Dynamics of circular arrangements of vorticity in two dimensions

The merger of two like-signed vortices is a well-studied problem, but in a turbulent flow, we may often have more than two like-signed vortices interacting. We study the merger of three or more identical co-rotating vortices initially arranged on the vertices of a regular polygon. At low to moderate Reynolds numbers, we find an additional stage in the merger process, absent in the merger of two vortices, where an annular vortical structure is formed and is long-lived. Vortex merger is slowed down significantly due to this. Such annular vortices are known at far higher Reynolds numbers in studies of tropical cyclones, which have been noticed to a break down into individual vortices. In the pre-annular stage, vortical structures in a viscous flow are found here to tilt and realign in a manner similar to the inviscid case, but the pronounced filaments visible in the latter are practically absent in the former. Interestingly at higher Reynolds numbers, the merger of an odd number of vortices is found to proceed very differently from that of an even number. The former process is rapid and chaotic whereas the latter proceeds more slowly via pairing events. The annular vortex takes the form of a generalised Lamb-Oseen vortex (GLO), and diffuses inwards until it forms a standard Lamb-Oseen vortex. For lower Reynolds number, the numerical (fully nonlinear) evolution of the GLO vortex follows exactly the analytical evolution until merger. At higher Reynolds numbers, the annulus goes through instabilities whose nonlinear stages show a pronounced difference between even and odd mode disturbances. It is hoped that the present findings, that multiple vortex merger is qualitatively different from the merger of two vortices, will motivate studies on how multiple vortex interactions affect the inverse cascade in two-dimensional turbulence.Comment: Abstract truncated. Paper to appear in Physical Review

PRESCRIPTION ERRORS IN THE DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY: A CROSS-SECTIONAL, OBSERVATIONAL STUDY

ABSTRACTObjective:  Prescription writing is an art. Writing a correct prescription in compliance with the WHO guidelines requires regular practice. Mistakesin prescription writing are inevitable. Hence, this study was done to analyze the prescriptions from the Outpatient Department of Obstetrics andGynaecology for errors. To analyze the prevalence and types of common prescribing errors in the Outpatient Department of Obstetrics and Gynaecology.Methods:  This cross-sectional study was conducted in the Department of Pharmacy, Pondicherry Institute of Medical Sciences, Puducherry. 500prescriptions from the Obstetrics and Gynaecology Outpatient Department were collected and analyzed. The study duration was 6 months (JulyDecember2014). The prescriptionswereanalyzedforerrors.Results: Our study revealed that 30.8% of the prescriptions had, at least, one error in them. The majority of the prescriptions had the doctors' signand patient details written in them. The dose of the drug was missing in about 38% of the prescriptions. None of the prescriptions had Type A errorin our study.Conclusion: It was found that prescription errors are still prevalent. The prescribers' have to be updated about the prescribing guidelines and regularauditing should be done to avoid these errors.Keywords: Prescription errors, Obstetrics and gynaecology, Classification of errors

Electrostatic Steering Accelerates C3d:CR2 Association.

Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts

Structure based de novo design of IspD inhibitors as anti-tubercular agents

Tuberculosis is one of the leading contagious diseases, caused by Mycobacterium tuberculosis. Despite improvements in anti-tubercular agents, it remains one of the most prevalent infectious diseases worldwide, responsible for a total of 1.6 million deaths annually. The emergence of multidrug resistant strains highlighted the need of discovering novel drug targets for the development of anti-tubercular agents. 2-C-methyl-D-erythritol-4-phosphate cytidyltransferase (IspD) is an enzyme involved in MEP pathway for isoprenoid biosynthesis, which is considered an attractive target for the discovery of novel antibiotics for its essentiality in bacteria and absence in mammals. In the present study, we have employed structure based drug design approach to develop novel and potent inhibitors for IspD receptor. To explore binding affinity and hydrogen bond interaction between the ligand and active site of IspD receptor, docking studies were performed. ADMET and synthetic accessibility filters were used to screen designed molecules. Finally, ten compounds were selected and subsequently submitted for the synthesis and in vitro studies as IspD inhibitors

Effect of shape on mechanical properties and deformation behavior of Cu nanowires: An atomistic simulations study

We study the effect of nanowire shape on mechanical properties and deformation behaviour of Cu nanowires using atomistic simulations. Simulations were carried out on $[100]$ nanowires with different shapes such as triangular, square, pentagon, hexagon and circular.Results indicate yield strength is different for different shapes. In both cases, triangular nanowire exhibit the lowest yield strength, while circular nanowire is the strongest. Deformation in all the nanowires is dominated by partials slip and twinning. Due to twinning, different shapes expose different surfaces at the twinned region. All nanowires show ductile failure and square nanowire exhibits the highest failure strain, while it is lowest for triangular nanowire.Comment: 14 pages, 10 Figure

Prescription pattern of fixed dose drug combinations in obstetrics and gynecology department of a tertiary care hospital in Puducherry, India: an observational study

Background: Fixed drug combinations (FDCs)have various advantages and disadvantages. In countries like India there are numerous irrational prescriptions as highlighted by the recent banning of FDCs in October 2018. Studying the prescription pattern helps in developing national database which can be used to promote rational use of drugs.Methods: All the Outdoor Patient Department (OPD) prescriptions from department of Obstetrics and Gynecology (OBG) during the study period were used for the study. The drugs were classified according to Anatomical Therapeutic Chemical (ATC) classification. Other data studied were the number of FDCs and the number of currently banned combinations which were used during the study period.Results: The 41% of the drugs prescribed as FDCs. Most FDCs belonged to alimentary system followed by anti-infectives and blood and blood forming organs group. Vitamin D3 and Calcium combination was the most commonly prescribed FDC. Approximately 20% of these prescribed drugs are currently banned.Conclusions: A significant number of drugs are being prescribed as FDCs which also includes various irrational combinations

Peptide redesign for inhibition of the complement system: Targeting age-related macular degeneration.

PurposeTo redesign a complement-inhibiting peptide with the potential to become a therapeutic for dry and wet age-related macular degeneration (AMD).MethodsWe present a new potent peptide (Peptide 2) of the compstatin family. The peptide is developed by rational design, based on a mechanistic binding hypothesis, and structural and physicochemical properties derived from molecular dynamics (MD) simulation. The inhibitory activity, efficacy, and solubility of Peptide 2 are evaluated using a hemolytic assay, a human RPE cell-based assay, and ultraviolet (UV) absorption properties, respectively, and compared to the respective properties of its parent peptide (Peptide 1).ResultsThe sequence of Peptide 2 contains an arginine-serine N-terminal extension (a characteristic of parent Peptide 1) and a novel 8-polyethylene glycol (PEG) block C-terminal extension. Peptide 2 has significantly improved aqueous solubility compared to Peptide 1 and comparable complement inhibitory activity. In addition, Peptide 2 is more efficacious in inhibiting complement activation in a cell-based model that mimics the pathobiology of dry AMD.ConclusionsWe have designed a new peptide analog of compstatin that combines N-terminal polar amino acid extensions and C-terminal PEGylation extensions. This peptide demonstrates significantly improved aqueous solubility and complement inhibitory efficacy, compared to the parent peptide. The new peptide overcomes the aggregation limitation for clinical translation of previous compstatin analogs and is a candidate to become a therapeutic for the treatment of AMD