Mechanisms of substrate selection by the signal recognition particle

The signal recognition particle (SRP) targets membrane and secretory proteins to their correct cellular destination with remarkably high fidelity. Previous studies have shown that multiple checkpoints exist within this targeting pathway that allows ‘correct cargo’ to be quickly and efficiently targeted and for ‘incorrect cargo’ to be promptly rejected. In this work, we delved further into understanding the mechanisms of how substrates are selected or discarded by the SRP. First, we discovered the role of the SRP fingerloop and how it activates the SRP and SRP receptor (SR) GTPases to target and unload cargo in response to signal sequence binding. Second, we learned how an ‘avoidance signal’ found in the bacterial autotransporter, EspP, allows this protein to escape the SRP pathway by causing the SRP and SR to form a ‘distorted’ complex that is inefficient in delivering the cargo to the membrane. Lastly, we determined how Trigger Factor, a co-translational chaperone, helps SRP discriminate against ‘incorrect cargo’ at three distinct stages: SRP binding to RNC; targeting of RNC to the membrane via SRP-FtsY assembly; and stronger antagonism of SRP targeting of ribosomes bearing nascent polypeptides that exceed a critical length. Overall, results delineate the rich underlying mechanisms by which SRP recognizes its substrates, which in turn activates the targeting pathway and provides a conceptual foundation to understand how timely and accurate selection of substrates is achieved by this protein targeting machinery.

A search for fractionally charged particles in cosmic rays and a theoretical interpretation of the results

An array of two spark chambers and six trays of plastic scintillation counters was used to search for unaccompanied fractionally charged particles in cosmic rays near sea level. No acceptable events were found with energy losses by ionization between 0.04 and 0.7 that of unit-charged minimum-ionizing particles. New 90%-confidence upper limits were thereby established for the fluxes of fractionally charged particles in cosmic rays, namely, (1.04 ± 0.07)x10^-10 and (2.03 ± 0.16)x10^-10 cm^-2sr^-1sec^-1 for minimum-ionizing particles with charges 1/3 and 2/3, respectively.

In order to be certain that the spark chambers could have functioned for the low levels of ionization expected from particles with small fractional charges, tests were conducted to estimate the efficiency of the chambers as they had been used in this experiment. These tests showed that the spark-chamber system with the track-selection criteria used might have been over 99% efficient for the entire range of energy losses considered.

Lower limits were then obtained for the mass of a quark by considering the above flux limits and a particular model for the production of quarks in cosmic rays. In this model, which is one involving the multi-peripheral Regge hypothesis, the production cross section and a corresponding mass limit are critically dependent on the Regge trajectory assigned to a quark. If quarks are "elementary'' with a flat trajectory, the mass of a quark can be expected to be at least 6 ± 2 BeV/c². If quarks have a trajectory with unit slope, just as the existing hadrons do, the mass of a quark might be as small as 1.3 ± 0.2 BeV/c². For a trajectory with unit slope and a mass larger than a couple of BeV/c², the production cross section may be so low that quarks might never be observed in nature.

Some central limit theorems for doubly restricted partitions

Let P_{K, L}(N) be the number of unordered partitions of a positive integer N into K or fewer positive integer parts, each part not exceeding L. A distribution of the form

Ʃ/N≤x P_K,L(N)

is considered first. For any fixed K, this distribution approaches a piecewise polynomial function as L increases to infinity. As both K and L approach infinity, this distribution is asymptotically normal. These results are proved by studying the convergence of the characteristic function.

The main result is the asymptotic behavior of P_K,K(N) itself, for certain large K and N. This is obtained by studying a contour integral of the generating function taken along the unit circle. The bulk of the estimate comes from integrating along a small arc near the point 1. Diophantine approximation is used to show that the integral along the rest of the circle is much smaller.

Computational Microscopy: Breaking the Limit of Conventional Optics

Computational imaging is flourishing thanks to the recent advancement in array photodetectors and image processing algorithms. This thesis presents Fourier ptychography, which is a computational imaging technique implemented in microscopy to break the limit of conventional optics. With the implementation of Fourier ptychography, the resolution of the imaging system can surpass the diffraction limit of the objective lens's numerical aperture; the quantitative phase information of a sample can be reconstructed from intensity-only measurements; and the aberration of a microscope system can be characterized and computationally corrected. This computational microscopy technique enhances the performance of conventional optical systems and expands the scope of their applications.