Combining Optimal Control Theory and Molecular Dynamics for Protein Folding

A new method to develop low-energy folding routes for proteins is presented. The novel aspect of the proposed approach is the synergistic use of optimal control theory with Molecular Dynamics (MD). In the first step of the method, optimal control theory is employed to compute the force field and the optimal folding trajectory for the atoms of a Coarse-Grained (CG) protein model. The solution of this CG optimization provides an harmonic approximation of the true potential energy surface around the native state. In the next step CG optimization guides the MD simulation by specifying the optimal target positions for the atoms. In turn, MD simulation provides an all-atom conformation whose positions match closely the reference target positions determined by CG optimization. This is accomplished by Targeted Molecular Dynamics (TMD) which uses a bias potential or harmonic restraint in addition to the usual MD potential. Folding is a dynamical process and as such residues make different contacts during the course of folding. Therefore CG optimization has to be reinitialized and repeated over time to accomodate these important changes. At each sampled folding time, the active contacts among the residues are recalculated based on the all-atom conformation obtained from MD. Using the new set of contacts, the CG potential is updated and the CG optimal trajectory for the atoms is recomputed. This is followed by MD. Implementation of this repetitive CG optimization - MD simulation cycle generates the folding trajectory. Simulations on a model protein Villin demonstrate the utility of the method. Since the method is founded on the general tools of optimal control theory and MD without any restrictions, it is widely applicable to other systems. It can be easily implemented with available MD software packages

Soft tissue tumor imaging in adults: European Society of Musculoskeletal Radiology-Guidelines 2023—overview, and primary local imaging: how and where?

Objectives: Early, accurate diagnosis is crucial for the prognosis of patients with soft tissue sarcomas. To this end, standardization of imaging algorithms, technical requirements, and reporting is therefore a prerequisite. Since the first European Society of Musculoskeletal Radiology (ESSR) consensus in 2015, technical achievements, further insights into specific entities, and the revised WHO-classification (2020) and AJCC staging system (2017) made an update necessary. The guidelines are intended to support radiologists in their decision-making and contribute to interdisciplinary tumor board discussions. Materials and methods: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements were scored online by level of agreement (0 to 10) during two iterative rounds. Either “group consensus,” “group agreement,” or “lack of agreement” was achieved. Results: Eight sections were defined that finally contained 145 statements with comments. Overall, group consensus was reached in 95.9%, and group agreement in 4.1%. This communication contains the first part consisting of the imaging algorithm for suspected soft tissue tumors, methods for local imaging, and the role of tumor centers. Conclusion: Ultrasound represents the initial triage imaging modality for accessible and small tumors. MRI is the modality of choice for the characterization and local staging of most soft tissue tumors. CT is indicated in special situations. In suspicious or likely malignant tumors, a specialist tumor center should be contacted for referral or teleradiologic second opinion. This should be done before performing a biopsy, without exception. Clinical relevance: The updated ESSR soft tissue tumor imaging guidelines aim to provide best practice expert consensus for standardized imaging, to support radiologists in their decision-making, and to improve examination comparability both in individual patients and in future studies on individualized strategies. Key Points: • Ultrasound remains the best initial triage imaging modality for accessible and small suspected soft tissue tumors. • MRI is the modality of choice for the characterization and local staging of soft tissue tumors in most cases; CT is indicated in special situations. Suspicious or likely malignant tumors should undergo biopsy. • In patients with large, indeterminate or suspicious tumors, a tumor reference center should be contacted for referral or teleradiologic second opinion; this must be done before a biopsy

Soft tissue tumor imaging in adults: European Society of Musculoskeletal Radiology-Guidelines 2023-overview, and primary local imaging: how and where?

OBJECTIVES: Early, accurate diagnosis is crucial for the prognosis of patients with soft tissue sarcomas. To this end, standardization of imaging algorithms, technical requirements, and reporting is therefore a prerequisite. Since the first European Society of Musculoskeletal Radiology (ESSR) consensus in 2015, technical achievements, further insights into specific entities, and the revised WHO-classification (2020) and AJCC staging system (2017) made an update necessary. The guidelines are intended to support radiologists in their decision-making and contribute to interdisciplinary tumor board discussions. MATERIALS AND METHODS: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements were scored online by level of agreement (0 to 10) during two iterative rounds. Either "group consensus," "group agreement," or "lack of agreement" was achieved. RESULTS: Eight sections were defined that finally contained 145 statements with comments. Overall, group consensus was reached in 95.9%, and group agreement in 4.1%. This communication contains the first part consisting of the imaging algorithm for suspected soft tissue tumors, methods for local imaging, and the role of tumor centers. CONCLUSION: Ultrasound represents the initial triage imaging modality for accessible and small tumors. MRI is the modality of choice for the characterization and local staging of most soft tissue tumors. CT is indicated in special situations. In suspicious or likely malignant tumors, a specialist tumor center should be contacted for referral or teleradiologic second opinion. This should be done before performing a biopsy, without exception. CLINICAL RELEVANCE: The updated ESSR soft tissue tumor imaging guidelines aim to provide best practice expert consensus for standardized imaging, to support radiologists in their decision-making, and to improve examination comparability both in individual patients and in future studies on individualized strategies. KEY POINTS: • Ultrasound remains the best initial triage imaging modality for accessible and small suspected soft tissue tumors. • MRI is the modality of choice for the characterization and local staging of soft tissue tumors in most cases; CT is indicated in special situations. Suspicious or likely malignant tumors should undergo biopsy. • In patients with large, indeterminate or suspicious tumors, a tumor reference center should be contacted for referral or teleradiologic second opinion; this must be done before a biopsy

Using Personality Facets to Understand the Nature of Personality-Satisfaction Relationships Findings from Meta-Analytic Bifactor Latent Modeling

Purpose – The relationships between the Big Five personality traits and life and job satisfaction have been examined extensively. Despite this attention, however, most existing theories focus on a few global dimensions of the Big Five while relying primarily upon a selection of theoretically relevant but unmeasured facets to illuminate their factor-level explanations. The purpose of this paper is to examine personality – satisfaction relationships for job and life domains at the facet level to better identify and explain why certain global Big Five traits consistently relate to satisfaction, taking both factors and facets into account. Design/methodology/approach – Data from over 20 specific occupational samples were pooled metaanalytically to examine personality facet of job/life satisfaction relationships and their generalizability. Bifactor latent variable modeling using meta-analytic input was used to examine independent contributions of general and unique personality facets. Findings – The dominance facet of extraversion, low self-esteem facet of neuroticism, and responsibility facet of conscientiousness were most closely related to satisfaction variables. There were independent contributions of general and unique facet level personality – satisfaction relations for the neuroticism and conscientiousness domains, but not for the extraversion domain. Research limitations/implications – Findings contribute to the literature on the bandwidth – fidelity dilemma in measuring personality and theories involving personality at work. Originality/value – This study established the generalizability of Big Five traits – satisfaction relations and identified the empirically supported personality paths to understanding job and life satisfaction. This study also demonstrated how meta-analysis can be combined with bifactor models to understand substantive relations

MRI evaluation of patellar tendon defect after harvesting its central third

WOS: 000221828300011PubMed ID: 15145490Purpose: the purpose of this study was to evaluate defect width of patellar tendon after harvest for anterior cruciate ligament reconstruction. Materials and methods: we performed MRI at various time interval after graft harvest (2-96 months) on 28 patients who had had reconstruction of the anterior cruciate ligament using mid-third patellar tendon. T1 and T2 weighted axial images were obtained to assess donor site defect of the patellar tendon. Measurement of the defect width was performed at the level of menisci on the axial images. The patients were divided into two groups according to the time interval between operation and imaging. The defect width of patients with short time interval (2-12 months) was compared to the defect width of patients with long time interval (12-96 months). Results: the average defect width of patients with short time interval was 6.4 mm and it was 2.2 rum for the patients with long time interval. Decreased defect width was obtained from MRI images in the patients with long time interval. Closed donor site defect was detected in I out of 14 patients with short time interval and 6 out of 14 patients with long time interval. Discussion and conclusion: these results show that there is no complete closure of donor site defect up to I year. However, it seems to be nearly complete Closure of patellar tendon defect in the long time period. (C) 2003 Elsevier Ireland Ltd. All rights reserved

Spinal Intradural, Extramedullary Ependymoma with Astrocytoma Component: A Case Report and Review of the Literature

Ependymomas are common spinal lesions, with the vast majority arising in an intramedullary location. Several cases have been described in the literature of ependymomas in an intradural, extramedullary location. The authors present a case of a 56-year-old female who presented with several weeks of lower back pain and weakness. MRI revealed an intradural, extramedullary enhancing mass at L1-L2. The mass was successfully resected surgically. Pathologic evaluation revealed a low grade glioma with components of both ependymoma and pilocytic astrocytoma with MUTYH G382D mutation. Extramedullary ependymomas are very rare tumors. To the authors’ knowledge, this is the first case of ependymoma/astrocytoma collision tumors described in an extramedullary location