Pilot Quality-Assurance Study of a Third-Generation Batch-Mode Clinical-Scale Automated Xenon-129 Hyperpolarizer

We present a pilot quality assurance (QA) study of a clinical-scale, automated, third-generation (GEN-3) ¹²⁹Xe hyperpolarizer employing batch-mode spin-exchange optical pumping (SEOP) with high-Xe densities (50% natural abundance Xe and 50% N₂ in ~2.6 atm total pressure sourced from Nova Gas Technologies) and rapid temperature ramping enabled by an aluminum heating jacket surrounding the 0.5 L SEOP cell. ¹²⁹Xe hyperpolarization was performed over the course of 700 gas loading cycles of the SEOP cell, simulating long-term hyperpolarized contrast agent production in a clinical lung imaging setting. High levels of ¹²⁹Xe polarization (avg. %P_Xe = 51.0% with standard deviation σ_PXe = 3.0%) were recorded with fast ¹²⁹Xe polarization build-up time constants (avg. T_b = 25.1 min with standard deviation σ_Tb = 3.1 min) across the first 500 SEOP cell refills, using moderate temperatures of 75 °C. These results demonstrate a more than 2-fold increase in build-up rate relative to previously demonstrated results in a comparable QA study on a second-generation (GEN-2) ¹²⁹Xe hyperpolarizer device, with only a minor reduction in maximum achievable %P_Xe and with greater consistency over a larger number of SEOP cell refill processes at a similar polarization lifetime duration (avg. T₁ = 82.4 min, standard deviation σ_T1 = 10.8 min). Additionally, the effects of varying SEOP jacket temperatures, distribution of Rb metal, and preparation and operation of the fluid path are quantified in the context of device installation, performance optimization and maintenance to consistently produce high ¹²⁹Xe polarization values, build-up rates (T_b as low as 6 min) and lifetimes over the course of a typical high-throughput ¹²⁹Xe polarization SEOP cell life cycle. The results presented further demonstrate the significant potential for hyperpolarized ¹²⁹Xe contrast agent in imaging and bio-sensing applications on a clinical scale.     

On the Reaction of Triaryl Trithioarsenites, (ArS)3As,with Iodine

Iodine in dry nonprotic solvents oxidizes triaryl trithioarsenites, (ArS)₃As, to As(III) iodide, AsI₃, and disulfides, ArSSAr. The reaction most likely involves arylsulfenyl iodide, ArSI, as an intermediate. With triphenyl and tris(4-chlorophenyl) trithioarsenites, AsI₃ is prepared in very good yields. When the disulfide, which is produced, has MeCONH─ or ─NH─CMe₂─OH groups, then it acts as a Lewis base towards AsI₃ forming complexes with stoichiometry 2AsI₃·3ArSSAr. Probable coordination modes of the AsI₃ are discussed.     

Luminescent poly(phenylene vinylene) derivatives with m‐terphenyl or 2,6‐diphenylpyridine kinked segments along the main chain: Synthesis,characterization, and stimulated emission

Two new poly(phenylene vinylene)s containing m‐terphenyl or 2,6‐diphenylpyridine kinked units along the main chain were synthesized and were used as luminescent and laser materials. They were prepared from Heck coupling of 2,5‐didodecyloxy‐1,4‐divinylbenzene with 4,4″‐dibromo‐3′‐phenyl‐m‐terphenyl or 2,6‐di(4‐bromophenyl)‐4‐phenylpyridine. The kinked units along the main chain caused a partial interruption of the conjugation leading to emission at a shorter wavelength as compared with poly(p‐phenylene vinylene). The polymers presented blue‐green emission in solution and green‐yellow emission in the solid state with photoluminescence maxima at 465–497 and 546–550 nm, respectively. Polymer containing 2,6‐diphenylpyridine segments emitted at a longer wavelength than that containing m‐terphenyl and displayed higher quantum yields in solution (0.61 and 0.40, respectively). The influence of the solvent and polymer concentration on the photoluminescence characteristics was investigated. The photoluminescence properties of protonated polymer containing 2,6‐diphenylpyridine segments were investigated both in solution and in film. Amplified spontaneous emission and tunable laser action were also obtained from the two polymers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2214–2224, 2004     

Synthesis of poly(n‐hexyl isocyanate‐b‐N‐vinylpyrrolidone) block copolymers by the combination of anionic and nitroxide‐mediated radical polymerizations: Micellization properties in aqueous solutions

A combination of anionic and nitroxide‐mediated radical polymerizations (dual initiator) was employed for the synthesis of poly(n‐hexyl isocyanate‐b‐N‐vinylpyrrolidone) (PHIC‐b‐PNVP) block copolymers. The samples were characterized with a size exclusion chromatograph equipped with refractive‐index and light scattering detectors as well as ¹H NMR spectroscopy. Relatively good control over the molecular weights was achieved. However, rather broad molecular weight distributions were obtained. The micellar properties of the PHIC‐b‐PNVP block copolymers were studied in water, which is a selective solvent for the poly(N‐vinylpyrrolidone) blocks. Static and dynamic light scattering revealed the presence of equilibrium between the micelles and clusters. The clusters partially deaggregated with increasing temperature. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5719–5728, 2006     

3,4,5-triarylisothiazoles via C-C coupling chemistry

The regiocontrolled preparation of triarylisothiazoles is presented. 3-Halo-5-phenylisothiazole-4-carbonitriles, 1 (hal=Cl) and 18 (hal=I), are converted into the corresponding 4-bromo derivatives 5 (3-hal=Cl) and 24 (3-hal=I) via a Hunsdiecker strategy while the 4-iodo analogues 7 (3-hal=Cl) and 22 (3-hal=I) are prepared via a Hoffmann and Sandmeyer strategy. Regioselective Suzuki, Stille and Negishi reactions occur at C-4 with both the 4-bromo- and 4-iodoisothiazoles 5 and 7 , the latter being more reactive than the former. 3-Iodoisothiazoles 22 and 24 fail to give regiocontrolled Suzuki, Stille or Negishi couplings, however, 4-bromo-3-iodo-5-phenylisothiazole 24 gives the regiospecific palladium catalysed Ullmann-type reaction product 3,3'-bi(4-bromo-5-phenylisothiazole) 25 . Alkali hydrolysis of 3-chloro-4,5-diphenylisothiazole 8 gives the 3-hydroxy analogue 12 which is converted into 3-bromo-4,5-diphenylisothiazole 13 with POBr(3). 3-Bromoisothiazole 13 reacts with phenylzinc chloride to give 3,4,5-triphenylisothiazole 17 but fails to undergo effective Suzuki or Stille couplings. 3,5-Diphenylisothiazole-4-carbonitrile 26 is converted into the 4-bromo- and 4-iodo-3,5-diphenylisothiazoles 30 and 34 both of which are effective for Suzuki and Stille couplings. A series of triarylisothiazoles are prepared in this manner and fully characterised.     

Identification of redox sensitive thiols of protein disulfide isomerase using isotope coded affinity technology and mass spectrometry

Regulation of the redox state of protein disulfide isomerase (PDI) is critical for its various catalytic functions. Here we describe a procedure utilizing isotope-coded affinity tag (ICAT) technology and mass spectrometry that quantitates relative changes in the dynamic thiol and disulfide states of human PDI. Human PDI contains six cysteine residues, four present in two active sites within the a and a' domains, and two present in the b' domain. ICAT labeling of human PDI indicates a difference between the redox state of the two active sites. Furthermore, under auto-oxidation conditions an approximately 80% decrease in available thiols within the a domain was detected. Surprisingly, the redox state of one of the two cysteines, Cys-295, within the b' domain was altered between the fully reduced and the auto-oxidized state of PDI while the other b' domain cysteine remained fully reduced. An interesting mono- and dioxidation modification of an invariable tryptophan residue, Trp-35, within the active site was also mapped by tandem mass spectrometry. Our findings indicate that ICAT methodology in conjunction with mass spectrometry represents a powerful tool to monitor changes in the redox state of individual cysteine residues within PDI under various conditions.     

Traces of self-organisation and long-range memory in variations of environmental radon in soil: comparative results from monitoring in Lesvos Island and Ileia (Greece)

This paper addresses issues of self-affinity, long-memory and self-organisation in variations of radon in soil recorded in Lesvos Island, Greece. Several techniques were employed, namely (a) power-law wavelet spectral fractal analysis, (b) estimation of Hurst exponents through (b1) rescaled-range, (b2) roughness-length, (b3) variogram and (a), (c) detrended fluctuation analysis, (d) investigation of fractal dimensions and (e) analysis of five block entropies: (e1) Shannon entropy, (e2) Shannon entropy per letter, (e3) conditional entropy, (e4) Tsallis entropy, and (e5) normalised Tsallis entropy. Long-lasting antipersistency was identified during a period of anomalous radon variations following fractional Brownian modelling. Remaining variations did not exhibit analogous behaviour and followed fractional Gaussian modelling. Antipersistent power-law-beta-exponent-values between 1.5 and 2.0 were detected during anomalies. Persistent values were also found. Hurst exponents were mainly within 0 < H < 0.5. Some persistent exponents (0.5 < H < 1) were also observed. Fractal dimensions were within 1.5 < D < 2. Radon anomalies presented lower fractal dimensions. Shannon entropy ranged between 0.77 ≤ H(n) ≤ 2.38, Shannon entropy per letter, between 0.19 ≤ h ⁽ⁿ⁾ ≤ 0.59, conditional entropy, between 0.01 ≤ h _(n) ≤ 0.58, Tsallis entropy, between 0.55 ≤ S _q  ≤ 1.01 and normalised Tsallis entropy between, 0.98 ≤  $\hat{S}$  ≤ 5.42 (block-size n = 4). Entropies were lower during anomalies, indicating strong self-organisation. Persistency–antipersistency switching was observed, consistent with long-memory dynamics. Potential geological sources were discussed. The asperity-model was proposed. Findings were compared to results obtained under analogous methodologies in Ileia, Greece.     

Estimates for the low‐frequency electromagnetic fields scattered by two adjacent metal spheres in a lossless medium

Inductive electromagnetic means, currently employed in real physical applications and dealing with voluminous bodies embedded in lossless media, often call for analytically demanding tools of field calculation at modeling stage and later on at numerical stage. Here, one is considering two closely adjacent perfect conductors, possibly almost touching one another, for which the 3D bispherical geometry provides a good approximation. The particular scattering problem is modeled with respect to the two solid impenetrable metallic spheres, which are excited by a time‐harmonic magnetic dipole, arbitrarily orientated in the 3D space. The incident, the scattered, and the total non‐axisymmetric electromagnetic fields yield rigorous low‐frequency expansions in terms of positive integral powers of the real‐valued wave number in the exterior medium. We keep the most significant terms of the low‐frequency regime, that is, the static Rayleigh approximation and the first three dynamic terms, while the additional terms are small contributors and they are neglected. The typical Maxwell‐type problem is transformed into intertwined either Laplace's or Poisson's potential‐type boundary value problem with impenetrable boundary conditions. In particular, the fields are represented via 3D infinite series expansions in terms of bispherical eigenfunctions, obtaining analytical closed‐form solutions in a compact fashion. This procedure leads to infinite linear systems, which can be solved approximately within any order of accuracy through a cutoff technique.