FragBuilder:an efficient Python library to setup quantum chemistry calculations on peptides models

We present a powerful Python library to quickly and efficiently generate realistic peptide model structures. The library makes it possible to quickly set up quantum mechanical calculations on model peptide structures. It is possible to manually specify a specific conformation of the peptide. Additionally the library also offers sampling of backbone conformations and side chain rotamer conformations from continuous distributions. The generated peptides can then be geometry optimized by the MMFF94 molecular mechanics force field via convenient functions inside the library. Finally, it is possible to output the resulting structures directly to files in a variety of useful formats, such as XYZ or PDB formats, or directly as input files for a quantum chemistry program. FragBuilder is freely available at https://github.com/jensengroup/fragbuilder/ under the terms of the BSD open source license

Mentalizing Bodies:Explicit Mentalizing Without Words in Psychotherapy

Introduction: Mentalization concerns the human ability to understand the actions of others (and oneself) in terms of intentional mental states. Theoretically, the notion has been described via the poles of automatic, non-verbal implicit mentalization as opposed to conscious and verbal explicit mentalization. In this article, we challenge this standard distinction by examining examples from psychotherapy. We argue that explicit mentalization can also be carried out via embodied non-verbal actions. Method: Four cases of real-life interaction from psychotherapy sessions are analyzed from the qualitative perspective of embodied cognition and multimodal interaction analysis. The analyses are based on video data transformed into transcriptions and anonymized drawings from a larger cognitive ethnography study conducted at a psychiatric hospital in Denmark. Results: The analyses demonstrate the gradual development from predominantly implicit mentalizing to predominantly explicit mentalizing. In the latter part of the examples, the mentalizing activity is initiated by the therapist on an embodied level but in an enlarged and complex manner indicating a higher level of awareness, imagination, and reflection. Thus, the standard assumption of explicit mentalization as contingent on verbal language is challenged, since it is demonstrated how processes of explicit mentalization can take place on an embodied level without the use of words. Conclusion: Based on real-life data, the study demonstrates that online processes of implicit and explicit mentalization are gradual and interwoven with embodied dynamics in real-life interaction. Thus, the analyses establish a window into how mentalization is carried out by psychotherapists through interaction, which testifies to the importance of embodied non-verbal behavior in psychotherapy. Further, informed by the notion of affordance-space, the study points to alternative ways of conceptualizing the intertwined nature of bodies and environment in relation to conveying more complex understandings of other people

Bayesian inference of protein structure from chemical shift data

Protein chemical shifts are routinely used to augment molecular mechanics force fields in protein structure simulations, with weights of the chemical shift restraints determined empirically. These weights, however, might not be an optimal descriptor of a given protein structure and predictive model, and a bias is introduced which might result in incorrect structures. In the inferential structure determination framework, both the unknown structure and the disagreement between experimental and back-calculated data are formulated as a joint probability distribution, thus utilizing the full information content of the data. Here, we present the formulation of such a probability distribution where the error in chemical shift prediction is described by either a Gaussian or Cauchy distribution. The methodology is demonstrated and compared to a set of empirically weighted potentials through Markov chain Monte Carlo simulations of three small proteins (ENHD, Protein G and the SMN Tudor Domain) using the PROFASI force field and the chemical shift predictor CamShift. Using a clustering-criterion for identifying the best structure, together with the addition of a solvent exposure scoring term, the simulations suggests that sampling both the structure and the uncertainties in chemical shift prediction leads more accurate structures compared to conventional methods using empirical determined weights. The Cauchy distribution, using either sampled uncertainties or predetermined weights, did, however, result in overall better convergence to the native fold, suggesting that both types of distribution might be useful in different aspects of the protein structure prediction

Are progressive shoulder exercises feasible in patients with glenohumeral osteoarthritis or rotator cuff tear arthropathy?

BACKGROUND: Little is known about the feasibility of progressive shoulder exercises (PSE) for patients with glenohumeral osteoarthritis (OA) or rotator cuff tear arthropathy (CTA). The aim of this study was to investigate whether 12 weeks of PSE is feasible in patients with glenohumeral OA or CTA eligible for shoulder arthroplasty. Moreover, to report changes in shoulder function and range of motion (ROM) following the exercise program. METHODS: Twenty patients were included. Eighteen patients (11 women, 15 with OA), mean age 70 years (range 57–80), performed 12 weeks of PSE with one weekly physiotherapist-supervised and two weekly home-based sessions. Feasibility was measured by dropout rate, adverse events, pain, and adherence to PSE. At baseline and end of intervention, patients completed the Western Ontario Osteoarthritis of the Shoulder (WOOS) score and Disabilities of the Arm, Shoulder and Hand (DASH). Data to assess feasibility were analyzed using descriptive statistics. RESULTS: Two patients dropped out and no adverse events were observed. Sixteen of the eighteen patients (89%) had a high adherence (≥ 70%) to the physiotherapist-supervised sessions. Acceptable pain levels were reported; in 76% of all exercise sessions with no numeric rating scale (NRS) score over five for any exercise. WOOS improved with a mean of 23 points (95% CI 13;33), and DASH improved with a mean of 13 points (95% CI 6;19). CONCLUSION: Adherence to PSE was high and dropout rates were low. PSE is feasible, safe and may relieve shoulder pain, improve function and ROM in patients with glenohumeral OA or CTA. The patient-experienced gains after PSE seem clinically relevant and should be compared to arthroplasty surgery in a RCT setting. TRIAL REGISTRATION: According to Danish law, this study did not need an approval by the Central Denmark Region Committee on Health Research Ethics. Approval from The Danish Data Protection Agency (journal number 1-16-02-15-20) was obtained

Hvad er effekten af ren-luftzoner for luftforureningen i København?

Ren-luftzoner, hvor der stilles højere miljøkrav til køretøjer inden for et geografisk område, er et muligt virkemiddel til at forbedre luftkvaliteten i de større byer og til at reducere antallet af overskridelser af grænseværdien for kvælstofdioxid (NO2). Ren-luftzoner er et nyt ord for miljøzoner. Det nye ved ren- luftzoner er, at de stiller miljøkrav til ældre person- og varebiler, og ikke kun som de eksisterende miljøzoner til lastbiler og busser. Denne artikel vurderer effekten af forskellige udformninger af ren- luftzoner, og hvilken betydning det har for emission og luftkvalitet i 2013, 2015 og 2017 med udgangspunkt i scenarieberegninger gennemført i 2012. Dette sker med udgangspunkt i H.C. Andersens Boulevard i København, hvor NO2 grænseværdien er overskrevet. Den mest vidtgående ren-luftzone beskrevet i denne artikel vil føre til en beregnet reduktion i NOx emissionen på knap 13% svarende til en reduktion af NO2 koncentrationen på knap 3 μg/m3 i 2015

The ClpXP protease is dispensable for degradation of unfolded proteins in <i>Staphylococcus aureus</i>

Abstract In living cells intracellular proteolysis is crucial for protein homeostasis, and ClpP proteases are conserved between eubacteria and the organelles of eukaryotic cells. In Staphylococcus aureus, ClpP associates to the substrate specificity factors, ClpX and ClpC forming two ClpP proteases, ClpXP and ClpCP. To address how individual ClpP proteases impact cell physiology, we constructed a S. aureus mutant expressing ClpX with an I265E substitution in the ClpP recognition tripeptide of ClpX. This mutant cannot degrade established ClpXP substrates confirming that the introduced amino acid substitution abolishes ClpXP activity. Phenotypic characterization of this mutant showed that ClpXP activity controls cell size and is required for growth at low temperature. Cells expressing the ClpXI265E variant, in contrast to cells lacking ClpP, are not sensitive to heat-stress and do not accumulate protein aggregates showing that ClpXP is dispensable for degradation of unfolded proteins in S. aureus. Consistent with this finding, transcriptomic profiling revealed strong induction of genes responding to protein folding stress in cells devoid of ClpP, but not in cells lacking only ClpXP. In the latter cells, highly upregulated loci include the urease operon, the pyrimidine biosynthesis operon, the betA-betB operon, and the pathogenicity island, SaPI5, while virulence genes were dramatically down-regulated