Scene Graph Parsing as Dependency Parsing

In this paper, we study the problem of parsing structured knowledge graphs from textual descrip- tions. In particular, we consider the scene graph representation that considers objects together with their attributes and relations: this representation has been proved useful across a variety of vision and language applications. We begin by introducing an alternative but equivalent edge-centric view of scene graphs that connect to dependency parses. Together with a careful redesign of label and action space, we combine the two-stage pipeline used in prior work (generic dependency parsing followed by simple post-processing) into one, enabling end-to-end training. The scene graphs generated by our learned neural dependency parser achieve an F-score similarity of 49.67% to ground truth graphs on our evaluation set, surpassing best previous approaches by 5%. We further demonstrate the effective- ness of our learned parser on image retrieval applications.This material is based upon work supported by the Center for Brains, Minds and Machines (CBMM), funded by NSF STC award CCF-1231216

HCO3−/Cl− Exchange Inactivation and Reactivation during Mouse Oocyte Meiosis Correlates with MEK/MAPK-Regulated Ae2 Plasma Membrane Localization

Background: Germinal Vesicle (GV) stage mouse oocytes in first meiotic prophase exhibit highly active HCO3−/Cl− exchange—a class of transport nearly ubiquitously involved in regulation of intracellular pH and cell volume. During meiosis, however, oocyte HCO3−/Cl− exchange becomes inactivated during first metaphase (MI), remains inactive in second metaphase (MII), and is reactivated only after egg activation. Previous work using pharmacological manipulations had indicated that activity of the MEK/MAPK signaling pathway was negatively correlated with HCO3−/Cl− exchange activity during meiosis. However, the mechanism by which the exchanger is inactivated during meiotic progression had not been determined, nor had the role of MEK/MAPK been directly established. Methodology/Principal Findings: Expression of a constitutively active form of MEK (MAP kinase kinase), which prevented the normal downregulation of MAPK after egg activation, also prevented reactivation of HCO3−/Cl− exchange. Conversely, suppression of endogenous MAPK activity with dominant negative MEK activated the normally quiescent HCO3−/Cl− exchange in mature MII eggs. A GFP-tagged form of the HCO3−/Cl− exchanger isoform Ae2 (Slc4a2) was strongly expressed at the GV oocyte plasma membrane, but membrane localization decreased markedly during meiotic progression. A similar pattern for endogenous Ae2 was confirmed by immunocytochemistry. The loss of membrane-localized Ae2 appeared selective, since membrane localization of a GFP-tagged human dopamine D1 receptor did not change during meiotic maturation. Conclusions: Direct manipulation of MAPK activity indicated that GFP-tagged Ae2 localization depended upon MAPK activity. Inactivation of HCO3−/Cl− exchange during the meiotic cell cycle may therefore reflect the loss of Ae2 from the oocyte plasma membrane, downstream of MEK/MAPK signaling. This identifies a novel role for MEK/MAPK-mediated cytostatic factor (CSF) activity during meiosis in membrane protein trafficking in mouse oocytes, and shows for the first time that selective retrieval of membrane proteins is a feature of meiosis in mammalian oocytes

Follicle-stimulating Hormone is Independently Associated with Lean Mass but not BMD in Younger Postmenopausal Women

PURPOSE: Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated.METHODS: We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT).RESULTS: FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β=-0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD.CONCLUSIONS: After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight

Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors.

PurposeThis study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition.MethodsThis was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD.ResultsAdverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses).ConclusionsContinuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested

Transcriptional Regulation by ERR and Its Role in NAFLD Pathogenesis

Members of estrogen-related receptors (ERRs) are orphan nuclear receptors (NRs) that play primary roles in mitochondrial biogenesis and bioenergetics. The ERRs regulate a range of cellular functions, including oxidative phosphorylation (OXPHOS) as well as glucose and lipid metabolism. ERRs are considered important targets for the treatment of metabolic diseases, particularly type II diabetes (T2D), insulin resistance (IR) and obesity. In this review, we will overview the transcriptional network regulated by the members of ERR transcriptional factors and elaborate on the regulation of ERR via its binding to PGC-1α, the primary co-activator of ERR as well as post-translational regulation of ERRs by upstream kinase signals. Recent development in ERR’s cellular function has identified lipid metabolism/lipogenesis as a process that ERR regulates, and this function significantly impacts metabolic syndrome. Here, we will focus on their roles in lipid metabolic regulation and discuss the in vivo functions of ERRs in the development of non-alcoholic fatty liver disease (NAFLD), a comorbid metabolic syndrome concurrent with T2D, IR as well as obesity. Finally, we will explore ERRs as potential therapeutic targets by discussing the ligands that serve as antagonist/agonists for ERRs as well as efforts that target DNA binding of ERR as a transcriptional factor

Carbon Monitor Cities, near-real-time daily estimates of CO2 emissions from 1500 cities worldwide

Building on near-real-time and spatially explicit estimates of daily carbon dioxide (CO2) emissions, here we present and analyze a new city-level dataset of fossil fuel and cement emissions. Carbon Monitor Cities provides daily, city-level estimates of emissions from January 2019 through December 2021 for 1500 cities in 46 countries, and disaggregates five sectors: power generation, residential (buildings), industry, ground transportation, and aviation. The goal of this dataset is to improve the timeliness and temporal resolution of city-level emission inventories and includes estimates for both functional urban areas and city administrative areas that are consistent with global and regional totals. Comparisons with other datasets (i.e. CEADs, MEIC, Vulcan, and CDP) were performed, and we estimate the overall uncertainty to be 21.7%. Carbon Monitor Cities is a near-real-time, city-level emission dataset that includes cities around the world, including the first estimates for many cities in low-income countries