Atomic Resolution X-Ray Crystal Structure of HIV-1 Protease in Complex with Atazanavir

Human immunodeficiency virus (HIV) is a pandemic that has infected nearly 1% of the world population. Despite numerous FDA approved antiviral drugs, HIV drug resistance remains a large challenge. HIV protease is an enzyme that is required by the virus to cleave Gag and Gag-Pol polyproteins into functional and structural proteins necessary for viral maturation. Currently, nine clinical inhibitors target HIV protease, but multiple clinical viral strains have developed resistance to these drugs. Therefore, it is necessary to continue developing new drugs to tackle the problem of HIV drug resistance, and X-ray crystallography is one tool that is used to study how drug candidates bind to HIV-1 protease. In order to study the interactions between inhibitor atazanavir and HIV-1 protease, the crystal structure of the complex has been solved at atomic resolution (1.09 Å). This structure will improve the design of new inhibitors for resistant protease

Strong impact of light induced conical intersections on the spectrum of diatomic molecules

We show that dressing of diatomic molecules by running laser waves gives rise to conical intersections (CIs). Due to presence of such CIs, the rovibronic molecular motions are strongly coupled. A pronounced impact of the CI on the spectrum of $Na_2$ molecule is demonstrated via numerical calculation for weak and moderate laser intensity, and an experiment is suggested on this basis. The position of the light induced CI and the strength of its non-adiabatic couplings can be chosen by changing the frequency and intensity of the used running laser wave. This offers new possibilities to control the photo-induced rovibronic molecular dynamics.Comment: 4 pages, 7 figure

Coherent strong-field control of multiple states by a single chirped femtosecond laser pulse

We present a joint experimental and theoretical study on strong-field photo-ionization of sodium atoms using chirped femtosecond laser pulses. By tuning the chirp parameter, selectivity among the population in the highly excited states 5p, 6p, 7p and 5f, 6f is achieved. Different excitation pathways enabling control are identified by simultaneous ionization and measurement of photoelectron angular distributions employing the velocity map imaging technique. Free electron wave packets at an energy of around 1 eV are observed. These photoelectrons originate from two channels. The predominant 2+1+1 Resonance Enhanced Multi-Photon Ionization (REMPI) proceeds via the strongly driven two-photon transition $4s\leftarrow\leftarrow3s$, and subsequent ionization from the states 5p, 6p and 7p whereas the second pathway involves 3+1 REMPI via the states 5f and 6f. In addition, electron wave packets from two-photon ionization of the non-resonant transiently populated state 3p are observed close to the ionization threshold. A mainly qualitative five-state model for the predominant excitation channel is studied theoretically to provide insights into the physical mechanisms at play. Our analysis shows that by tuning the chirp parameter the dynamics is effectively controlled by dynamic Stark-shifts and level crossings. In particular, we show that under the experimental conditions the passage through an uncommon three-state "bow-tie" level crossing allows the preparation of coherent superposition states

Aerodynamics of aero-engine installation

This paper describes current progress in the development of methods to assess aero-engine airframe installation effects. The aerodynamic characteristics of isolated intakes, a typical transonic transport aircraft as well as a combination of a through-flow nacelle and aircraft configuration have been evaluated. The validation task for an isolated engine nacelle is carried out with concern for the accuracy in the assessment of intake performance descriptors such as mass flow capture ratio and drag rise Mach number. The necessary mesh and modelling requirements to simulate the nacelle aerodynamics are determined. Furthermore, the validation of the numerical model for the aircraft is performed as an extension of work that has been carried out under previous drag prediction research programmes. The validation of the aircraft model has been extended to include the geometry with through flow nacelles. Finally, the assessment of the mutual impact of the through flow nacelle and aircraft aerodynamics was performed. The drag and lift coefficient breakdown has been presented in order to identify the component sources of the drag associated with the engine installation. The paper concludes with an assessment of installation drag for through-flow nacelles and the determination of aerodynamic interference between the nacelle and the aircraft

Coherent control using adaptive learning algorithms

We have constructed an automated learning apparatus to control quantum systems. By directing intense shaped ultrafast laser pulses into a variety of samples and using a measurement of the system as a feedback signal, we are able to reshape the laser pulses to direct the system into a desired state. The feedback signal is the input to an adaptive learning algorithm. This algorithm programs a computer-controlled, acousto-optic modulator pulse shaper. The learning algorithm generates new shaped laser pulses based on the success of previous pulses in achieving a predetermined goal.Comment: 19 pages (including 14 figures), REVTeX 3.1, updated conten

Behaviour patterns preceding a railway suicide: Explorative study of German Federal Police officers' experiences

<p>Abstract</p> <p>Background</p> <p>Constant high-level numbers of railway suicides indicate that prevention strategies against railway suicides are urgently needed. The main question of the present study was whether pre-crash railway suicide behaviour can be identified, using German Federal Police officers experience with suicidal events in railway related environments.</p> <p>Methods</p> <p>To collect information on pre-crash railway suicide behaviour, a questionnaire was used and made available on the German Federal Police intranet. A total of 202 subjects (mean age: 41 years, sex: 84.9% male) were included in the analysis. Multivariate logistic regression analyses were performed to predict the prevention of suicide (first model) or demand for counselling (second model) as outcomes. Sex, age, years of service, number of experienced suicides, suicides personally observed, information on suicides obtained from witnesses and finally either counselling/debriefing (first model) or whether officers had prevented a suicide (second model) were used as predictors.</p> <p>Results</p> <p>A considerable proportion of police officers reported behavioural patterns preceding a suicide. Half of them observed the dropping or leaving behind of personal belongings or the avoidance of eye contact, more than a third erratic gesture, mimic or movement. Erratic communication patterns and general confusion were each reported by about one quarter. One fifth indicated the influence of alcohol. Less frequently observed behaviour was aimlessly wandering (14.3%) and out of the ordinary clothing (4%). About one third of all railway suicide victims committed suicide in stations. Of those, 70% had chosen an eminent spot. The multivariate logistic regression model using prevented suicides as the outcome identified the number of suicides experienced, counselling/debriefing and having personally observed a suicide as variables with significant impact. The model using counselling/debriefing as the outcome identified age and having prevented a suicide as variables with a significant association.</p> <p>Conclusions</p> <p>Our results provide evidence that railway suicides are preceded by identifiable behavioural patterns. This emphasizes the importance of educational efforts, taking into account the knowledge and skills of experienced police officers.</p

Solitary coherent structures in viscoelastic shear flow: computation and mechanism

Starting from stationary bifurcations in Couette-Dean flow, we compute nontrivial stationary solutions in inertialess viscoelastic circular Couette flow. These solutions are strongly localized vortex pairs, exist at arbitrarily large wavelengths, and show hysteresis in the Weissenberg number, similar to experimentally observed ``diwhirl'' patterns. Based on the computed velocity and stress fields, we elucidate a heuristic, fully nonlinear mechanism for these flows. We propose that these localized, fully nonlinear structures comprise fundamental building blocks for complex spatiotemporal dynamics in the flow of elastic liquids.Comment: 5 pages text and 4 figures. Submitted to Physical Review Letter

The optical response of Ba_{1-x}K_xBiO_3: Evidence for an unusual coupling mechanism of superconductivity?

We have analysed optical reflectivity data for Ba_{1-x}K_xBiO_3 in the far-infrared region using Migdal-Eliashberg theory and found it inconsistent with standard electron-phonon coupling: Whereas the superconducting state data could be explained using moderate coupling, \lambda=0.7, the normal state properties indicate \lambda \le 0.2. We have found that such behaviour could be understood using a simple model consisting of weak standard electron-phonon coupling plus weak coupling to an unspecified high energy excitation near 0.4 eV. This model is found to be in general agreement with the reflectivity data, except for the predicted superconducting gap size. The additional high energy excitation suggests that the dominant coupling mechanism in Ba_{1-x}K_xBiO_3 is not standard electron-phonon.Comment: 5 pages REVTex, 5 figures, 32 refs, accepted for publication in Phys. Rev.