Marcus Theory of Thermoelectricity in Molecular Junctions

Thermoelectric energy conversion is perhaps the most promising of the potential applications of molecular electronics. Ultimately, it is desirable for this technology to operate at around room temperature, and it is therefore important to consider the role of dissipative effects in these conditions. Here, we develop a theory of thermoelectricity which accounts for the vibrational coupling within the framework of Marcus theory. We demonstrate that the inclusion of lifetime broadening is necessary in the theoretical description of this phenomenon. We further show that the Seebeck coefficient and the power factor decrease with increasing reorganisation energy, and identify the optimal operating conditions in the case of non-zero reorganisation energy. Finally, with the aid of DFT calculations, we consider a prototypical fullerene-based molecular junction. We estimate the maximum power factor that can be obtained in this system, and confirm that C$_{60}$ is an excellent candidate for thermoelectric heat-to-energy conversion. This work provides general guidance that should be followed in order to achieve high-efficiency molecular thermoelectric materials.Comment: Supporting Information available at https://doi.org/10.1021/acs.jpcc.8b1216

Beyond Marcus theory and the Landauer-Büttiker approach in molecular junctions: A unified framework.

Charge transport through molecular junctions is often described either as a purely coherent or a purely classical phenomenon, and described using the Landauer-Büttiker formalism or Marcus theory (MT), respectively. Using a generalised quantum master equation, we here derive an expression for current through a molecular junction modelled as a single electronic level coupled with a collection of thermalised vibrational modes. We demonstrate that the aforementioned theoretical approaches can be viewed as two limiting cases of this more general expression and present a series of approximations of this result valid at higher temperatures. We find that MT is often insufficient in describing the molecular charge transport characteristics and gives rise to a number of artefacts, especially at lower temperatures. Alternative expressions, retaining its mathematical simplicity, but rectifying those shortcomings, are suggested. In particular, we show how lifetime broadening can be consistently incorporated into MT, and we derive a low-temperature correction to the semi-classical Marcus hopping rates. Our results are applied to examples building on phenomenological as well as microscopically motivated electron-vibrational coupling. We expect them to be particularly useful in experimental studies of charge transport through single-molecule junctions as well as self-assembled monolayers

Distinguishing Lead and Molecule States in Graphene-Based Single-Electron Transistors

Graphene provides a two-dimensional platform for contacting individual molecules, which enables transport spectroscopy of molecular orbital, spin and vibrational states. Here we report single-electron tunneling through a molecule that has been anchored to two graphene leads. Quantum interference within the graphene leads gives rise to an energy-dependent transmission and fluctuations in the sequential tunnel-rates. The lead states are electrostatically tuned by a global back-gate, resulting in a distinct pattern of varying intensity in the measured conductance maps. This pattern could potentially obscure transport features that are intrinsic to the molecule under investigation. Using ensemble averaged magneto-conductance measurements, lead and molecule states are disentangled, enabling spectroscopic investigation of the single molecule

Two Nuclear Localization Signals in USP1 Mediate Nuclear Import of the USP1/UAF1 Complex

The human deubiquitinase USP1 plays important roles in cancer-related processes, such as the DNA damage response, and the maintenance of the undifferentiated state of osteosarcoma cells. USP1 deubiquitinase activity is critically regulated by its interaction with the WD40 repeat-containing protein UAF1. Inhibiting the function of the USP1/UAF1 complex sensitizes cancer cells to chemotherapy, suggesting that this complex is a relevant anticancer target. Intriguingly, whereas UAF1 has been reported to locate in the cytoplasm, USP1 is a nuclear protein, although the sequence motifs that mediate its nuclear import have not been functionally characterized. Here, we identify two nuclear localization signals (NLSs) in USP1 and show that these NLSs mediate the nuclear import of the USP1/UAF1 complex. Using a cellular relocation assay based on these results, we map the UAF1-binding site to a highly conserved 100 amino acid motif in USP1. Our data support a model in which USP1 and UAF1 form a complex in the cytoplasm that subsequently translocates to the nucleus through import mediated by USP1 NLSs. Importantly, our findings have practical implications for the development of USP1-directed therapies. First, the UAF1-interacting region of USP1 identified here might be targeted to disrupt the USP1/UAF1 interaction with therapeutic purposes. On the other hand, we describe a cellular relocation assay that can be easily implemented in a high throughput setting to search for drugs that may dissociate the USP1/UAF1 complex

PTTG1 Attenuates Drug-Induced Cellular Senescence

As PTTG1 (pituitary tumor transforming gene) abundance correlates with adverse outcomes in cancer treatment, we determined mechanisms underlying this observation by assessing the role of PTTG1 in regulating cell response to anti-neoplastic drugs. HCT116 cells devoid of PTTG1 (PTTG1−/−) exhibited enhanced drug sensitivity as assessed by measuring BrdU incorporation in vitro. Apoptosis, mitosis catastrophe or DNA damage were not detected, but features of senescence were observed using low doses of doxorubicin and TSA. The number of drug-induced PTTG1−/− senescent cells increased ∼4 fold as compared to WT PTTG1-replete cells (p<0.001). p21, an important regulator of cell senescence, was induced ∼3 fold in HCT116 PTTG1−/− cells upon doxorubicin or Trichostatin A treatment. Binding of Sp1, p53 and p300 to the p21 promoter was enhanced in PTTG1−/− cells after treatment, suggesting transcriptional regulation of p21. p21 knock down abrogated the observed senescent effects of these drugs, indicating that PTTG1 likely suppresses p21 to regulate drug-induced senescence. PTTG1 also regulated SW620 colon cancer cells response to doxorubicin and TSA mediated by p21. Subcutaneously xenografted PTTG1−/− HCT116 cells developed smaller tumors and exhibited enhanced responses to doxorubicin. PTTG1−/− tumor tissue derived from excised tumors exhibited increased doxorubicin-induced senescence. As senescence is a determinant of cell responses to anti-neoplastic treatments, these findings suggest PTTG1 as a tumor cell marker to predict anti-neoplastic treatment outcomes

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Role of Histone Acetylation in the Stimulatory Effect of Valproic Acid on Vascular Endothelial Tissue-Type Plasminogen Activator Expression

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Separation of Recombination and SOS Response in Escherichia coli RecA Suggests LexA Interaction Sites

RecA plays a key role in homologous recombination, the induction of the DNA damage response through LexA cleavage and the activity of error-prone polymerase in Escherichia coli. RecA interacts with multiple partners to achieve this pleiotropic role, but the structural location and sequence determinants involved in these multiple interactions remain mostly unknown. Here, in a first application to prokaryotes, Evolutionary Trace (ET) analysis identifies clusters of evolutionarily important surface amino acids involved in RecA functions. Some of these clusters match the known ATP binding, DNA binding, and RecA-RecA homo-dimerization sites, but others are novel. Mutation analysis at these sites disrupted either recombination or LexA cleavage. This highlights distinct functional sites specific for recombination and DNA damage response induction. Finally, our analysis reveals a composite site for LexA binding and cleavage, which is formed only on the active RecA filament. These new sites can provide new drug targets to modulate one or more RecA functions, with the potential to address the problem of evolution of antibiotic resistance at its root

Recombinant Mouse PAP Has pH-Dependent Ectonucleotidase Activity and Acts through A1-Adenosine Receptors to Mediate Antinociception

Prostatic acid phosphatase (PAP) is expressed in nociceptive neurons and functions as an ectonucleotidase. When injected intraspinally, the secretory isoforms of human and bovine PAP protein have potent and long-lasting antinociceptive effects that are dependent on A1-adenosine receptor (A1R) activation. In this study, we purified the secretory isoform of mouse (m)PAP using the baculovirus expression system to determine if recombinant mPAP also had antinociceptive properties. We found that mPAP dephosphorylated AMP, and to a much lesser extent, ADP at neutral pH (pH 7.0). In contrast, mPAP dephosphorylated all purine nucleotides (AMP, ADP, ATP) at an acidic pH (pH 5.6). The transmembrane isoform of mPAP had similar pH-dependent ectonucleotidase activity. A single intraspinal injection of mPAP protein had long-lasting (three day) antinociceptive properties, including antihyperalgesic and antiallodynic effects in the Complete Freund's Adjuvant (CFA) inflammatory pain model. These antinociceptive effects were transiently blocked by the A1R antagonist 8-cyclopentyl-1, 3-dipropylxanthine (CPX), suggesting mPAP dephosphorylates nucleotides to adenosine to mediate antinociception just like human and bovine PAP. Our studies indicate that PAP has species-conserved antinociceptive effects and has pH-dependent ectonucleotidase activity. The ability to metabolize nucleotides in a pH-dependent manner could be relevant to conditions like inflammation where tissue acidosis and nucleotide release occur. Lastly, our studies demonstrate that recombinant PAP protein can be used to treat chronic pain in animal models