324,309 research outputs found
"Plasmodium falciparum" transfection technology for the analysis of "var" gene regulation and knockout investigation
Malaria is an infectious disease caused by protozoans of the genus
Plasmodium, which are injected by the bite of an infected female Anopheles
mosquito during a blood meal. Out of the four species that infect humans, P.
falciparum is the most important. About 40% of the world’s population is at
risk and 500 million cases of malaria occur every year, mainly in sub-
Saharan Africa. Due arising resistance of mosquitoes against insecticides,
the lack of a malaria vaccine, and emerging resistance of parasites against
established drugs, research into new drugs and vaccine targets is most
important.
Morbidity is associated with adherence of infected red blood cells (iRBC) to
endothelial tissue thereby obstructing the blood flow. The major protein
conferring this cytoadherence is the P. falciparum erythrocyte membrane
protein 1 (PfEMP1) anchored in the erythrocyte membrane of infected red
blood cells (iRBCs). PfEMP1 is encoded by the var gene family that consists
of approximately 60 members in the haploid genome of the 3D7 strain. var
genes are expressed mutually exclusive, i.e. only one var gene is expressed
in a parasite at a time and the rest is silenced. In this thesis we were
interested in the regulation of expression and silencing of var genes. For this
purpose we generated transgenic parasite lines that harbored plasmids
expressing luciferase under the control of various fragments of the var gene
upstream region. By comparing luciferase activities in the different lines we
identified the core promoter, two activator-binding sites and a repressorbinding
site. Additionally, we identified a regulatory sequence on the var
upstream region that interacts with the var intron during silencing. Using
quantitative RT-PCR with specific primers for every var gene we were unable
to confirm that the var upstream regions on the transfected plasmids were
recognized by the machinery that ensures mutually exclusive transcription.
In the second part of this thesis, we evaluated phosphodiesterase 1 (PDE1)
as a possible drug target in P. falciparum by creating a knockout parasite
line. PDEs are known drug targets in humans where selective PDE inhibitors
are being used to treat a wide range of diseases. In trypanosomiasis
research PDE inhibitors are promising drug candidates against sleeping
sickness, Nagana or Chagas’ disease. Out of the four PDEs described for P.
falciparum we focused on PfPDE1, which is expressed in blood stage
parasites and in gametocytes and sporozoites. We observed a slightly faster
growth of the knockout parasite line compared to the wildtype indicating that
the knockout parasite had a shorter erythrocytic lifecycle. We found that
PfPDE1 is responsible for 20% of the total cGMP activity observed in late
blood stage parasites and that there is no rescue mechanism of the
remaining PDEs to compensate for the loss of activity. We were not able to
localize PfPDE1 in the parasite. The fact that we could delete PfPDE1 clearly
shows that it is not an essential gene in blood stage forms of P. falciparum
and hence not a good drug target. Nevertheless we created a useful tool to
investigate the role of PfPDE1 in the development of sexual parasite forms
Influence of low amounts of nanostructured silica and calcium carbonate fillers on the large-area dielectric breakdown performance of bi-axially oriented polypropylene
Influence of low amounts (1.0-2.0wt-%) of nanostructured silica and calcium carbonate fillers on the large area dielectric breakdown performance of bi-axially oriented polypropylene (BOPP) is analyzed. A multi-breakdown measurement method based on the self-healing breakdown capability of metallized film is utilized for the breakdown characterization in order to cover relatively large total film areas, thus leading to results of higher relevance from the practical point-of-view. The dispersion and distribution qualities of filler particles at the nanoscale are evaluated with transmission electron microscopy (TEM) imaging. Weibull statistical analysis suggests that the breakdown distribution homogeneity can be improved with both the filler types. The 1.0wt-% silica-BOPP composite also shows a shift of the weakest points towards higher dielectric strength in comparison to the neat BOPP. However, with increasing filler content, new failure modes are introduced into the nanocomposites, hence decreasing the overall breakdown performance in the >5% breakdown probability region in comparison to the un-filled reference BOPP film
Prognose und Behandlung makulärer Blutungen bei neovaskulärer altersabhängiger Makuladegeneration
Macular bleeding is associated with an acute loss of visual function and is frequently a complication of neovascular age-related macular degeneration. Blood degradation products can lead to permanent retinal neuronal damage over time. The extent of the bleeding is correlated to the coagulation status of the patient. The treatment strategy depends on the age, size and exact location of the bleeding. The spectrum of therapeutic options ranges from watchful waiting to large scale vitrectomy with removal of subretinal mass bleeding
EXISTENCE AND ASYMPTOTIC BEHAVIOR OF SOLUTIONS TO EIGENVALUE PROBLEMS FOR SCHRÖDINGER-BOPP-PODOLSKY EQUATIONS
We study the existence and multiplicity of solutions for the Schrödinger-Bopp-Podolsky system (formula presented) where Ω is an open bounded and smooth domain in R3, a > 0 is the Bopp-Podolsky parameter. The unknowns are u, φ: Ω → R and ω ∈ R. By using variational methods we show that for any a > 0 there are infinitely many solutions with diverging energy and divergent in norm. We show that ground states solutions converge to a ground state solution of the related classical Schrödinger-Poisson system, as a → 0
A masing Hale-Bopp
Comets such as Hale-Bopp look spectacular in the night skies, but also have hidden depths at wavelengths other than optical. The Lovell telescope at Jodrell Bank was used to observe Hale-Bopp around perihelion at frequencies that arise from OH maser activity. Results are consistent with the coma expanding as a shell spreading out from the core at up to 4 km s-1. If the coma is symmetrical, the overall size of the emission region reaches up to 40' at perihelion. Intensities of absorption and emission vary with the heliocentric velocity of the coma; repeated observations can be used to assess whether jets play a role in outgassing from this amazing and masing comet
A masing Hale-Bopp
Comets such as Hale-Bopp look spectacular in the night skies, but also have hidden depths at wavelengths other than optical. The Lovell telescope at Jodrell Bank was used to observe Hale-Bopp around perihelion at frequencies that arise from OH maser activity. Results are consistent with the coma expanding as a shell spreading out from the core at up to 4 km s-1. If the coma is symmetrical, the overall size of the emission region reaches up to 40' at perihelion. Intensities of absorption and emission vary with the heliocentric velocity of the coma; repeated observations can be used to assess whether jets play a role in outgassing from this amazing and masing comet
Small-body encounters using solar sail propulsion
Cometary Rendezvous and Flybys have large V requirements, which impose almost unattainable, and sometimes prohibitive, demands on the propellant budget of conventional, chemical propulsion. Ion Propulsion is a viable alternative, but as the number and difficulty of target objectives increases then the potential of this technology becomes rapidly less attractive. Solar sails exhibit an extremely high effective specific impulse over long mission durations. No propellant is required so that large changes in V could be realised without necessitating the introduction of complex gravity assists, which prolong mission duration and restrict launch opportunities. The endurance of the structures and materials are thus the only limiting factors dictating the number and range of bodies with which the solar-sail propelled vehicle can encounter throughout its lifetime. In this paper we have analysed a number of high-energy, small-body mission scenarios using a parameterised approach to sail control representation. The sail cone and clock angle histories were characterised by linear interpolation across a set of discrete nodes. The optimal control problem was thus transcribed to a Non-Linear Programming problem to select the optimal controls at the nodes that minimised the transfer time while enforcing the cartesian end-point boundary constraints (6 states for rendezvous, 3 for flypast). The Fortran77 optimisation package NPSOL 5.0 was used for this purpose with the variational equations of motion formulated in modified equinoctial orbital elements and integrated using a variable-order, adaptive step-size Adams-Moulton-Bashforth method. We present optimal rendezvous trajectories to Short-Period Comets such as 46P/Wirtanen in 484 days with a sail characteristic acceleration of 1.9 mms-2, and with 2P/Encke in 574 days with a characteristic acceleration of 1.0 mms-2. An analysis using high-performance sails has been conducted to permit fast flyby intercepts of newly discovered Long Period Comets (LPCs). Previous examples adopted were C/1995 O1/Hale- Bopp, C/1995 Y1/Hyakutake, C/1999 T1/McNaught-Hartley, C/1999 F1/Catalina, C/1999 N2/Lynn and C/1999 H1/Lee, to demonstrate the feasibility of a late launch to quickly intercept a new LPC using a solar sail. Since the time between discovery of a new LPC such as Hale-Bopp and perihelion passage was less then 2 years, this then leaves a very short time-span for orbit determination, preparation, planning and operational phases. Preliminary mission analysis shows that a Hale-Bopp perihelion flypast could have been achieved, with a sail characteristic acceleration of 5.0 mms-2, by launching just 209 days before comet perihelion passage. With a characteristic acceleration of 2.0 mms-2 Hale-Bopp could also have been intercepted at its descending node by launching 270 days before nodal descent. The sail could then have returned to rendezvous with the Earth 261 days later, giving a minimum total mission turn-around time of 531 days. An alternative, dual flyby scenario has been investigated, to continue on to C/1997 D1/Mueller, after which solar system escape was reached and arrival at Heliopause would occur in 12 years. Solar Electric Propulsion has been adopted as the primary propulsion system for the DAWN dual asteroid rendezvous mission scheduled for launch in 2006. The objective of this mission is to rendezvous with inner main-belt asteroids, Vesta and Ceres. We have also investigated solar sail adaptation to this mission, for the same launch date and 11 month orbiter stay-times. We have extended the mission objectives to two further asteroids, Lucina and Lutetia, with the aim of demonstrating a Mainbelt Asteroid Survey scenario
GUILLÉN E BOPP: DUAS VOZES NEGRAS NA AMÉRICA
Este texto procura estudar possíveis relações entre as obras Motivos de son do escritor cubano Nicolás Guillén e Urucungo: Poemas negros do poeta brasileiro Raul Bopp. Salientam-se aqui o conceito de negrismo e suas realizações nos poemas "Negrobembón" de Guillén e "Serra do balalão" e "Monjolo" de Bopp
Microfibrillated cellulose and borax as mechanical, O2-barrier, and surface-modulating agents of pullulan biocomposite coatings on BOPP
Multifunctional composite coatings on bi-oriented polypropylene (BOPP) films were obtained using borax and microfibrillated cellulose (MFC) added to the main pullulan coating polymer. Spectroscopy analyses suggested that a first type of interaction occurred via hydrogen bonding between the C6OH group of pullulan and the hydroxyl groups of boric acid, while monodiol and didiol complexation represented a second mechanism. The deposition of the coatings yielded an increase in the elastic modulus of the entire plastic substrate (from 2GPa of the neat BOPP to 3.1GPa of the P/B+/MFC-coated BOPP). The addition of MFC yielded a decrease of both static and kinetic coefficients of friction of approximately 22% and 25%, respectively, as compared to the neat BOPP. All composite coatings dramatically increased the oxygen barrier performance of BOPP, especially under dry conditions. The deposition of the high hydrophilic coatings allowed to obtain highly wettable surfaces (water contact angle of 18°)
Influence of colloidal silica nanoparticles on pullulan-coated BOPP film
The influence of two different types of colloidal silica (CS) nanoparticles in a main pullulan coating on bi-oriented polypropylene (BOPP) was evaluated in this work with the goal of exploring new and more advantageous applications in the food packaging sector. It was observed that the addition of the nanoparticles did not affect the friction properties of the pristine pullulan coating, with the static and kinetic coefficient mean values being 0.35 and 0.22, respectively. An improvement in the barrier properties against O2 and CO2 was observed for all the tested nanocomposite coatings. The best performance was provided by the particles with the highest surface area (750 m2 g-1) (O2TR ~30 mL m-2 24 h-1 and CO2TR ~80 mL m-2 24 h-1 at 23 °C under dry conditions) compared to the pristine pullulan-coated BOPP (O2TR ~480 mL m-2 24 h-1 and CO2TR ~1245 mL m-2 24 h-1). Noteworthy, the change in the permeability properties ultimately yielded a decrease of the CO2/O2 selectivity towards 1. The addition of CS nanoparticles did not modify the optical attributes of the pullulan coating, with the final haze values being approximately 1.5% for all nanocomposite layers. The wettability of the final coatings was influenced by the addition of the CS nanoparticles, with a remarkable decrease of the water contact angle to ~19° for the formulation loaded with the lowest concentration of silica nanoparticles that have the smallest size and the highest surface area. The potential application of the pullulan-CS coatings for MAP-packaged fruit and vegetables is suggested
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