Object-oriented query language facilitating construction of new objects

In object-oriented database systems, messages can be used to manipulate the database; however, a query language is still a required component of any kind of database system. In the paper, we describe a query language for object-oriented databases where both objects as well as behaviour defined in them are handled. Not only existing objects are manipulated; the introduction of new relationships and new objects constructed out of existing ones is also facilitated. The operations supported in the described query language subsumes those of the relational algebra aiming at a more powerful query language than the relational algebra. Among the additional operators, there is an operator that handles the application of an aggregate function on objects in an operand while still having the result possessing the characteristics of an operand. The result of a query as well as the operands are considered to have a pair of sets, a set of objects and a set of message expressions; where a message expression is a sequence of messages. A message expression handles both stored and derived values and hence provides a full computational power without having an embedded query language with impedance mismatch. Therefore the closure property is maintained by having the result of a query possessing the characteristics of an operand. Furthermore, we define a set of objects and derive a set of message expressions for every class; hence any class can be an operand. Moreover, the result of a query has the characteristics of a class and its superclass/subclass relationships with the operands are established to make it persistent. © 1993

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

Prediction of Optimal Folding Routes of Proteins That Satisfy the Principle of Lowest Entropy Loss: Dynamic Contact Maps and Optimal Control

An optimization model is introduced in which proteins try to evade high energy regions of the folding landscape, and prefer low entropy loss routes during folding. We make use of the framework of optimal control whose convenient solution provides practical and useful insight into the sequence of events during folding. We assume that the native state is available. As the protein folds, it makes different set of contacts at different folding steps. The dynamic contact map is constructed from these contacts. The topology of the dynamic contact map changes during the course of folding and this information is utilized in the dynamic optimization model. The solution is obtained using the optimal control theory. We show that the optimal solution can be cast into the form of a Gaussian Network that governs the optimal folding dynamics. Simulation results on three examples (CI2, Sso7d and Villin) show that folding starts by the formation of local clusters. Non-local clusters generally require the formation of several local clusters. Non-local clusters form cooperatively and not sequentially. We also observe that the optimal controller prefers “zipping” or small loop closure steps during folding. The folding routes predicted by the proposed method bear strong resemblance to the results in the literature

Parasitic and fungal disease of bones and joints

Among the musculoskeletal infections, fungal and parasitic diseases are infrequent and may have a nonspecific imaging factor. The incidences of fungal and parasitic bone infections are related to geographic distribution, ethnic and nutritional factors, and occupation. Immunocompromise and ease of travel can lead to increased incidence. These are a group of chronic disorders, and delayed diagnosis is common because radiographs, computed tomography, isotope studies, and magnetic resonance imaging are useful but often do not have specific signs for determination of the causative infective fungal or parasitic organism. Definitive diagnosis is possible with a high index of clinical suspicion and aspiration

Tumor-like Lesions of Bone and Soft Tissues and Imaging Tips for Differential Diagnosis

In the musculoskeletal system, tumor-like lesions may present similar imaging findings as bone and soft tissue tumors and can be defined as tumors on radiologic examinations. Misinterpretation of the imaging findings can lead to inappropriate clinical management of the patient. There is still some debate regarding the pathophysiology and origin of tumor-like lesions that include congenital, developmental, inflammatory, infectious, metabolic, reactive, posttraumatic, post-therapeutic changes, and some miscellaneous entities causing structural changes. Although tumor-like lesions are historically defined as non-neoplastic lesions, some of them are classified as real neoplasms. We discuss a spectrum of entities mimicking tumors of bone and soft tissues that include various non-neoplastic diseases and anatomical variants based on imaging findings. © 2020 BMJ Publishing Group. All rights reserved