Measuring quantitative effects of methylation on transcription factor-DNA binding affinity

We describe a new method for measuring the effects of epigenetic marks on protein-DNA interactions.</jats:p

Social Pharmacy and Clinical Pharmacy:Joining Forces

This commentary seeks to define the areas of social pharmacy and clinical pharmacy to uncover what they have in common and what still sets them apart. Common threats and challenges of the two areas are reviewed in order to understand the forces in play. Forces that still keep clinical and social pharmacy apart are university structures, research traditions, and the management of pharmacy services. There are key (but shrinking) differences between clinical and social pharmacy which entail the levels of study within pharmaceutical sciences, the location in which the research is carried out, the choice of research designs and methods, and the theoretical foundations. Common strengths and opportunities are important to know in order to join forces. Finding common ground can be developed in two areas: participating together in multi-disciplinary research, and uniting in a dialogue with internal and external key players in putting forth what is needed for the profession of pharmacy. At the end the question is posed, “What’s in a name?” and we argue that it is important to emphasize what unifies the families of clinical pharmacy and social pharmacy for the benefit of both fields, pharmacy in general, and society at large

Correlation effects and orbital magnetism of Co clusters

Recent experiments on isolated Co clusters have shown huge orbital magnetic moments in comparison with their bulk and surface counterparts. These clusters hence provide the unique possibility to study the evolution of the orbital magnetic moment with respect to the cluster size and how competing interactions contribute to the quenching of orbital magnetism. We investigate here different theoretical methods to calculate the spin and orbital moments of Co clusters, and assess the performances of the methods in comparison with experiments. It is shown that density functional theory in conventional local density or generalized gradient approximations, or even with a hybrid functional, severely underestimates the orbital moment. As natural extensions/corrections we considered the orbital polarization correction, the LDA+U approximation as well as the LDA+DMFT method. Our theory shows that of the considered methods, only the LDA+DMFT method provides orbital moments in agreement with experiment, thus emphasizing the importance of dynamic correlations effects for determining fundamental magnetic properties of magnets in the nano-size regime

Severe and fatal medication errors in hospitals:Findings from the Norwegian Incident Reporting System

BACKGROUND: Even with global efforts to prevent medication errors, they still occur and cause patient harm. Little systematic research has been done in Norway to address this issue. OBJECTIVES: To describe the frequency, stage and types of medication errors in Norwegian hospitals, with emphasis on the most severe and fatal medication errors. METHODS: Medication errors reported in 2016 and 2017 (n=3557) were obtained from the Norwegian Incident Reporting System, based on reports from 64 hospitals in 2016 and 55 in 2017. Reports contained categorical data (eg, patient age, incident date) and free text data describing the incident. The errors were classified by error type, stage in the medication process, therapeutic area and degree of harm, using a modified version of the WHO Conceptual Framework for the International Classification for Patient Safety. RESULTS: Overall, 3372 reports were included in the study. Most medication errors occurred during administration (68%) and prescribing (24%). The leading types of errors were dosing errors (38%), omissions (23%) and wrong drug (15%). The therapeutic areas most commonly involved were analgesics, antibacterials and antithrombotics. Over half of all errors were harmful (62%), of which 5.2% caused severe harm, and 0.8% were fatal. CONCLUSIONS: Medication errors most commonly occurred during medication administration. Dosing errors were the most common error type. The substantial number of severe and fatal errors causing preventable patient harm and death emphasises an urgent need for error-prevention strategies. Additional studies and interventions should further investigate the error-prone medication administration stage in hospitals and explore the dynamics of severe incidents

Whole genome sequencing identifies a deletion in protein phosphatase 2A that affects its stability and localization in Chlamydomonas reinhardtii

Whole genome sequencing is a powerful tool in the discovery of single nucleotide polymorphisms (SNPs) and small insertions/deletions (indels) among mutant strains, which simplifies forward genetics approaches. However, identification of the causative mutation among a large number of non-causative SNPs in a mutant strain remains a big challenge. In the unicellular biflagellate green alga Chlamydomonas reinhardtii, we generated a SNP/indel library that contains over 2 million polymorphisms from four wild-type strains, one highly polymorphic strain that is frequently used in meiotic mapping, ten mutant strains that have flagellar assembly or motility defects, and one mutant strain, imp3, which has a mating defect. A comparison of polymorphisms in the imp3 strain and the other 15 strains allowed us to identify a deletion of the last three amino acids, Y313F314L315, in a protein phosphatase 2A catalytic subunit (PP2A3) in the imp3 strain. Introduction of a wild-type HA-tagged PP2A3 rescues the mutant phenotype, but mutant HA-PP2A3 at Y313 or L315 fail to rescue. Our immunoprecipitation results indicate that the Y313, L315, or YFLΔ mutations do not affect the binding of PP2A3 to the scaffold subunit, PP2A-2r. In contrast, the Y313, L315, or YFLΔ mutations affect both the stability and the localization of PP2A3. The PP2A3 protein is less abundant in these mutants and fails to accumulate in the basal body area as observed in transformants with either wild-type HA-PP2A3 or a HA-PP2A3 with a V310T change. The accumulation of HA-PP2A3 in the basal body region disappears in mated dikaryons, which suggests that the localization of PP2A3 may be essential to the mating process. Overall, our results demonstrate that the terminal YFL tail of PP2A3 is important in the regulation on Chlamydomonas mating

The structure of preserved information in quantum processes

We introduce a general operational characterization of information-preserving structures (IPS) -- encompassing noiseless subsystems, decoherence-free subspaces, pointer bases, and error-correcting codes -- by demonstrating that they are isometric to fixed points of unital quantum processes. Using this, we show that every IPS is a matrix algebra. We further establish a structure theorem for the fixed states and observables of an arbitrary process, which unifies the Schrodinger and Heisenberg pictures, places restrictions on physically allowed kinds of information, and provides an efficient algorithm for finding all noiseless and unitarily noiseless subsystems of the process