Energetics in Condensate Star and Wormholes

It is known that the total gravitational energy in localized sources having static spherical symmetry and satisfying energy conditions is negative (attractive gravity). A natural query is how the gravitational energy behaves under circumstances where energy conditions are violated. To answer this, the known expression for the gravitational energy is suitably modified to account for situations like the ones occurring in wormhole spacetime. It is then exemplified that in many cases the modified expression yields desirable answers. The implications are discussed.Comment: 16 pages, 1 figure, references added, To appear in PR

Analyzing X-Ray Pulsar Profiles: Geometry and Beam Pattern of Her X-1

We report on our analysis of a large sample of energy dependent pulse profiles of the X-ray binary pulsar Hercules X-1. We find that all data are compatible with the assumption of a slightly distorted magnetic dipole field as sole cause of the asymmetry of the observed pulse profiles. Further the analysis provides evidence that the emission from both poles is equal. We determine an angle of 20 deg between the rotation axis and the local magnetic axis. One pole has an offset of 5 deg from the antipodal position of the other pole. The beam pattern shows structures that can be interpreted as pencil- and fan-beam configurations. Since no assumptions on the polar emission are made, the results can be compared with various emission models. A comparison of results obtained from pulse profiles of different phases of the 35-day cycle indicates different attenuation of the radiation from the poles being responsible for the change of the pulse shape during the main-on state. These results also suggest the resolution of an ambiguity within a previous analysis of pulse profiles of Cen X-3, leading to a unique result for the beam pattern of this pulsar as well. The analysis of pulse profiles of the short-on state indicates that a large fraction of the radiation cannot be attributed to the direct emission from the poles. We give a consistent explanation of both the evolution of the pulse profile and the spectral changes with the 35-day cycle in terms of a warped precessing accretion disk.Comment: 24 pages, 12 figures. To appear in ApJ 529 #2, 1 Feb 200

Digital receivers for low-frequency radio telescopes UTR-2, URAN, GURT

This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. Since 1998, digital receivers performing on-the-fly dynamic spectrum calculations or waveform data recording without data loss have been used at the UTR-2 radio telescope, the URAN VLBI system, and the GURT new generation radio telescope. Here we detail these receivers developed for operation in the strong interference environment that prevails in the decameter wavelength range. Data collected with these receivers allowed us to discover numerous radio astronomical objects and phenomena at low frequencies, a summary of which is also presented.Comment: 24 pages, 15 figure

Anti-leprosy drug clofazimine inhibits growth of triple-negative breast cancer cells via inhibition of canonical Wnt signaling

Research on existing drugs often discovers novel mechanisms of their action and leads to the expansion of their therapeutic scope and subsequent remarketing. The Wnt signaling pathway is of the immediate therapeutic relevance, as it plays critical roles in cancer development and progression. However, drugs which disrupt this pathway are unavailable despite the high demand. Here we report an attempt to identify antagonists of the Wnt-FZD interaction among the library of the FDA-approved drugs. We performed an in silico screening which brought up several potential antagonists of the ligand-receptor interaction. 14 of these substances were tested using the TopFlash luciferase reporter assay and four of them identified as active and specific inhibitors of the Wnt3a-induced signaling. However, further analysis through GTP-binding and β-catenin stabilization assays showed that the compounds do not target the Wnt-FZD pair, but inhibit the signaling at downstream levels. We further describe the previously unknown inhibitory activity of an anti-leprosy drug clofazimine in the Wnt pathway and provide data demonstrating its efficiency in suppressing growth of Wnt-dependent triple-negative breast cancer cells. These data provide a basis for further investigations of the efficiency of clofazimine in treatment of Wnt-dependent cancers. © 2013 Elsevier Inc

MMDB: 3D structures and macromolecular interactions

Close to 60% of protein sequences tracked in comprehensive databases can be mapped to a known three-dimensional (3D) structure by standard sequence similarity searches. Potentially, a great deal can be learned about proteins or protein families of interest from considering 3D structure, and to this day 3D structure data may remain an underutilized resource. Here we present enhancements in the Molecular Modeling Database (MMDB) and its data presentation, specifically pertaining to biologically relevant complexes and molecular interactions. MMDB is tightly integrated with NCBI's Entrez search and retrieval system, and mirrors the contents of the Protein Data Bank. It links protein 3D structure data with sequence data, sequence classification resources and PubChem, a repository of small-molecule chemical structures and their biological activities, facilitating access to 3D structure data not only for structural biologists, but also for molecular biologists and chemists. MMDB provides a complete set of detailed and pre-computed structural alignments obtained with the VAST algorithm, and provides visualization tools for 3D structure and structure/sequence alignment via the molecular graphics viewer Cn3D. MMDB can be accessed at http://www.ncbi.nlm.nih.gov/structure

Complex experiment on studying the microphysical, chemical, and optical properties of aerosol particles and estimating the contribution of atmospheric aerosol-to-earth radiation budget

The primary objective of this complex aerosol experiment was the measurement of microphysical, chemical, and optical properties of aerosol particles in the surface air layer and free atmosphere. The measurement data were used to retrieve the whole set of aerosol optical parameters, necessary for radiation calculations. Three measurement cycles were performed within the experiment during 2013: in spring, when the aerosol generation is maximal; in summer (July), when atmospheric boundary layer altitude and, hence, mixing layer altitude are maximal; and in late summer/early autumn, during the period of nucleation of secondary particles. Thus, independently obtained data on the optical, meteorological, and microphysical parameters of the atmosphere allow intercalibration and inter-complement of the data and thereby provide for qualitatively new information which explains the physical nature of the processes that form the vertical structure of the aerosol field

A Novel Biclustering Approach to Association Rule Mining for Predicting HIV-1–Human Protein Interactions

Identification of potential viral-host protein interactions is a vital and useful approach towards development of new drugs targeting those interactions. In recent days, computational tools are being utilized for predicting viral-host interactions. Recently a database containing records of experimentally validated interactions between a set of HIV-1 proteins and a set of human proteins has been published. The problem of predicting new interactions based on this database is usually posed as a classification problem. However, posing the problem as a classification one suffers from the lack of biologically validated negative interactions. Therefore it will be beneficial to use the existing database for predicting new viral-host interactions without the need of negative samples. Motivated by this, in this article, the HIV-1–human protein interaction database has been analyzed using association rule mining. The main objective is to identify a set of association rules both among the HIV-1 proteins and among the human proteins, and use these rules for predicting new interactions. In this regard, a novel association rule mining technique based on biclustering has been proposed for discovering frequent closed itemsets followed by the association rules from the adjacency matrix of the HIV-1–human interaction network. Novel HIV-1–human interactions have been predicted based on the discovered association rules and tested for biological significance. For validation of the predicted new interactions, gene ontology-based and pathway-based studies have been performed. These studies show that the human proteins which are predicted to interact with a particular viral protein share many common biological activities. Moreover, literature survey has been used for validation purpose to identify some predicted interactions that are already validated experimentally but not present in the database. Comparison with other prediction methods is also discussed

Insertions and the emergence of novel protein structure: a structure-based phylogenetic study of insertions

<p>Abstract</p> <p>Background</p> <p>In protein evolution, the mechanism of the emergence of novel protein domain is still an open question. The incremental growth of protein variable regions, which was produced by stochastic insertions, has the potential to generate large and complex sub-structures. In this study, a deterministic methodology is proposed to reconstruct phylogenies from protein structures, and to infer insertion events in protein evolution. The analysis was performed on a broad range of SCOP domain families.</p> <p>Results</p> <p>Phylogenies were reconstructed from protein 3D structural data. The phylogenetic trees were used to infer ancestral structures with a consensus method. From these ancestral reconstructions, 42.7% of the observed insertions are nested insertions, which locate in previous insert regions. The average size of inserts tends to increase with the insert rank or total number of insertions in the variable regions. We found that the structures of some nested inserts show complex or even domain-like fold patterns with helices, strands and loops. Furthermore, a basal level of structural innovation was found in inserts which displayed a significant structural similarity exclusively to themselves. The β-Lactamase/D-ala carboxypeptidase domain family is provided as an example to illustrate the inference of insertion events, and how the incremental growth of a variable region is capable to generate novel structural patterns.</p> <p>Conclusion</p> <p>Using 3D data, we proposed a method to reconstruct phylogenies. We applied the method to reconstruct the sequences of insertion events leading to the emergence of potentially novel structural elements within existing protein domains. The results suggest that structural innovation is possible via the stochastic process of insertions and rapid evolution within variable regions where inserts tend to be nested. We also demonstrate that the structure-based phylogeny enables the study of new questions relating to the evolution of protein domain and biological function.</p

Характеристика пациентов с активным онкологическим процессом и венозными тромбоэмболическими осложнениями, получающих курс химиотерапии (по данным реальной клинической практики ГБУЗ «МГОБ №62 ДЗМ»)

Introduction. Pulmonary embolism (PE) accounts for about 10% in the mortality pattern among cancer patients, which is the second most frequent cause of death.Aim. To identify and characterize patients with active cancer and VTEC receiving chemotherapy (CT) based on the retrospective review of medical records provided by Moscow City Oncology Hospital No. 62 (MCOH No. 62) for the period from 01.2018 to 04.2020.Materials and methods. Medical records of 3,912 patients receiving chemotherapy treatment cycles in the departments of MCOH No. 62 were reviewed. 227 (5.8%) patients in whom the underlying disease course was complicated by VTEC were selected. Sites of primary tumours, n (%): stomach – 37 (16.3); colon and rectum – 36 (15.9); uterus, cervix, ovaries – 31 (13.7); lungs – 23 (10.1); kidneys, ureters and bladder, testicles – 19 (8.4); pancreas – 18 (7.9); soft tissues – 14 (6.2); mammary gland – 13 (5.7); lymphoma, myeloma – 8 (3.5); Ear Nose Throat (ENT) tumours – 7 (3); others – 21 (9.3).Results. The majority of patients (176 (77.5%)) had a sum Khorana score &lt;3, 51 (22.5%) patients had Khorana scores ≥ 3, which corresponds to a high thrombotic risk. 29 (12.7%) patients died. The hospital physicians assessed the causes of death as follows: 16 patients died from pulmonary embolism, of which 13 (81%) had a sum Khorana score &lt;3; 13 patients died due to progression of cancer.Conclusions. VTEC most commonly occurred in patients with gastrointestinal cancer (32.2%) and genito-urinary system cancer (22.1%). Half (54.5%) of VTEC occurred in the first 3 months of chemotherapy treatment. The Khorana scale is non-perfect in ‘real-life’ clinical practice (only 22.5% of patients with verified VTEC had a high thrombotic risk, and 81% of patients who died due to PE had a low and medium risk of VTEC).Введение. В структуре смертности онкобольных на тромбоэмболию легочной артерии (ТЭЛА) приходится около 10%, что является второй по частоте причиной смерти. Цель исследования. На основе ретроспективного анализа медицинской документации МГОБ №62 за период с 01.2018 по 04.2020 г. найти и охарактеризовать пациентов с активным раком и ВТЭО, получающих химиотерапию (ХТ). Материалы и методы. Были проанализированы случаи лечения 3 912 пациентов, получавших циклические курсы ХТ в отделениях МГОБ №62. Были отобраны 227 (5,8%) пациентов, у которых течение основного заболевания осложнилось ВТЭО. Локализация первичной опухоли, n (%): желудок – 37 (16,3); толстая и прямая кишка – 36 (15,9); матка, шейка матки, яичники – 31 (13,7); легкие – 23 (10,1); почки, мочеточники и мочевой пузырь, яички – 19 (8,4); поджелудочная железа – 18 (7,9); мягкие ткани – 14 (6,2); молочная железа – 13 (5,7); лимфома, миелома – 8 (3,5); опухоли лор-органов – 7 (3); другие – 21 (9,3). Результаты. Сумма баллов по шкале Khorana &lt; 3 отмечалась у большинства пациентов – 176 (77,5%), ≥ 3 баллов по шкале Khorana – у 51 (22,5%) пациента, что соответствует высокому тромботическому риску. Умерли 29 (12,7%) пациентов. Оценка причин смерти, по мнению лечащих врачей: 16 пациентов – от ТЭЛА, из них у 13 (81%) сумма баллов по шкале Khorana &lt; 3 баллов; у 13 пациентов причина смерти – прогрессирование онкологического заболевания. Выводы. Чаще всего ВТЭО возникали у больных раком ЖКТ (32,2%) и раком МПС (22,1%). Половина (54,5%) ВТЭО возникали в первые 3 мес. ХТ. Шкала Khoranа несовершенна в реальной клинической практике (только 22,5% больных с верифицированным ВТЭО имели высокий тромботический риск, а 81% больных, умерших от ТЭЛА, имели низкий и средний риск ВТЭО)

A Novel Side-Chain Orientation Dependent Potential Derived from Random-Walk Reference State for Protein Fold Selection and Structure Prediction

An accurate potential function is essential to attack protein folding and structure prediction problems. The key to developing efficient knowledge-based potential functions is to design reference states that can appropriately counteract generic interactions. The reference states of many knowledge-based distance-dependent atomic potential functions were derived from non-interacting particles such as ideal gas, however, which ignored the inherent sequence connectivity and entropic elasticity of proteins.We developed a new pair-wise distance-dependent, atomic statistical potential function (RW), using an ideal random-walk chain as reference state, which was optimized on CASP models and then benchmarked on nine structural decoy sets. Second, we incorporated a new side-chain orientation-dependent energy term into RW (RWplus) and found that the side-chain packing orientation specificity can further improve the decoy recognition ability of the statistical potential.RW and RWplus demonstrate a significantly better ability than the best performing pair-wise distance-dependent atomic potential functions in both native and near-native model selections. It has higher energy-RMSD and energy-TM-score correlations compared with other potentials of the same type in real-life structure assembly decoys. When benchmarked with a comprehensive list of publicly available potentials, RW and RWplus shows comparable performance to the state-of-the-art scoring functions, including those combining terms from multiple resources. These data demonstrate the usefulness of random-walk chain as reference states which correctly account for sequence connectivity and entropic elasticity of proteins. It shows potential usefulness in structure recognition and protein folding simulations. The RW and RWplus potentials, as well as the newly generated I-TASSER decoys, are freely available in http://zhanglab.ccmb.med.umich.edu/RW