Plasmodium falciparum Gametes and Sporozoites Hijack Plasmin and Factor H To Evade Host Complement Killing.

parasites are the etiological agents of malaria, a disease responsible for over half a million deaths annually. Successful completion of the parasite's life cycle in the vertebrate host and transmission to a mosquito vector is contingent upon the ability of the parasite to evade the host's defenses. The extracellular stages of the parasite, including gametes and sporozoites, must evade complement attack in both the mammalian host and in the blood ingested by the mosquito vector.

The impact of human complement on the clinical outcome of malaria infection.

The tropical disease malaria remains a major cause of global morbidity. Once transmitted to the human by a blood-feeding mosquito, the unicellular malaria parasite comes into contact with the complement system and continues to interact with human complement during its intraerythrocytic replication cycles. In the course of infection, both the classical and the alternative pathway of complement are activated, leading to parasite opsonization and lysis as well as the induction of complement-binding antibodies.

Cutting Edge: FHR-1 Binding Impairs Factor H-Mediated Complement Evasion by the Malaria Parasite .

Human complement is the first line of defense against invading pathogens, including the malaria parasite We previously demonstrated that human complement represents a particular threat for the clinically relevant blood stages of the parasite. To evade complement-mediated destruction, the parasites acquire factor H (FH) via specific receptors. We now report that the FH-related protein FHR-1 competes with FH for binding to the parasites.

Exploring the limits of polarization transfer efficiency in homonuclear three spin systems.

The limits of polarization transfer efficiency are explored for systems consisting of three isotropically coupled spins 1/2 in the absence of relaxation. An idealized free evolution and control Hamiltonian is studied, which provides an upper limit of transfer efficiency (in terms of transfer amplitude and transfer time) for realistic homonuclear spin systems with arbitrary Heisenberg-type coupling constants J12, J13, and J23. It is shown that optimal control based pulse sequences have significantly improved transfer efficiencies compared to conventional transfer schemes.

Optimal control of coupled spin dynamics: design of NMR pulse sequences by gradient ascent algorithms.

In this paper, we introduce optimal control algorithm for the design of pulse sequences in NMR spectroscopy. This methodology is used for designing pulse sequences that maximize the coherence transfer between coupled spins in a given specified time, minimize the relaxation effects in a given coherence transfer step or minimize the time required to produce a given unitary propagator, as desired. The application of these pulse engineering methods to design pulse sequences that are robust to experimentally important parameter variations, such as chemical shift dispersion or radiofrequency (rf) variations due to imperfections such as rf inhomogeneity is also explained.

Tailoring the optimal control cost function to a desired output: application to minimizing phase errors in short broadband excitation pulses.

The de facto standard cost function has been used heretofore to characterize the performance of pulses designed using optimal control theory. The freedom to choose new, creative quality factors designed for specific purposes is demonstrated. While the methodology has more general applicability, its utility is illustrated by comparison to a consistently chosen example--broadband excitation.

Improving solid-state NMR dipolar recoupling by optimal control.

We present the first solid-state NMR experiments developed using optimal control theory. Taking heteronuclear dipolar recoupling in magic-angle-spinning NMR as an example, it proves possible to significantly improve the efficiency of the experiments while introducing robustness toward instrumental imperfections such as radio frequency inhomogeneity. The improvements are demonstrated by numerical simulations as well as practical experiments on a 13Calpha,15N-labeled powder of glycine.

Reducing the duration of broadband excitation pulses using optimal control with limited RF amplitude.

Combining optimal control theory with a new RF limiting step produces pulses with significantly reduced duration and improved performance for a given maximum RF amplitude compared to previous broadband excitation by optimized pulses (BEBOP). The resulting pulses tolerate variations in RF homogeneity relevant for standard high-resolution NMR probes. Design criteria were transformation of Iz-->Ix over resonance offsets of +/-20kHz and RF variability of +/-5%, with a pulse length of 500 micros and peak RF amplitude equal to 17.

Broadband geodesic pulses for three spin systems: time-optimal realization of effective trilinear coupling terms and indirect SWAP gates.

Broadband implementations of time-optimal geodesic pulse elements are introduced for the efficient creation of effective trilinear coupling terms for spin systems consisting of three weakly coupled spins 1/2. Based on these pulse elements, the time-optimal implementation of indirect SWAP operations is demonstrated experimentally. The duration of indirect SWAP gates based on broadband geodesic sequence is reduced by 42.

Application of optimal control theory to the design of broadband excitation pulses for high-resolution NMR.

Optimal control theory is considered as a methodology for pulse sequence design in NMR. It provides the flexibility for systematically imposing desirable constraints on spin system evolution and therefore has a wealth of applications. We have chosen an elementary example to illustrate the capabilities of the optimal control formalism: broadband, constant phase excitation which tolerates miscalibration of RF power and variations in RF homogeneity relevant for standard high-resolution probes.

Optimal control of spin dynamics in the presence of relaxation.

Experiments in coherent spectroscopy correspond to control of quantum mechanical ensembles guiding them from initial to final target states. The control inputs (pulse sequences) that accomplish these transformations should be designed to minimize the effects of relaxation and to optimize the sensitivity of the experiments. For example in nuclear magnetic resonance (NMR) spectroscopy, a question of fundamental importance is what is the maximum efficiency of coherence or polarization transfer between two spins in the presence of relaxation.

Time-optimal coherence-order-selective transfer of in-phase coherence in heteronuclear IS spin systems.

Based on principles of geometric optimal control theory, coherence transfer building blocks can be derived which achieve optimal sensitivity. Here, experimental pulse sequences are presented that achieve the best possible coherence-order-selective in-phase transfer (S(-)-->I(-)) for a heteronuclear 2-spin system for any given mixing time in the absence of relaxation. For short mixing times, the optimal experiment improves the sensitivity of isotropic mixing by up to 12.