128 research outputs found
Assessing the local structural quality of transmembrane protein models using statistical potentials (QMEANBrane)
Motivation: Membrane proteins are an important class of biological macromolecules involved in many cellular key processes including signalling and transport. They account for one third of genes in the human genome and >50% of current drug targets. Despite their importance, experimental structural data are sparse, resulting in high expectations for computational modelling tools to help fill this gap. However, as many empirical methods have been trained on experimental structural data, which is biased towards soluble globular proteins, their accuracy for transmembrane proteins is often limited. Results: We developed a local model quality estimation method for membrane proteins (‘QMEANBrane') by combining statistical potentials trained on membrane protein structures with a per-residue weighting scheme. The increasing number of available experimental membrane protein structures allowed us to train membrane-specific statistical potentials that approach statistical saturation. We show that reliable local quality estimation of membrane protein models is possible, thereby extending local quality estimation to these biologically relevant molecules. Availability and implementation: Source code and datasets are available on request. Contact: [email protected] Supplementary Information: Supplementary data are available at Bioinformatics onlin
La Gestione dei trasporti in emergenza: attività , prodotti e risultati dell'esercitazione nazionale di Protezione Civile in Valtellina
L'articolo riporta l’esperienza maturata dal Laboratorio Mobilità e Trasporti del Politecnico di Milano in qualità di Centro di Competenza per la Gestione e la Sicurezza dei Trasporti per il Dipartimento di Protezione Civile Nazionale durante l’esercitazione nazionale di Protezione Civile in Valtellina.
Le attività svolte, i prodotti realizzati e utilizzati ma soprattutto i risultati e l’esperienza emersi da una esercitazione temporalmente estesa e di estremo rilievo in ambito di Protezione Civile, si ritiene siano ancora estremamente attuali e utili come esempio per la gestione dei trasporti in caso di emergenze rilevanti
The microRNA miR-21 Is a Mediator of FGF8 Action on Cortical COUP-TFI Translation
The morphogen FGF8 plays a pivotal role in neocortical area patterning through its inhibitory effect on COUP-TFI/Nr2f1 anterior expression, but its mechanism of action is poorly understood. We established an in vitro model of mouse embryonic stem cell corticogenesis in which COUP-TFI protein expression is inhibited by the activation of FGF8 in a time window corresponding to cortical area patterning. Interestingly, overexpression of the COUP-TFI 3′UTR reduces the inhibitory effect of FGF8 on COUP-TFI translation. FGF8 induces the expression of few miRNAs targeting COUP-TFI 3′UTR in silico. We found that the functional inhibition of miR-21 can effectively counteract the inhibitory effect of FGF8 in vitro and regulate COUP-TFI protein levels in vivo. Accordingly, miR-21 expression is complementary to COUP-TFI expression during corticogenesis. These data support a translational control of COUP-TFI gradient expression by FGF8 via miR-21 and contribute to our understanding of how regionalized expression is established during neocortical area mapping
Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis
Genetic ablation of type-1 cannabinoid receptors (CB1Rs) exacerbates the neurodegenerative damage of experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS). To address the role on CB1Rs in the pathophysiology of human MS, we first investigated the impact of AAT trinucleotide short tandem repeat polymorphism of CNR1 gene on CB1R cell expression, and secondly on the inflammatory neurodegeneration process responsible for irreversible disability in MS patients. We found that MS patients with long AAT repeats within the CNR1 gene (≥12 in both alleles) had more pronounced neuronal degeneration in response to inflammatory white matter damage both in the optic nerve and in the cortex. Optical Coherence Tomography (OCT), in fact, showed more severe alterations of the retinal nerve fiber layer (RNFL) thickness and of the macular volume (MV) after an episode of optic neuritis in MS patients carrying the long AAT genotype of CNR1. MS patients with long AAT repeats also had magnetic resonance imaging (MRI) evidence of increased gray matter damage in response to inflammatory lesions of the white matter, especially in areas with a major role in cognition. In parallel, visual abilities evaluated at the low contrast acuity test, and cognitive performances were negatively influenced by the long AAT CNR1 genotype in our sample of MS patients. Our results demonstrate the biological relevance of the (AAT)n CNR1 repeats in the inflammatory neurodegenerative damage of MS
SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information
Protein structure homology modelling has become a routine technique to generate 3D models for proteins when experimental structures are not available. Fully automated servers such as SWISS-MODEL with user-friendly web interfaces generate reliable models without the need for complex software packages or downloading large databases. Here, we describe the latest version of the SWISS-MODEL expert system for protein structure modelling. The SWISS-MODEL template library provides annotation of quaternary structure and essential ligands and co-factors to allow for building of complete structural models, including their oligomeric structure. The improved SWISS-MODEL pipeline makes extensive use of model quality estimation for selection of the most suitable templates and provides estimates of the expected accuracy of the resulting models. The accuracy of the models generated by SWISS-MODEL is continuously evaluated by the CAMEO system. The new web site allows users to interactively search for templates, cluster them by sequence similarity, structurally compare alternative templates and select the ones to be used for model building. In cases where multiple alternative template structures are available for a protein of interest, a user-guided template selection step allows building models in different functional states. SWISS-MODEL is available at http://swissmodel.expasy.or
SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information
Protein structure homology modelling has become a routine technique to generate 3D models for proteins when experimental structures are not available. Fully automated servers such as SWISS-MODEL with user-friendly web interfaces generate reliable models without the need for complex software packages or downloading large databases. Here, we describe the latest version of the SWISS-MODEL expert system for protein structure modelling. The SWISS-MODEL template library provides annotation of quaternary structure and essential ligands and co-factors to allow for building of complete structural models, including their oligomeric structure. The improved SWISS-MODEL pipeline makes extensive use of model quality estimation for selection of the most suitable templates and provides estimates of the expected accuracy of the resulting models. The accuracy of the models generated by SWISS-MODEL is continuously evaluated by the CAMEO system. The new web site allows users to interactively search for templates, cluster them by sequence similarity, structurally compare alternative templates and select the ones to be used for model building. In cases where multiple alternative template structures are available for a protein of interest, a user-guided template selection step allows building models in different functional states. SWISS-MODEL is available at http://swissmodel.expasy.org/
A Forward Regridding Method With Minimal Oversampling for Accurate and Efficient Iterative Tomographic Algorithms
The impact of pharmacist-led medication reconciliation and interprofessional ward rounds on drug-related problems at hospital discharge
BACKGROUND
During transitions of care, including hospital discharge, patients are at risk of drug-related problems (DRPs).
AIM
To investigate the impact of pharmacist-led services, specifically medication reconciliation at admission and/or interprofessional ward rounds on the number of DRPs at discharge.
METHOD
In this retrospective, single-center cohort study, we analyzed routinely collected data of patients discharged from internal medicine wards of a regional Swiss hospital that filled their discharge prescriptions in the hospital's community pharmacy between June 2016 and May 2019. Patients receiving one of the two or both pharmacist-led services (Study groups: Best Care = both services; MedRec = medication reconciliation at admission; Ward Round = interprofessional ward round), were compared to patients receiving standard care (Standard Care group). Standard care included medication history taken by a physician and regular ward rounds (physicians and nurses). At discharge, pharmacists reviewed discharge prescriptions filled at the hospital's community pharmacy and documented all DRPs. Multivariable Poisson regression analyzed the independent effects of medication reconciliation and interprofessional ward rounds as single or combined service on the frequency of DRPs.
RESULTS
Overall, 4545 patients with 6072 hospital stays were included in the analysis (Best Care n = 72 hospital stays, MedRec n = 232, Ward Round n = 1262, and Standard Care n = 4506). In 1352 stays (22.3%) one or more DRPs were detected at hospital discharge. The combination of the two pharmacist-led services was associated with statistically significantly less DRPs compared to standard care (relative risk: 0.33; 95% confidence interval: 0.16, 0.65). Pharmacist-led medication reconciliation alone showed a trend towards fewer DRPs (relative risk: 0.75; 95% confidence interval: 0.54, 1.03).
CONCLUSION
Our results support the implementation of pharmacist-led medication reconciliation at admission in combination with interprofessional ward rounds to reduce the number of DRPs at hospital discharge
Possible Impacts of C-ITS on Supply-Chain Logistics System
The purpose of this research is to introduce an analysis, which is qualitative and whenever possible quantitative, on how Cooperative Intelligent Transport Systems (C-ITS) can affect a Supply-Chain Logistics System by adopting a three-level approach. Considerations are made on the role and importance of Logistics within a company, its cost structure and the strategic relevance it assumes within the Supply-Chain, while considering its evolution from a Physical Distribution Management to a Supply-Chain Management. The increasing importance of logistics requires more sophisticated solutions to reduce or optimize its costs, as well as to find new opportunities to redesign the network configuration and the value-chain. These applications require a careful evaluation method in order to assess their effective adoption. The research is based on a literature review of the most relevant European Road ITS and C-ITS projects evaluation methods and benefits. The result of the investigation is an analysis that classifies the impact of C-ITS on the structure of the Supply-Chain according to different levels. Firstly, the paper reports the different impacts of a large-scale C-ITS deployment on the Logistics cost structure of a company and more in general, on the expected costs. After that, a second level of analysis deals with a possible redesign of the Distribution Network, oriented to the optimization of transportation costs over long distances. Finally, the third step of the analysis investigates a possible impact of C-ITS on the value-chain from several perspectives within the different roles of the subjects involved in the Supply Chain
- …