Companies inadvertently fund online misinformation despite consumer backlash.

The financial motivation to earn advertising revenue has been widely conjectured to be pivotal for the production of online misinformation1-4. Research aimed at mitigating misinformation has so far focused on interventions at the user level5-8, with little emphasis on how the supply of misinformation can itself be countered. Here we show how online misinformation is largely financed by advertising, examine how financing misinformation affects the companies involved, and outline interventions for reducing the financing of misinformation. First, we find that advertising on websites that publish misinformation is pervasive for companies across several industries and is amplified by digital advertising platforms that algorithmically distribute advertising across the web. Using an information-provision experiment9, we find that companies that advertise on websites that publish misinformation can face substantial backlash from their consumers. To examine why misinformation continues to be monetized despite the potential backlash for the advertisers involved, we survey decision-makers at companies. We find that most decision-makers are unaware that their companies' advertising appears on misinformation websites but have a strong preference to avoid doing so. Moreover, those who are unaware and uncertain about their company's role in financing misinformation increase their demand for a platform-based solution to reduce monetizing misinformation when informed about how platforms amplify advertising placement on misinformation websites. We identify low-cost, scalable information-based interventions to reduce the financial incentive to misinform and counter the supply of misinformation online.

Climate change framing and innovator attention: Evidence from an email field experiment.

Drawing the attention of innovators to climate change is important for green innovation. We report an email field experiment with MIT using messages about the impact of climate change to invite innovators (SBIR grantees) to apply to a technology competition. We vary our messages on the time frame and scale of the human cost of climate change across scientifically valid scenarios. Innovator attention (clicks) is sensitive to climate change messaging. These changes in clicks also predict higher application rates. The response varies by individual characteristics such as location-based exposure to climate change risks and whether innovators have climate-related innovations. Finally, using a structural model of innovator attention, we provide estimates of the implied discount rate of time and the elasticity of attention to lives at stake.

Production of Metastable CO3+ through the Strong-Field Ionization and Coulomb Explosion of Formic Acid Dimer.

Femtosecond laser pulses are utilized to drive multiple ionization of formic acid dimers and the resulting ions are studied using time-of-flight mass spectrometry. The interaction of formic acid dimer with 200 fs linearly polarized laser pulses of 400 nm with intensities of up to 3.7 × 1015 W/cm2 produces a metastable carbon monoxide trication. Experimental kinetic energy release (KER) measurements of the ions are consistent with molecular dynamics simulations of the Coulomb explosion of a formic acid dimer and suggest that no significant movement occurs during ionization. KER values were recorded as high as 44 eV for CO3+, in agreement with results from a classical Molecular Dynamics simulation of fully ionized formic acid dimers. Potential energy curves for CO3+ are calculated using the multireference configuration interaction (MRCI+Q) method to confirm the existence of an excited metastable 2Σ state with a significant potential barrier with respect to dissociation. This combined experimental and theoretical effort reveals the existence of metastable CO3+ through direct observation for the first time.

During Oxidative Stress the Clp Proteins of Escherichia coli Ensure that Iron Pools Remain Sufficient To Reactivate Oxidized Metalloenzymes.

Hydrogen peroxide (H2O2) is formed in natural environments by both biotic and abiotic processes. It easily enters the cytoplasms of microorganisms, where it can disrupt growth by inactivating iron-dependent enzymes. It also reacts with the intracellular iron pool, generating hydroxyl radicals that can lethally damage DNA. Therefore, virtually all bacteria possess H2O2-responsive transcription factors that control defensive regulons. These typically include catalases and peroxidases that scavenge H2O2 Another common component is the miniferritin Dps, which sequesters loose iron and thereby suppresses hydroxyl-radical formation. In this study, we determined that Escherichia coli also induces the ClpS and ClpA proteins of the ClpSAP protease complex. Mutants that lack this protease, plus its partner, ClpXP protease, cannot grow when H2O2 levels rise. The growth defect was traced to the inactivity of dehydratases in the pathway of branched-chain amino acid synthesis. These enzymes rely on a solvent-exposed [4Fe-4S] cluster that H2O2 degrades. In a typical cell the cluster is continuously repaired, but in the clpSA clpX mutant the repair process is defective. We determined that this disability is due to an excessively small iron pool, apparently due to the oversequestration of iron by Dps. Dps was previously identified as a substrate of both the ClpSAP and ClpXP proteases, and in their absence its levels are unusually high. The implication is that the stress response to H2O2 has evolved to strike a careful balance, diminishing iron pools enough to protect the DNA but keeping them substantial enough that critical iron-dependent enzymes can be repaired.IMPORTANCE Hydrogen peroxide mediates the toxicity of phagocytes, lactic acid bacteria, redox-cycling antibiotics, and photochemistry. The underlying mechanisms all involve its reaction with iron atoms, whether in enzymes or on the surface of DNA. Accordingly, when bacteria perceive toxic H2O2, they activate defensive tactics that are focused on iron metabolism. In this study, we identify a conundrum: DNA is best protected by the removal of iron from the cytoplasm, but this action impairs the ability of the cell to reactivate its iron-dependent enzymes. The actions of the Clp proteins appear to hedge against the oversequestration of iron by the miniferritin Dps. This buffering effect is important, because E. coli seeks not just to survive H2O2 but to grow in its presence.

Circular dichroism in photoelectron images from aligned nitric oxide molecules.

We have used velocity map photoelectron imaging to study circular dichroism of the photoelectron angular distributions (PADs) of nitric oxide following two-color resonance-enhanced two-photon ionization via selected rotational levels of the A 2Σ+, v'=0 state. By using a circularly polarized pump beam and a counter-propagating, circularly polarized probe beam, cylindrical symmetry is preserved in the ionization process, and the images can be reconstructed using standard algorithms. The velocity map imaging set up enables individual ion rotational states to be resolved with excellent collection efficiency, rendering the measurements considerably simpler to perform than previous measurements conducted with a conventional photoelectron spectrometer. The results demonstrate that circular dichroism is observed even when cylindrical symmetry is maintained, and serve as a reminder that dichroism is a general feature of the multiphoton ionization of atoms and molecules. The observed PADs are in good agreement with calculations based on parameters extracted from previous experimental results obtained by using a time-of-flight electron spectrometer.

UV laser photoactivation of hexachloroplatinate bound to individual nucleobases in vacuo as molecular level probes of a model photopharmaceutical.

Isolated molecular clusters of adenine, cytosine, thymine and uracil bound to hexachloroplatinate, PtCl6(2-), have been studied using laser electronic photodissociation spectroscopy to investigate photoactivation of a platinum complex in the vicinity of a nucleobase. These metal complex-nucleobase clusters represent model systems for identifying the fundamental photochemical processes occurring in photodynamic platinum drug therapies that target DNA. This is the first study to explore the specific role of a strongly photoactive platinum compound in the aggregate complex. Each of the clusters studied displays a broadly similar absorption spectra, with a strong λmax ∼ 4.6 eV absorption band and a subsequent increase in the absorption intensity towards higher spectral-energy. The absorption bands are traced to ligand-to-metal-charge-transfer excitations on the PtCl6(2-) moiety within the cluster, and result in Cl(-)·nucleobase and PtCl5(-) as primary photofragments. These results demonstrate how selective photoexcitation can drive distinctive photodecay channels for a model photo-pharmaceutical. In addition, cluster absorption due to excitation of nucleobase-centred chromophores is observed in the region around 5 eV. For the uracil cluster, photofragments consistent with ultrafast decay of the excited state and vibrational predissociation on the ground-state surface are observed. However, this decay channel becomes successively weaker on going from thymine to cytosine to adenine, due to differential coupling of the excited states to the electron detachment continuum. These effects demonstrate the distinctive photophysical characteristics of the different nucleobases, and are discussed in the context of the recently recorded photoelectron spectra of theses clusters.

Photoelectron spectroscopy of hexachloroplatinate-nucleobase complexes: Nucleobase excited state decay observed via delayed electron emission.

We report low-temperature photoelectron spectra of isolated gas-phase complexes of the hexachloroplatinate dianion bound to the nucleobases uracil, thymine, cytosine, and adenine. The spectra display well-resolved, distinct peaks that are consistent with complexes where the hexachloroplatinate dianion is largely intact. Adiabatic electron detachment energies for the hexachloroplatinate-nucleobase complexes are measured as 2.26-2.36 eV. The magnitudes of the repulsive Coulomb barriers (RCBs) of the complexes are all ∼1.7 eV, values that are lower than the RCB of the uncomplexed PtCl6 (2-) dianion as a result of charge solvation by the nucleobases. In addition to the resolved spectral features, broad featureless bands indicative of delayed electron detachment are observed in the 193 nm photoelectron spectra of the four clusters. The 266 nm spectra of the PtCl6 (2-) ⋅ thymine and PtCl6 (2-) ⋅ adenine complexes also display very prominent delayed electron emission bands. These results mirror recent results on the related Pt(CN)4 (2-) ⋅ nucleobase complexes [A. Sen et al., J. Phys. Chem. B 119, 11626 (2015)]. The observation of delayed electron emission bands in the PtCl6 (2-) ⋅ nucleobase spectra obtained in this work, as for the previously studied Pt(CN)4 (2-) ⋅ nucleobase complexes, is attributed to one-photon excitation of nucleobase-centred excited states that can effectively couple to the electron detachment continuum, producing strong electron detachment. Moreover, the selective, strong excitation of the delayed emission bands in the 266 nm spectra is linked to fundamental differences in the individual nucleobase photophysics at this excitation energy. This strongly supports our previous suggestion that the dianion within these clusters can be viewed as a "dynamic tag" which has the propensity to emit electrons when the attached nucleobase decays over a time scale long enough to allow autodetachment.

Solvent evaporation versus proton transfer in nucleobase-Pt(CN)(4,6)²â» dianion clusters: a collisional excitation and electronic laser photodissociation spectroscopy study.

Isolated molecular clusters of adenine, cytosine, thymine and uracil with Pt(CN)6(2-) and Pt(CN)4(2-) were studied for the first time to characterize the binding and reactivity of isolated transition metal complex ions with nucleobases. These clusters represent model systems for understanding metal complex-DNA adducts, as a function of individual nucleobases. Collisional excitation revealed that the clusters decay on the ground electronic surface by either solvent evaporation (i.e. loss of a nucleobase unit from the cluster) or via proton transfer from the nucleobase to the dianion. The Pt(CN)6(2-)-nucleobase clusters decay only by solvent evaporation, while the Pt(CN)4(2-) clusters fragment by both pathways. The enhanced proton-transfer reactivity of Pt(CN)4(2-) is attributed to the higher charge-density of the ligands in this transition metal anion. % fragmentation curves of the clusters reveal that the adenine clusters display distinctively higher fragmentation onsets, which are traced to the propensity of adenine to form the shortest intercluster H-bond. We also present laser electronic photodissociation measurements for the Pt(CN)6(2-)·Ur, Pt(CN)4(2-)·Ur and Pt(CN)4(2-)·Ur2 clusters to illustrate the potential of exploring metal complex DNA photophysics as a function of nucleobase within well-defined gaseous clusters. The spectra reported herein represent the first such measurements. We find that the electronic excited states decay with production of the same fragments (associated with solvent evaporation and proton transfer) observed upon collisional excitation of the electronic ground state, indicating ultrafast deactivation of the excited-state uracil-localized chromophore followed by vibrational predissociation.

Communication: Photoactivation of nucleobase bound platinum(II) metal complexes: probing the influence of the nucleobase.

We present UV laser action spectra (220-300 nm) of isolated nucleobase-bound Pt(II)(CN)4(2-) complexes, i.e., Pt(CN)4(2-)⋅M, where M = uracil, thymine, cytosine, and adenine. These metal complex-nucleobase clusters represent model systems for identifying the fundamental photophysical and photochemical processes occurring in photodynamic platinum (II) drug therapies that target DNA. This is the first study to explore the specific role of the nucleobase in the photophysics of the aggregate complex. Each of the complexes studied displays a broadly similar absorption spectra, with a strong λmax ∼ 4.7 eV absorption band (nucleobase localized chromophore) and a subsequent increase in the absorption intensity towards higher spectral-energy (Pt(CN)4(2-) localized chromophore). However, strikingly different band widths are observed across the series of complexes, decreasing in the order Pt(CN)4(2-)⋅Thymine > Pt(CN)4(2-)⋅Uracil > Pt(CN)4(2-)⋅Adenine > Pt(CN)4(2-)⋅Cytosine. Changes in the bandwidth of the ∼4.7 eV band are accompanied by distinctive changes in the photofragment product ions observed following photoexcitation, with the narrower-bandwidth complexes showing a greater propensity to decay via electron detachment decay. We discuss these observations in the context of the distinctive nucleobase-dependent excited state lifetimes.

How do pseudoenantiomers structurally differ in the gas phase? An IR/UV spectroscopy study of jet-cooled hydroquinine and hydroquinidine.

The gas-phase structures of the cinchona alkaloids, hydroquinine and its pseudoenantiomer hydroquinidine, are studied in a supersonic expansion by means of laser-induced fluorescence and IR/UV double-resonance spectroscopy. Vibrational spectroscopy combined with density functional calculations show that the conformational properties of the two pseudoenantiomers are identical. In both cases, they exist in two isoenergetic forms, with similar IR spectra. Both conformers are similar to the most stable cis-γ-open form of quinine; they differ from each other by the position of the ethyl substituent attached to the quinuclidine ring. Further differences between the two conformers are observed in the laser-induced fluorescence spectrum. The first electronic transition is characterized by time-dependent density functional theory and RI-cc2 calculations, and is of ππ* nature. The results described here emphasize the role of the ethyl substituent in the structural differences between pseudoenantiomers of cinchona alkaloids.

Performance of M06, M06-2X, and M06-HF density functionals for conformationally flexible anionic clusters: M06 functionals perform better than B3LYP for a model system with dispersion and ionic hydrogen-bonding interactions.

We present a comparative assessment of the performance of the M06 suite of density functionals (M06, M06-2X, and M06-HF) against an MP2 benchmark for calculating the relative energies and geometric structures of the Cl(-)·arginine and Br(-)·arginine halide ion-amino acid clusters. Additional results are presented for the popular B3LYP density functional. The Cl(-)·arginine and Br(-)·arginine complexes are important prototypes for the phenomenon of anion-induced zwitterion formation. Results are presented for the canonical (noncharge separated) and zwitterionic (charge separated) tautomers of the clusters, as well as the numerous conformational isomers of the clusters. We find that all of the M06 functions perform well in terms of predicting the general trends in the conformer relative energies and identifying the global minimum conformer. This is in contrast to the B3LYP functional, which performed significantly less well for the canonical tautomers of the clusters where dispersion interactions contribute more significantly to the conformer energetics. We find that the M06 functional gave the lowest mean unsigned error for the relative energies of the canonical conformers (2.10 and 2.36 kJ/mol for Br(-)·arginine and Cl(-)·arginine), while M06-2X gave the lowest mean unsigned error for the zwitterionic conformers (0.85 and 1.23 kJ/mol for Br(-)·arginine and Cl(-)·arginine), thus providing insight into the types of physical systems where each of these functionals should perform best.

Mass spectrometry study and infrared spectroscopy of the complex between camphor and the two enantiomers of protonated alanine: the role of higher-energy conformers in the enantioselectivity of the dissociation rate constants.

The properties of the protonated complexes built from S camphor and R or S alanine were studied in a Paul ion trap at room temperature by collision-induced dissociation (CID) and infrared multiple-photon dissociation spectroscopy (IRMPD), as well as molecular dynamics and ab initio calculations. While the two diastereomer complexes display very similar vibrational spectra in the fingerprint region, in line with similar structures, and almost identical calculated binding energies, their collision-induced dissociation rates are different. Comparison of the IRMPD results to computed spectra shows that the SS and SR complexes both contain protonated alanine strongly hydrogen-bonded to the keto group of camphor. The floppiness of this structure around the NH⁺...O=C hydrogen bond results in a complex potential energy surface showing multiple minima. Calculating the dissociation rate constant within the frame of the transition state theory shows that the fragmentation rate larger for the heterochiral SR complex than the homochiral SS complex can be explained in terms of two almost isoenergetic low-energy conformers in the latter that are not present for the former.

Prognostic value of high-sensitivity C-reactive protein among chronic kidney disease patients undergoing percutaneous coronary intervention.

BACKGROUND: Data on the prognostic value of high-sensitivity C-reactive protein (hs-CRP) levels in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) are limited. METHODS: Patients undergoing PCI at a tertiary center from January 2012 to December 2019 were included. CKD was defined as a glomerular filtration rate (GFR) <60 mL/min/1.73m2 and elevated hs-CRP was defined as >3 mg/L. Acute myocardial infarction (MI), acute heart failure, neoplastic disease, patients undergoing hemodialysis, or hs-CRP >10 mg/L were exclusion criteria. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, MI, and target vessel revascularization at 1-year after PCI. RESULTS: Out of 12,410 patients, 3029 (24.4 %) had CKD. Elevated hs-CRP levels were found in 31.8 % of CKD and 25.8 % of no-CKD patients. At 1 year, MACE occurred in 87 (11.0 %) CKD patients with elevated hs-CRP and 163 (9.5 %) with low hs-CRP (adj. HR 1.26, 95 % CI 0.94-1.68); among no-CKD patients, in 200 (10 %) and 470 (8.1 %), respectively (adj. HR 1.21, 95 % CI 1.00-1.45). Hs-CRP was associated with an increased risk of all-cause death in both CKD (Adj. HR 1.92, 95 % CI 1.07-3.44) and no-CKD patients (adj. HR 3.02, 95 % CI 1.74-5.22). There was no interaction between hs-CRP and CKD status. CONCLUSIONS: Among patients undergoing PCI without acute MI, elevated hs-CRP values were not associated with a higher risk of MACE at 1 year, but with increased mortality hazards consistently in patients with or without CKD.

Conformational analysis of quinine and its pseudo enantiomer quinidine: a combined jet-cooled spectroscopy and vibrational circular dichroism study.

Laser-desorbed quinine and quinidine have been studied in the gas phase by combining supersonic expansion with laser spectroscopy, namely, laser-induced fluorescence (LIF), resonance-enhanced multiphoton ionization (REMPI), and IR-UV double resonance experiments. Density funtional theory (DFT) calculations have been done in conjunction with the experimental work. The first electronic transition of quinine and quinidine is of π-π* nature, and the studied molecules weakly fluoresce in the gas phase, in contrast to what was observed in solution (Qin, W. W.; et al. J. Phys. Chem. C2009, 113, 11790). The two pseudo enantiomers quinine and quinidine show limited differences in the gas phase; their main conformation is of open type as it is in solution. However, vibrational circular dichroism (VCD) experiments in solution show that additional conformers exist in condensed phase for quinidine, which are not observed for quinine. This difference in behavior between the two pseudo enantiomers is discussed.

Jet-cooled hydrates of chiral (S) 1,2,3,4-tetrahydro-3-isoquinoline methanol (THIQM): structure and mechanism of formation.

The mechanism of formation of hydrates of chiral (S) 1,2,3,4-tetrahydro-3-isoquinoline (THIQM) with two water molecules has been investigated in jet-cooled condition by means of resonance-enhanced two-photon ionization and IR-UV double resonance experiments. Quantum chemical calculations reveal that only one isomer of the THIQM is involved in the THIQM-(H(2)O)(2) complex formation, in contrast with what was observed for THIQM-(H(2)O). Anharmonic vibration calculations allowed unambiguous assignment of THIQM-(H(2)O)(2) to a complex resulting from the addition of a water molecule on the most stable THIQM-(H(2)O) complex. A sequential mechanism for complex formation has been deduced from these results.

How Microbes Defend Themselves From Incoming Hydrogen Peroxide.

Microbes rely upon iron as a cofactor for many enzymes in their central metabolic processes. The reactive oxygen species (ROS) superoxide and hydrogen peroxide react rapidly with iron, and inside cells they can generate both enzyme and DNA damage. ROS are formed in some bacterial habitats by abiotic processes. The vulnerability of bacteria to ROS is also apparently exploited by ROS-generating host defense systems and bacterial competitors. Phagocyte-derived O2- can toxify captured bacteria by damaging unidentified biomolecules on the cell surface; it is unclear whether phagocytic H2O2, which can penetrate into the cell interior, also plays a role in suppressing bacterial invasion. Both pathogenic and free-living microbes activate defensive strategies to defend themselves against incoming H2O2. Most bacteria sense the H2O2via OxyR or PerR transcription factors, whereas yeast uses the Grx3/Yap1 system. In general these regulators induce enzymes that reduce cytoplasmic H2O2 concentrations, decrease the intracellular iron pools, and repair the H2O2-mediated damage. However, individual organisms have tailored these transcription factors and their regulons to suit their particular environmental niches. Some bacteria even contain both OxyR and PerR, raising the question as to why they need both systems. In lab experiments these regulators can also respond to nitric oxide and disulfide stress, although it is unclear whether the responses are physiologically relevant. The next step is to extend these studies to natural environments, so that we can better understand the circumstances in which these systems act. In particular, it is important to probe the role they may play in enabling host infection by microbial pathogens.

Electron Detachment as a Probe of Intrinsic Nucleobase Dynamics in Dianion-Nucleobase Clusters: Photoelectron Spectroscopy of the Platinum II Cyanide Dianion Bound to Uracil, Thymine, Cytosine, and Adenine.

We report the first low-temperature photoelectron spectra of isolated gas-phase complexes of the platinum II cyanide dianion bound to nucleobases. These systems are models for understanding platinum-complex photodynamic therapies, and a knowledge of the intrinsic photodetachment properties is crucial for characterizing their broader photophysical properties. Well-resolved, distinct peaks are observed in the spectra, consistent with complexes where the Pt(CN)4(2-) moiety is largely intact. Adiabatic electron detachment energies for the dianion-nucleobase complexes are measured to be 2.39-2.46 eV. The magnitudes of the repulsive Coulomb barriers of the complexes are estimated to be between 1.9 and 2.1 eV, values that are lower than for the bare Pt(CN)4(2-) dianion as a result of charge solvation by the nucleobases. In addition to the resolved spectral features, broad featureless bands indicative of delayed electron detachment are observed in the 193 nm photoelectron spectra of the four dianion-nucleobase complexes and also in the 266 nm spectra of the Pt(CN)4(2-)·thymine and Pt(CN)4(2-)·adenine complexes. The selective excitation of these features in the 266 nm spectra is attributed to one-photon excitation of [Pt(CN)4(2-)·thymine]* and [Pt(CN)4(2-)·adenine]* long-lived excited states that can effectively couple to the electron detachment continuum, producing strong electron detachment signals. We attribute the delayed electron detachment bands observed here for Pt(CN)4(2-)·thymine and Pt(CN)4(2-)·adenine but not for Pt(CN)4(2-)·uracil and Pt(CN)4(2-)·cytosine to fundamental differences in the individual nucleobase photophysics following 266 nm excitation. This indicates that the Pt(CN)4(2-) dianion in the clusters can be viewed as a "dynamic tag" which has the propensity to emit electrons when the attached nucleobase displays a long-lived excited state.