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Sea surface temperature (SST) variability has been shown to have predictive value for land precipitation, although SSTs are unable to fully predict intraseasonal to interannual hydrologic extremes. The possible remote effects of large-scale land surface temperature (LST) and subsurface temperature (SUBT) anomalies in geographical areas upstream and closer to the areas of drought/flood have largely been ignored. Here evidence from climate observations and model simulations addresses these effects. Evaluation of observational data using Maximum Covariance Analysis identifies significant correlations between springtime 2-m air temperature (T2 m) cold (warm) anomalies in both the western U.S. and the Tibetan Plateau and downstream drought (flood) events in late spring/summer. To support these observational findings, climate models are used in sensitivity studies, in which initial LST/SUBT anomaly is imposed to produce observed T2 m anomaly, to demonstrate a causal relationship for two important cases: between spring warm T2 m/LST/SUBT anomalies in western U.S. and the extraordinary 2015 flood in Southern Great Plains and adjacent regions and between spring cold T2 m/LST/SUBT anomalies in the Tibetan Plateau and the severe 2003 drought south of the Yangtze River region. The LST/SUBT downstream effects in North America are associated with a large-scale atmospheric stationary wave extending eastward from the LST/SUBT anomaly region. The effects of SST in these cases are also tested and compared with the LST/SUBT effects. These results suggest that consideration of LST/SUBT anomalies has the potential to add value to intraseasonal prediction of dry and wet conditions, especially extreme drought/flood events. The results suggest the importance of developing land data and models capable of preserving observed soil memory.

Recurrent drought and associated heatwave episodes are important features of the US climate. Many studies have examined the connection between ocean surface temperature changes and conterminous US droughts. However, remote effects of large-scale land surface temperature variability, over shorter but still considerable distances, on US regional droughts have been largely ignored. The present study combines two types of evidence to address these effects: climate observations and model simulations. Our analysis of observational data shows that springtime land temperature in northwest US is significantly correlated with summer rainfall and surface temperature changes in the US Southern Plains and its adjacent areas. Our model simulations of the 2011 Southern Plains drought using a general circulation model and a regional climate model confirm the observed relationship between land temperature anomaly and drought, and suggest that the long-distance effect of land temperature changes in the northwest US on Southern Plains droughts is probably as large as the more familiar effects of ocean surface temperatures and atmospheric internal variability. We conclude that the cool 2011 springtime climate conditions in the northwest US increased the probability of summer drought and abnormal heat in the Southern Plains. The present study suggests a strong potential for more skillful intra-seasonal predictions of US Southern Plains droughts when such facts as ones presented here are considered.

Regional climate models (RCMs) have been developed and extensively applied for dynamically downscaling coarse resolution information from different sources, such as general circulation models (GCMs) and reanalyses, for different purposes including past climate simulations and future climate projection. Thus far, the nature, the methods, and a number of crucial issues concerning the use of dynamic downscaling are still not well understood. The most important issue is whether, and if so, under what conditions dynamic downscaling is really capable of adding more information at different scales compared to the GCM or reanalysis that imposes lateral boundary conditions (LBCs) to the RCMs. There are controversies regarding the downscaling ability. In this review paper we present several factors that have consistently demonstrated strong impact on dynamic downscaling ability in intraseasonal and seasonal simulations/predictions and future projection. Those factors include setting of the RCM experiment (e.g. imposed LBC quality, domain size and position, LBC coupling, and horizontal resolution); as well as physical processes, mainly convective schemes and vegetation and soil processes that include initializations, vegetation specifications, and planetary boundary layer and surface coupling. These studies indicate that RCMs have downscaling ability in some aspects but only under certain conditions. Any significant weaknesses in one of these aspects would cause an RCM to lose its dynamic downscaling ability. This paper also briefly presents challenges faced in current RCM dynamic downscaling and future prospective, which cover the application of coupled ocean-atmosphere RCMs, ensemble applications, and future projections. © 2014 Elsevier B.V.

Dielectric measurements are used for characterizing magnetic phase transitions in the doped ferroelectric oxides [Ho.sub.1-x][Y.sub.x]Mn[O.sub.3] (x=0.4). The magnetic field anisotropy is very important in understanding the magnetic and electric phase competition in the diluted 4f system by the nonmagnetic yttrium (Y) ion and the dielectric response is a very good probe for analyzing the spin-spin interactions in diluted [Ho.sub.1-x][Y.sub.x]Mn[O.sub.3].

Dielectric measurements are used for characterizing the magnetic phase transitions in the doped ferroelectric oxides [Ho.sub.1-x][Y.sub.x]Mn[O.sub.3] (x = 0-0.8) and the effects of the magnetic field direction and Y doping on the reentrant T-B-[THETA] phase diagrams below Neel temperature are examined. The magnetic field anisotropic study is very important for understanding the magnetic and electric phase competition in the diluted Ho 4 f hexagonal system by the nonmagnetic ion yttrium.

Dielectric measurements are used to characterize magnetic phase transitions in the doped ferroelectric oxides Ho1-xYxMnO3 (x=0–0.8). The focus of this study is on the effects of the magnetic field direction and Y doping on the reentrant T-B-θ phase diagrams below the Néel temperature. The response of Ho sublattice to the applied magnetic field plays a major role in all magnetic phase transitions for Y doping (x=0.0–0.8), consistent with previous results (x=0,0.6,0.8). Two successive Mn spin rotations in the ab plane in the antiferromagnetic state are driven by the exchange interaction with the Ho subsystem, through magnetodielectric coupling. Difference in energy between two ground Mn spin states is correlated with magnetic field induced perturbations in Ho lattice. The coupling between Ho and Mn can be explained by simple geometric relations of uniaxial anisotropy between magnetic field direction and c-axis of hexagonal HoMnO3. The magnetic field anisotropy study is an important step toward the understanding of magnetic and electric phase competition in the diluted Ho 4 f hexagonal system by the nonmagnetic ion yttrium (Y). [ABSTRACT FROM AUTHOR]

Dielectric measurements are used to characterize magnetic phase transitions in the doped ferroelectric oxides Ho1-xYxMnO3 (x=0–0.8). The focus of this study is on the effects of the magnetic field direction and Y doping on the reentrant T-B-θ phase diagrams below the Néel temperature. The response of Ho sublattice to the applied magnetic field plays a major role in all magnetic phase transitions for Y doping (x=0.0–0.8), consistent with previous results (x=0,0.6,0.8). Two successive Mn spin rotations in the ab plane in the antiferromagnetic state are driven by the exchange interaction with the Ho subsystem, through magnetodielectric coupling. Difference in energy between two ground Mn spin states is correlated with magnetic field induced perturbations in Ho lattice. The coupling between Ho and Mn can be explained by simple geometric relations of uniaxial anisotropy between magnetic field direction and c-axis of hexagonal HoMnO3. The magnetic field anisotropy study is an important step toward the understanding of magnetic and electric phase competition in the diluted Ho 4 f hexagonal system by the nonmagnetic ion yttrium (Y). [ABSTRACT FROM AUTHOR]

Dielectric measurements are used to characterize magnetic phase transitions in the doped ferroelectric oxides Ho1-xYxMnO3 (x=0.4). The focus of this experiment is on the effects of the magnetic field direction on the reentrant T-B-θ phase diagram below the Néel temperature. The Ho sublattice plays a major role in all magnetic phase transitions for Y doping (x=0.4), consistent with previous results (x=0,0.6,0.8). Two successive Mn spin rotations in the ab plane in the antiferromagnetic state are driven by the interaction with the Ho subsystem, although the Ho ordering peak in data is not pronounced. The dielectric response is a very sensitive probe for fine analysis of all aspects of spin-spin interactions in diluted Ho1-xYxMnO3. The magnetic field anisotropy study is an important step towards the understanding of magnetic and electric phase competition in the diluted 4f system by the nonmagnetic yttrium (Y) ion. [ABSTRACT FROM AUTHOR]

Abstract: There is considerable interest in the direct bonding between Si and Ge substrates and high-K nano-crystalline transition metal elemental and complex oxides. Implicit in this is the elimination of lower-K interfacial transition regions (ITRs) in gate stacks which limit device down-scaling of advanced devices to meet roadmap targets. A novel approach is presented in this article for (i) deposition of HfO2 onto N-passivated Ge(111) and Ge(100) substrates, a process that also prevents subcutaneous oxidation of the Ge substrate during the deposition of nano-crystalline HfO2 and non-crystalline Hf Si oxynitride dielectrics as well, and (ii) the effective removal of Ge–N, during an 800°C rapid thermal annealing. Removal of Ge–N bonding has been confirmed by X-ray absorption N K1 spectra (XAS). However, even though X-ray photoelectron spectroscopy (XPS) studies has indicated no detectable Ge–O bonding at the Ge-dielectric interfaces as-deposited, a significant amount of Ge–O bonding throughout the entire HfO2 film is detected by XPS and XAS after the 800°C anneal. Current–voltage measurements indicate significantly higher leakage for HfO2 films on Ge(111) compared with Ge(100). These correlate with differences in band edge defect state densities obtained from spectroscopic measurements, and are consistent with a more columnar, bonding morphology for direct bonding of HfO2 on Ge(111) than for Ge(100). [Copyright &y& Elsevier]

N 6 -methyladenosine (m 6 A) RNA modification controls numerous cellular processes. To what extent these post-transcriptional regulatory mechanisms play a role in hematopoiesis has not been fully elucidated. We here show that the m 6 A demethylase alkB homolog 5 (ALKBH5) controls mitochondrial ATP production and modulates hematopoietic stem and progenitor cell (HSPC) fitness in an m 6 A-dependent manner. Loss of ALKBH5 results in increased RNA methylation and instability of oxoglutarate-dehydrogenase (Ogdh) messenger RNA and reduction of OGDH protein levels. Limited OGDH availability slows the tricarboxylic acid (TCA) cycle with accumulation of α-ketoglutarate (α-KG) and conversion of α-KG into L-2-hydroxyglutarate (L-2-HG). L-2-HG inhibits energy production in both murine and human hematopoietic cells in vitro. Impaired mitochondrial energy production confers competitive disadvantage to HSPCs and limits clonogenicity of Mll-AF9-induced leukemia. Our study uncovers a mechanism whereby the RNA m 6 A demethylase ALKBH5 regulates the stability of metabolic enzyme transcripts, thereby controlling energy metabolism in hematopoiesis and leukemia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Genome-wide CRISPR screens have been extremely useful in identifying therapeutic targets in diverse cancers by defining genes that are essential for malignant growth. However, most CRISPR screens were performed in vitro and thus cannot identify genes that are essential for interactions with the microenvironment in vivo. Here, we report genome-wide CRISPR screens in 2 in vivo murine models of acute myeloid leukemia (AML) driven by the KMT2A/MLLT3 fusion or by the constitutive coexpression of Hoxa9 and Meis1. Secondary validation using a focused library identified 72 genes specifically essential for leukemic growth in vivo, including components of the major histocompatibility complex class I complex, Cd47, complement receptor Cr1l, and the β-4-galactosylation pathway. Importantly, several of these in vivo-specific hits have a prognostic effect or are inferred to be master regulators of protein activity in human AML cases. For instance, we identified Fermt3, a master regulator of integrin signaling, as having in vivo-specific dependency with high prognostic relevance. Overall, we show an experimental and computational pipeline for genome-wide functional screens in vivo in AML and provide a genome-wide resource of essential drivers of leukemic growth in vivo., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Purpose of Review: RNA epigenetic modifications have been identified as novel, dynamic regulators of gene expression, with important impacts on stem cell fate decisions. Here we examine the functions of RNA modifications, with a focus on N 6 -methyladenosine (m 6 A), in hematopoietic stem cells under normal conditions and in malignancy., Recent Findings: The m 6 A RNA modification is a critical regulator of hematopoiesis. Disruption of different elements of the m 6 A machinery can skew the balance of self-renewal and differentiation in normal hematopoietic stem cells. The m 6 A reader, writer, and eraser proteins are also overexpressed in myeloid leukemia, and disruption of their function impairs leukemogenesis. RNA m 6 A modification governs important aspects of immune system function, including immune cell development, immune signaling, and recognition of RNA as foreign or self. In hematopoietic stem cells, endogenously-derived double stranded RNA can form in the absence of m 6 A, inducing deleterious inflammatory pathways which compromise stem cell function., Summary: The RNA modification m 6 A exerts a variety of functions in normal hematopoietic stem cells as well as leukemic cells. Pharmacologic modulation of different elements of the m 6 A machinery provides a promising avenue for ex vivo expansion of hematopoietic stem cells in the transplant setting, as well as for leukemia therapy., Competing Interests: Compliance with Ethical Standards Radovan Vasic, Yimeng Gao, Chengyang Liu, and Stephanie Halene declare that they have no conflict of interest. Conflict of Interest The authors declare that they have no conflict of interest.

N 6 -methyladenosine (m 6 A) is the most abundant RNA modification, but little is known about its role in mammalian hematopoietic development. Here, we show that conditional deletion of the m 6 A writer METTL3 in murine fetal liver resulted in hematopoietic failure and perinatal lethality. Loss of METTL3 and m 6 A activated an aberrant innate immune response, mediated by the formation of endogenous double-stranded RNAs (dsRNAs). The aberrantly formed dsRNAs were long, highly m 6 A modified in their native state, characterized by low folding energies, and predominantly protein coding. We identified coinciding activation of pattern recognition receptor pathways normally tasked with the detection of foreign dsRNAs. Disruption of the aberrant immune response via abrogation of downstream Mavs or Rnasel signaling partially rescued the observed hematopoietic defects in METTL3-deficient cells in vitro and in vivo. Our results suggest that m 6 A modification protects against endogenous dsRNA formation and a deleterious innate immune response during mammalian hematopoietic development., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Recurrent mutations in the splicing factor SRSF2 are associated with poor clinical outcomes in myelodysplastic syndromes (MDS). Their high frequency suggests these mutations drive oncogenesis, yet the molecular explanation for this process is unclear. SRSF2 mutations could directly affect pre-mRNA splicing of a vital gene product; alternatively, a whole network of gene products could be affected. Here we determine how SRSF2 mutations globally affect RNA binding and splicing in vivo using HITS-CLIP. Remarkably, the majority of differential binding events do not translate into alternative splicing of exons with SRSF2 P95H binding sites. Alternative splice alterations appear to be dominated by indirect effects. Importantly, SRSF2 P95H targets are enriched in RNA processing and splicing genes, including several members of the hnRNP and SR families of proteins, suggesting a "splicing-cascade" phenotype wherein mutation of a single splicing factor leads to widespread modifications in multiple RNA processing and splicing proteins. We show that splice alteration of HNRNPA2B1, a splicing factor differentially bound and spliced by SRSF2 P95H , impairs hematopoietic differentiation in vivo. Our data suggests a model whereby the recurrent mutations in splicing factors set off a cascade of gene regulatory events that together affect hematopoiesis and drive cancer.