Understanding charge transport in lead iodide perovskite thin-film field-effect transistors

Fundamental understanding of the charge transport physics of hybrid lead halide perovskite semiconductors is important for advancing their use in high-performance optoelectronics. We use field-effect transistors (FETs) to probe the charge transport mechanism in thin films of methylammonium lead iodide (MAPbI$_{3}$). We show that through optimization of thin-film microstructure and source-drain contact modifications, it is possible to significantly minimize instability and hysteresis in FET characteristics and demonstrate an electron field-effect mobility (μ$_{FET}$) of 0.5 cm$^{2}$/Vs at room temperature. Temperature-dependent transport studies revealed a negative coefficient of mobility with three different temperature regimes. On the basis of electrical and spectroscopic studies, we attribute the three different regimes to transport limited by ion migration due to point defects associated with grain boundaries, polarization disorder of the MA$^{+}$ cations, and thermal vibrations of the lead halide inorganic cages.S.P.S. acknowledges funding from the Royal Society London for a Newton Fellowship. B.Y. acknowledges support from China Council Scholarship and Cambridge Overseas Trust. A.S. and R.H.F. acknowledge funding and support from the Engineering and Physical Sciences Research Council (EPSRC) through the India-U.K. APEX project. P.D. acknowledges support from the European Union through the award of a Marie Curie Intra-European Fellowship. X.M. is grateful for the support from the Royal Society. B.N. is grateful for the support from Gates Cambridge and the Winton Program for the Physics of Sustainability. We acknowledge funding from the EPSRC through a program grant (EP/M005143/1). We acknowledge funding from the German Federal Ministry of Education and Research under agreement number 01162525/1. This work was performed in part on the SAXS/WAXS beamline of the Australian Synchrotron, Victoria, Australia (55, 56). C.R.M. acknowledges support from the Australian Research Council (DP13012616)

A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson's Disease

BACKGROUND: Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a mitochondrial rescue agent across a range of preclinical in vitro and in vivo models of PD. OBJECTIVES: To investigate the safety and tolerability of high-dose UDCA in PD and determine midbrain target engagement. METHODS: The UP (UDCA in PD) study was a phase II, randomized, double-blind, placebo-controlled trial of UDCA (30 mg/kg daily, 2:1 randomization UDCA vs. placebo) in 30 participants with PD for 48 weeks. The primary outcome was safety and tolerability. Secondary outcomes included 31-phosphorus magnetic resonance spectroscopy (31 P-MRS) to explore target engagement of UDCA in PD midbrain and assessment of motor progression, applying both the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) and objective, motion sensor-based quantification of gait impairment. RESULTS: UDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain 31 P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis. Sensor-based gait analysis indicated a possible improvement of cadence (steps per minute) and other gait parameters in the UDCA group compared to placebo. In contrast, subjective assessment applying the MDS-UPDRS-III failed to detect a difference between treatment groups. CONCLUSIONS: High-dose UDCA is safe and well tolerated in early PD. Larger trials are needed to further evaluate the disease-modifying effect of UDCA in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Regulation of expression of the rat orthologue of mouse double minute 2 (MDM2) by H2O2-induced oxidative stress in neonatal rat cardiac myocytes.

The Mdm2 ubiquitin ligase is an important regulator of p53 abundance and p53-dependent apoptosis. Mdm2 expression is frequently regulated by a p53 Mdm2 autoregulatory loop whereby p53 stimulates Mdm2 expression and hence its own degradation. Although extensively studied in cell lines, relatively little is known about Mdm2 expression in heart where oxidative stress (exacerbated during ischemia-reperfusion) is an important pro-apoptotic stimulus. We demonstrate that Mdm2 transcript and protein expression are induced by oxidative stress (0.2 mm H(2)O(2)) in neonatal rat cardiac myocytes. In other cells, constitutive Mdm2 expression is regulated by the P1 promoter (5' to exon 1), with inducible expression regulated by the P2 promoter (in intron 1). In myocytes, H(2)O(2) increased Mdm2 expression from the P2 promoter, which contains two p53-response elements (REs), one AP-1 RE, and two Ets REs. H(2)O(2) did not detectably increase expression of p53 mRNA or protein but did increase expression of several AP-1 transcription factors. H(2)O(2) increased binding of AP-1 proteins (c-Jun, JunB, JunD, c-Fos, FosB, and Fra-1) to an Mdm2 AP-1 oligodeoxynucleotide probe, and chromatin immunoprecipitation assays showed it increased binding of c-Jun or JunB to the P2 AP-1 RE. Finally, antisense oligonucleotide-mediated reduction of H(2)O(2)-induced Mdm2 expression increased caspase 3 activation. Thus, increased Mdm2 expression is associated with transactivation at the P2 AP-1 RE (rather than the p53 or Ets REs), and Mdm2 induction potentially represents a cardioprotective response to oxidative stress

Persistent elastic behavior above a megathrust rupture patch: Nias island, West Sumatra

We quantify fore-arc deformation using fossil reefs to test the assumption commonly made in seismic cycle models that anelastic deformation of the fore arc is negligible. Elevated coral microatolls, paleoreef flats, and chenier plains show that the Sumatran outer arc island of Nias has experienced a complex pattern of relatively slow long-term uplift and subsidence during the Holocene epoch. This same island rose up to 2.9 m during the Mw 8.7 Sunda megathrust rupture in 2005. The mismatch between the 2005 and Holocene uplift patterns, along with the overall low rates of Holocene deformation, reflects the dominance of elastic strain accumulation and release along this section of the Sunda outer arc high and the relatively subordinate role of upper plate deformation in accommodating long-term plate convergence. The fraction of 2005 uplift that will be retained permanently is generally <4% for sites that experienced more than 0.25 m of coseismic uplift. Average uplift rates since the mid-Holocene range from 1.5 to −0.2 mm/a and are highest on the eastern coast of Nias, where coseismic uplift was nearly zero in 2005. The pattern of long-term uplift and subsidence is consistent with slow deformation of Nias along closely spaced folds in the north and trenchward dipping back thrusts in the southeast. Low Holocene tectonic uplift rates provide for excellent geomorphic and stratigraphic preservation of the mid-Holocene relative sea level high, which was under way by ∼7.3 ka and persisted until ∼2 ka

Aqueous-phase mechanism for secondary organic aerosol formation from isoprene: application to the southeast United States and co-benefit of SO2 emission controls

Isoprene emitted by vegetation is an important precursor of secondary organic aerosol (SOA), but the mechanism and yields are uncertain. Aerosol is prevailingly aqueous under the humid conditions typical of isoprene-emitting regions. Here we develop an aqueous-phase mechanism for isoprene SOA formation coupled to a detailed gas-phase isoprene oxidation scheme. The mechanism is based on aerosol reactive uptake coefficients (γ) for water-soluble isoprene oxidation products, including sensitivity to aerosol acidity and nucleophile concentrations. We apply this mechanism to simulation of aircraft (SEAC4RS) and ground-based (SOAS) observations over the southeast US in summer 2013 using the GEOS-Chem chemical transport model. Emissions of nitrogen oxides (NOx ≡ NO + NO2) over the southeast US are such that the peroxy radicals produced from isoprene oxidation (ISOPO2) react significantly with both NO (high-NOx pathway) and HO2 (low-NOx pathway), leading to different suites of isoprene SOA precursors. We find a mean SOA mass yield of 3.3 % from isoprene oxidation, consistent with the observed relationship of total fine organic aerosol (OA) and formaldehyde (a product of isoprene oxidation). Isoprene SOA production is mainly contributed by two immediate gas-phase precursors, isoprene epoxydiols (IEPOX, 58 % of isoprene SOA) from the low-NOx pathway and glyoxal (28 %) from both low- and high-NOx pathways. This speciation is consistent with observations of IEPOX SOA from SOAS and SEAC4RS. Observations show a strong relationship between IEPOX SOA and sulfate aerosol that we explain as due to the effect of sulfate on aerosol acidity and volume. Isoprene SOA concentrations increase as NOx emissions decrease (favoring the low-NOx pathway for isoprene oxidation), but decrease more strongly as SO2 emissions decrease (due to the effect of sulfate on aerosol acidity and volume). The US Environmental Protection Agency (EPA) projects 2013-2025 decreases in anthropogenic emissions of 34 % for NOx (leading to a 7 % increase in isoprene SOA) and 48 % for SO2 (35 % decrease in isoprene SOA). Reducing SO2 emissions decreases sulfate and isoprene SOA by a similar magnitude, representing a factor of 2 co-benefit for PM2.5 from SO2 emission controls

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie