26 research outputs found
Genome Sequence of Mycobacterium Phage Waterfoul
Waterfoul is a new isolated temperate siphovirus of Mycobacterium smegmatis mc2155. It was identified as a member of the K5 cluster of Mycobacterium phages and has a 61,248-bp genome with 95 predicted genes
Integrating Omic Technologies into Aquatic Ecological Risk Assessment and Environmental Monitoring: Hurdles, Achievements, and Future Outlook
Background: In this commentary we present the findings from an international consortium on fish toxicogenomics sponsored by the U.K. Natural Environment Research Council (Fish Toxicogenomics—Moving into Regulation and Monitoring, held 21–23 April 2008 at the Pacific Environmental Science Centre, Vancouver, BC, Canada).
Objectives: The consortium from government agencies, academia, and industry addressed three topics: progress in ecotoxicogenomics, regulatory perspectives on roadblocks for practical implementation of toxicogenomics into risk assessment, and dealing with variability in data sets.
Discussion: Participants noted that examples of successful application of omic technologies have been identified, but critical studies are needed to relate molecular changes to ecological adverse outcome. Participants made recommendations for the management of technical and biological variation. They also stressed the need for enhanced interdisciplinary training and communication as well as considerable investment into the generation and curation of appropriate reference omic data.
Conclusions: The participants concluded that, although there are hurdles to pass on the road to regulatory acceptance, omics technologies are already useful for elucidating modes of action of toxicants and can contribute to the risk assessment process as part of a weight-of-evidence approach
Impaired neurocognitive functioning 3 months following diagnosis of high-risk acute lymphoblastic leukemia: A report from the Children\u27s Oncology Group
PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer diagnosis. Cognitive late effects develop in 20%-40% of ALL survivors, but the course of declines is unclear. The aim of this paper is to characterize cognitive functioning, and its association with patient-reported outcomes, early in treatment. PATIENTS AND METHODS: A total of 483 children with high-risk ALL, aged 6-12 years at diagnosis, consented to the neurocognitive study embedded in a prospective therapeutic trial, Children\u27s Oncology Group (COG) AALL1131. A computerized neurocognitive battery (Cogstate) was administered 3 months post diagnosis assessing reaction time, visual attention, working memory, visual learning, and executive functioning. Parent-reported executive functioning and patient-reported physical symptoms were also collected. RESULTS: Data from 390 participants (mean age at diagnosis = 9.2 years, 55.4% male) were obtained. Relatively few patients reported pain (16.0%) or nausea (22.6%), but a majority (68.5%) reported feeling at least some fatigue at testing. Mean Cogstate Z-scores were within normal limits across tasks; however, rates of impairment (Z-scores ≤ -1.5) for reaction time, working memory, visual learning, and visual attention were all higher than expected compared to the standardization sample. Patients reporting fatigue were significantly more likely to have impaired reaction time and visual attention compared to those reporting no fatigue. CONCLUSION: Findings support feasibility of computerized cognitive assessments and suggest higher-than-expected rates of impaired cognitive performance early during treatment for pediatric ALL, notably within 3 months of diagnosis, suggesting intervention efforts may be indicated. These results also highlight acute factors that may impact reliability of baseline assessments conducted soon after diagnosis
Mechanistic Study of Diketopiperazine Formation during Solid-Phase Peptide Synthesis of Tirzepatide
This study focused on investigating diketopiperazine
(DKP) and
the formation of associated double-amino-acid deletion impurities
during linear solid-phase peptide synthesis (SPPS) of tirzepatide
(TZP). We identified that the DKP formation primarily occurred during
the Fmoc-deprotection reaction and post-coupling aging of the unstable
Fmoc-Pro-Pro-Ser-resin active pharmaceutical ingredient (API) intermediate.
Similar phenomena have also been observed for other TZP active pharmaceutical
ingredient (API) intermediates that contain a penultimate proline
amino acid, such as Fmoc-Ala-Pro-Pro-Pro-Ser-resin, Fmoc-Pro-Pro-Pro-Ser-resin,
and Fmoc-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-resin, which are
intermediates for both hybrid and linear synthesis approaches. During
post-coupling aging, it is found that Fmoc deprotection can proceed
in dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), and acetonitrile (ACN) solvents without
any piperidine addition. Density functional theory (DFT) calculations
showed that a peptide that has a penultimate proline stabilizes the
transition state through the C–H···π interaction
during Fmoc decomposition, which causes those peptides to be more
prone to cascade-deprotection reactions. Pseudo-reaction pathways
are then proposed, and a corresponding macrokinetics model is developed
to allow accurate prediction of the TZP peptide intermediate self-deprotection
and DKP formation rate. Based on those studies, control strategies
for minimizing DKP formation were further investigated and an alternative
to Fmoc protection was identified (Bsmoc-protected amino acids), which
eliminated the formation of the DKP byproducts. In addition, the use
of oxyma additives and lower storage temperature was demonstrated
to markedly improve the peptide intermediate stability to DKP degradation
pathways
Electron Results for the ATLAS Electromagnetic Forward Calorimeter Module 0 Test Beam 1998 011
The ATLAS Forward Calorimeter (FCal) is a unique calorimeter featuring cylindrical electrodes wit
Construction and initial beam tests of the ATLAS tungsten forward calorimeter
Due to the severe radiation environment, the ATLAS experiment has chosen a compact tungsten/liquid argon forward hadronic calorimeter. The electrode design is unique and consists of hexagonally packed, tubular, thin gap electrodes $9 running parallel to the beam direction. We describe the design criteria, the novel construction methods based on sintered tungsten components, and initial high energy beam tests at CERN. (3 refs)