Contrast enhanced maximum intensity projection ultrasound imaging for assessing angiogenesis in murine glioma and breast tumor models: A comparative study

The purpose of this study was to prospectively compare noninvasive, quantitative measures of vascularity obtained from four contrast enhanced ultrasound (US) techniques to four invasive immunohistochemical markers of tumor angiogenesis in a large group of murine xenografts. Glioma (C6) or breast cancer (NMU) cells were implanted in 144 rats. The contrast agent Optison (GE Healthcare, Princeton, NJ) was injected in a tail vein (dose: 0.4 ml/kg). Power Doppler imaging (PDI), pulse-subtraction harmonic imaging (PSHI), flash-echo imaging (FEI), and Microflow imaging (MFI; a technique creating maximum intensity projection images over time) was performed with an Aplio scanner (Toshiba America Medical Systems, Tustin, CA) and a 7.5 MHz linear array. Fractional tumor neovascularity was calculated from digital clips of contrast US, while the relative area stained was calculated from specimens. Results were compared using a factorial, repeated measures ANOVA, linear regression and z-tests. The tortuous morphology of tumor neovessels was visualized better with MFI than with the other US modes. Cell line, implantation method and contrast US imaging technique were significant parameters in the ANOVA model (p < 0.05). The strongest correlation determined by linear regression in the C6 model was between PSHI and percent area stained with CD31 (r = 0.37, p < 0.0001). In the NMU model the strongest correlation was between FEI and COX-2 (r = 0.46, p < 0.0001). There were no statistically significant differences between correlations obtained with the various US methods (p > 0.05). In conclusion, the largest study of contrast US of murine xenografts to date has been conducted and quantitative contrast enhanced US measures of tumor neovascularity in glioma and breast cancer xenograft models appear to provide a noninvasive marker for angiogenesis; although the best method for monitoring angiogenesis was not conclusively established.     

A Survey of Orbitrap All Ion Fragmentation Analysis Assessed by an R MetaboList Package to Study Small-Molecule Metabolites

Leukemia cell and melanoma tumor tissue extracts were studied for small (mostly m/z?<?250) polar metabolites by LC-ESI-HRMSⁿ analysis powered by a hybrid Quadrupole-Orbitrap. MS data were simultaneously acquired in fast polarity switching mode operating in MS¹ and MS/MS (All Ion Fragmentation, AIF) full-scan analyses at high mass resolution. Positive metabolite assignments were achieved by AIF analysis considering at least two characteristic transitions. Targeted metabolite profiling was achieved by the relative quantification of 18 metabolites through spiking of their respective deuterated counterparts. Manual data processing of MS¹ and AIF scans were compared for the accurate determination of natural metabolites and their deuterated analogs by chromatographic alignment and peak area integration. Evaluation of manual and automated (MetaboList R package) AIF data processing yielded comparable results. The versatility of AIF analysis also enabled the untargeted metabolite profiling of leukemia and melanoma samples in which 22 and 53 compounds were, respectively, identified outside those studied by labeling. The main limitation of this method was that low abundance metabolites with scan rates below 8 scans/peak could not be accurately quantified by AIF analysis. The combination of AIF analysis with MetaboList R package represents an opportunity to move towards automated, faster, and more global metabolomics approaches supported by an entirely flexible open source data processing platform freely available from Comprehensive R Archive Network (CRAN, https://CRAN.R-project.org/package=MetaboList).     

Immobilization of Tyrosinase on Chitosan — An Optimal Approach to Enhance the Productivity of L‐DOPA from L‐Tyrosine

Tyrosinase was immobilized on Chitosan (CTS) beads to produce 3,4‐dihydroxy‐L‐phenylalanine (L ‐DOPA) from L ‐tyrosine. Epichlorohydrin (ECH), ethylene glycol diglycidyl ether (EGDE), and glutaraldehyde (GLU) were used as coupling agents, respectively. Ultraviolet/visible measurements on CTS films showed that the reaction intermediate (L ‐dopaquinone) attacked the amino groups on CTS, so the amine residues on chitosan were capped by acetic acid anhydride (Ac) or formaldehyde (Fm) to avoid the deactivation of the immobilized tyrosinase. The pH and temperature of the maximal rate to produce L‐DOPA were investigated. GLU (coupling agent) and Ac (capping agent) were selected for practical utility. A 7.5% (w/v) concentration of GLU was found to attain maximal activity of the immobilized enzyme. The thermal stability of tyrosinase immobilized on CTS‐GLU‐Ac, and after treatment with sodium borohydride, was enhanced to a great extent. The L ‐DOPA converting efficiency in the environmental conditions of this study decreased from 45.1% to 39.9% (between 1^st and 30^th batch). This immobilized tyrosinase can be used practically in the production of L‐DOPA from L‐tyrosine.     

Mononuclear Ni(II)-thiolate complexes with pendant thiol and dinuclear Ni(III/II)-thiolate complexes with Ni...Ni interaction regulated by the oxidation levels of nickels and the coordinated ligands

Compared to [Ni(II)(SePh)(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2-SH))]- (1a) and [Ni(II)(Cl)(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2-SH))]- (3a) with a combination of the intramolecular [Ni...H-S] and [Ni-S...H-S] interactions, complexes [NiII(SePh)(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2-SH))]- (1b) and [Ni(II)(Cl)(P (o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2-SH))]- (3b) with intramolecular [Ni...H-S] interaction exhibit lower nu(S-H) stretching frequencies (2137 and 2235 cm(-1) for 1b and 3b vs 2250 and 2287 cm(-1) for 1a and 3a, respectively) and smaller torsion angles (27.2 degrees for 3b vs 58.9 and 59.1 degrees for 1a and 3a, respectively). The pendant thiol interaction modes of 1a, 3a, and 3b in the solid state are controlled by the solvent pairs of crystallization. Oxygen oxidation of dinuclear [Ni(II)(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2-SH))](2) (4) yielded thermally stable dinuclear [Ni(III)(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2-mu-S))](2) (5). The two paramagnetic d(7) Ni(III) cores (S = 1/2) with antiferromagnetic coupling (J = -3.13 cm(-1)) rationalize the diamagnetic property of 5. The fully delocalized mixed-valence [Ni(II)-Ni(III)] complexes [Ni2(P(o-C(6)H(3)-3-SiMe(3)-2-S)(3))(2)]- (6) and [Ni(2)(P(o-C(6)H(3)-3-SiMe(3)-2-S)(3))(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2-SCH(3)))] (7) were isolated upon the reduction of 5 and the methylation of 6, respectively. The electronic perturbation from the sulfur methylation of 6 triggers the stronger Ni...Ni interaction and the geometrical rearrangement from the diamond shape of the [NiS(2)Ni] core to the butterfly structure of [Ni(mu-S)(2)Ni] to yield 7 with Ni...Ni distances of 2.6088(1) A. The distinctly different Ni...Ni distances (2.6026(7) for 5 and 2.8289(15) A for 6) and the coordination number of the nickels indicate a balance of geometrical requirements for different oxidation levels of [PS(3)Ni-NiPS(3)] cores of 5 and 6.     

Aromatic polybenzoxazoles containing ether–sulfone linkages

A series of poly(o‐hydroxy amide)s having both ether and sulfone linkages in the main chain were synthesized via the low‐temperature solution polycondensation of 4,4′‐[sulfonylbis(1,4‐phenylene)dioxy]dibenzoyl chloride and 4,4′‐[sulfonylbis(2,6‐dimethyl‐1,4‐phenylene)dioxy]dibenzoyl chloride with three bis(o‐aminophenol)s including 4,4′‐diamino‐3,3′‐dihydroxybiphenyl, 3,3′‐diamino‐4,4′‐dihydroxybiphenyl, and 2,2‐bis(3‐diamino‐4‐hydroxyphenyl)hexafluoropropane. Subsequent thermal cyclodehydration of the poly(o‐hydroxy amide)s afforded polyethersulfone benzoxazoles. Most of the poly(o‐hydroxy amide)s were soluble in polar organic solvents such as N‐methyl‐2‐pyrrolidone; however, the polybenzoxazoles without the hexafluoroisopropylidene group were organic‐insoluble. The polybenzoxazoles exhibited glass‐transition temperatures (T_g) in the range of 219–282 °C by DSC and softening temperatures (T_s) of 242–320 °C by thermomechanical analysis. Thermogravimetric analyses indicated that most polybenzoxazoles were stable up to 450 °C in air or nitrogen. The 10% weight loss temperatures were recorded in the ranges of 474–593 °C in air and 478–643 °C in nitrogen. The methyl‐substituted polybenzoxazoles had higher T_g's but lower T_s's and initial decomposition temperatures compared with the corresponding unsubstituted polybenzoxazoles. For a comparative purpose, the synthesis and characterization of a series of sulfonyl polybenzoxazoles without the ether group that derived from 4,4′‐sulfonyldibenzoyl chloride and bis(o‐aminophenol)s were also reported. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2262–2270, 2001     

Empirical study and prediction of liquids retention on structured polymer surfaces

Liquids' contact angle hysteresis and critical retention volumes on five commonly used plastics with surface structures were studied. The chevron‐like groove structures, which are orthogonally arranged, make the liquid–solid contact line elongated while the droplet found staying in the Wenzel state. Various dimensions of surface structures were represented by contact length ratio σ. Advancing and receding contact angles of liquids on polymer surfaces with various conditions were reported. Reduced hysteresis H, which links between advancing and receding contact angles, was also studied and found to extend its availability on structured surfaces. The research found that surface structures have linear effects on liquids' advancing contact angles in the range of σ = 1.0 to 1.42. Linear regression analysis was hence proposed to predict advancing contact angles, and the results indicate that approximate 80% of data points have less than 6% error. An empirical model, which adopts liquid–solid surface tension as the source of liquids' retention force, was proposed to estimate liquids' critical retention volumes on inclined surfaces. The proposed model found good agreements with existing experiment data and demonstrated its superiority over previous ones. The present model provides an approach to predict liquids' storage/repellency on structured surfaces when the advancing contact angles are predictable. Copyright © 2016 John Wiley & Sons, Ltd.     

The Cycloalkyl Ring Effect on the Spin State of Di(Thiocyanato)Bis(N-Cycloalkyl-Substituted-2-Pyridinaldimine) Iron(II)

A new series of octahedral iron(II) complexes with the composition Fe(II) (N-R-2-pyridinaldimine)₂(NCS)₂, where R=cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl, have been synthesized and the spin states of the iron atom have been studied by means of Mössbauer spectroscopy and magnetic measurement.     

Crystallization behavior and morphological development of isotactic polypropylene blended with nanostructured polyhedral oligomeric silsesquioxane molecules

The thermal properties and morphological development of isothermally crystallized isotactic polypropylene (iPP) blended with nanostructured polyhedral oligomeric silsesquioxane (POSS) molecules at very small loading of POSS were studied with differential scanning calorimeter (DSC), thermal gravimetric analysis, dynamic mechanical analysis, polarized optical microscopy (POM), and wide‐angle X‐ray diffraction (WAXD). The result of DSC indicated that the crystallization rate of iPP increases with the increase in POSS contents during crystallization; moreover, the melting temperature of iPP/POSS nanocomposites slightly decreases, while the heat of fusion increases with the addition of POSS molecules at melting and remelting traces. The storage modulus and thermal stability, respectively, remarkably decrease, while the glass transition temperature of isothermally crystallized iPP/POSS nanocomposites increases slightly with the increase in POSS contents. The morphologies results of WAXD and POM show that the POSS molecules form about 35 nm sized nanocrystals and aggregate to form thread‐like and network structure morphologies, respectively, in the molten state even when the POSS content is very small. These results, therefore, suggest that the interaction force between the POSS molecules should be larger than the force between POSS molecules and iPP matrix; however, those interactions depend on the chain length of functionalized substituents on the POSS cage. Therefore, the POSS molecules aggregate forming nanocrystals and act as an effective nucleating agent for iPP and influence the thermal properties of iPP/POSS nanocomposites due to the shorter chain length of functionalized substituents, methyl, on the POSS cage. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2122–2134, 2006