and inflammation were predictors of positive and negative changes in HRV indices, respectively.

Conclusions

 In participants without significant metabolic abnormalities, metabolic syndrome components were still associated with less favourable HRV profiles. Physical activity and inflammation were both able to predict changes in HRV, albeit in different directions. It appears that the process of autonomic dysfunction starts at a young age and may be mediated in part by inflammation. Metabolic syndrome prevalence is increasing in younger populations; promoting the metabolic and autonomic benefits of exercise remains imperative. Copyright © 2012 John Wiley & Sons, Ltd.
Dye coupling and connexin expression by cortical radial glia in the early postnatal subventricular zone
Authors: Freitas Andressa S. , Xavier Anna L.R. , Furtado Carla M. , Hedin‐Pereira Cecilia , Fróes Maira M. , Menezes João R.L.
Published: January 2012

In this study, we have analyzed the specific contribution of the cortical radial glia (RG) for gap junctional communication (GJC) within the postnatal subventricular zone (SVZ). To specifically target RG as source of dye‐coupling in situ, we have developed a new technique that involves direct cell loading through the processes that reach the pial surface, with a mix of gap junction permeant (Lucifer yellow, LY) and nonpermeant (rhodamine‐conjugated dextran 3 KDa, RD) fluorochromes, the latter used as a marker for direct loaded cells. Tissue sections were analyzed for identification of directly loaded (LY+RD+) and coupled cells (LY+RD–) in the SVZ. Directly loaded cells were restricted to the region underlying the pial loading surface area. Coupled cells were distributed in a bistratified manner, along the outer dorsal surface of the SVZ and aligning the ventricle, leaving the SVZ core relatively free. Blocking GJC prior to pial loading greatly reduced dye coupling. Phenotypic analysis indicated that coupling by RG excludes neuroblasts and is mostly restricted to cells of glial lineage. Notwithstanding, no corresponding restriction to specific cell phenotype was found for two connexin isotypes, Cx43 and Cx45, in the postnatal SVZ. The extensive homocellular cell coupling by RG suggests an important role in the regulation of neurogenesis and functional compartmentalization of the postnatal SVZ. © 2012 Wiley Periodicals, Inc. Develop Neurobiol 2012
Structure–Photoluminescence Quenching Relationships of Iridium(III)–Tris(phenylpyridine) Complexes
Authors: Ruggi Albert , Mauro Matteo , Polo Federico , Reinhoudt David N. , De Cola Luisa , Velders Aldrik H.
Published: January 2012

The synthesis, structural, photophysical, theoretical, and electrochemical characterization of four tris(2‐phenylpyridine)‐based IrIII complexes are reported. The complexes were functionalized on the pyridine or on the phenyl rings with amide moieties substituted with a tris(ethyl)amine or ethyl groups, thereby yielding a family of compounds with hemicaged or open (without a capping unit but with similar functional groups on the ligand) structure. Within the context of the parent tris(2‐phenylpyridine) and the full‐cage iridium(III) complexes, structure–photoluminescence quenching relationships (SPQR) of the four complexes have been investigated. Luminescence quenching by oxygen has been studied with Stern–Volmer plots and through evaluation of the thermodynamic parameters involved in the quenching process. Density functional theory (DFT) and time‐dependent DFT (TD‐DFT) calculations have been performed on the complexes to gain insights into structural and electronicfeatures and the nature of the excited states involved in the electronic absorption processes. Interestingly, shielding by the capping unit of moieties in which the LUMO orbital is mostly localized (on the pyridines) results in a dramatic 40 % decrease in oxygen quenching. Conversely, shielding ofmoieties in which the HOMO orbital is partially localized (on the phenyl rings) does not induce any change in the oxygen quenching degree. In both sets of compounds, the thermodynamic feasibility of oxygen quenching is the same for the hemicaged and open compounds, thus giving evidence of the structural origin of such quenching decrease. The SPQRopens up new routes to the design of tailored, more or less sensitive to oxygen, luminescent iridium complexes (e.g., for use as biolabels).
Effect of cultivation area and climatic conditions on volatiles of virgin olive oil
Authors: Kiralan Mustafa , Ozkan Gulcan , Koyluoglu Fatma , Ugurlu Hatice Asik , Bayrak Ali , Kiritsakis Apostolos
Published: January 2012

To elucidate the influence of the cultivation area and climatic conditions on volatiles of virgin olive oil from Gemlik cultivar, an investigation was carried out. Five Turkish geographical zones (Balıkesir, Aydın, Manisa, Antalya and Hatay) were chosen. From these areas, fruits were collected at the same maturity stage and processed using a small experimental olive oil mill, applying identical processing conditions for all olive samples. Headspace solid‐phase microextraction (HS‐SPME) technique coupled to GC/MS was used for volatile analysis. Twenty‐seven compounds were identified and characterised, representing 96.40–98.74% of the total GC area. The major volatile representing about 50% was the (E)‐2‐hexenal. This compound was found in higher concentrations on olive oils from Antalya than from Hatay area. Hexanal was the second most abundant volatile compound and varied between 13.89 and 28.96%. Comparing the olive growing areas Hatay and Antalya, the hexanal concentration was about 29 and 14%, respectively. Generally, a significant difference in the composition of volatile compounds between the oils from the same olive cultivar and from different geographic regions was recorded. The results suggest that climatic factors, latitude and longitude affect the formation of volatiles.
Enzymatic strategies for solvent‐free production of short and medium chain phytosteryl esters
Authors: Torrelo Guzman , Torres Carlos F. , Reglero Guillermo
Published: January 2012

Transesterification of phytosterols with short and medium chain fatty acids (MCFAs) ethyl esters and with tributyrin catalyzed by Candida rugosa and Pseudomonas stutzeri TL lipases in solvent‐free medium was studied including the effects of temperature, fatty acid specificity, enzyme quantity, the residual activity of each lipase and reduced pressure. More than the 90% of the original phytosterols were transformed into their corresponding phystosteryl esters after 3–4 h reaction at 50–60°C and at 100–350 mbar. The product mixtures containing 40–50% (w/w) phystosteryl esters were then vacuum distilled to remove molar excess of SCFA and MCFA ethyl esters utilized in the enzymatic reaction. By this methodology, purities >95% in short and medium chain phytosteryl esters were finally obtained.

Practical applications: The methodology presented here describes a rapid and easy process to prepare phytosteryl esters with short and medium chain fatty acids. The phytosteryl esters produced in this study are expected to have improved their hydrodispersibility and bioavailability in comparison with their corresponding free phytosterols. A lower melting point than the original phytosterol and an improved oil and fat solubility are also expected. Moreover, the SCFA and MCFA could act as a lipid vehicle for fatty acids, improving their half‐life in the body and promoting their biological activities.
The New Age of Electrophilic Perfluoro­alk­ylation Reactions
Authors: Macé Yohan , Magnier Emmanuel
Published: January 2012

The introduction of a perfluoroalkyl group, with emphasis on the trifluoromethyl moiety, is a challenging topic. Of the synthetic methods available in the repertoire of chemists, electrophilic introduction was until recently the least developed. In five years, however, a renaissance of this chemistry has happened. This renewal has been made possible thanks to reports both of numerous new reagents (stable, easy tohandle and to prepare) and of easier preparation of older reagents. Their availability rapidly inspired highly original works involving their use, in particular with the help of catalysis. This virtuous spiral, as well as all these exciting new developments, is described in this microreview.
Efficient Preparation of Anhydrous Metallic Triflates and Triflimides under Ultrasonic Activation
Authors: Legrave Nathalie , Couhert Audrey , Olivero Sandra , Desmurs Jean‐Roger , Duñach Elisabet
Published: January 2012

Several metallic triflates and triflimides, among them anhydrous salts, were prepared in high yields under ultrasonic activation from the corresponding metal powders andstoichiometric amounts of triflic or triflimidic acid in different solvents. Different InIII and BiIII salts were tested as catalysts in hydrothiolation of olefins and in hydroarylation processes, respectively.
A vectorial algorithm with finite element method for prediction of powder segregation in metal injection molding
Authors: Cheng Zhiqiang , Barriere Thierry , Liu Baosheng , Gelin Jean‐Claude
Published: January 2012

The design of the mold and the choice of the injection parameters for metal injection molding (MIM) is required to maintain homogeneity of the filled mixture. However, powder segregation is unavoidable in MIM because of the significant difference in densities of the metallic powder and the polymer binder. To achieve an effective prediction of segregation effect, a biphasic model based on mixture theory is employed. The viscous behaviors of each phase and the interaction coefficient between the flows of the two phases should be determined. The solution of two coupled Navier–Stokes equations results in a tremendous computation effort. The previous development of an explicit algorithm makes the biphasic simulation much faster than that of the classic methods. However, it is strongly desired to reduce or even eliminate the numerous global solutions for pressure fields at each time step. Hence, a new vectorial algorithm is proposed and developed to perform the simulation only by vectorial operations. It provides the anticipated efficiency in the simulation of biphasic modeling, and the advantage to use the classic elements of equal‐order interpolations. Some results produced by the two algorithms are compared with the experimental values to validate the new vectorial algorithm. Copyright © 2012 John Wiley & Sons, Ltd.
Spontaneous clearance of primary acute hepatitis C virus infection correlated with high initial viral RNA level and rapid HVR1 evolution
Authors: Liu Lin , Fisher Brian E. , Thomas David L. , Cox Andrea L. , Ray Stuart C.
Published: January 2012

The aim of this study is to determine whether early viral dynamics and evolution predict outcome of primary acute hepatitis C virus (HCV) infection. HCV- and human immunodeficiency virus–negative injection drug users were enrolled prospectively and followed monthly to identify acute HCV infection using RNA detection. Subjects with more than 1 month between HCV-RNA-negative and -positive visits were excluded to ensure stringent acute infection. Differences in medians of log-transformed viral RNA levels and evolutionary rates in each gene of a 5′-hemigenomic amplicon were assessed using Mann-Whitney's rank-sum test. Correlation coefficient was calculated using Spearman's rank order. Initial viremia level was 50-fold higher in subjects with spontaneous clearance (compared with persistence) of primary acute HCV infection (median, 7.1 versus 5.4 log10 IU/mL;

P

= 0.002). Initial viremia level in subjects with interleukin (
IL) 28B
-C allele at rs12979860 and clearance was higher than that in subjects with

IL28B
-T allele and persistence (
P

= 0.001). Evolutionary rates in the hypervariable region 1 (HVR1) region of the E2 gene were significantly higher in self-resolvers than those in persistence subjects during early infection, whereas other genes or regions had comparable rates. All major substitutions in HVR1 in persistence subjects were convergent changes, whereas over the same time interval clearance subjects displayed divergent evolution, indicating different immune responses between the two groups.

Conclusion:

Spontaneous clearance of acute HCV infection is predicted by high initial viremia as well as favorable IL28B genotype and is associated with rapid envelope-sequence evolution. This linkage of host genetics, viral dynamics, and evolution provides new directions for mechanistic studies.
MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma
Authors: Fang YuXiang , Xue Jing-Lun , Shen Qi , Chen Jinzhong , Tian Ling
Published: January 2012

MicroRNAs (miRNAs) are known to be involved in carcinogenesis and tumor progression in hepatocellular carcinoma (HCC). Recently, microRNA-7 (miR-7) has been proven to play a substantial role in glioblastoma and breast cancer, but its functions in the context of HCC remain unknown. Here, we demonstrate that miR-7 inhibits HCC cell growth and metastasis

in vitro

and

in vivo
. We first screened and identified a novel miR-7 target, phosphoinositide 3-kinase catalytic subunit delta (PIK3CD). Overexpression of miR-7 would specifically and markedly down-regulate its expression. miR-7-overexpressing subclones showed significant cell growth inhibition by G0/G1-phase cell-cycle arrest and significant impairment of cell migration

in vitro
. To identify the mechanisms, we investigated the phosphoinositide 3-kinase (PI3K)/Akt pathway and found that Akt, mammalian target of rapamycin (mTOR), and p70S6K were down-regulated, whereas 4EBP1 was up-regulated in miR-7-overexpressing subclones. We also identified two novel, putative miR-7 target genes, mTOR and p70S6K, which further suggests that miR-7 may be a key regulator of the PI3K/Akt pathway. In xenograft animal experiments, we found that overexpressed miR-7 effectively repressed tumor growth (3.5-fold decrease in mean tumor volume; n = 5) and abolished extrahepatic migration from liver to lung in a nude mouse model of metastasis (n = 5). The number of visible nodules on the lung surface was reduced by 32-fold. A correlation between miR-7 and PIK3CD expression was also confirmed in clinical samples of HCC.

Conclusion:

These findings indicate that miR-7 functions as a tumor suppressor and plays a substantial role in inhibiting the tumorigenesis and reversing the metastasis of HCC through the PI3K/Akt/mTOR-signaling pathway

in vitro

and

in vivo
. By targeting PIK3CD, mTOR, and p70S6K, miR-7 efficiently regulates the PI3K/Akt pathway. Given these results, miR-7 may be a potential therapeutic or diagnostic/prognostic target for treating HCC.
Impact of a baseline polymorphism on the emergence of resistance to the hepatitis C virus nonstructural protein 5a replication complex inhibitor, BMS-790052
Authors: Sun Jin-Hua , O'Boyle Donald R. , Zhang Yan , Wang Chunfu , Nower Peter , Valera Lourdes , Roberts Susan , Nettles Richard E. , Fridell Robert A. , Gao Min
Published: January 2012

The influence of naturally occurring polymorphisms on the potency of the HCV nonstructural protein 5A (NS5A) replication complex inhibitor, BMS-790052, was investigated by evaluating hybrid replicons in which the entire NS5A coding region of genotype (GT) la and 1b laboratory (lab) strains (H77c and Con1) were replaced with the corresponding regions of specimens collected from 10 GT-1a- and 6 GT-1b-infected subjects. For baseline (BL) specimens, with no previously observed resistance variants identified by population sequencing, the median 50% effective concentration (EC50) values for BMS-790052 were similar for the clinically derived and lab strains. A Q30R variant was observed at viral breakthrough (VBT) in one of the GT-1a-infected subjects. Because the lowest plasma exposure of BMS-790052 observed in this subject was 117 nM and the median 50% effective concentration value for a GT-1a H77c replicon containing a Q30R substitution is ˜7 nM, a rigorous investigation was initiated to determine the basis for resistance. Three approaches were used: (1) replacement of the entire H77c NS5A or (2) replacement of the N-terminal region of NS5A, with sequence from BL and day 14, and (3) substitution of specific amino acids. A BL polymorphism (E62D) did not contribute resistance to BMS-790052; however, the linked variant, Q30R-E62D, conferred high-level resistance

in vitro

and is likely responsible for VBT

in vivo.

Conclusion:

Our data show that a BL polymorphism with minimal effect on the anti-HCV effect of BMS-790052 can affect the emergence of resistance and significantly affect clinical outcome. This work establishes a clear, systematic approach to monitor resistance to NS5A inhibitors in the clinic.
In‐vivo Tumor detection using diffusion reflection measurements of targeted gold nanorods – a quantitative study
Authors: Ankri Rinat , Duadi Hamootal , Motiei Menachem , Fixler Dror
Published: January 2012

The ability to quantitatively and non‐invasively detect nanoparticles has important implications on their development as an in‐vivo cancer diagnostic tool. The Diffusion Reflection (DR) method is a simple, non‐invasive imaging technique which has been proven useful for the investigation of tissue's optical parameters. In this study, Monte Carlo (MC) simulations, tissue‐like phantom experiments and in‐vivo measurements of the reflected light intensity from tumor bearing mice are presented. Following intravenous injection of antibody conjugated poly (ethylene glycol)‐coated (PEGylated) gold nanorods (GNR) to tumor‐bearing mice, accumulation of GNR in the tumor was clearly detected by the DR profile of the tumor. The ability of DR measurements to quantitate in‐vivo the concentration of the GNR in the tumor was demonstrated and validated with Flame Atomic Absorption spectroscopy results. With GNR as absorbing contrast agents, DR has important potential applications in the image guided therapy of superficial tumors such as head and neck cancer, breast cancer and melanoma. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ethane cation decomposition characterization by EBMI spectroscopy: gas‐phase dissociative recombination as a source of secondary products
Authors: Parnis J. Mark , King Kaitlynn A. , Campbell Sasha E. , Thompson Matthew G.K.
Published: January 2012

The decomposition products of the d6‐ethane cation following charge‐transfer ionization with Ar+, under conditions of varying ionization electron current, have been isolated in solid argon matrices at 18 K and examined using Fourier transform infrared spectroscopy. Gas samples containing 1 : 1600 d6‐ethane : Ar were subjected to electron bombardment by using either a high (pin) or a low (plate) ionization density anode configuration with ionization currents between 20 and 150 μA. Under high ionization density conditions, the observed major products were d4‐ethene (C2D4) and d2‐acetylene (C2D2), with smaller yields of C2D5, C2D3, and C2D. The yield of each dehydrogenation product was enhanced with increased current. Analogous experiments employing the low ionization density plate anode resulted in reduced C2D6 destruction and the formation of only C2D4 and C2D2. The results suggest the onset of dissociative recombination processes under high ion density conditions. In this context, the results can be interpreted as a dissociative recombination of primary ion products, which gives rise to further dehydrogenation, and appearance of additional neutral radical products. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of turbulent flow on the corrosion inhibition properties of 2‐mercaptobenzimidazole
Authors: Olvera‐Martinez M. E. , Mendoza‐Flores J. , Rodriguez‐Gomez F. J. , Palomar‐Pardave M. E. , Genesca J.
Published: January 2012

The electrochemical techniques, that is, polarization resistance (Rp) and potentiodynamic polarization curves, were used in order to determine the effect of turbulent flow on the corrosion inhibiting effect of 2‐mercaptobenzimidazole (2‐MBI) on API 5L X52 grade steel samples immersed in a 3% NaCl aqueous solution saturated with CO2 at 60 °C. Turbulent flow conditions were controlled using a rotating cylinder electrode (RCE). An inhibition efficiency of 98% was measured at a concentration of 10 ppm of 2‐MBI at a rotation rate of 5000 rpm. This efficiency value is similar to those efficiency values measured at 25 and 40 ppm 2‐MBI and at the same rotation rate. These observations suggest that as the turbulent flow conditions increase the corrosion inhibiting effect of 2‐MBI is enhanced. 2‐MBI follows a Langmuir adsorption isotherm. The calculated values of adsorption equilibrium constant (Kads) and adsorption free energy ($\Delta G_{{\rm ads}}^{{\rm o}} $) suggest that the adsorption process taking place is chemical. The polarization curves indicate that the 2‐MBI does not modify the electrochemical mechanism of the anodic (Fe dissolution) and cathodic (hydrogen evolution) reactions. It is suggested that 2‐MBI decreases the rate at which these reactions occur, blocking the active sites on the steel surface.
The synergistic effect of Na3PO4 and benzotriazole on the inhibition of copper corrosion in tetra‐n‐butylammonium bromide aerated aqueous solution
Authors: Liu S. , Dong J. , Guan W. W. , Duan J. M. , Jiang R. Y. , Feng Z. P. , Song W. J.
Published: January 2012

The effect of Na3PO4 and the mixture of benzotriazole (BTA) and Na3PO4 (SP) on the corrosion of copper in 17 wt% (0.534 mol/L) tetra‐n‐butylammonium bromide (TBAB) aerated aqueous solution has been investigated by means of weight‐loss test, potentiodynamic polarization test, electrochemical impedance spectroscopy (EIS), and scanning electron microscopy/energy dispersive X‐ray techniques. The experimental results showed that a dosage of Na3PO4 stimulated the copper corrosion, and the corrosion rate increased with increasing Na3PO4 concentration, whereas the mixture of BTA and Na3PO4 could protect copper in aqueous TBAB solution. The inhibition action of the mixture of BTA and Na3PO4 on the corrosion of copper is mainly due to the inhibition of the anodic process of corrosion. The inhibition efficiency of a mixture consisting of 2 g/L BTA and 1 g/L Na3PO4 was about 96%. The mixture of BTA and Na3PO4 inhibits the corrosion of copper better than BTA by itself, indicating that Na3PO4 has a synergistic role with BTA on the corrosion inhibition of copper in TBAB aqueous solution.
Corrosion behavior of wrought Mg–6%Zn–1%Mn–XSi–YCa alloy
Authors: Ben‐Hamu G. , Eliezer D.
Published: January 2012

Different quantities of silicon and calcium were added to Mg–6%Zn–1%Mn alloy and its effect on corrosion behavior investigated. AC and DC polarization were carried out on the extruded rods, which contain different quantities of silicon and calcium. The phases present in the alloys have been identified by optical microscopy and TEM. Four different phases were found, i.e., intermetallics containing Si–Mn, Mg–Si, Mg–Zn, and Mg–Si–Ca phase. The corrosion behavior of the studied alloys were influenced by the amount and distribution of the second phases.
Modeling steel corrosion under supercritical CO2 conditions
Authors: Zhang Y. , Gao K. , Schmitt G. , Hausler R. H.
Published: January 2012

Corrosion in the presence of CO2 was studied under supercritical conditions (high pressure and moderate temperature) using different carbon steels and various corrosion resistant alloys (CRA's). An objective of this work was, among others, to put the results in perspective relative to various CO2 corrosion models that have been developed and published over the years. In particular, the NORSOK, FREECORP, and OLI models were used for comparison, while others were discussed as well. The systems investigated were (a) supercritical CO2 (SC CO2) saturated with water (no separate water phase), (b) a water mist phase in equilibrium with SC CO2, (c) a water/brine phase in equilibrium with SC CO2. It was found that the OLI model best simulates the experimental corrosion rates observed in system (c) where coupons were corroded in the aqueous phase at high velocities in the rotating cage. The varying susceptibility of different carbon steels to corrosion under these conditions is highlighted. CRA steels are comparatively more resistant.
Impact of Red Blood Cell Transfusion on Global and Regional Measures of Oxygenation
Authors: Roberson Russell S. , Bennett‐Guerrero Elliott
Published: January 2012

Anemia is common in critically ill patients. Although the goal of transfusion of red blood cells is to increase oxygen‐carrying capacity, there are contradictory results about whether red blood cell transfusion to treat moderate anemia (eg, hemoglobin 7–10 g/dL) improves tissue oxygenation or changes outcomes. Whereas increasing levels of anemia eventually lead to a level of critical oxygen delivery, increased cardiac output and oxygen extraction are homeostatic mechanisms the body uses to prevent a state of dysoxia in the setting of diminished oxygen delivery due to anemia. In order for cardiac output to increase in the face of anemia, normovolemia must be maintained. Transfusion of red blood cells increases blood viscosity, which may actually decrease cardiac output (barring a state of hypovolemia prior to transfusion). Studies have generally shown that transfusion of red blood cells fails to increase oxygen uptake unless oxygen uptake/oxygen delivery dependency exists (eg, severe anemia or strenuous exercise). Recently, near‐infrared spectroscopy, which approximates the hemoglobin saturation of venous blood, has been used to investigate whether transfusion of red blood cells increases tissue oxygenation in regional tissue beds (eg, brain, peripheral skeletal muscle). These studies have generally shown increases in near‐infrared spectroscopy derived measurements of tissue oxygenation following transfusion. Studies evaluating the effect of transfusion on the microcirculation have shown that transfusion increases the functional capillary density. This article will review fundamental aspects of oxygen delivery and extraction, and the effects of red blood cell transfusion on tissue oxygenation as well as the microcirculation. Mt Sinai J Med 79:66–74, 2012. © 2012 Mount Sinai School of Medicine
From Bloodless Surgery to Patient Blood Management
Authors: Shander Aryeh , Javidroozi Mazyar , Perelman Seth , Puzio Thomas , Lobel Gregg
Published: January 2012

Safety and efficacy concerns of allogeneic blood transfusions and their impact on patient outcomes and associated staggering costs and restricted supply have fueled the quest for other modalities and strategies to reduce use of blood components. Patient blood management focuses on multidisciplinary and multimodal preventive measures to reduce or obviate the need for transfusions and ultimately to improve the clinical outcomes of patients. Patient blood management strategies can be applied at every stage of care to surgical and nonsurgical patients, and they generally fall under one of these three categories (the so‐called pillars of blood management): optimizing hematopoiesis and appropriate management of anemia, minimizing bleeding and blood loss, and harnessing and optimizing physiological tolerance of anemia through employing all available modalities while treatment is initiated. Several tools and modalities are available to address each of these pillars. Examples include hematinic agents, systemic and topical hemostatic agents, autotransfusion, and blood‐sparing perfusion and surgical techniques. Additionally, changes in practice of clinicians (eg, adherence to restrictive, evidence‐based transfusion strategies with emphasis on physiologic indications for transfusion, minimization of iatrogenic blood loss, and adequate planning) play an important role in patient blood management. Emerging evidence supports that appropriate use of these strategies as part of a multimodal program is a safe and effective way of reducing allogeneic transfusions and improving patient outcomes. Mt Sinai J Med 79:56–65, 2012. © 2012 Mount Sinai School of Medicine
Utilizing a handheld electrode array for localized muscle impedance measurements
Authors: Narayanaswami Pushpa , Spieker Andrew J. , Mongiovi Phillip , Keel John C. , Muzin Stefan C. , Rutkove Seward B.
Published: January 2012

INTRODUCTION:

Electrical impedance myography (EIM) is a noninvasive technique used for assessment of muscle health in which a high‐frequency, low‐amplitude electric current is applied to the skin overlying a muscle, and the resulting surface voltage is measured. We have previously used adhesive electrodes, application of which is inconvenient. We present data using a handheld electrode array (HEA) that we devised to expedite the EIM procedure in a clinical setting.

Methods:

Thirty‐four healthy volunteers and 24 radiculopathy subjects underwent EIM testing using the HEA and adhesive electrodes.

Results:

The HEA was shown to have good test–retest reproducibility, with intraclass correlation coefficients as high as 0.99. HEA data correlated strongly with data from adhesive electrodes, ρ = 0.85 in healthy volunteers (P < 0.001) and ρ = 0.75 in radiculopathy subjects (P < 0.001).

Conclusions:

These data support the potential use of a handheld array for performing rapid localized surface impedance measurements. Muscle Nerve 46: 257–263, 2012
Haploidentical stem cell transplantation for children with high‐risk leukemia
Authors: Palma Julia , Salas Lucia , Carrión Flavio , Sotomayor Cristián , Catalán Paula , Paris Claudia , Turner Victoria , Jorquera Hugo , Handgretinger Rupert , Rivera Gastón K
Published: January 2012

Background

The Chilean population is ethnically diverse, and more than 50% of children referred for hematopoietic stem cell transplantation (HSCT) lack a suitable donor.

Procedure

To expand the donor pool, we assessed the feasibility, tolerance, and efficacy of using a haploidentical (HI) donor and a reduced‐intensity conditioning regimen for high‐risk pediatric leukemia. This study was facilitated by technology transfer from St. Jude Children's Research Hospital over the 2 preceding years.

Results

Between March 2006 and April 2009, 10 patients (median age, 9.8 years) received T cell‐depleted grafts at Calvo Mackenna Hospital in Santiago. Median cell doses were CD34+: 7.45 × 106/kg (range, 4.00–20.20 × 106/kg); CD3+: 0.88 × 105/kg (0.11–1.35 × 105/kg); and CD56+: 71.30 × 106/kg (31.50–131.80 × 106/kg). Nine patients experienced complete engraftment; six of the nine remain alive and clinically well 13–50 months post‐HSCT. Three patients died after bone marrow relapse, while only one died of transplant‐related causes. Virus reactivation was the main post‐transplant complication: 5/10 had positive CMV PCR but none had CMV disease. One patient developed acute GvHD > grade II and only one had chronic GvHD.

Conclusions

HI‐HSCT is feasible in our setting, offers a rational treatment option, and expands the donor pool significantly for children with high‐risk leukemia in a developing country. This information is especially relevant to other ethnically diverse populations that are poorly represented in international donor registries. Pediatr Blood Cancer 2012; 59: 895–901. © 2012 Wiley Periodicals, Inc.
Feasibility of neurobehavioral screening following diagnosis of pediatric cancer
Authors: Pejnovic Laura P. , De Luca Cinzia R. , Gentle Ellen , Anson Katie , Ashley David M. , Anderson Vicki A. , McCarthy Maria C.
Published: January 2012

Background

Neurobehavioral deficits will affect up to 50% of pediatric cancer survivors treated with central nervous system (CNS)‐directed therapies. Guidelines suggest assessment of neurobehavioral skills at diagnosis be extended from patients with brain tumors to include all patients requiring CNS‐directed therapies. However, comprehensive neuropsychological assessment at diagnosis is difficult to implement and resource intensive. A screening assessment targeted at the neurobehavioral domains known to be impacted by cancer treatments may be more feasible. This study aimed to assess the feasibility of implementing baseline neurobehavioral screening following childhood cancer diagnosis.

Procedure

A consecutive sample of 59 recently diagnosed patients requiring CNS‐directed therapies, and 49 healthy controls were assessed using a targeted neurobehavioral screen, which included measures of developmental, cognitive, academic, behavioral, and psychosocial functioning. Feasibility was assessed using a formal feasibility framework, with criteria of brevity, simplicity, relevance, acceptability, and value. Neurobehavioral assessment was compared to standard care to determine the quality of information acquired from the screen.

Results

Mean time from diagnosis to assessment was 5.17 weeks. Assessments were completed within 1 hour for 87% of patients. Participant and researcher evaluation indicated the screen was acceptable across a range of criteria, with no differences between clinical and control groups. Compared to standard medical record documentation, the screen provided significant additional information on developmental and neurobehavioral status of patients at diagnosis.

Conclusion

A brief neurobehavioral screen in the early period following cancer diagnosis is feasible and provides valuable baseline data for children at risk of neurobehavioral late‐effects of cancer treatments. Pediatr Blood Cancer 2012;59:295–300. © 2012 Wiley Periodicals, Inc.
18F‐FDG microPET imaging detects early transient response to an IGF1R inhibitor in genetically engineered rhabdomyosarcoma models
Authors: Soundararajan Anuradha , Abraham Jinu , Nelon Laura D. , Prajapati Suresh I. , Zarzabal Lee Ann , Michalek Joel E. , McHardy Stanton F. , Hawkins Douglas S. , Malempati Suman , Keller Charles
Published: January 2012

Background

Alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) are among the most common and most treatment resistant soft tissue sarcomas of childhood. Here, we evaluated the potential of 18F‐Fluorodeoxyglucose (FDG) as a marker of therapeutic response to picropodophyllin (PPP), an IGF1R inhibitor, in a conditional mouse model of ARMS and a conditional model of ERMS/undifferentiated pleomorphic sarcoma (UPS).

Procedure

Primary tumor cell cultures from Myf6Cre,Pax3:Fkhr,p53 and Pax7CreER,Ptch1,p53 conditional models of ARMS and ERMS/UPS were found to be highly sensitive to PPP (IC50 values 150 and 200 nM, respectively). Animals of each model were then treated with 80 mg/kg/day PPP by intraperitoneal injection for 12 days and imaged by 18F‐FDG microPET.

Results

Tumor volumes on day 4 for PPP‐treated ARMS and ERMS mice were lower than untreated control mouse tumor volumes, although treated tumors were larger than day 0. However, tumor FDG uptake was significantly reduced on day 4 for PPP‐treated mice compared to pretreatment baseline or untreated control mice on day 4 (P < 0.05). Nevertheless, by day 12 tumor volumes and FDG uptake for treated mice had increased significantly, indicating rapidly evolving resistance to therapy.

Conclusions

18F‐FDG PET imaging is a potential imaging biomarker of molecular susceptibility to targeted agents early in treatment for this aggressive form of sarcoma, but may find best use serially for Phase I/II studies where chemotherapy and targeted agents are combined to cytoreduce tumors and abrogate Igf1r inhibitor resistance. Pediatr Blood Cancer 2012;59:485–492. © 2012 Wiley Periodicals, Inc.