UV Spectra and Excitation Delocalization in DNA: Influence of the Spectral Width

The singlet excited states of the model DNA duplex (dA)10.(dT)10 are studied. Calculations are performed in the exciton theory framework. Molecular dynamics calculations provide the duplex geometry. The dipolar coupling is determined using atomic transition charges. The monomer transition energies are simulated by Gaussian functions resembling the absorption bands of nucleosides in aqueous solutions. Most of the excited states are found to be delocalized over at least two bases and result from the mixing of different monomer states. Their properties are only weakly affected by conformational changes of the double helix. On average, the highest oscillator strength is carried by the upper eigenstates. The duplex absorption spectra are shifted a few nanometers to higher energies with respect to the spectra of noninteracting monomers. The states with larger spatial extent are located close to the maximum of the absorption spectrum

Exciton States of Dynamic DNA Double Helices: Alternating dCdG Sequences

The present communication deals with the excited states of the alternating DNA oligomer (dCdG)5·(dCdG)5 which correspond to the UV absorption band around 260 nm. Their properties are studied in the frame of the exciton theory, combining molecular dynamics simulations and quantum chemistry data. It is shown that the dipolar coupling undergoes important variations with the site and the helix geometry. In contrast, the energy of the monomer transitions within the double helix is not sensitive to the local environment. It is thus considered to be distributed over Gaussian curves whose maximum and width are derived from the experimental absorption spectra of nucleosides in aqueous solution. The influence of the spectral width on the excited state delocalization and the absorption spectra is much stronger than that of the oligomer plasticity. About half of the excited states are delocalized over at least two bases. Many of them result from the mixing of different monomer states and extend on both strands. The trends found in the simulated spectra, when going from non-interacting monomers to the duplex, are in agreement with experimental observations. Conformational changes enhance the diversity of the states which can be populated upon excitation at a given energy. The states with larger spatial extent are located close to the maximum of the absorption spectrum

A Performance Improvement Project to Improve Hand-off Communication Documentation within the Surgical Services Department

Over 80% of adverse events in healthcare are due to miscommunication. To improve patient safety, The Joint Commission recommended the use of standardized hand-off communication tools in 2012. One acute care hospital in Southeast Florida implemented standardized handoff reports in 2014 with few revisions since that time. The COVID-19 pandemic brought to light additional critical information was needed to keep patients and staff safe, such as laboratory results indicating the need for isolation precautions. The nurses within the surgical services noticed this critical information was not sufficiently included in the handoff report. The lack of this information led to unnecessary staff exposures and delays in treatment. The quality improvement nurse noticed a significant drop in the use of the standardized hand-off report form used during this time. This drop in compliance lead to concerns for patient and staff safety. The purpose of this performance improvement project was to improve the quality of handoff reports as measured by the level of documentation using the standardized handoff report. The project followed the Plan-Do-Check-Act model for performance improvement, monitoring documentation compliance and reporting the results to the leaders and staff. The handoff report form was revised with input from the staff, resulting in improved efficiency. The nurses’ level of satisfaction with the form improved resulting in improved compliance and reducing miscommunications

Spring Phytoplankton Photosynthesis, Growth, and Primary Production and Relationships to a Recurrent Coastal Sediment Plume and River Inputs in Southeastern Lake Michigan

[1] A recurrent coastal sediment plume (RCP) is an episodic event in the southern basin of Lake Michigan that typically coincides with the spring diatom bloom. Strong winter storm activity during El Nino conditions in 1998 resulted in a large and intense RCP event. Consistently higher values of the light-saturated rate of photosynthesis, P-max(B), were observed in spring 1998 compared to 1999 and 2000. Higher values of P-max(B) in 1998 appeared to be related to increased availability of phosphorus, as evidenced by significant correlations of P-max(B) with soluble reactive phosphorus (SRP). Light-saturated growth rates were also significantly correlated with SRP concentrations. These findings were consistent the view that the RCP was a source of enrichment. However, incubation experiments involving lake water enriched with sediments showed relatively small increases in growth and photosynthetic parameters, while enrichments with river water exhibited elevated rates. This result, along with increased levels of river discharge in 1998 and high levels of dissolved phosphorus in river water, supported the view that riverine inputs rather than the RCP were responsible for the higher photosynthetic parameters and growth seen for coastal margin assemblages. Despite the higher levels of P-max(B) in 1998, model analyses revealed that reduced light availability resulting from the intense RCP event constrained phytoplankton growth rates and primary production during this season and apparently suppressed the development of a typical spring bloom. These findings indicate a potential for reduced ecosystem productivity in response to extreme storm events, the frequency of which may increase with projected long-term climate changes

Discovery of macrocyclic inhibitors of apurinic/apyrimidinic endonuclease 1

Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential base excision repair enzyme that is upregulated in a number of cancers, contributes to resistance of tumors treated with DNA-alkylating or -oxidizing agents, and has recently been identified as an important therapeutic target. In this work, we identified hot spots for binding of small organic molecules experimentally in high resolution crystal structures of APE1 and computationally through the use of FTMAP analysis (http://ftmap.bu.edu/). Guided by these hot spots, a library of drug-like macrocycles was docked and then screened for inhibition of APE1 endonuclease activity. In an iterative process, hot-spot-guided docking, characterization of inhibition of APE1 endonuclease, and cytotoxicity of cancer cells were used to design next generation macrocycles. To assess target selectivity in cells, selected macrocycles were analyzed for modulation of DNA damage. Taken together, our studies suggest that macrocycles represent a promising class of compounds for inhibition of APE1 in cancer cells.This work was supported by grants from the National Institutes of Health (Grant R01CA205166 to M.R.K. and M.M.G. and Grant R01CA167291 to M.R.K.) and by the Earl and Betty Herr Professor in Pediatric Oncology Research, Jeff Gordon Children's Foundation, and the Riley Children's Foundation (M.R.K.). Work at the BU-CMD (J.A.P., L.E.B., R.T.) is supported by the National Institutes of Health, Grant R24 GM111625. D.B. and S.V. were supported by the National Institutes of Health, Grant R35 GM118078. (R35 GM118078 - National Institutes of Health; R01CA205166 - National Institutes of Health; R01CA167291 - National Institutes of Health; R24 GM111625 - National Institutes of Health; Earl and Betty Herr Professor in Pediatric Oncology Research; Jeff Gordon Children's Foundation; Riley Children's Foundation)Accepted manuscriptSupporting documentatio

Presumed Pyogenic Granuloma Associated with Intravitreal Anti-Vascular Endothelial Growth Factor Therapy

To report a case of a presumed pyogenic granuloma at the site of multiple intravitreal anti-Vascular Endothelial Growth Factor (VEGF) injections. Intravitreal anti-VEGF injections can be complicated by a localized reaction of the conjunctiva

Hachimoji DNA and RNA: A genetic system with eight building blocks

Reported here are DNA and RNA-like systems built from eight (hachi-) nucleotide letters (-moji) that form four orthogonal pairs. This synthetic genetic biopolymer meets the structural requirements needed to support Darwinism, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to double the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos

The Iowa Homemaker vol.1, no.5-6

Table of Contents Dean MacKay Takes Well Earned Vacaion by F. W. Beckman, page 1 Playing the Game of Health With Yardstick and Scales by Grace McIlrath and Gladys Dodge, page 2 A Parent-Teacher Association in Every School! by Carolyne E. Forgrave, page 3 Artificial Feeding of Infants Up-to-Date by Belle Lowe, page 4 Making the Most of Your Old Reed Furniture by Glenna Hesse, page 5 The “Little House” That You Will Like by Helen Paschal, page 6 “The High School Girls’ Clothes Line” a Playlet, page 7 Practical Phases of the Love Nest by Eda Lord Murphy, page 8 Putting the Jell Into Jellies and Jams by Millie Lerdall, page

Changing shape of disease: Nonalcoholic fatty liver disease in Crohnʼs disease—A case series and review of the literature:

With improvements in therapy for inflammatory bowel disease (IBD) and changes in the prevalence of obesity, the phenotype of Crohn's Disease (CD) is changing. These changes may herald an increase in the incidence of non-alcoholic fatty liver disease (NAFLD) in this population

Ir(III) Diamine Transfer Hydrogenation Catalysts in Cancer Cells

The development of catalytic metallodrugs is an emerging field that may offer new approaches to cancer chemotherapeutic design. By exploiting the unique properties of transition metal complexes, in‐cell catalysis can be applied to modulate the cellular redox balance as part of a multi‐targeting mechanism of action. We describe the synthesis and characterization of six coordinatively unsaturated iridium(III) diamine catalysts that are stable at physiological pH in aqueous solution. Reduction of the colorimetric substrate 2,6‐dichlorophenolindophenol by transfer hydrogenation under biologically compatible conditions achieved turnover frequencies up to 63 ± 2 h−1 and demonstrated that the source of hydride (sodium formate) is the limiting reagent, despite being in a 1000‐fold excess of the catalyst. The catalyst showed low in vivo acute toxicity in zebrafish embryos and modest in vitro potency towards cancer cells. When administered alone, the catalyst generated oxidative stress in cells (an effect that was conserved in vivo), but co‐treatment with a nontoxic dose of sodium formate negated this effect. Co‐treatment with sodium formate significantly enhanced catalyst potency in cancer cells (A2780 ovarian and MCF7 breast cancer cells) and drug‐resistant cells (A2780cis and MCF7‐TAMR1) but not in non‐tumorigenic cells (MRC5), demonstrating that a redox‐targeting mechanism may generate selectivity for cancer cells