Anatomy of Summertime Upslope Events in Northeastern Colorado: Ammonia (NH) Transport to the Rocky Mountains.

The Transport and Transformation of Ammonia (TRANSAm) airborne field campaign occurred over northeastern Colorado during the summers of 2021 and 2022. A subset of the TRANSAm flights investigated easterly wind conditions capable of moving agricultural emissions of ammonia (NH) through urban areas and into the Rocky Mountains. TRANSAm captured 6 of these events, unveiling important commonalities.

Human plasma-derived alpha -proteinase inhibitor in patients with new-onset type 1 diabetes mellitus: A randomized, placebo-controlled proof-of-concept study.

Background: While circulating levels of alpha -proteinase inhibitor (alpha -PI) are typically normal, antiprotease activity appears to be compromised in patients with Type 1 diabetes mellitus (T1DM). Because alpha -PI [human] (alpha -PI[h]) therapy can inhibit pro-inflammatory mediators associated with β-cell destruction and reduced insulin production, it has been proposed for T1DM disease prevention. The aim of this study was to evaluate safety, tolerability, and efficacy of intravenous (IV) alpha -PI[h] in preserving C-peptide production in newly diagnosed T1DM patients.

Variation in pesticide use across crops in California agriculture: Economic and ecological drivers.

Pesticide use is a key component of efficient crop production, but is associated with a suite of costs. Understanding the main drivers of pesticide use will help us target research to develop effective alternatives. Although economic models predict, and empirical tests confirm, that the value of the crop being protected is an important determinant of between-crop variation in pesticide use, previous tests of this prediction have examined only modest numbers of crops and have not assessed the relative importance of crop value versus ecological determinants of pesticide use.

Safety and pharmacokinetics of Alpha-1 MP (Prolastin-C) in Japanese patients with alpha-antitrypsin (AAT) deficiency.

Background: Alpha-Proteinase Inhibitor, Modified Process (Alpha-1 MP) is used for augmentation therapy in alpha1-antitrypsin deficiency (AATD), an extremely rare disease in Japan. Weekly doses of 60 mg/kg Alpha-1 MP have been shown to be safe and well tolerated in non-Japanese subjects, but the safety and pharmacokinetics (PK) have not been evaluated in Japanese subjects. The objectives of this study were to evaluate the safety and PK of 60 mg/kg Alpha-1 MP administered by weekly IV infusions over 8 weeks in Japanese subjects with AATD.

Impact of Empowering Leadership on Antimicrobial Stewardship: A Single Center Study in a Neonatal and Pediatric Intensive Care Unit and a Literature Review.

Antimicrobial stewardship (AMS) is an important strategy of quality improvement for every hospital. Leadership is an important factor for implementation of quality improvement and AMS programs. Recent publications show successful AMS programs in children's hospitals, but successful implementation is often difficult to achieve and literature of AMS in neonatal and pediatric intensive care units (NICU/PICU) is scarce.

An Ecoinformatics Approach to Field-Scale Evaluation of Insecticide Effects in California Citrus: Are Citrus Thrips and Citrus Red Mite Induced Pests?

Experimental approaches to studying the consequences of pesticide use, including impacts on beneficial insects, are vital; however, they can be limited in scale and realism. We show that an ecoinformatics approach that leverages existing data on pesticides, pests, and beneficials across multiple fields can provide complementary insights. We do this using a multi-year dataset (2002-2013) on pesticide applications and density estimates of two pests, citrus thrips (Scirtothrips citri (Moulton [Thysanoptera: Thripidae])) and citrus red mites (Panonychus citri McGregor [Acari: Tetranychidae]), and a natural enemy (Euseius spp.

Bioequivalence of a Liquid Formulation of Alpha-Proteinase Inhibitor Compared with Prolastin®-C (Lyophilized Alpha-PI) in Alpha-Antitrypsin Deficiency.

This study evaluated the bioequivalence, safety, and immunogenicity of a new liquid formulation of human plasma-derived alpha-proteinase inhibitor, Liquid Alpha-PI, compared with the Lyophilized Alpha-PI formulation (Prolastin®-C), for augmentation therapy in patients with alpha-antitrypsin deficiency (AATD). In this double-blind, randomized, 20-week crossover study, 32 subjects with AATD were randomized to receive 8 weekly infusions of 60 mg/kg of Liquid Alpha-PI or Lyophilized Alpha-PI. Serial blood samples were drawn for 7 days after the last dose followed by 8 weeks of the alternative treatment.

The SARAH Domain of RASSF1A and Its Tumor Suppressor Function.

The Ras association domain family 1A (RASSF1A) tumor suppressor encodes a Sav-RASSF-Hpo domain (SARAH), which is an interaction domain characterized by hWW45 (dSAV) and MST1/2 (dHpo). In our study, the interaction between RASSF1A and RASSF1C with MST1 and MST2 was demonstrated and it was shown that this interaction depends on the SARAH domain. SARAH domain-deleted RASSF1A had a similar growth-reducing effect as full-length RASSF1A and inhibited anchorage independent growth of the lung cancer cell lines A549 significantly.

Improving the performance of true single molecule sequencing for ancient DNA.

Background: Second-generation sequencing technologies have revolutionized our ability to recover genetic information from the past, allowing the characterization of the first complete genomes from past individuals and extinct species. Recently, third generation Helicos sequencing platforms, which perform true Single-Molecule DNA Sequencing (tSMS), have shown great potential for sequencing DNA molecules from Pleistocene fossils. Here, we aim at improving even further the performance of tSMS for ancient DNA by testing two novel tSMS template preparation methods for Pleistocene bone fossils, namely oligonucleotide spiking and treatment with DNA phosphatase.

Genome-wide identification and characterization of replication origins by deep sequencing.

Background: DNA replication initiates at distinct origins in eukaryotic genomes, but the genomic features that define these sites are not well understood.

Results: We have taken a combined experimental and bioinformatic approach to identify and characterize origins of replication in three distantly related fission yeasts: Schizosaccharomyces pombe, Schizosaccharomyces octosporus and Schizosaccharomyces japonicus. Using single-molecule deep sequencing to construct amplification-free high-resolution replication profiles, we located origins and identified sequence motifs that predict origin function.

Does use of pesticides known to harm natural enemies of spider mites (Acari: Tetranychidae) result in increased number of miticide applications? An examination of California walnut orchards.

Integrated pest management (IPM) offers guidelines to reduce spider mite (Acari: Tetranychidae) outbreaks by avoiding pesticides known to be harmful to the natural enemies of spider mites. However, in practice, these guidelines can be inconsistent in their effectiveness. The project examined whether California walnut (Juglans L.

True single-molecule DNA sequencing of a pleistocene horse bone.

Second-generation sequencing platforms have revolutionized the field of ancient DNA, opening access to complete genomes of past individuals and extinct species. However, these platforms are dependent on library construction and amplification steps that may result in sequences that do not reflect the original DNA template composition. This is particularly true for ancient DNA, where templates have undergone extensive damage post-mortem.

Epigenetic silencing of erythropoietin in human cancers.

The glycoprotein hormone erythropoietin (EPO) is a key regulator in the production of red blood cells. EPO is produced mainly in the embryonic liver and kidney of adults. Other organs are also known to express varying amounts of EPO.

Single-step capture and sequencing of natural DNA for detection of BRCA1 mutations.

Genetic testing for disease risk is an increasingly important component of medical care. However, testing can be expensive, which can lead to patients and physicians having limited access to the genetic information needed for medical decisions. To simplify DNA sample preparation and lower costs, we have developed a system in which any gene can be captured and sequenced directly from human genomic DNA without amplification, using no proteins or enzymes prior to sequencing.

Helicos single-molecule sequencing of bacterial genomes.

With the advent of high-throughput sequencing technologies, multiple bacterial genomes can be sequenced in days. While the ultimate goal of de novo assembly of bacterial genomes is progressing, changes in the genomic sequence of closely related bacterial strains and isolates are now easily monitored by comparison of their sequences to those of a reference genome. Such studies can be applied to the fields of bacterial evolution, epidemiology, and diagnostics.

Frequent epigenetic inactivation of RASSF2 in thyroid cancer and functional consequences.

Background: The Ras association domain family (RASSF) encodes for distinct tumor suppressors and several members are frequently silenced in human cancer. In our study, we analyzed the role of RASSF2, RASSF3, RASSF4, RASSF5A, RASSF5C and RASSF6 and the effectors MST1, MST2 and WW45 in thyroid carcinogenesis.

Results: Frequent methylation of the RASSF2 and RASSF5A CpG island promoters in thyroid tumors was observed.

Single molecule sequencing with a HeliScope genetic analysis system.

Helicos™ Single Molecule Sequencing (SMS) provides a unique view of genome biology through direct sequencing of cellular nucleic acids in an unbiased manner, providing both accurate quantitation and sequence information. Sample preparation does not require ligation or PCR amplification, avoiding the GC-content and size biases observed in other technologies. DNA is simply sheared, tailed with poly(A), and hybridized to a flow cell surface containing oligo(dT) for sequencing-by-synthesis of billions of molecules in parallel.

Protein kinase A-mediated phosphorylation of the RASSF1A tumour suppressor at Serine 203 and regulation of RASSF1A function.

Epigenetic inactivation of the Ras-Association Domain Family 1A (RASSF1A) gene is one of the most frequent alterations detected in cancer. The tumour suppressor function of RASSF1A contributes to cell cycle progression, microtubule stabilisation and apoptotic signalling. Here we investigated the putative phosphorylation sites of RASSF1A and the functional consequences.

Single-molecule sequencing: sequence methods to enable accurate quantitation.

Helicos Single-Molecule Sequencing provides a unique view of genome biology through direct sequencing of cellular and extracellular nucleic acids in an unbiased manner, providing both quantitation and sequence information. Using a simple sample preparation, involving no ligation or amplification, genomic DNA is sheared, tailed with poly-A and hybridized to the flow-cell surface containing oligo-dT for initiating sequencing-by-synthesis. RNA measurements involving direct RNA hybridization to the flow cell allows for the direct sequencing and quantitation of RNA molecules.

A novel third type of recurrent NF1 microdeletion mediated by nonallelic homologous recombination between LRRC37B-containing low-copy repeats in 17q11.2.

Large microdeletions encompassing the neurofibromatosis type-1 (NF1) gene and its flanking regions at 17q11.2 belong to the group of genomic disorders caused by aberrant recombination between segmental duplications. The most common NF1 microdeletions (type-1) span 1.

Frequent promoter hypermethylation of tumor-related genes in head and neck squamous cell carcinoma.

Squamous cell carcinomas of head and neck (HNSCC) are a result of multiple genetic and epigenetic alterations. Epigenetic inactivation of tumor suppressor genes is an important event in head and neck carcinogenesis. Here we analyzed the promoter methylation of 15 genes (RASSF1A, p16, MGMT, DAPK, RARbeta, MLH1, CDH1, GSTP1, RASSF2, RASSF4, RASSF5, MST1, MST2, LATS1, LATS2) in 54 HNSCC and in matching 23 normal tissues.

Virtual terminator nucleotides for next-generation DNA sequencing.

We synthesized reversible terminators with tethered inhibitors for next-generation sequencing. These were efficiently incorporated with high fidelity while preventing incorporation of additional nucleotides, and we used them to sequence canine bacterial artificial chromosomes in a single-molecule system that provided even coverage for over 99% of the region sequenced. This single-molecule approach generated high-quality sequence data without the need for target amplification and thus avoided concomitant biases.