Maize Brittle Stalk2-Like3, encoding a COBRA protein, functions in cell wall formation and carbohydrate partitioning.

Carbohydrate partitioning from leaves to sink tissues is essential for plant growth and development. The maize (Zea mays) recessive carbohydrate partitioning defective28 (cpd28) and cpd47 mutants exhibit leaf chlorosis and accumulation of starch and soluble sugars. Transport studies with 14C-sucrose (Suc) found drastically decreased export from mature leaves in cpd28 and cpd47 mutants relative to wild-type siblings. Consistent with decreased Suc export, cpd28 mutants exhibited decreased phloem pressure in mature leaves, and altered phloem cell wall ultrastructure in immature and mature leaves. We identified the causative mutations in the Brittle Stalk2-Like3 (Bk2L3) gene, a member of the COBRA family, which is involved in cell wall development across angiosperms. None of the previously characterized COBRA genes are reported to affect carbohydrate export. Consistent with other characterized COBRA members, the BK2L3 protein localized to the plasma membrane, and the mutants condition a dwarf phenotype in dark-grown shoots and primary roots, as well as the loss of anisotropic cell elongation in the root elongation zone. Likewise, both mutants exhibit a significant cellulose deficiency in mature leaves. Therefore, Bk2L3 functions in tissue growth and cell wall development, and this work elucidates a unique connection between cellulose deposition in the phloem and whole-plant carbohydrate partitioning.

Group 10 Bis(iminosemiquinone) Complexes: Measurement of Singlet-Triplet Gaps and Analysis of the Effects of Metal and Geometry on Electronic Structure.

Bis(iminosemiquinone) complexes of divalent group 10 metals have been described as having open-shell singlet ground states characteristic of very strong coupling between the two ligand radicals. By using the nonlinear temperature dependence of the chemical shifts of the 1H NMR spectra, the singlet-triplet gaps in seven of these compounds have been measured, with the nickel compounds having gaps of about 2400 cm-1 and the palladium compounds about 1800 cm-1. Bis(iminosemiquinone)platinum complexes have singlet-triplet gaps too large to measure by this technique (over 2800 cm-1, estimated to be about 3000 cm-1), though bis(3,5-di- tert-butylbenzosemiquinonato)platinum(II) has a measurable singlet-triplet gap of 1850 cm-1. In combination with near-IR absorption data of the neutral, cationic, and anionic bis(iminosemiquinone) complexes, a simplified two-electron, two-orbital bonding model describing these compounds can be fully parametrized based on experimental data. The identity of the central metal principally affects the difference in energy between metal-ligand π nonbonding and metal-ligand π antibonding orbitals, with the strength of the bonding interactions increasing in the order Pd < Ni < Pt. Twisting the ligands out of planarity (by using a 2,2'-biphenylenediyl linker) has a marked effect on the optical spectra of the compounds but not on their singlet-triplet gaps; this indicates that the effect is not due to changes in bonding interactions but rather due to a decrease in the magnitude of the quantum mechanical exchange interactions in the twisted compared to the flat compounds.

When Do Strongly Coupled Diradicals Show Strongly Coupled Reactivity? Thermodynamics and Kinetics of Hydrogen Atom Transfer Reactions of Palladium and Platinum Bis(iminosemiquinone) Complexes.

The 2,2'-biphenylene-bridged bis(iminosemiquinone) complexes ( tBuClip)M [ tBuClipH4 = 4,4'-di- tert-butyl- N, N'-bis(3,5-di- tert-butyl-2-hydroxyphenyl)-2,2'-diaminobiphenyl; M = Pd, Pt] can be reduced to the bis(aminophenoxide) complexes ( tBuClipH2)M by reaction with hydrazobenzene (M = Pd) or by catalytic hydrogenation (M = Pt). The palladium complex with one aminophenoxide ligand and one iminosemiquinone ligand, ( tBuClipH)Pd, is generated by comproportionation of ( tBuClip)Pd with ( tBuClipH2)Pd in a process that is both slow (0.06 M-1 s-1 in toluene at 23 °C) and only modestly favorable ( Kcom = 1.9 in CDCl3), indicating that both N-H bonds have essentially the same bond strength. The mono(iminoquinone) complex ( tBuClipH)Pt has not been observed, indicating that the platinum analogue shows no tendency to comproportionate ( Kcom < 0.1). The average bond dissociation free energies (BDFE) of the complexes have been established by equilibration with suitably substituted hydrazobenzenes, and the palladium bis(iminosemiquinone) is markedly more oxidizing than the platinum compound, with hydrogen transfer from ( tBuClipH2)Pt to ( tBuClip)Pd occurring with Δ G° = -8.9 kcal mol-1. The palladium complex ( tBuClipH2)Pd reacts with nitroxyl radicals in two observable steps, with the first hydrogen transfer taking place slightly faster than the second. In the platinum analogue, the first hydrogen transfer is much slower than the second, presumably because the N-H bond in the monoradical complex ( tBuClipH)Pt is unusually weak. Using driving force-rate correlations, it is estimated that this bond has a BDFE of 55.1 kcal mol-1, which is 7.1 kcal mol-1 weaker than that of the first N-H bond in ( tBuClipH2)Pt. The two radical centers in the platinum, but not the palladium, complex thus act in concert with each other and display a strong thermodynamic bias toward two-electron reactivity. The greater thermodynamic and kinetic coupling in the platinum complex is attributed to the stronger metal-ligand π interactions in this compound.

The automation of clinical trial serious adverse event reporting workflow.

BACKGROUND: The reporting of serious adverse events is a requirement when conducting a clinical trial involving human subjects, necessary for the protection of the participants. The reporting process is a multi-step procedure, involving a number of individuals from initiation to final review, and must be completed in a timely fashion. PURPOSE: The purpose of this project was to automate the adverse event reporting process, replacing paper-based processes with computer-based processes, so that personnel effort and time required for serious adverse event reporting was reduced, and the monitoring of reporting performance and adverse event characteristics was facilitated. METHODS: Use case analysis was employed to understand the reporting workflow and generate software requirements. The automation of the workflow was then implemented, employing computer databases, web-based forms, electronic signatures, and email communication. RESULTS: In the initial year (2007) of full deployment, 588 SAE reports were processed by the automated system, eSAEy. The median time from initiation to Principal Investigator electronic signature was <2 days (mean 7 +/- 0.7 days). This was a significant reduction from the prior paper-based system, which had a median time for signature of 24 days (mean of 45 +/- 5.7 days). With eSAEy, reports on adverse event characteristics (type, grade, etc.) were easily obtained and had consistent values based on standard terminologies.Limitation The automated system described was designed specifically for the workflow at Thomas Jefferson University. While the methodology for system design, and the system requirements derived from common clinical trials adverse reporting procedures are applicable in general, specific workflow details may not be relevant at other institutions. CONCLUSION: The system facilitated analysis of individual investigator reporting performance, as well as the aggregation and analysis of the nature of reported adverse events.

Institutional review board approval: why it matters.

The modern institutional review boards originated in the 1970s. They exist to protect human subjects participating in research from potential harm. The Belmont Report provided the ethical principles (respect for persons, beneficence, and justice) that should be observed while conducting research on human subjects. Compliance with the ethical principles of the Belmont Report is a first step in successful submissions to an institutional review board. Regulations regarding conflict of interest represent an attempt to ensure that research is not biased by financial or other interest and to maintain public trust.

A chelating bis(aminophenol) ligand bridged by a 1,1'-ferrocene-bis(para-phenylene) linker.

1,1'-Bis(4-(2-hydroxy-3,5-di-tert-butylphenyl)aminophenyl)ferrocene (pFlipH4) is prepared in three steps from commercially available 1,1'-ferrocenediboronic acid or its pinacol ester. The suitability of the ligand to bind as a tetradentate ligand in a cis, planar fashion has been confirmed by formation of a square planar palladium bis-iminosemiquinone (pFlip)Pd. The linker unit appears to be structurally similar to 1,1'-ferrocenediyl, but the electronic interaction of the ferrocene with the aminophenols is minimal.