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Rydberg states of calcium monofluoride in the n* = 17-20 region have been observed by ionization-detected optical--optical double-resonance spectroscopy via the [D.sup.2][[SIGMA].sup.+] v = 1 intermediate state. All members of the six core-penetrating Rydberg series in the n* = 17-20 region and several components of the 17f and 17g core-nonpenetrating Rydberg states have been assigned. While the assignment of core-penetrating Rydberg states is straightforward without use of an effective Hamiltonian model, "spectrum-only" assignment of core-nonpenetrating states is complicated because strong l-uncoupling causes the core-nonpenetrating stores to evolve rapidly from Hund's case (b) to Hund's case (d) coupling. We describe "spectrum-only" assignment procedures, developed in the spirit of Gerhard Herzberg, that can be used to assign optical-optical double-resonance spectra of core-penetrating and core-nonpenetrating Rydberg states using only information contained in the spectrum rather than predictions derived from an effective Hamiltonian model. The ambiguities that arise in the assignment of each class of states are discussed in detail. Key words: CaF, etectric quadrupole moment, Rydberg states, laser spectroscopy.

Research has been conducted on mixed-ligand compound (eta (super)4 -cycloocta-1,5-diene)(eta (super)5 -cyclopentadienyl)cobalt. The authors describe the gas-phase photoreactions and photoproducts of this compound.

We study the reaction efficiency of a surficial process in which a diffusing, tumbling dipole A reacts (eventually and irreversibly) with a stationary target dipole B. In contrast to earlier studies of such irreversible diffusion-reaction events (A+B→C), we consider the situation where at each and every site of the space accessible to the diffusing coreactant A, there is also embedded a fixed dipole. To quantify the influence on the reaction efficiency of (angle-averaged, dipole–dipole) potential interactions between the tumbling dipole A and the ensemble of stationary dipoles, we design a lattice-statistical model to describe this problem and use both analytical methods and numerical techniques rooted in the theory of finite Markov processes to work out its consequences. Specifically, we define the reaction space to be an n×n=N square-planar lattice with the target dipole occupying the centrosymmetric site in that space and determine the mean number of steps required before the irreversible event, A+B→C, occurs. Our results reveal two qualitatively-distinct regimes of behavior for this diffusion-reaction process, a low temperature (or strong coupling) regime dominated by nearest-neighbor excursions only, and a high-temperature (or weak-coupling) regime dominated by non-nearest neighbor excursions of the tumbling dipole A, with the transition between these two regimes occurring over a relatively narrow range of interparticle couplings. This behavior has the character of an ‘‘order–disorder’’ transition and is interpreted here in terms of an ‘‘order parameter’’ W related to a generalized Onsager length. The behavior uncovered is studied as a function of system size and of the boundary conditions imposed. © 1995 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The gas-phase photolysis of Pd(hfac)(sub2) showed that PdC+ is a common photoproduct although the ration of Pd+ to PdC+ is sensitive to wavelength.

Gas-phase photoreactions and photoproducts of the mixed-ligand compound (η[sup 4]-cycloocta-1,5-diene)(η[sup 5]cyclopentadienyl)cobalt are reported. Significant amounts of the monoligated complexes CoCOD and CoCp are produced, and the relative amounts are wavelength dependent. The COD ligand (with the weakest metal-ligand bonds) is always preferentially labilized as expected, but the relative amounts of the CoCOD and CoCp fragments change by 1 order of magnitude as the excitation wavelength is changed. The gas-phase photoreactions exhibit other surprising features that are uncommon in the photoreactions of organometallic compounds in the gas phase. Significant amounts of the intact cation are formed, in contrast to most reported reactions where fragmentation of the weak metal-ligand bonds precedes ionization. Most surprisingly, fragmentation of the ligands occurs while the ligands are still coordinated. The resulting metal complexes contain ligand fragments that remain coordinated to the metal. Breaking several carbon-carbon bonds with retention of weaker metal-ligand bonds is unexpected. For example, C[sub 5]H[sub 5] undergoes fragmentation while still coordinated to the cobalt, yielding smaller compounds such as Co(CH)[sup +], Co(C[sub 2]H[sub 2])[sup +], Co(C[sub 3]H[sub 3])[sup +], and Co(C[sub 4]H[sub 6])[sup +]. Correspondingly, coordinated COD yields Co(C[sub 6]H[sub 6])[sup +], Co(C[sub 5]H[sub 5])[sup +], Co(C[sub 4]H[sub 6])[sup +], Co(C[sub 3]H[sub 3])[sup +], Co(C[sub 2]H[sub 2])[sup +], and Co(CH)[sup +]. The wavelength dependence of the ligand labilization is examined by utilizing mass-selected resonance enhanced multiphoton ionization spectroscopy. Both broad bands and sharp lines are observed in the mass-selected excitation spectra. The action spectra obtained in the gas phase while monitoring the cobalt ion follow the absorption onset found in solution. The changes in fragmentation pathways are interpreted in terms of the initially... [ABSTRACT FROM AUTHOR]

Preclinical models of breast cancer have established mechanistic links between psychological stress and cancer progression. However, epidemiological evidence linking stress and cancer is equivocal. We tested the impact of stress exposure in female mice expressing the mouse mammary tumor virus polyoma middle-T antigen (MMTV-PyMT), a spontaneous model of mammary adenocarcinoma that mimics metastatic hormone receptor-positive human breast cancer development. MMTV-PyMT mice were socially isolated at 6 to 7 weeks of age during premalignant hyperplasia. To increase the potency of the stressor, singly housed mice were exposed to acute restraint stress (2 hours per day for 3 consecutive days) at 8 to 9 weeks of age during early carcinoma. Exposure to this dual stressor activated both major stress pathways, the sympathetic nervous system and hypothalamic-pituitary-adrenal axis throughout malignant transformation. Stressor exposure reduced mammary tumor burden in association with increased tumor cleaved caspase-3 expression, indicative of increased cell apoptosis. Stress exposure transiently increased tumor vascular endothelial growth factor and reduced tumor interleukin-6, but no other significant alterations in immune/inflammation-associated chemokines and cytokines or changes in myeloid cell populations were detected in tumors. No stress-induced change in second-harmonic generation-emitting collagen, indicative of a switch to a metastasis-promoting tumor extracellular matrix, was detected. Systemic indicators of slowed tumor progression included reduced myeloid-derived suppressor cell (MDSC) frequency in lung and spleen, and decreased transforming growth factor β (TGF-β) content in circulating exosomes, nanometer-sized particles associated with tumor progression. Chronic β-adrenergic receptor (β-AR) blockade with nadolol abrogated stress-induced alterations in tumor burden and cleaved caspase-3 expression, lung MDSC frequency, and exosomal TGF-β content. Despite the evidence for reduced tumor growth, metastatic lesions in the lung were not altered by stress exposure. Unexpectedly, β-blockade in nonstressed mice increased lung metastatic lesions and splenic MDSC frequency, suggesting that in MMTV-PyMT mice, β-AR activation also inhibits tumor progression in the absence of stress exposure. Together, these results suggest stress exposure can act through β-AR signaling to slow primary tumor growth in MMTV-PyMT mice., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Hepatitis C virus (HCV) infection presents an unmet medical need requiring more effective treatment options. Nucleoside inhibitors (NI) of HCV polymerase (NS5B) have demonstrated pan-genotypic activity and durable antiviral response in the clinic, and they are likely to become a key component of future treatment regimens. NI candidates that have entered clinical development thus far have all been N-nucleoside derivatives. Herein, we report the discovery of a C-nucleoside class of NS5B inhibitors. Exploration of adenosine analogs in this class identified 1'-cyano-2'-C-methyl 4-aza-7,9-dideaza adenosine as a potent and selective inhibitor of NS5B. A monophosphate prodrug approach afforded a series of compounds showing submicromolar activity in HCV replicon assays. Further pharmacokinetic optimization for sufficient oral absorption and liver triphosphate loading led to identification of a clinical development candidate GS-6620. In a phase I clinical study, the potential for potent activity was demonstrated but with high intra- and interpatient pharmacokinetic and pharmacodynamic variability.

Investigation of thiophene-2-carboxylic acid HCV NS5B site II inhibitors, guided by measurement of cell culture medium binding, revealed the structure-activity relationships for intrinsic cellular potency. The pharmacokinetic profile was enhanced through incorporation of heterocyclic ethers on the N-alkyl substituent. Hydroxyl groups were incorporated to modulate protein binding. Intrinsic potency was further improved through enantiospecific introduction of an olefin in the N-acyl motif, resulting in the discovery of the phase 2 clinical candidate GS-9669. The unexpected activity of this compound against the clinically relevant NS5B M423T mutant, relative to the wild type, was shown to arise from both the N-alkyl substituent and the N-acyl group.