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

Aeroload Simulation of Interceptor Missile using Fin Load Simulator

Interceptor missiles are designed to destroy enemy targets in air. Targets can be destroyed either in atmosphere or out of atmosphere. So for Air Defence scenario, a two layer protection system is required with one taking care of exo atmosphere and another endo atmosphere. In this Air Defence scenario, irrespective of target trajectory interceptor should neutralise it. So the control, guidance are to be designed and validated thoroughly with various scenarios of interceptor and target. These interceptors sense the rates from rate gyroscopes and accelerations from accelerometers which are fitted on board the interceptor. The navigation algorithm calculates the interceptor’s position and velocity from these rates and accelerations from time to time. Using these interceptor data and target information received from ground RADAR or on board seeker, guidance calculates accelerations demand and subsequently rate demand. The control algorithm runs in on board mission computer along with guidance. The control algorithm calculates the commanded rate and eventually commanded deflections to the control fins to move towards the target. The fins have to move as per commanded deflections to meet the mission objective of hitting the target. But the load known as aeroload which comes on the control fins during mission, causes control fins not to move as per command. Due to the difference between control command and physical movement of fin, the expected path towards target deviates. This increases the miss distance and also misses the target hit. This aeroload scenario is to be simulated on ground and some feature is to be designed to take care of it during mission. By studying the control system behaviour due to load, the control autopilot is to be automatically tuned to compensate for the loss in commanded deflections. This scenario can be carried out in Hardware-in-Loop simulation (HILS) setup. Mission load conditions can be applied on hardware actuation system in HILS setup and mission performance can be seen and also with different loads and different autopilot tunings

COMPARATIVE EVALUATION OF HYPERBARIC BUPIVACAINE AND LEVOBUPIVACAINE AS SPINAL ANESTHESIA AGENTS IN FEMALES UNDERGOING CESAREAN SECTION: A CLINICAL STUDY.

Background: Obstetric anesthesia procedures must achieve appropriate muscular relaxation and enough analgesia with not too few side effects on the mother or fetus due to the anesthetic drug utilized. The purpose of the current study was to compare the clinical outcomes of lower-segment cesarean section (LSCS) patients who received hyperbaric bupivacaine with levobupivacaine as a spinal anesthetic agent. Materials and methods: The research study included 240 pregnant women in the American Society of Anesthesiologists (ASA) I–II groups who were scheduled to undergo elective cesarean operations. Two groups of patients were randomly assigned. It took 2.3 cc to administer the mixtures of 10 mg levobupivacaine (0.5%) + 15 cg fentanyl for Group L (n = 60) patients, and 10 mg hyperbaric bupivacaine (0.5%) + 15 cg fentanyl for B (n = 60) patients. Pinprick and Bromage scales were used to evaluate the sensory and motor block features of the groups and side effects and observed hemodynamic alterations were noted. Results: It turned out that Group B had considerably longer times to achieve the maximal dermatome for the sensory block, to regress by two dermatomes, and to regress to the T12 dermatome. It was shown that Group B's motor block evolution progressed more quickly and lasted longer. While hypotension, bradycardia, and nausea were less common in Group L, Group B required more ephedrine (p<0.05). Conclusion: Levobupivacaine and fentanyl together can be a suitable choice for cesarean sections since the motor block time is shorter, the adverse effects of hypotension, bradycardia, and nausea are less common, and it maintains hemodynamic stability at higher sensory block levels

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe

Pseudorapidity and transverse-momentum distributions of charged particles in proton-proton collisions at root s=13 TeV

The pseudorapidity (eta) and transverse-momentum (p(T)) distributions of charged particles produced in proton-proton collisions are measured at the centre-of-mass energy root s = 13 TeV. The pseudorapidity distribution in vertical bar eta vertical bar <1.8 is reported for inelastic events and for events with at least one charged particle in vertical bar eta vertical bar <1. The pseudorapidity density of charged particles produced in the pseudorapidity region vertical bar eta vertical bar <0.5 is 5.31 +/- 0.18 and 6.46 +/- 0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15 <p(T) <20 GeV/c and vertical bar eta vertical bar <0.8 for events with at least one charged particle in vertical bar eta vertical bar <1. The evolution of the transverse momentum spectra of charged particles is also investigated as a function of event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Elliptic flow of muons from heavy-flavour hadron decays at forward rapidity in Pb-Pb collisions at root s(NN)=2.76TeV

The elliptic flow, v(2), of muons from heavy-flavour hadron decays at forward rapidity (2.5 <y <4) is measured in Pb-Pb collisions at root s(NN)= 2.76TeVwith the ALICE detector at the LHC. The scalar product, two- and four-particle Q cumulants and Lee-Yang zeros methods are used. The dependence of the v(2) of muons from heavy-flavour hadron decays on the collision centrality, in the range 0-40%, and on transverse momentum, p(T), is studied in the interval 3 <p(T)<10 GeV/c. A positive v(2) is observed with the scalar product and two-particle Q cumulants in semi-central collisions (10-20% and 20-40% centrality classes) for the p(T) interval from 3 to about 5GeV/c with a significance larger than 3 sigma, based on the combination of statistical and systematic uncertainties. The v(2) magnitude tends to decrease towards more central collisions and with increasing pT. It becomes compatible with zero in the interval 6 <p(T)<10 GeV/c. The results are compared to models describing the interaction of heavy quarks and open heavy-flavour hadrons with the high-density medium formed in high-energy heavy-ion collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.Peer reviewe