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Discovery and Optimization of the First Highly Effective and Orally Available Galectin-3 Inhibitors for Treatment of Fibrotic Disease

Galectin-3 is a carbohydrate-binding protein central to regulating mechanisms of diseases such as fibrosis, cancer, metabolic, inflammatory, and heart disease. We recently found a high affinity (nM) thiodigalactoside GB0139 which currently is in clinical development (PhIIb) as an inhaled treatment of idiopathic pulmonary fibrosis. To enable treatment of systemically galectin-3 driven disease, we h

Atmospheric Mercury Concentrations in Guangzhou City, Measured by Spectroscopic Techniques

Atmospheric levels of atomic mercury pollution were measured using spectroscopic techniques in the city of Guangzhou, Guangdong Province, China. Assessments were mainly performed at ground level using a portable (vehicle mounted or hand carried) Zeeman modulation correlation spectrometer (Lumex RA-915M), and the results are given in easily comprehensible diagrams. Measurements were made with conti

Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5- a]pyridine Scaffold : SAR of the Aryloxyaryl Moiety

In recent years, human dihydroorotate dehydrogenase inhibitors have been associated with acute myelogenous leukemia as well as studied as potent host targeting antivirals. Starting from MEDS433 (IC50 1.2 nM), we kept improving the structure-activity relationship of this class of compounds characterized by 2-hydroxypyrazolo[1,5-a]pyridine scaffold. Using an in silico/crystallography supported desig

Assessment of Polluted Soil Remediation Using Bacterial Community Tolerance to Heavy Metals as an Indicator

The assessment of remediation on metal-polluted soils is usually focused on total and/or bioavailable metal content. However, these chemical variables do not provide direct information about reductions in heavy metals pressure on soil microorganisms. We propose the use of bacterial communities to evaluate the efficiency of three remediation techniques: crushed mussel shell (CMS) and pine bark (PB)

An Interdisciplinary Perspective on Evaluation and Experimental Design for Visual Text Analytics : Position Paper

Appropriate evaluation and experimental design are fundamental for empirical sciences, particularly in data-driven fields. Due to the successes in computational modeling of languages, for instance, research outcomes are having an increasingly immediate impact on end users. As the gap in adoption by end users decreases, the need increases to ensure that tools and models developed by the research co

Risk for Mood, Anxiety, and Psychotic Disorders in Individuals at High and Low Genetic Liability for Bipolar Disorder and Major Depression

Importance: The nature of the genetic relationship between major depression and bipolar disorder remains unclear and might be clarified by considering disorders outside of the mood spectrum. Objective: To better understand the relationship between genetic liabilities for major depression (MD) and bipolar disorder (BD). Design, Setting, and Participants: A cohort study was conducted with data for i

Prognostic Value of High-Sensitivity Cardiac Troponin in Women

High-sensitivity cardiac troponin assays have become the gold standard for diagnosing acute and chronic myocardial injury. The detection of troponin levels beyond the 99th percentile is included in the fourth universal definition of myocardial infarction, specifically recommending the use of sex-specific thresholds. Measurable concentrations below the proposed diagnostic thresholds have been shown

Patient consultations during SARS-CoV-2 pandemic : a mixed-method cross-sectional study in 16 European countries

INTRODUCTION: Remote consultations help reduce contact between people and prevent cross-contamination. Little is known about the changes in consultation in European rural primary care during the SARS-CoV-2 (COVID-19) pandemic. The purpose of this mixed-methods cross-sectional study was to find out more about the effects of the pandemic on changes in patient consultations in European rural primary

Converting the genomic knowledge base to build protein specific machine learning prediction models; a classification study on thermophilic serine protease

Several machine learning models have been formulated for protein classification based on an important prerequisite for industrial usage, thermostability, and described herein a classification model for a specific enzyme; serine protease. For building the classifier, 283 thermophilic and 200 mesophilic bacterial genomes were mined for their respective serine protease sequences. Features were extrac

Community-onset urosepsis : incidence and risk factors for 30-day mortality–a retrospective cohort study

Background: Urosepsis is a life-threatening condition that needs to be addressed without delay. Two critical issues in its management are: (1) Appropriate empirical antibiotic therapy, considering the patients general condition, comorbidity, and the pathogen expected; and (2) Timing of imaging to identify obstruction requiring decompression. Objectives: To identify risk factors associated with 30-

Phenomenology of a flavored multiscalar Branco-Grimus-Lavoura-like model with three generations of massive neutrinos

In this paper, we present several possible anomaly free implementations of the Branco-Grimus-Lavoura (BGL) model with two Higgs doublets and one singlet scalar. The model also includes three generations of massive neutrinos that get their mass via a type-I seesaw mechanism. A particular anomaly free realization, which we dub νBGL-1 scenario, is subjected to an extensive phenomenological analysis,

Thomas-Reiche-Kuhn correction for truncated configuration-interaction spaces : Case of laser-assisted dynamical interference

The Thomas-Reiche-Kuhn sum rule is used to form an effective potential that is added to the time-dependent configuration-interaction singles (TDCIS) equations of motion in velocity gauge. The purpose of the effective potential is to include virtual coupling from singles to doubles, which is required for size-consistent velocity-gauge TDCIS results. The proposed method is compared to length-gauge T

Crop Water Productivity Mapping and Benchmarking Using Remote Sensing and Google Earth Engine Cloud Computing

Scarce water resources present a major hindrance to ensuring food security. Crop water productivity (WP), embraced as one of the Sustainable Development Goals (SDGs), is playing an integral role in the performance-based evaluation of agricultural systems and securing sustainable food production. This study aims at developing a cloud-based model within the Google Earth Engine (GEE) based on Landsat

Estimating the Legacy Effect of Post-Cutting Shelterbelt on Crop Yield Using Google Earth and Sentinel-2 Data

Shelterbelts (or windbreaks) can effectively improve the microclimate and soil conditions of adjacent farmland and thus increase crop yield. However, the individual contribution of these two factors to yield changes is still unclear since the short-term effect from the microclimate and the accumulated effect from the soil jointly affect crop yield. The latter (soil effect) is supposed to remain af

A new genus in the diverse Andean Pedaliodes complex uncovered using target enrichment (Lepidoptera, Nymphalidae)

A new genus of Neotropical Satyrinae butterflies, Viloriodes Pyrcz & Espeland gen. n. is described in the Pedaliodes Butler complex comprising 11–13 genera and more than 400 species. Support for the new genus is provided by a phylogenetic analysis based on target enrichment (TE) data including 618 nuclear loci with a total of 248,940 nucleotides, and the mitochondrial gene cytochrome oxidase s

Characterizing Uncertainty in the Visual Text Analysis Pipeline

Current visual text analysis approaches rely on sophisticated processing pipelines. Each step of such a pipeline potentially amplifies any uncertainties from the previous step. To ensure the comprehensibil- ity and interoperability of the results, it is of paramount importance to clearly communicate the uncertainty not only of the output but also within the pipeline. In this paper, we characterize

Sparse optimization for nonlinear group delay mode estimation

Nonlinear group delay signals with frequency-varying characteristics are common in a wide variety of fields, for instance, structural health monitoring and fault diagnosis. For such applications, the signal is composed of multiple modes, where each mode may overlap in the frequency-domain. The resulting decomposition and forming of time-frequency representations of the nonlinear group delay modes

Association of PET index quantifying skeletal uptake in NaF PET/CT images with overall survival in prostate cancer patients

Background: Bone Scan Index (BSI) derived from 2D whole-body bone scans is considered an imaging biomarker of bone metastases burden carrying prognostic information. Sodium fluoride (NaF) PET/CT is more sensitive than bone scan in detecting bone changes due to metastases. We aimed to develop a semi-quantitative PET index similar to the BSI for NaF PET/CT imaging and to study its relationship to BS