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While heteroatom-centered radicals are understood to be highly electrophilic, their ability to serve as transient electron-withdrawing groups and facilitate polar reactions at distal sites has not been extensively developed. Here, we report a new strategy for the electronic activation of halophenols, wherein generation of a phenoxyl radical via formal homolysis of the aryl O-H bond enables direct nucleophilic aromatic substitution of the halide with carboxylate nucleophiles under mild conditions. Pulse radiolysis and transient absorption studies reveal that the neutral oxygen radical (O

Here we report the use of pulse radiolysis and spectroelectrochemistry to generate low-valent nickel intermediates relevant to synthetically important Ni-catalyzed cross-coupling reactions and interrogate their reactivities toward comproportionation and oxidative addition processes. Pulse radiolysis provided a direct means to generate singly reduced [(dtbbpy)NiBr], enabling the identification of a rapid Ni(0)/Ni(II) comproportionation process taking place under synthetically relevant electrolysis conditions. This approach also permitted the direct measurement of Ni(I) oxidative addition rates with electronically differentiated aryl iodide electrophiles (kOA = 1.3 × 104-2.4 × 105 M-1 s-1), an elementary organometallic step often proposed in nickel-catalyzed cross-coupling reactions. Together, these results hold implications for a number of Ni-catalyzed cross-coupling processes.

Non-natural photoenzymatic reactions reported to date have depended on the excitation of electron donor-acceptor complexes formed between substrates and cofactors within protein active sites to facilitate electron transfer. While this mechanism has unlocked new reactivity, it limits the types of substrates that can be involved in this area of catalysis. Here we demonstrate that direct excitation of flavin hydroquinone within "ene"-reductase active sites enables new substrates to participate in photoenzymatic reactions. We found that by using photoexcitation these enzymes gain the ability to reduce acrylamides through a single electron transfer mechanism.

For more than a decade, photoredox catalysis has been demonstrating that when photoactive catalysts are irradiated with visible light, reactions occur under milder, cheaper, and environmentally friendlier conditions. Furthermore, this methodology allows for the activation of abundant chemicals into valuable products through novel mechanisms that are otherwise inaccessible. The photoredox approach, however, has been primarily used for pharmaceutical applications, where its implementation has been highly effective, but typically with a more rudimentary understanding of the mechanisms involved in these transformations. From a global perspective, the manufacture of everyday chemicals by the chemical industry as a whole currently accounts for 10% of total global energy consumption and generates 7% of the world's greenhouse gases annually. In this context, the Bio-Inspired Light-Escalated Chemistry (BioLEC) Energy Frontier Research Center (EFRC) was founded to supercharge the photoredox approach for applications in chemical manufacturing aimed at reducing its energy consumption and emissions burden, by using bioinspired schemes to harvest multiple electrons to drive endothermically uphill chemical reactions. The Center comprises a diverse group of researchers with expertise that includes synthetic chemistry, biophysics, physical chemistry, and engineering. The team works together to gain a deeper understanding of the mechanistic details of photoredox reactions while amplifying the applications of these light-driven methodologies.In this Account, we review some of the major advances in understanding, approach, and applicability made possible by this collaborative Center. Combining sophisticated spectroscopic tools and photophysics tactics with enhanced photoredox reactions has led to the development of novel techniques and reactivities that greatly expand the field and its capabilities. The Account is intended to highlight how the interplay between disciplines can have a major impact and facilitate the advance of the field. For example, techniques such as time-resolved dielectric loss (TRDL) and pulse radiolysis are providing mechanistic insights not previously available. Hypothesis-driven photocatalyst design thus led to broadening of the scope of several existing transformations. Moreover, bioconjugation approaches and the implementation of triplet-triplet annihilation mechanisms created new avenues for the exploration of reactivities. Lastly, our multidisciplinary approach to tackling real-world problems has inspired the development of efficient methods for the depolymerization of lignin and artificial polymers.

Redox potentials, especially as measured by cyclic voltammetry and related electrochemical techniques, are the basis for understanding energetics of photochemical solar energy storage, organic photovoltaics, light-emitting diodes, and even photosynthesis. These very popular techniques are dominant although none of the energy systems just mentioned contain large concentrations, typically 100 mM, of supporting electrolyte needed for electrochemical techniques to work. At the same time, the added electrolytes often have large, but unknown effects on the energetics studied. Despite substantial efforts using microelectrodes, it has not been possible to utilize electrochemical techniques to measure redox potentials in the absence of electrolytes. This chapter will be an account of new techniques applying the method of pulse radiolysis to partly answer the question: what is the effect of electrolytes on redox potentials?

Pulse radiolysis (PR) enables the full redox window of a solvent to be accessed, as it does not require electrodes or electrolyte which limit the potentials accessible in voltammetry measurements. PR in chloroform has the additional possibility to enable reaching highly positive potentials because of its large ionization potential (IP). PR experiments demonstrated the formation of the (deuterated) chloroform radical cation CDCl3+˙, identifying it as the source of the broad absorption in the visible part of the spectrum. Results indicated that solutes with a redox potential up to +3.7 V vs. Fc/Fc+ can be oxidized by CDCl3+˙, which is far beyond what is possible with electrochemical techniques. Oxidation is not efficient because of rapid geminate recombination with chloride counterions, but also due to rapid decomposition of CDCl3+˙ which limits the yield of otherwise longer-lived free ions. The rapid, 6 ± 3 ns, decomposition, confirmed by two independent experiments, means that a solute must be present at a concentration >100 mM to capture >90% of the free holes formed. Addition of ethene removes the broad, overlapping absorptions from ubiquitous (chlorine atom, solute) complexes created by PR in halogenated solvents enabling clear observation of solute cations. The results also unravel the complex radiation chemistry of chloroform including the large reported value G(-CHCl3) = 12 molecules/100 eV for the decomposition of chloroform molecules.

A series of weakly coordinating cations/anions (TAPR/TFAB) ion pairs are, herein, being proposed as non-aqueous electrolytes for high capacity ORFBs. These were accessed via a Palladiumcatalyzed approach followed by the simple filtration/isolation of the product. These substituted tetraarylphosphonium/tetrakis(pentafluorophenyl)borate salts 1-4 where the substituents are a pmethoxy (1), a 3,4-dimethoxy (2), a p-phenyl (3), and a p-trimethylsilylacetylene (TMSA) (4) have potential use in several industries owing to their unique solubility in low polarity solvents. These salts constitute a new class of molecular ion pairs which can promote charge dissociation even in low polarity solvents because of their large size and bulkiness. The result being an increased conductivity in those media that can be useful for electrochemistry, advances in catalysis, battery technology, petroleum handling etc. This work supports the national security goal of fostering the development of affordable, clean and renewable energy source and storage.

Carrier mobility in doped conjugated polymers is limited by Coulomb interactions with dopant counterions. This complicates studying the effect of the dopant's oxidation potential on carrier generation because different dopants have different Coulomb interactions with polarons on the polymer backbone. Here, dodecaborane (DDB)‐based dopants are used, which electrostatically shield counterions from carriers and have tunable redox potentials at constant size and shape. DDB dopants produce mobile carriers due to spatial separation of the counterion, and those with greater energetic offsets produce more carriers. Neutron reflectometry indicates that dopant infiltration into conjugated polymer films is redox‐potential‐driven. Remarkably, X‐ray scattering shows that despite their large 2‐nm size, DDBs intercalate into the crystalline polymer lamellae like small molecules, indicating that this is the preferred location for dopants of any size. These findings elucidate why doping conjugated polymers usually produces integer, rather than partial charge transfer: dopant counterions effectively intercalate into the lamellae, far from the polarons on the polymer backbone. Finally, it is shown that the IR spectrum provides a simple way to determine polaron mobility. Overall, higher oxidation potentials lead to higher doping efficiencies, with values reaching 100% for driving forces sufficient to dope poorly crystalline regions of the film.

A novel method to determine redox potentials without electrolyte is presented. The method is based on a new ability to determine the dissociation constant, K°d, for ion pairs formed between any radical anion and any inert electrolyte counterion. These dissociation constants can be used to determine relative shifts of redox potential as a function of electrolyte concentration, connecting referenced potentials determined with electrochemistry (with 0.1 M electrolyte) to electrolyte-free values. Pulse radiolysis created radical anions enabling determination of equilibrium constants for electron transfer between anions of donor and acceptor molecules as a function of electrolyte concentration in THF. The measurements determined "composite equilibrium constants", KeqC, which contain information about the dissociation constant for the electrolyte cations, X+, with the radical anions of both the donor, K°d(D-•,X+) and the acceptor, K°d(A-•,X+). Dissociation constants were obtained for a selection of radical anions with tetrabutylammonium (TBA+). The electrolyte was found to shift the reduction potentials of small molecules 1-methylpyrene and trans-stilbene by close to +130 mV whereas oligo-fluorenes and polyfluorenes experienced shifts of only (+25 ± 6) mV due to charge delocalization weakening the ion pair. These shifts for reduction of aromatic hydrocarbon molecules are smaller than shifts of +232 and +451 mV seen previously for benzophenone radical anion with TBA+ and Na+ respectively where the charge on the radical anion is localized largely on one C═O bond, thus forming a more tightly bound ion pair.

Reduction potentials have been determined for two molecules, benzophenone (BzPh) and perylene (Per), effectively in the complete absence of electrolyte as well as in the presence of three different supporting electrolytes in the moderately polar solvent THF. A description of how this can be so, and qualifications, are described in the discussion section. The primary tool in this work, pulse radiolysis, measures electron transfer (ET) equilibria in solution to obtain differences in redox potentials. Voltammetry measures redox potentials by establishing ET equilibria at electrodes, but electrolytes are needed for current flow. Results here show that without electrolyte the redox potentials were 100–451 mV more negative than those with 100 mM electrolyte. These changes depended both on the molecule and the electrolyte. In THF the dominant contributor to stabilization of radical anions by electrolyte was ion pairing. An equation was derived to give changes in redox potentials when electrolyte is added in terms of ion pair dissociation constants and activity coefficients. Definite values were determined for energetics, ΔG d °, of ion pairing. Values of ΔG d ° for pairs with TBA + give some doubt that it is a “weakly-coordinating cation.” Computations with DFT methods were moderately successful at describing the ion paring energies.

The nature of electron and hole polarons on poly(9,9-di-n-hexylfluorenyl-2,7-diyl) (pF) and a copolymer poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,8-diyl)] (F8BT) has been studied by chemical doping, pulse radiolysis, charge modulation spectroscopy, quantum chemical calculations, and microwave conductivity. While pF exhibits very similar behavior in all respects for the electron and the hole, this paper explores the hypothesis that the donor acceptor (push–pull) nature of F8BT will tend to localize charges. Optical spectra and quantum chemical calculations point to an electron localized on the thiadiazole unit in polar liquids but becoming more delocalized as the solvent polarity decreases. Indeed, in the nonpolar solvent benzene, the electron mobility is only 2.7 times lower than that of the hole, which conversely is shown to be delocalized in all environments and has a similar mobility to polarons on the homopolymer polyfluorene. Advantageous modifications to the optoelectroni...

Here, we offer you a high-throughput assay to measure the ATP synthesis capacity in cells or isolated mitochondria. More specifically, the assay is linked to the mitochondrial' electron transport chain components of your interest being either through complex I (with or without a linkage to pyruvate dehydrogenase activity), through complex II, or through the electron transport flavoprotein and complex I (β-oxidation of fatty acids).

Triplet excitons created in poly-2,7-(9,9-dihexyl)fluorene (pF) chains with end trap groups in solution are efficiently transported to and captured by the end groups. The triplets explore the entire lengths of the chains, even for ∼100 nm long chains, enabling determination of the completeness of end-capping. The results show that the chains are continuous: they may contain transient barriers or traps, such as those from fluctuations of dihedral angles, but they are free of major defects that stop motion of the triplets. Quantitative determinations are aided by the addition of a strong electron donor, TMPD, which removes absorption bands of the end-trapped triplets. For chains having at least one end trap, triplet capture is quantitative on the 1 μs time scale imposed by the use of the donor. Fractions of chains having no end traps were 0.15 for pF samples with anthraquinone (AQ) end traps and 0.063 with naphthylimide (NI) end traps. These determinations agreed with measurements by NMR for short (40 polymer repeat units (PRU)) chains, where NMR determinations are accurate. The results find no evidence for traps or barriers to the transport of triplets, and places limits on the possible presence of defects as impenetrable barriers to less than one per 300 PRU. The present results present a paradigm different from the current consensus, derived from observations of singlet excitons, that conjugated chains are divided into "segments," perhaps by some kind of defects. For the present pF chains, the segmentation either does not apply to triplet excitons or is transient so that the defects are healed or surmounted in times much shorter than 1 μs. Triplets on chains without end trap groups transfer to chains with end traps on a slower time scale. Rate constants for these bimolecular triplet transfer reactions were found to increase with the length of the accepting chain, as did rate constants for triplet transfer to the chains from small molecules like biphenyl. A second set of polyfluorenes with 2-butyloctyl side chains was found to have a much lower completeness of end-capping.

Background The neuropathology of mitochondrial disease is well characterised. However, pathophysiological mechanisms at the level of biochemistry and cell biology are less clear. Progress in this area has been hampered by the limited accessibility of neurologically relevant material for analysis. Scope of review Here we discuss the recent development of a variety of model systems that have greatly extended our capacity to understand the biochemical features associated with mitochondrial neuropathology. These include animal and cell based models, with mutations in both nuclear and mitochondrial DNA encoded genes, which aim to recapitulate the neuropathology and cellular biochemistry of mitochondrial diseases. Major conclusions Analysis of neurological tissue and cells from these models suggests that although there is no unifying mode of pathogenesis, dysfunction of the oxidative phosphorylation (OXPHOS) system is often central. This can be associated with altered reactive oxygen species (ROS) generation, disruption of the mitochondrial membrane potential (Δ Ψ m ) and inadequate ATP synthesis. Thus, other cellular processes such as calcium (Ca 2 + ) homeostasis, cellular signaling and mitochondrial morphology could be altered, ultimately compromising viability of neuronal cells. General significance Mechanisms of neuronal dysfunction in mitochondrial disease are only just beginning to be characterised, are system dependent and complex, and not merely driven by energy deficiency. The diversity of pathogenic mechanisms emphasises the need for characterisation in a wide range of models, as different therapeutic strategies are likely to be needed for different diseases. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.

The high-frequency mobility of positive charges (holes) moving along the backbones of an extensive data set of 7 oligomers (n = 2–16) and 6 polymers (⟨n⟩ = 26–138) of fluorene was measured using pulse-radiolysis time-resolved microwave conductivity (PR-TRMC) in benzene. As expected, at 8.9 GHz, the measured isotropic ac mobility, μac,measiso, was observed to be strongly dependent on the lengths of the chains due to the charges encountering chain ends during one microwave cycle. Values of the measured mobility, μac,measiso, ranged from 5 × 10–4 cm2/(V s) for an n = 2 repeat unit oligomer to 0.18 cm2/(V s) for a polymer with an average length of ⟨n⟩ = 86 repeat units. Global fits to the entire set of lengths extracted the chain-length-independent intramolecular mobility, μacintra, using the Kubo formula, assuming normal diffusion along the contour of the molecule with reflecting boundary conditions at the ends. The effects of chain conformation, chain defects, polymer length distributions, and a finite pola...

The electron acceptor F4TCNQ p-dopes aggregates "nanowires" of poly(3-hexylthiophene) in nonpolar solvents but does not dope unaggregated chains. The standard free energy change for the charge transfer to form an ion pair is ΔG°et = -0.21 eV. The dissociation constant to produce free ions in toluene by DC conductivity is K°d = 1 × 10-8 ± 50% (ΔG°d = 0.48 ± 0.05 eV). This remarkably large K°d , for ions in such a low polarity medium, may reflect interchain delocalization of the hole. The particular characteristics of this material system enables determination of both ΔG°et and ΔG°d , to find the overall free energy change from the two neutral species to completely separated ions in nonpolar media. It is endergonic by +0.27 ± 0.05 eV in contrast to -0.6 eV estimated from reported HOMO LUMO differences, illustrating the challenges that persist in determining such energetics. Steady state microwave conductivity experiments on doped aggregates confirm that holes in the aggregates cannot easily escape their dopant counterion, but at higher dopant concentrations, holes become mobile. These results provide insight into the mechanisms of charge separation involving intermolecularly delocalized charges in nonpolar media, an integral process in organic photovoltaic devices and doped molecular films.

The fundamental process of hole capture in solution was investigated following pulse radiolysis with polyfluorene and 4-cyano-4″-pentyl-p-terphenyl scavengers. Contrary to expectation, a large fraction of holes were captured in experimental time-resolution limited ∼20 ps steps, by a process much faster than diffusion of the initially formed solvent molecular cation. At the highest concentrations, 1.92 mM for a 52 unit long polyfluorene and 800 mM for 4-cyano-4″-pentyl-p-terphenyl, 66% and 99%, respectively, of the initially formed holes were captured by 20 ps, with radiation chemical yield G = 1.2 × 10(-7) and 1.7 × 10(-7) mol J(-1). The data can be explained by capture of presolvated holes, analogous to presolvated electrons, possibly possessing extended wave functions, high mobilities, or excess kinetic energy for the first few picoseconds after their creation. Such a process is not generally known in solution; however, the observed step capture as a function of solute concentration is shown to be well explained by this model. In addition to understanding the capture process in solution, the very large step yields formed in 20 ps will provide the ability to resolve subsequent hole transfer on the polymers with2 orders of magnitude better time resolution than expected.

In an attempt to disentangle the effects of permittivity and surface energy of the gate insulator (expressed by its dielectric constant k and water contact angle, respectively) on the performance of organic field-effect transistors (FETs), we fabricated top- and bottom-gate FET architectures with poly(3 - alkylthiophenes) (P3ATs) of different side-chain lengths, using a range of gate dielectrics. We find that this class of semiconductor, including the short butyl-(C 4 –) substituted derivative, is significantly less susceptible to the often detrimental effects that high- k dielectrics can have on the performance of many organic FETs. For bottom gate devices we identify the surface energy of the gate dielectric to predominantly dictate the device mobility.

We identified Mrpl44 in a search for mammalian proteins that contain RNase III domains. This protein was previously found in association with the mitochondrial ribosome of bovine liver extracts. However, the precise Mrpl44 localization had been unclear. Here, we show by immunofluorescence microscopy and subcellular fractionation that Mrpl44 is localized to the matrix of the mitochondria. We found that it can form multimers, and confirm that it is part of the large subunit of the mitochondrial ribosome. By manipulating its expression, we show that Mrpl44 may be important for regulating the expression of mtDNA-encoded genes. This was at the level of RNA expression and protein translation. This ultimately impacted ATP synthesis capability and respiratory capacity of cells. These findings indicate that Mrpl44 plays an important role in the regulation of the mitochondrial OXPHOS capacity. ispartof: PLoS One vol:10 issue:7 pages:1-16 ispartof: location:United States status: published

Charge transport is investigated in high-mobility n-channel organic field-effect transistors (OFETs) based on poly{[N,N′-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5′-(2,2′-bithiophene)} (P(NDI2OD-T2), Polyera ActivInk™ N2200) with variable-temperature electrical measurements and charge-modulation spectroscopy. Results indicate an unusually uniform energetic landscape of sites for charge-carrier transport along the channel of the transistor as the main reason for the observed high-electron mobility. Consistent with a lateral field-independent transport at temperatures down to 10 K, the reorganization energy is proposed to play an important role in determining the activation energy for the mobility. Quantum chemical calculations, which show an efficient electronic coupling between adjacent units and a reorganization energy of a few hundred meV, are consistent with these findings.

Field-effect transistors based on conjugated polymers are being developed for large-area electronic applications on flexible substrates, but they also provide a very useful tool to probe the charge transport physics of these complex materials. In this review we discuss recent progress in polymer semiconductor materials, which have brought the performance and mobility of polymer devices to levels comparable to that of small-molecule organic semiconductors. These new materials have also enabled deeper insight into the charge transport physics of high-mobility polymer semiconductors gained from experiments with high charge carrier concentration and better molecular-scale understanding of the electronic structure at the semiconductor/ dielectric interface.

The diffusion of singlet and triplet excitons along single polyfluorene chains in solution has been studied by monitoring their transport to end traps. Time-resolved transient absorption and steady state fluorescence were used to determine fractions of excitons that reach the end caps. In order to accurately determine the singlet diffusion coefficient, the fraction of polymer ends that have end traps was determined through a combination of NMR and triplet quenching experiments. The distributions of polymer lengths were also taken into account and the resulting analysis points to a surprisingly long singlet diffusion length of 34 nm. Experiments on triplet transport also suggest that the entire 100nm+ chain is accessible to the triplet during its lifetime suggesting a lack of hindrance by defects or traps on this timescale. Time Resolved Microwave Conductivity measurements were also performed on a series of different length oligo- and polyfluorenes in solution allowing a global fit to be performed to extract an accurate intrachain mobility of 1.1 cm2/Vs.

Leigh syndrome (LS) is the most common pediatric presentation of a defined mitochondrial disease. This progressive encephalopathy is characterized pathologically by the development of bilateral symmetrical lesions in the brainstem and basal ganglia that show gliosis, vacuolation, capillary proliferation, relative neuronal preservation, and by hyperlacticacidemia in the blood and/or cerebrospinal fluid. Understanding the molecular mechanisms underlying this unique pathology has been challenging, particularly in view of the heterogeneous and not yet fully determined genetic basis of LS. Moreover, animal models that mimic features of LS have only been created relatively recently. Here, we review the pathology of LS and consider what might be the molecular mechanisms underlying its pathogenesis. Data from a wide range of sources, including patient samples, animal models, and studies of hypoxic-ischemic encephalopathy (a condition that shares features with LS), were used to provide insight into the pathogenic mechanisms that may drive lesion development. Based on current data, we suggest that severe ATP depletion, gliosis, hyperlacticacidemia, reactive oxygen species, and potentially excitotoxicity cumulatively contribute to the neuropathogenesis of LS. An intimate understanding of the molecular mechanisms causing LS is required to accelerate the development of LS treatments.

Photoexcitation of conjugated poly-2,7-(9,9-dihexylfluorene) polyfluorenes with naphthylimide (NI) and anthraquinone (AQ) electron-acceptor end traps produces excitons that form charge transfer states at the end traps. Intramolecular singlet exciton transport to end traps was examined by steady state fluorescence for polyfluorenes of 17-127 repeat units in chloroform, dimethylformamide (DMF), tetrahydrofuran (THF), and p-xylene. End traps capture excitons and form charge transfer (CT) states at all polymer lengths and in all solvents. The CT nature of the end-trapped states is confirmed by their fluorescence spectra, solvent and trap group dependence, and DFT descriptions. Quantum yields of CT fluorescence are as large as 46%. This strong CT emission is understood in terms of intensity borrowing. Energies of the CT states from onsets of the fluorescence spectra give the depths of the traps which vary with solvent polarity. For NI end traps, the trap depths are 0.06 (p-xylene), 0.13 (THF), and 0.19 eV (CHCl3). For AQ, CT fluorescence could be observed only in p-xylene where the trap depth is 0.27 eV. Quantum yields, emission energies, charge transfer energies, solvent reorganization, and vibrational energies were calculated. Fluorescence measurements on chains >100 repeat units indicate that end traps capture ∼50% of the excitons, and that the exciton diffusion length is LD = 34 nm, which is much larger than diffusion lengths reported in polymer films or than previously known for diffusion along isolated chains. The efficiency of exciton capture depends on chain length but not on trap depth, solvent polarity, or which trap group is present.

Mitochondrial dysfunction causes a range of early-onset neurological diseases and contributes to neurodegenerative conditions. The mechanisms of neurological damage however are poorly understood, as accessing relevant tissue from patients is difficult, and appropriate models are limited. Hence, we assessed mitochondrial function in neurologically relevant primary cell lines from a CI (complex I) deficient Ndufs4 KO (knockout) mouse (Ndufs4fky/fky) modelling aspects of the mitochondrial disease LS (Leigh syndrome), as well as MEFs (mouse embryonic fibroblasts). Although CI structure and function were compromised in all Ndufs4fky/fky cell types, the mitochondrial membrane potential was selectively impaired in the MEFs, correlating with decreased CI-dependent ATP synthesis. In addition, increased ROS (reactive oxygen species) generation and altered sensitivity to cell death were only observed in Ndufs4fky/fky primary MEFs. In contrast, Ndufs4fky/fky primary isocortical neurons and primary isocortical astrocytes displayed only impaired ATP generation without mitochondrial membrane potential changes. Therefore the neurological dysfunction in the Ndufs4fky/fky mouse may partly originate from a more severe ATP depletion in neurons and astrocytes, even at the expense of maintaining the mitochondrial membrane potential. This may provide protection from cell death, but would ultimately compromise cell functionality in neurons and astrocytes. Furthermore, RET (reverse electron transfer) from complex II to CI appears more prominent in neurons than MEFs or astrocytes, and is attenuated in Ndufs4fky/fky cells., We describe how the metabolic response in neurologically relevant primary astrocytes and neurons diverges from that of mouse embryonic fibroblasts isolated from the Ndufs4fky/fky mouse model of mitochondrial disease.

Understanding the mechanisms limiting ambipolar transport in conjugated polymer field-effect transistors (FETs) is of both fundamental and practical interest. Here, we present a systematic study comparing hole and electron charge transport in an ambipolar conjugated polymer, semicrystalline poly(3,3${}^{\ensuremath{'}\ensuremath{'}}$-di-$n$-decylterselenophene) (PSSS). Starting from a detailed analysis of the device characteristics and temperature/charge-density dependence of the mobility, we interpret the difference between hole and electron transport through both the Vissenberg-Matters and the mobility-edge model. To obtain microscopic insight into the quantum mechanical wave function of the charges at a molecular level, we combine charge modulation spectroscopy (CMS) measuring the charge-induced absorption signatures from positive and negative polarons in these ambipolar FETs with corresponding density functional theory (DFT) calculations. We observe a significantly higher switch-on voltage for electrons than for holes due to deep electron trap states, but also a higher activation energy of the mobility for mobile electrons. The CMS spectra reveal that the electrons that remain mobile and contribute to the FET current have a wave function that is more localized onto a single polymer chain than that of holes, which is extended over several polymer chains. We interpret this as evidence that the transport properties of the mobile electrons in PSSS are still affected by the presence of deep electron traps. The more localized electron state could be due to the mobile electrons interacting with shallow trap states in the vicinity of a chemical, potentially water-related, impurity that might precede the capture of the electron into a deeply trapped state.

BackgroundFrameshift mutations in microsatellite instability high (MSI-High) colorectal cancers are a potential source of targetable neo-antigens. Many nonsense transcripts are subject to rapid degradation due to nonsense-mediated decay (NMD), but nonsense transcripts with a cMS in the last exon or near the last exon-exon junction have intrinsic resistance to nonsense-mediated decay (NMD). NMD-resistant transcripts are therefore a likely source of expressed mutant proteins in MSI-High tumours.MethodsUsing antibodies to the conserved N-termini of predicted mutant proteins, we analysed MSI-High colorectal cancer cell lines for examples of naturally expressed mutant proteins arising from frameshift mutations in coding microsatellites (cMS) by immunoprecipitation and Western Blot experiments. Detected mutant protein bands from NMD-resistant transcripts were further validated by gene-specific short-interfering RNA (siRNA) knockdown. A genome-wide search was performed to identify cMS-containing genes likely to generate NMD-resistant transcripts that could encode for antigenic expressed mutant proteins in MSI-High colon cancers. These genes were screened for cMS mutations in the MSI-High colon cancer cell lines.ResultsMutant protein bands of expected molecular weight were detected in mutated MSI-High cell lines for NMD-resistant transcripts (CREBBP, EP300, TTK), but not NMD-sensitive transcripts (BAX, CASP5, MSH3). Expression of the mutant CREBBP and EP300 proteins was confirmed by siRNA knockdown. Five cMS-bearing genes identified from the genome-wide search and without existing mutation data (SFRS12IP1, MED8, ASXL1, FBXL3 and RGS12) were found to be mutated in at least 5 of 11 (45%) of the MSI-High cell lines tested.ConclusionNMD-resistant transcripts can give rise to expressed mutant proteins in MSI-High colon cancer cells. If commonly expressed in primary MSI-High colon cancers, MSI-derived mutant proteins could be useful as cancer specific immunological targets in a vaccine targeting MSI-High colonic tumours.

We have used time resolved spectroscopy to measure the relaxation of spin polarization in InSb/AlInSb quantum wells (QWs) as a function of temperature and mobility. The results are consistent with the D'yakonov–Perel (DP) mechanism for high mobility samples over the temperature range from 50 to 300 K. For low mobility samples at high temperature the Elliott–Yafet and DP mechanisms become comparable. We show that the mobility can in certain circumstances determine which mechanism is dominant, and that above 1 m2 V-1 s-1 in 20 nm wide InSb QWs it is the DP mechanism. We also give a criterion for the maximum spin lifetime in terms of mobility and temperature, and show that for our 20 nm wide QWs this corresponds to 0.5 ps at 300 K and mobility 1 m2 V-1 s-1.

We have used time-resolved spectroscopy to measure the relaxation of spin polarizations in the narrow gap semiconductor material n-InAs as a function of temperature, doping, and pump wavelength. The results are consistent with the D'Yakonov-Perel mechanism for temperatures between 77 and 300 K. However, the data suggest that electron-electron scattering should be taken into account in determining the dependence of the spin lifetime on the carrier concentration in the range 5.2×1016–8.8×1017 cm–3. For a sample with doping of 1.22×1017 cm–3 the spin lifetime was 24 ps at room temperature. By applying a magnetic field in the sample plane we also observed coherent precession of the spins in the time domain, with a g>/i> factor g*=–13, also at room temperature.

Friedreich ataxia (FRDA) is an autosomal recessive disease characterised by neurodegeneration and cardiomyopathy that is caused by an insufficiency of the mitochondrial protein, frataxin. Our previous studies described the generation of FRDA induced pluripotent stem cell lines (FA3 and FA4 iPS) that retained genetic characteristics of this disease. Here we extend these studies, showing that neural derivatives of FA iPS cells are able to differentiate into functional neurons, which don't show altered susceptibility to cell death, and have normal mitochondrial function. Furthermore, FA iPS-derived neural progenitors are able to differentiate into functional neurons and integrate in the nervous system when transplanted into the cerebellar regions of host adult rodent brain. These are the first studies to describe both in vitro and in vivo characterization of FA iPS-derived neurons and demonstrate their capacity to survive long term. These findings are highly significant for developing FRDA therapies using patient-derived stem cells.

Polymer light-emitting field-effect transistors (LEFETs) require high and balanced electron and hole mobilities to achieve high current densities. Here we demonstrate a novel gate dielectric for polymer LEFETs that enables mobilities of 0.01cm2∕Vs for both electrons and holes. The low-k dielectric polycyclohexylethylene is placed in direct contact with the poly(9,9-di-n-octylfluorene-alt-benzothiadiazole) semiconductor. A second dielectric layer comprising the high-k material poly(vinylidene fluoride-trifluoroethylene) is used to apply a high electric field onto the low-k dielectric layer. The attainable electron-hole recombination current in such optimized polymer LEFETs is measured and the implications for achieving electrically pumped lasing in a LEFET are discussed.

Understanding the electronic structure of organic-organic heterointerfaces is crucial for many device applications of organic semiconductors. Here we have developed a simple analytical model to describe the effect of static dipolar disorder in a polymer dielectric on the density of states of an adjacent organic semiconductor. The degree of energetic disorder varies strongly with distance from the interface. Using a simple mobility model, we have been able to explain quantitatively both the magnitude as well as the gate voltage dependence of the field-effect mobility for polymer gate dielectrics with different dielectric constants.

The emission characteristics and external quantum efficiencies of ambipolar polymer light-emitting field-effect transistors are investigated as a function of applied voltage, current density, and ratio of hole to electron mobility. Green-emitting poly(9,9-di-n-octylfluorene-alt-benzothiadiazole) (F8BT) with balanced electron and hole mobilities and red-emitting poly((9,9-dioctylfluorene)-2,7- diyl-alt-[4,7-bis(3-hexylthien-5-yl)-2,1,3-benzothiadiazole]-2′,2″-diyl) (F8TBT) with strongly unbalanced hole and electron mobilities as semiconducting and emissive polymers are compared. The current-voltage and light output characteristics of the two types of light-emitting transistors were found to be fundamentally alike independent of mobility ratio. Device modeling allowing for a single (Langevin-type) charge recombination mechanism was able to reproduce the device characteristics for both cases but could not replicate the experimentally observed dependence of external quantum efficiency on current density. The ...