Understanding the value of curation: A survey of US data repository curation practices and perceptions.

Data curators play an important role in assessing data quality and take actions that may ultimately lead to better, more valuable data products. This study explores the curation practices of data curators working within US-based data repositories. We performed a survey in January 2021 to benchmark the levels of curation performed by repositories and assess the perceived value and impact of curation on the data sharing process.

Seek and you may (not) find: A multi-institutional analysis of where research data are shared.

Research data sharing has become an expected component of scientific research and scholarly publishing practice over the last few decades, due in part to requirements for federally funded research. As part of a larger effort to better understand the workflows and costs of public access to research data, this project conducted a high-level analysis of where academic research data is most frequently shared. To do this, we leveraged the DataCite and Crossref application programming interfaces (APIs) in search of Publisher field elements demonstrating which data repositories were utilized by researchers from six academic research institutions between 2012-2022.

Protodemetalation of (Bipyridyl)Ni(II)-Aryl Complexes Shows Evidence for Five-, Six-, and Seven-Membered Cyclic Pathways.

Protonation of C-M bonds and its microscopic reverse, metalation of C-H bonds, are fundamental steps in a variety of metal-catalyzed processes. As such, studies on protonation of C-M bonds can shed light on C-H activation. We present here studies on the rate of protodemetalation (PDM) of a suite of arylnickel(II) complexes with various acids that provide evidence for a concerted, cyclic transition state for the PDM of C-Ni bonds and demonstrate that five-, six-, and seven-membered transition states are particularly favorable.

Arguments against the Requirement of a Biological License Application for Human Pancreatic Islets: The Position Statement of the Islets for US Collaborative Presented during the FDA Advisory Committee Meeting.

The Food and Drug Administration (FDA) has been regulating human islets for allotransplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. Herein, we provide our commentary to the multiple FDA's position papers and guidance for industry arguing that BLA requirement has been inappropriately applied to allogeneic islets, which was delivered to the FDA Cellular, Tissue and Gene Therapies Advisory Committee on 15 April 2021.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices.

Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques.

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the potentially protective immune responses necessary to inhibit HIV-1 infection of infants through breastfeeding. In the present study, we tested the efficacy of a maternal vaccine regimen consisting of a modified vaccinia virus Ankara (MVA) 1086.

Effect of Reducing Field of View on Multidetector Quantitative Computed Tomography Parameters of Airway Wall Thickness in Asthma.

Objective: We reduced the computed tomography (CT)-reconstructed field of view (FOV), increasing pixel density across airway structures and reducing partial volume effects, to determine whether this would improve accuracy of airway wall thickness quantification.

Methods: We performed CT imaging on a lung phantom and 29 participants. Images were reconstructed at 30-, 15-, and 10-cm FOV using a medium-smooth kernel.

Longitudinal changes in airway remodeling and air trapping in severe asthma.

Rationale And Objectives: Previous cross-sectional studies have demonstrated that airway wall thickness and air trapping are greater in subjects with severe asthma than in those with mild-to-moderate asthma. However, a better understanding of how airway remodeling and lung density change over time is needed. This study aimed to evaluate predictors of airway wall remodeling and change in lung function and lung density over time in severe asthma.

Novel TNF-α converting enzyme (TACE) inhibitors as potential treatment for inflammatory diseases.

Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency (K(i)) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles.

Structure and activity relationships of tartrate-based TACE inhibitors.

The syntheses and structure-activity relationships of the tartrate-based TACE inhibitors are discussed. The optimization of both the prime and non-prime sites led to compounds with picomolar activity. Several analogs demonstrated good rat pharmacokinetics.

Discovery and SAR of hydantoin TACE inhibitors.

We disclose inhibitors of TNF-alpha converting enzyme (TACE) designed around a hydantoin zinc binding moiety. Crystal structures of inhibitors bound to TACE revealed monodentate coordination of the hydantoin to the zinc. SAR, X-ray, and modeling designs are described.

The discovery of novel tartrate-based TNF-alpha converting enzyme (TACE) inhibitors.

A novel series of TNF-alpha convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMP's.

Discovery of novel spirocyclopropyl hydroxamate and carboxylate compounds as TACE inhibitors.

We have discovered nanomolar inhibitors of TNF-alpha convertase (TACE) comprised of a novel spirocyclic scaffold and either a carboxylate or hydroxamate zinc binding moiety. X-ray crystal structures and computer models of selected compounds binding to TACE explain the observed SAR. We report the first TACE X-ray crystal structure for an inhibitor with a carboxylate zinc ligand.

Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket.

A series of cyclopropyl hydroxamic acids were prepared. Many of the compounds displayed picomolar affinity for the TACE enzyme while maintaining good to excellent selectivity profiles versus MMP-1, -2, -3, -7, -14, and ADAM-10. X-ray analysis of an inhibitor in the TACE active site indicated that the molecules bound to the enzyme in the S1'-S3' pocket.

De novo chiral amino alcohols in catalyzing asymmetric additions to aryl aldehydes.

[reaction: see text] A de novo structural class of chiral amino alcohol catalysts has been identified through a synergistic effort combining novel architectures from [4 + 3] cycloadditions and quantum mechanical interaction field predictions that closely match subsequent experimental measurements.

Quantifying mixed populations of drug-resistant human immunodeficiency virus type 1.

In order to survive prolonged treatment with antiretroviral nucleoside analogs, the human immunodeficiency virus type 1 (HIV-1) is selectively forced to acquire mutations in the reverse transcriptase (RT) gene. Some of these mutations are more common than others and have become markers for antiretroviral resistance. For the early detection of these markers, a novel MultiCode-RTx one-step testing system to rapidly and simultaneously characterize mixtures of HIV-1 targets was designed.

Effect of finasteride on bother and other health-related quality of life aspects associated with benign prostatic hyperplasia. PLESS Study Group. Proscar Long-term Efficacy and Safety Study.

Objectives: To investigate the long-term effects of finasteride on bother and health-related quality of life (HRQOL) in men with symptomatic benign prostatic hyperplasia.

Methods: A large prospective 4-year placebo-controlled trial (PLESS) of 3040 men with moderate to severe lower urinary tract symptoms and an enlarged prostate was performed that included self-administered questionnaires assessing HRQOL.

Results: Significantly greater reductions in bother score were seen for finasteride compared with placebo at every time point after 4 months.

The role of stomata in sensitivity of Betula papyrifera seedlings to SO at different humidities.

Stomata of paper birch (Betula papyrifera Marsh.) seedlings were more open at high humidity than at low humidity and responded rapidly to changes in vapor pressure deficit. SO at 0.

Ethylene, Ethane, Acetaldehyde, and Ethanol Production By Plants under Stress.

Red pine (Pinus resinosa Ait.) and paper birch (Betula papyrifera Marsh.) seedlings exposed to sulfur dioxide produced acetaldehyde and ethanol, and exhibited increased production of ethylene and ethane.

Relative sensitivity of three species of woody plants to SO at high or low exposure temperature.

Seedlings of paper birch (Betula papyrifera Marsh.), green ash (Fraxinus pennsylvanica Marsh.), and red pine (Pinus resinosa Ait.