bluuebunny/crossref_metadata_2025_split huggingface dataset:
(Invited) Donor-Acceptor Systems from Triplet Photosensitizers for High Potential, Long-Lived Charge Separation
Authors: Shao Shuai , D'Souza Francis , Obondi Christopher , Subedi Diliraj , Lim Gary N. , Gobeze Haptom B. , Karr Paul , Poddutoori Prashanth K , van der Est Art 
Published: May 2020

Generation of high potential, long-lived charge separated states in donor-acceptor systems are invaluable for converting light energy into either electricity or fuels. The majority of the donor-acceptor conjugates designed for this purpose are derived mainly from short-lived singlet sensitizers.1,2 In such conjugates, charge separation from the singlet excited donor or acceptor results in a short-lived charge separated state of singlet spin character. Alternatively, by utilizing high-energy triplet sensitizers one could generate long-lived charge separated states. The radical ion-pairs of triplet spin character slowly charge recombine to the ground state due to spin forbidden process. However, witnessing such a process purely from the triplet-excited state without the interference of the singlet excited state and other competing photochemical events such as excitation energy transfer has been challenging to establish.3-5

Here, we summarize our efforts to synthesize donor-acceptor conjugates bearing triplet sensitizers wherein excited state electron transfer exclusively occurs from the triplet excited state.3-6 To achieve the goal, two types of triplet sensitizers, viz., palladium and platinum porphyrins, and b-iodo functionalized BODIPYs are covalently linked to the well-known electron acceptor, fullerene, C60. Using femtosecond transient absorption studies covering wide temporal and spatial regions, and time-resolved electron paramagnetic studies, photoinduced electron transfer from 3MP* (M = Pd or Pt) to C60 in these dyads, leading to the formation of MP•+-C60
•- charge separated state of triplet spin character is demonstrated. Similarly, the role of triplet sensitizers in promoting charge separation in I2BODIPY-C60 and I2azaBODIPY-C60 dyads6 is also highlighted.

1. B. KC, F. D’Souza, Coord. Chem. Rev. 2016, 322, 104-141.
2. D’Souza, and O. Ito ‘Chem. Soc. Rev. 2012,
41, 86-96.
3. Obondi, G. N. Lim, F. D’Souza, J. Phys. Chem. C 2015, 119, 176-185.
4. Obondi, G. N. Lim, B. Churchill, P. K. Poddutoori, A. van der Est, and F. D’Souza, Nanoscale, 2016, 8, 8333-8344.
5. K. Poddutoori,Y. E. Kandrashkin, C. O. Obondi, F. D’Souza and A. van der Est, Phys. Chem. Chem. Phys. 2018, 20, 28223-28231.
6. Shao, H. B. Gobeze, V. Bandi, C. Funk, B. Heine, M. J. Duffy, V. Nesterov, P. A. Karr, F. D’Souza, ChemPhotoChem, 2020, in press.
(Invited) Isolation and Structure Determination of Trifluoromethylated Gadoliniummetallofullerenes
Authors: Aoyagi Shinobu , Nakagawa Ayano , Omachi Haruka , Shinohara Hisanori 
Published: May 2020

Endohedral metallofullerenes have been extensively studied since the first experimental observation of La@C60 in a laser-vaporized supersonic beam in 1985. However, most of these studies have focused on metallofullerenes larger than C60 such as Ln@C82 (Ln: lanthanide). There are few examples for isolation of small-cage (C60, C70, C72, and C74) lanthanide metallofullerenes because of their extremely high chemical reactivity. Recently, we developed an in situ trifluoromethylation method for the extraction and purification of these missing metallofullerenes [1−3]. Here we report the isolation and structure determination of trifluoromethylated gadolinium metallofullerenes (Gd@C60(CF3)3, Gd@C60(CF3)5, Gd@C70(CF3)3, Gd@C74(CF3), and Gd@C74(CF3)3). Gd-metallofullerenes are promising as magnetic resonance imaging (MRI) contrast agents. The fully enclosing carbon cage completely prevents leaching of the Gd atoms, resulting in lower toxicity than commercially available metal chelate reagents such as Gd-DTPA.
Trifluoromethylated Gd-metallofullerenes were synthesized by the modified arc-discharge method. PTFE rods are placed near the discharge area as CF3 source. During arc discharge, PTFE was decomposed and evaporated to produce CF3 radicals. Gd-metallofullerenes and empty fullerenes were extracted from the raw soot with o-xylene. Rapid separation of Gd-metallofullerenes from empty fullerenes was carried out by the TiCl4 Lewis acid method. High-performance liquid chromatography (HPLC) purification was conducted for isolation of trifluoromethylated Gd-metallofullerenes. Single crystals of trifluoromethylated Gd-metallofullerenes were obtained from solution. The single-crystal X-ray diffraction data for structure determination were collected at SPring-8 large synchrotron radiation facility.
Figures show the molecular structures of Gd@C74(CF3) (I), Gd@C74(CF3) (II), and Gd@C74(CF3)3 derived from the X-ray crystal structure analysis. The closed-shell molecular structures are theoretically stable and have wide HOMO-LUMO energy gaps.
[1] Z. Wang et al. Angew. Chem. Int. Ed. 55, 199 (2016).
[2] A. Nakagawa et al. Nature. Commun. 9, 3073 (2018).
[3] A. Nakagawa et al. R. Soc. Open Sci. 5, 181015 (2018).

Figure 1
(Invited) Reactivity of Li+@C60@C240 and Photoinduced Charge Shift in Li+ Doped Giant Nested Fullerenes
Authors: Solà Miquel , Luque-Urrutia Jesús Antonio , Stasyuk Antony J. , Stasyuk Olga A. , Poater Albert , Voityuk Alexander A. 
Published: May 2020

Over the last years, carbon nano-onions (CNOs) have been in focus in material science research. Apart from its prospective use in solar cells, the number of potential applications of CNOs have grown in the last decades. Among them, we can mention their application in gas storage processes, solid lubrication, or heterogeneous catalysis, and also as electrode materials in capacitors, anode materials in lithium-ion batteries, catalyst support in fuel cells, or electro-optical devices. From the analysis of the polarizability of CNOs, it was concluded that CNOs behave as near perfect nanoscopic Faraday cages.[1] If CNOs behave as ideal Faraday cages, the reactivity of the C240 cage should be the same in Li+@C240 and Li+@C60@C240. In the first part of this work, we have analyzed the Diels-Alder reaction of cyclopentadiene to the free C240 cage and the C60@C240 CNO together with their Li+-doped counterparts using density functional theory. We find that in all cases the preferred cycloaddition is on bond [6,6] of type B of the C240 cage. From the comparison between the reactivity of Li+@C240 and Li+@C60@C240, we conclude that C60@C240 does not act as a perfect Faraday cage.[2] In the second part of this work, we perform a systematic study of excited state properties of six double-layered Li+ doped fullerenes of Ih

symmetry: [Li@C60@C240]+, [Li@C60@C540]+, [Li@C60@C960]+, [Li@C240@C540]+, [Li@C240@C960]+ and [Li@C540@C960]+. On the basis of TDDFT calculations, we show that the long-wave absorption by the Li+ doped species leads to charge transfer (CT) between the inner and the outer shells unlike their neutral double-layered precursors. The CT energy depends strongly on the size of the concentric fullerenes and it can easily be tuned by varying both the encapsulated metal ion and the size of the shells. Two types of low-lying excited states are identified (1) capacitor-like structures, as Li+@C60
-@C240
+, with alternating positive and negative charges, and (2) states, where the positive charge is delocalized over the outer shell, as in Li@C240@C540
+.[3]

References

[1] R. R. Zope, J. Phys. B: At. Mol. Opt. Phys. 41 (2008) 41, 085101; [b] R. R. Zope, S. Bhusal, L. Basurto, T. Baruah and K. Jackson, J. Chem. Phys. 143 (2015) 084306.
[2] A. J. Luque-Urrutia, A. Poater and M. Solà. Submitted for publication.
[3] A. J. Stasyuk, O. A. Stasyuk, M. Solà and A. A. Voityuk. J. Phys. Chem. C 123 (2019) 16525-16532.

Figure 1
Combination of PARP Inhibitor Olaparib, and PD-L1 Inhibitor Durvalumab, in Recurrent Ovarian Cancer: a Proof-of-Concept Phase II Study
Authors: Lampert Erika J. , Zimmer Alexandra , Padget Michelle , Cimino-Mathews Ashley , Nair Jayakumar R. , Liu Yingmiao , Swisher Elizabeth M. , Hodge James W. , Nixon Andrew B. , Nichols Erin , Bagheri Mohammad H. , Levy Elliott , Radke Marc R. , Lipkowitz Stanley , Annunziata Christina M. , Taube Janis M. , Steinberg Seth M. , Lee Jung-Min 
Published: May 2020

Abstract

Purpose:
Preclinical studies suggest PARP inhibition (PARPi) induces immunostimulatory micromilieu in ovarian cancer thus complementing activity of immune checkpoint blockade. We conducted a phase II trial of PARPi olaparib and anti–PD-L1 durvalumab and collected paired fresh core biopsies and blood samples to test this hypothesis.

Patients and Methods:
In a single-center, proof-of-concept phase II study, we enrolled women aged ≥18 with recurrent ovarian cancer. All patients were immune checkpoint inhibitor–naïve and had measurable disease per RECISTv1.1, ECOG performance status 0–2, and adequate organ and marrow function. Patients received olaparib 300 mg twice daily and durvalumab 1,500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Primary endpoint was overall response rate (ORR). Secondary objectives were safety and progression-free survival (PFS). Translational objectives included biomarker evaluation for relationships with clinical response and immunomodulatory effects by treatment.

Results:
Thirty-five patients with ovarian cancer [median, four prior therapies (IQR, 2–5.5), predominantly platinum-resistant (86%), BRCA wild-type (77%)] received at least one full cycle of treatment. ORR was 14% [5/35; 95% confidence interval (CI), 4.8%–30.3%]. Disease control rate (PR+SD) was 71% (25/35; 95% CI, 53.7%–85.4%). Treatment enhanced IFNγ and CXCL9/CXCL10 expression, systemic IFNγ/TNFα production, and tumor-infiltrating lymphocytes, indicating an immunostimulatory environment. Increased IFNγ production was associated with improved PFS [HR, 0.37 (95% CI, 0.16–0.87), P = 0.023], while elevated VEGFR3 levels were associated with worse PFS (HR, 3.22 (95% CI, 1.23–8.40), P = 0.017].

Conclusions:
The PARPi and anti–PD-L1 combination showed modest clinical activity in recurrent ovarian cancer. Our correlative study results suggest immunomodulatory effects by olaparib/durvalumab in patients and indicate that VEGF/VEGFR pathway blockade would be necessary for improved efficacy of the combination.
MMAE Delivery Using the Bicycle Toxin Conjugate BT5528
Authors: Bennett Gavin , Brown Amy , Mudd Gemma , Huxley Philip , Van Rietschoten Katerine , Pavan Silvia , Chen Liuhong , Watcham Sophie , Lahdenranta Johanna , Keen Nicholas 
Published: May 2020

Abstract
The EphA2 receptor is found at high levels in tumors and low levels in normal tissue and high EphA2 expression in biopsies is a predictor of poor outcome in patients. Drug discovery groups have therefore sought to develop EphA2-based therapies using small molecule, peptide, and nanoparticle-based approaches (1–3). However, until now only EphA2-targeting antibody–drug conjugates (ADC) have entered clinical development. For example, MEDI-547 is an EphA2-targeting ADC that displayed encouraging antitumor activity in preclinical models and progressed to phase I clinical testing in man. Here we describe the development of BT5528, a bicyclic peptide (“Bicycle”) conjugated to the auristatin derivative maleimidocaproyl-monomethyl auristatin E to generate the Bicycle toxin conjugate BT5528. The report compares and contrasts the Pharmacokinetics (PK) characteristics of antibody and Bicycle-based targeting systems and discusses how the PK and payload characteristics of different delivery systems impact the efficacy—toxicity trade off which is key to the development of successful cancer therapies. We show that BT5528 gives rise to rapid update into tumors and fast renal elimination followed by persistent toxin levels in tumors without prolonged exposure of parent drug in the vasculature. This fast in, fast out kinetics gave rise to more favorable toxicology findings in rats and monkeys than were observed with MEDI-547 in preclinical and clinical studies.
Graphical Abstract: http://mct.aacrjournals.org/content/molcanther/19/7/1385/F1.large.jpg.
Factors Associated With Potentially Inappropriate Phosphodiesterase-5 Inhibitor Use for Pulmonary Hypertension in the United States, 2006 to 2015
Authors: Gillmeyer Kari R. , Rinne Seppo T. , Glickman Mark E. , Lee Kyung Min , Shao Qing , Qian Shirley X. , Klings Elizabeth S. , Maron Bradley A. , Hanlon Joseph T. , Miller Donald R. , Wiener Renda Soylemez 
Published: May 2020

Background:
Use of phosphodiesterase-5 inhibitors (PDE5i) for groups 2 and 3 pulmonary hypertension (PH) is rising nationally, despite guidelines recommending against this low-value practice. Although receiving care across healthcare systems is encouraged to increase veterans’ access to specialists critical for PH management, receiving care in 2 systems may increase risk of guideline-discordant prescribing. We sought to identify factors associated with prescribing of PDE5i for group 2/3 PH, particularly, to test the hypothesis that veterans prescribed PDE5i for PH in the community (through Medicare) will have increased risk of subsequently receiving potentially inappropriate treatment in Veterans Health Administration (VA).

Methods and Results:
We constructed a retrospective cohort of 34 775 Medicare-eligible veterans with group 2/3 PH by linking national patient-level data from VA and Medicare from 2006 to 2015. We calculated adjusted odds ratios (ORs) of receiving daily PDE5i treatment for PH in VA using multivariable models with facility-specific random effects. In this cohort, 1556 veterans received VA prescriptions for PDE5i treatment for group 2/3 PH. Supporting our primary hypothesis, the variable most strongly associated with PDE5i treatment in VA for group 2/3 PH was prior treatment through Medicare (OR, 6.5 [95% CI, 4.9–8.7]). Other variables strongly associated with increased likelihood of VA treatment included more severe disease as indicated by recent right heart failure (OR, 3.3 [95% CI, 2.8–3.9]) or respiratory failure (OR, 3.7 [95% CI, 3.1–4.4]) and prior right heart catheterization (OR, 3.8 [95% CI, 3.4–4.3]).

Conclusions:
Our data suggest a missed opportunity to reassess treatment appropriateness when pulmonary hypertension patients seek prescriptions from VA—a relevant finding given policies promoting shared care across VA and community settings. Interventions are needed to reinforce awareness that pulmonary vasodilators are unlikely to benefit group 2/3 pulmonary hypertension patients and may cause harm.
Copayment Reduction Voucher Utilization and Associations With Medication Persistence and Clinical Outcomes
Authors: Fanaroff Alexander C. , Peterson Eric D. , Kaltenbach Lisa A. , Anstrom Kevin J. , Fonarow Gregg C. , Henry Timothy D. , Cannon Christopher P. , Choudhry Niteesh K. , Cohen David J. , Atreja Nipun , Bhalla Narinder , Eudicone James M. , Wang Tracy Y. 
Published: May 2020

Background:
Cost is frequently cited as a barrier to optimal medication use, but the extent to which copayment assistance interventions are used when available, and their impact on evidence-based medication persistence and major adverse cardiovascular events is unknown.

Methods and Results:

The ARTEMIS trial (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) randomized 301 hospitals to usual care versus the ability to provide patients with vouchers that offset copayment costs when filling P2Y
12
inhibitors in the 1 year post-myocardial infarction. In the intervention group, we used multivariable logistic regression to identify patient and medication cost characteristics associated with voucher use. We then used this model to stratify both intervention and usual care patients by likelihood of voucher use, and examined the impact of the voucher intervention on 1-year P2Y
12
inhibitor persistence (no gap in pharmacy supply >30 days) and major adverse cardiovascular events (all-cause death, myocardial infarction, or stroke). Among 10 102 enrolled patients, 6135 patients were treated at hospitals randomized to the copayment intervention. Of these, 1742 (28.4%) never used the voucher, although 1729 (99.2%) voucher never-users filled at least one P2Y
12
inhibitor prescription in the 1 year post-myocardial infarction. Characteristics most associated with voucher use included: discharge on ticagrelor, planned 1-year course of P2Y
12
inhibitor treatment, white race, commercial insurance, and higher out-of-pocket medication costs (c-statistic 0.74). Applying this propensity model to stratify all enrolled patients by likelihood of voucher use, the intervention improved medication persistence the most in patients with high likelihood of voucher use (adjusted interaction
P
=0.03, odds ratio, 1.86 [95% CI, 1.48–2.33]). The intervention did not significantly reduce major adverse cardiovascular events in any voucher use likelihood group, although the odds ratio was lowest (0.86 [95% CI, 0.56–1.16]) among patients with high likelihood of voucher use (adjusted interaction
P
=0.04).

Conclusions:
Among patients discharged after myocardial infarction, those with higher copayments and greater out-of-pocket medication costs were more likely to use a copayment assistance voucher, but some classes of patients were less likely to use a copayment assistance voucher. Patients at low likelihood of voucher use benefitted least from copayment assistance, and other interventions may be needed to improve medication-taking behaviors and clinical outcomes in these patients.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02406677.
Continued Increases in the Intensity of Strong Tropical Cyclones
Authors: Elsner James B. 
Published: May 2020

AbstractIn a 2008 paper, using satellite-derived wind speed estimates from tropical cyclones over the 25-yr period 1981–2006, we showed the strongest tropical cyclones getting stronger. We related the increasing intensity to rising ocean temperatures consistent with theory. Oceans have continued to warm since that paper was published, so the intensity of the strongest cyclones should have continued upward as well. Here I show that this is the case, with increases in the upper-quantile intensities of global tropical cyclones amounting to between 3.5% and 4.5% in the period 2007–19 relative to the earlier base period (1981–2006). All basins individually show upward intensity trends for at least one upper quantile considered, with the North Atlantic and western North Pacific basins showing the steepest and most consistent trends across the quantiles.
The Influences of Effective Inflow Layer Streamwise Vorticity and Storm-Relative Flow on Supercell Updraft Properties
Authors: Peters John M. , Nowotarski Christopher J. , Mulholland Jake P. , Thompson Richard L. 
Published: May 2020

Abstract
The relationship between storm-relative helicity (SRH) and streamwise vorticity ωs is frequently invoked to explain the often robust connections between effective inflow layer (EIL) SRH and various supercell updraft properties. However, the definition of SRH also contains storm-relative (SR) flow, and the separate influences of SR flow and ωs on updraft dynamics are therefore convolved when SRH is used as a diagnostic tool. To clarify this issue, proximity soundings and numerical experiments are used to disentangle the separate influences of EIL SR flow and ωs on supercell updraft characteristics. Our results suggest that the magnitude of EIL ωs has little influence on whether supercellular storm mode occurs. Rather, the transition from nonsupercellular to supercellular storm mode is largely modulated by the magnitude of EIL SR flow. Furthermore, many updraft attributes such as updraft width, maximum vertical velocity, vertical mass flux at all levels, and maximum vertical vorticity at all levels are largely determined by EIL SR flow. For a constant EIL SR flow, storms with large EIL ωs have stronger low-level net rotation and vertical velocities, which affirms previously established connections between ωs and tornadogenesis. EIL ωs also influences storms’ precipitation and cold-pool patterns. Vertical nonlinear dynamic pressure acceleration (NLDPA) is larger at low levels when EIL ωs is large, but differences in NLDPA aloft become uncorrelated with EIL ωs because storms’ midlevel dynamic pressure perturbations are substantially influenced by the tilting of midlevel vorticity. Our results emphasize the importance of considering EIL SR flow in addition to EIL SRH in the research and forecasting of supercell properties.
Regional Dynamic Sea Level Simulated in the CMIP5 and CMIP6 Models: Mean Biases, Future Projections, and Their Linkages
Authors: Lyu Kewei , Zhang Xuebin , Church John A. 
Published: May 2020

AbstractThe ocean dynamic sea level (DSL) is an important component of regional sea level projections. In this study, we analyze mean states and future projections of the DSL from the global coupled climate models participating in phase 5 and phase 6 of the Coupled Model Intercomparison Project (CMIP5 and CMIP6, respectively). Despite persistent biases relative to observations, both CMIP5 and CMIP6 simulate the mean sea level reasonably well. The equatorward bias of the Southern Hemisphere westerly wind stress is reduced from CMIP5 to CMIP6, which improves the simulated mean sea level in the Southern Ocean. The CMIP5 and CMIP6 DSL projections exhibit very similar features and intermodel uncertainties. With several models having a notably high climate sensitivity, CMIP6 projects larger DSL changes in the North Atlantic and Arctic associated with a larger weakening of the Atlantic meridional overturning circulation (AMOC). We further identify linkages between model mean states and future projections by looking for their intermodel relationships. The common cold-tongue bias leads to an underestimation of DSL rise in the western tropical Pacific. Models with their simulated midlatitude westerly winds located more equatorward tend to project larger DSL changes in the Southern Ocean and North Pacific. In contrast, a more equatorward location of the North Atlantic westerly winds or a weaker AMOC under current climatology is associated with a smaller weakening of the AMOC and weaker DSL changes in the North Atlantic and coastal Arctic. Our study provides useful emergent constraints for DSL projections and highlights the importance of reducing model mean-state biases for future projections.
Centrifugal and Symmetric Instability during Ekman Adjustment of the Bottom Boundary Layer
Authors: Wenegrat Jacob O. , Thomas Leif N. 
Published: May 2020

AbstractFlow along isobaths of a sloping lower boundary generates an across-isobath Ekman transport in the bottom boundary layer. When this Ekman transport is down the slope it causes convective mixing—much like a downfront wind in the surface boundary layer—destroying stratification and potential vorticity. In this manuscript we show how this can lead to the development of a forced centrifugal or symmetric instability regime, where the potential vorticity flux generated by friction along the boundary is balanced by submesoscale instabilities that return the boundary layer potential vorticity to zero. This balance provides a strong constraint on the boundary layer evolution, which we use to develop a theory that explains the evolution of the boundary layer thickness, the rate at which the instabilities extract energy from the geostrophic flow field, and the magnitude and vertical structure of the dissipation. Finally, we show using theory and a high-resolution numerical model how the presence of centrifugal or symmetric instabilities alters the time-dependent Ekman adjustment of the boundary layer, delaying Ekman buoyancy arrest and enhancing the total energy removed from the balanced flow field. Submesoscale instabilities of the bottom boundary layer may therefore play an important, largely overlooked, role in the energetics of flow over topography in the ocean.