Induction of dynamic hyperinflation by expiratory resistance breathing in healthy subjects - an efficacy and safety study.

New Findings: What is the central question of this study? The study aimed to establish a novel model to study the chronic obstructive pulmonary disease (COPD)-related cardiopulmonary effects of dynamic hyperinflation in healthy subjects. What is the main finding and its importance? A model of expiratory resistance breathing (ERB) was established in which dynamic hyperinflation was induced in healthy subjects, expressed both by lung volumes and intrathoracic pressures. ERB outperformed existing methods and represents an efficacious model to study cardiopulmonary mechanics of dynamic hyperinflation without potentially confounding factors as present in COPD.

CuAAC-based assembly and characterization of a ruthenium-copper dyad containing a diimine-dioxime ligand framework.

The design of molecular dyads combining a light-harvesting unit with an electroactive centre is highly demanded in the field of artificial photosynthesis. The versatile Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC) procedure was employed to assemble a ruthenium tris-diimine unit to an unprecedented azide-substituted copper diimine-dioxime moiety. The resulting RuCu dyad 4 was characterized by electrochemistry, H NMR, EPR, UV-visible absorption, steady-state fluorescence and transient absorption spectroscopies.

Direct Observation of a Charge-Transfer State Preceding High-Yield Singlet Fission in Terrylenediimide Thin Films.

Singlet exciton fission (SF) in organic chromophore assemblies results in the conversion of one singlet exciton (S) into two triplet excitons (T), provided that the overall process is exoergic, i.e., E(S) > 2E(T).

A reference data set of 5.4 million phased human variants validated by genetic inheritance from sequencing a three-generation 17-member pedigree.

Improvement of variant calling in next-generation sequence data requires a comprehensive, genome-wide catalog of high-confidence variants called in a set of genomes for use as a benchmark. We generated deep, whole-genome sequence data of 17 individuals in a three-generation pedigree and called variants in each genome using a range of currently available algorithms. We used haplotype transmission information to create a phased "Platinum" variant catalog of 4.

Enabling singlet fission by controlling intramolecular charge transfer in π-stacked covalent terrylenediimide dimers.

When an assembly of two or more molecules absorbs a photon to form a singlet exciton, and the energetics and intermolecular interactions are favourable, the singlet exciton can rapidly and spontaneously produce two triplet excitons by singlet fission. To understand this process is important because it may prove to be technologically significant for enhancing solar-cell performance. Theory strongly suggests that charge-transfer states are involved in singlet fission, but their role has remained an intriguing puzzle and, up until now, no molecular system has provided clear evidence for such a state.

Singlet Fission via an Excimer-Like Intermediate in 3,6-Bis(thiophen-2-yl)diketopyrrolopyrrole Derivatives.

Singlet fission (SF) in polycrystalline thin films of four 3,6-bis(thiophen-2-yl)diketopyrrolopyrrole (TDPP) chromophores with methyl (Me), n-hexyl (C6), triethylene glycol (TEG), and 2-ethylhexyl (EH) substituents at the 2,5-positions is found to involve an intermediate excimer-like state. The four different substituents yield four distinct intermolecular packing geometries, resulting in variable intermolecular charge transfer (CT) interactions in the solid. SF from the excimer state of Me, C6, TEG, and EH takes place in τSF = 22, 336, 195, and 1200 ps, respectively, to give triplet yields of 200%, 110%, 110%, and 70%, respectively.

Effects of Crystal Morphology on Singlet Exciton Fission in Diketopyrrolopyrrole Thin Films.

Singlet exciton fission (SF) is a promising strategy for increasing photovoltaic efficiency, but in order for SF to be useful in solar cells, it should take place in a chromophore that is air-stable, highly absorptive, solution processable, and inexpensive. Unlike many SF chromophores, diketopyrrolopyrrole (DPP) conforms to these criteria, and here we investigate SF in DPP for the first time. SF yields in thin films of DPP derivatives, which are widely used in organic electronics and photovoltaics, are shown to depend critically on crystal morphology.

Photoinduced Charge and Energy Transfer within meta- and para-Linked Chlorophyll a-Perylene-3,4:9,10-bis(dicarboximide) Donor-Acceptor Dyads.

Connecting electron donors and acceptors to a benzene ring in a meta or para relationship results in quantum interference effects that can strongly influence charge separation (CS) and charge recombination (CR) processes in these systems. We report on the energy and electron transfer behavior of chlorophyll-based para- and meta-linked donor-bridge-acceptor (D-B-A) dyads, where the semisynthetic chlorophyll a derivative, zinc methyl 3-ethyl-pyrochlorophyllide a (D), is covalently attached at its 20-position to the para position of one phenyl of diphenylacetylene (B). The meta or para position of the phenyl in B distal to the donor is in turn attached to perylene-3,4:9,10-bis(dicarboximide) (PDI) (A).

Charge and spin transport in an organic molecular square.

Understanding electronic communication among multiple chromophoric and redox units requires construction of well-defined molecular architectures. Herein, we report the modular synthesis of a shape-persistent chiral organic square composed of four naphthalene-1,8:4,5-bis(dicarboximide) (NDI) sides and four trans-1,2-cyclohexanediamine corners. Single crystal X-ray diffraction reveals some distortion of the cyclohexane chair conformation in the solid state.

Sub-Picosecond Singlet Exciton Fission in Cyano-Substituted Diaryltetracenes.

Thin films of 5,11-dicyano-6,12-diphenyltetracene (TcCN) have been studied for their ability to undergo singlet exciton fission (SF). Functionalization of tetracene with cyano substituents yields a more stable chromophore with favorable energetics for exoergic SF (2E(T1)-E(S1)=-0.17 eV), where S1 and T1 are singlet and triplet excitons, respectively.

Photogenerated Quartet State Formation in a Compact Ring-Fused Perylene-Nitroxide.

We report on a novel small organic molecule comprising a perylene chromophore fused to a six-membered ring containing a persistent nitroxide radical to give a perylene-nitroxide, or PerNO(•). This molecule is a robust, compact molecule in which the radical is closely bound to the chromophore but separated by saturated carbon atoms, thus limiting the electronic coupling between the chromophore and radical. We present both ultrafast transient absorption experiments and time-resolved EPR (TREPR) studies to probe the spin dynamics of photoexcited PerNO(•) and utilize X-ray crystallography to probe the molecular structure and stacking motifs of PerNO(•) in the solid state.

Singlet exciton fission in thin films of tert-butyl-substituted terrylenes.

Two terrylene chromophores, 2,5,10,13-tetra(tert-butyl)terrylene (1) and 2,5-di(tert-butyl)terrylene (2), were synthesized and studied to determine their singlet exciton fission (SF) efficiencies. Compound 1 crystallizes in one-dimensional stacks, whereas 2 packs in a slip-stacked, herringbone pattern of dimers motif. Strongly quenched fluorescence and rapid singlet exciton decay dynamics are observed in vapor-deposited thin films of 1 and 2.

Photochemical nitrogen conversion to ammonia in ambient conditions with FeMoS-chalcogels.

In nature, nitrogen fixation is one of the most important life processes and occurs primarily in microbial organisms containing enzymes called nitrogenases. These complex proteins contain two distinct subunits with different active sites, with the primary N2 binding site being a FeMoS core cluster that can be reduced by other nearby iron-sulfur clusters. Although nitrogen reduction to ammonia in biology does not require the absorption of light, there is considerable interest in developing catalyst materials that could drive the formation of ammonia from nitrogen photochemically.

Long-lived charge carrier generation in ordered films of a covalent perylenediimide-diketopyrrolopyrrole-perylenediimide molecule.

The photophysics of a covalently linked perylenediimide-diketopyrrolopyrrole-perylenediimide acceptor-donor-acceptor molecule (PDI-DPP-PDI, ) were investigated and found to be markedly different in solution in unannealed and solvent annealed films. Photoexcitation of in toluene results in quantitative charge separation in = 3.1 ± 0.

Photoinduced Electron Transfer in 2,5,8,11-Tetrakis-Donor-Substituted Perylene-3,4:9,10-bis(dicarboximides).

A series of electron donor-acceptor compounds based on substitution of perylene-3,4:9,10-bis(dicarboximide) (PDI) with four electron donors at the 2,5,8,11-positions were synthesized and characterized using femtosecond transient absorption spectroscopy. The distance between the PDI and the N,N-dimethylaniline or phenothiazine donors was varied using one or two phenyl groups. Photoexcitation of PDI results in rapid charge separation followed by charge recombination with time constants ranging from tens of picoseconds to nanoseconds.

Excimer formation in cofacial and slip-stacked perylene-3,4:9,10-bis(dicarboximide) dimers on a redox-inactive triptycene scaffold.

Excitation energy transfer in perylene-3,4:9,10-bis(dicarboximide) (PDI) aggregates is of interest for light-harvesting applications of this strongly absorbing and π-π stacking chromophore. Here we report the synthesis and characterization of two PDI dimers in which the chromophores are covalently linked by a redox-inactive triptycene bridge in orientations that are cofacial (1) and slip-stacked along their N-N axes (2). Femtosecond transient absorption experiments on 1 and 2 reveal rapid exciton delocalization resulting excimer formation.

Energy flow dynamics within cofacial and slip-stacked perylene-3,4-dicarboximide dimer models of π-aggregates.

Robust perylene-3,4-dicarboximide (PMI) π-aggregates provide important light-harvesting and electron-hole pair generation advantages in organic photovoltaics and related applications, but relatively few studies have focused on the electronic interactions between PMI chromophores. In contrast, structure-function relationships based on π-π stacking in the related perylene-3,4:9,10-bis(dicarboximides) (PDIs) have been widely investigated. The performance of both PMI and PDI derivatives in organic devices may be limited by the formation of low-energy excimer trap states in morphologies where interchromophore coupling is strong.

Protecting the triplet excited state in sterically congested platinum porphyrin.

Platinum tetrakis(2,4,6-triethylphenyl)porphyrin (Pt-1) was synthesized and its structural (X-ray), electrochemical and photophysical properties were fully characterized. Comparative studies of Pt-1 and its unsubstituted analog PtTPP show the effect of sterically congesting ortho-substituents on the dynamics of the triplet excited states. Lowered quenching rates by 3-4 times were observed for Pt-1vs.

Singlet exciton fission in polycrystalline thin films of a slip-stacked perylenediimide.

The crystal structure of N,N-bis(n-octyl)-2,5,8,11-tetraphenylperylene-3,4:9,10-bis(dicarboximide), 1, obtained by X-ray diffraction reveals that 1 has a nearly planar perylene core and π-π stacks at a 3.5 Å interplanar distance in well-separated slip-stacked columns. Theory predicts that slip-stacked, π-π-stacked structures should enhance interchromophore electronic coupling and thus favor singlet exciton fission.

Somatic mutations in MAP3K5 attenuate its proapoptotic function in melanoma through increased binding to thioredoxin.

Patients with advanced metastatic melanoma have poor prognosis and the genetics underlying its pathogenesis are poorly understood. High-throughput sequencing has allowed comprehensive discovery of somatic mutations in cancer samples. Here, on analysis of our whole-genome and whole-exome sequencing data of 29 melanoma samples, we identified several genes that harbor recurrent nonsynonymous mutations.

Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma.

Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683-691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples.

Adult pallium transcriptomes surprise in not reflecting predicted homologies across diverse chicken and mouse pallial sectors.

The thorniest problem in comparative neurobiology is the identification of the particular brain region of birds and reptiles that corresponds to the mammalian neocortex [Butler AB, Reiner A, Karten HJ (2011) Ann N Y Acad Sci 1225:14-27; Wang Y, Brzozowska-Prechtl A, Karten HJ (2010) Proc Natl Acad Sci USA 107(28):12676-12681]. We explored which genes are actively transcribed in the regions of controversial ancestry in a representative bird (chicken) and mammal (mouse) at adult stages. We conducted four analyses comparing the expression patterns of their 5,130 most highly expressed one-to-one orthologous genes that considered global patterns of expression specificity, strong gene markers, and coexpression networks.

Sequencing studies in human genetics: design and interpretation.

Next-generation sequencing is becoming the primary discovery tool in human genetics. There have been many clear successes in identifying genes that are responsible for Mendelian diseases, and sequencing approaches are now poised to identify the mutations that cause undiagnosed childhood genetic diseases and those that predispose individuals to more common complex diseases. There are, however, growing concerns that the complexity and magnitude of complete sequence data could lead to an explosion of weakly justified claims of association between genetic variants and disease.