A Computational-Experimental Approach Identifies Mutations That Enhance Surface Expression of an Oseltamivir-Resistant Influenza Neuraminidase

The His274 → Tyr (H274Y) oseltamivir (Tamiflu) resistance mutation causes a substantial decrease in the total levels of surface-expressed neuraminidase protein and activity in early isolates of human seasonal H1N1 influenza, and in the swine-origin pandemic H1N1. In seasonal H1N1, H274Y only became widespread after the occurrence of secondary mutations that counteracted this decrease. H274Y is currently rare in pandemic H1N1, and it remains unclear whether secondary mutations exist that might similarly counteract the decreased neuraminidase surface expression associated with this resistance mutation in pandemic H1N1. Here we investigate the possibility of predicting such secondary mutations. We first test the ability of several computational approaches to retrospectively identify the secondary mutations that enhanced levels of surface-expressed neuraminidase protein and activity in seasonal H1N1 shortly before the emergence of oseltamivir resistance. We then use the most successful computational approach to predict a set of candidate secondary mutations to the pandemic H1N1 neuraminidase. We experimentally screen these mutations, and find that several of them do indeed partially counteract the decrease in neuraminidase surface expression caused by H274Y. Two of the secondary mutations together restore surface-expressed neuraminidase activity to wildtype levels, and also eliminate the very slight decrease in viral growth in tissue-culture caused by H274Y. Our work therefore demonstrates a combined computational-experimental approach for identifying mutations that enhance neuraminidase surface expression, and describes several specific mutations with the potential to be of relevance to the spread of oseltamivir resistance in pandemic H1N1

Optimizations of preparative parameters in potentiodynamic synthesis of cobalt oxide thin films: Capacitive approach

The present article reports synthesis of Co3O4 thin films by facile potentiodynamic-electrodeposition technique using variations in the preparative parameters such as ingredient, solution concentration and deposition time. The prepared samples were analysed using XRD, FE-SEM, TEM, cyclic voltammetry, chronopotentiometry and electrochemical impedance spectroscopy. Crystallographic study shows polycrystalline face centered cubic spinel structure of the deposit. Cyclic voltammogram reveals pseudocapacitive behavior. The calculated highest value of specific capacitance at the scan rate 5 mV/s was 237.68 F/gin 1 M KOH, within the potential window -0.92 to 0.45 V versus Ag/AgCl. The calculated maximum value of specific energy, specific power and columbic efficiency from chronopotentiometry were 4.91 Wh/kg, 28.69 kW/kg and 94.78%, respectively. The internal resistance observed using electrochemical impedance spectroscopy was~ 3.55 Ω

A cross sectional study to estimate prevalence of obesity and its risk factors in adolescent school children in Western Maharashtra, India

Background: There is an increase in prevalence of childhood obesity and its chronic health effects especially in developing countries like India in last 2-3 decades. This study is small effort to know prevalence and risk factors causing obesity. Aim of the study was to estimate prevalence of obesity and its risk factors in school students of age group 11 to 16 years.Methods: About 207 adolescent school children from selected school were enrolled in the study. Research tool comprised of questions about demographic characteristics, daily physical activity, frequency of having junk food intake etc. Height and weight were measured on calibrated scales. For statistical analysis MS Excel and SPSS 16 were used.Results: Among participants 58.9% were boys. 66.7% students were in the 13 to 14 years of age group. As per body mass index, 46.9% children were underweight and 8.7% were obese. 77.3% participants were eating junk food more than once in a week.Conclusions: Health education on dietary habits and physical activity is needed for adolescent children to prevent development of obesity and complications related to it

Aerobic bacterial profile and their antimicrobial sensitivity pattern in patients of otitis media with ear discharge

Background: The average prevalence of Chronic suppurative otitis media (CSOM) in India is 5.2%. It is more prevalent due to various predisposing factors such as malnutrition, overcrowding, poor hygiene, inadequate health care, and recurrent upper respiratory tract infection. In recent years, there is increased preponderance of multi drug resistant organisms due to the irrational use of antibiotics, making treatment of CSOM more difficult.Methods: Samples from 100 subjects of uncomplicated CSOM who presented to the Oto-Rhino-Laryngology outpatient department of our hospital were collected. Aerobic bacterial profile and its Antimicrobial susceptibility were studied by conventional methods. Results were compiled and evaluated by descriptive statistics and inferential statistics.Results: Pseudomonas aeruginosa (50.7%) and Staphylococcus aureus (19.04%) were the predominant isolates in our study. Aminoglycosides and Fluoroquinolones were found to be effective first line drugs, followed by Carbapenems.Conclusions: These antibiotics can be used to prevent the life-long complications of CSOM. Timely culture and sensitivity helps in the management of these cases.

Differential scanning calorimetry and wide-angle X-ray scattering studies of bread staling

Wide angle X-ray scattering (WAXS) was used to follow the development of crystal size and strain during the staling of bread containing different additives. In this it was observed that one can classify the good anti-staling additives as gelatin, propylene glycol, maltodextrin and anti-staling enzyme corresponding to the order of increasing crystal size for a particular Bragg reflection in all the samples and correlate using DSC (differential scanning calorimetry) studies of all the bread compositions containing different additives. (C) 1998 John Wiley & Sons, Inc

Importance of etiologic diagnosis of hydrocephalus as illustrated by a case of Walker Warburg syndrome

This article does not have an abstract

Study of protein synthesis in rat liver mitochondria: use of cycloheximide

1. Effects of short-term and long-term administration of cycloheximide on rat liver mitochondrial protein synthesis have been examined and were found to be different. 2. Long-term administration of cycloheximide resulted in inhibition of total cellular protein synthesis including that of mitochondria while, at short-term intervals, 8–10% of mitochondrial protein synthesis was cycloheximide-resistant. 3. The inhibitory effect was also reflected in terms of protein synthesizing ability of mitochondria in vitro, the inhibition becoming apparent at 40 min and showing progressive increase with time. 4. The observed inhibition of mitochondrial protein synthesis by cycloheximide was not due to either inhibition of energy metabolism or alteration of amino-acid pool. 5. Cycloheximide did not enter mitochondria or sonic preparation under conditions in vitro. On the other hand, after administration of [3H]cycloheximide, significant quantities of the label were found to be associated with mitochondria and mitoribosomes. 6. These results indicated that cycloheximide reached the site of action in mitochondria under conditions in vivo but was unable to do so in vitro. 7. The results are discussed to elucidate the possible mechanisms involved in the inhibition of truly mitochondrial protein synthesis by cycloheximide

On Petri Nets with Hierarchical Special Arcs

We investigate the decidability of termination, reachability, coverability and deadlock-freeness of Petri nets endowed with a hierarchy of places, and with inhibitor arcs, reset arcs and transfer arcs that respect this hierarchy. We also investigate what happens when we have a mix of these special arcs, some of which respect the hierarchy, while others do not. We settle the decidability status of the above four problems for all combinations of hierarchy, inhibitor, reset and transfer arcs, except the termination problem for two combinations. For both these combinations, we show that deciding termination is as hard as deciding the positivity problem on linear recurrence sequences -- a long-standing open problem

Performance of Port Facilities During the Northridge Earthquake

During the January 17, 1994, Northridge earthquake, two of the Port of Los Angeles\u27 facilities called Berths 121-126 and Pier 300 sustained moderate damage. Lateral displacement of dikes up to five inches and liquefaction of hydraulic fills were observed. Several geotechnical analyses from simplified SPT -based method to sophisticated fully-coupled analyses are presented. Observed lateral displacements are predicted reasonably well by the fully-coupled analysis procedure and an intermediate analysis procedure which incorporates some results from a fully-coupled analysis in to a simplified Newmark-type deformation analysis. The potential for higher pore pressure generation underneath the dike compared to a level ground is also discussed