Hydrogen Bonds, Hydrophobicity Forces and the Character of the Collapse Transition

We study the thermodynamic behavior of a model protein with 54 amino acids that is designed to form a three-helix bundle in its native state. The model contains three types of amino acids and five to six atoms per amino acid, and has the Ramachandran torsion angles as its only degrees of freedom. The force field is based on hydrogen bonds and effective hydrophobicity forces. We study how the character of the collapse transition depends on the strengths of these forces. For a suitable choice of these two parameters, it is found that the collapse transition is first-order-like and coincides with the folding transition. Also shown is that the corresponding one- and two-helix segments make less stable secondary structure than the three-helix sequence.Comment: 14 pages, 8 figure

The Securities and Exchange Commission: Its Organization and Functions Under the Securities Act of 1933

As the semidefinite programs that result from integral quadratic contstraints are usually large it is important to implement efficient algorithms. The interior-point algorithms in this paper are primal-dual potential reduction methods and handle multiple constraints. Two approaches are made. For the first approach the computational cost is dominated by a least-squares problem that has to be solved in each iteration. The least squares problem is solved using an iterative method, namely the conjugate gradient method. The computational effort for the second approach is dominated by forming a linear system of equations. This systems of equations is used to compute the search direction in each iteration. If the number of variables are reduced by solving a smaller subproblem the resulting system has a very nice structure and can be solved efficiently. The first approach is more efficient for larger problems but is not as numerically stable

Regression Estimates of Damages in Price-Fixing Cases

Semidefinite programs (SDPs) originating from the Kalman-Yakubovich-Popov lemma often have a large number of variables. Standard solvers for semidefinite programs cannot handle problems of this size. Much research has been invested in developing customized solvers for such problems. In this paper we show that it is possible to use standard primal-dual SDP solvers if we reduce the number of variables in the dual SDP. The interesting variables in the primal SDP can be recovered from the solution

Optical Tweezers for Single Molecule Biology

Molecular machinery on the micro-scale, believed to be the fundamental building blocks of life, involve forces of 1-100 pN and movements of nanometers to micrometers. Micromechanical single-molecule experiments seek to understand the physics of nucleic acids, molecular motors, and other biological systems through direct measurement of forces and displacements. Optical tweezers are a popular choice among several complementary techniques for sensitive force-spectroscopy in the field of single molecule biology. The main objective of this thesis was to design and construct an optical tweezers instrument capable of investigating the physics of molecular motors and mechanisms of protein/nucleic-acid interactions on the single-molecule level. A double-trap optical tweezers instrument incorporating acousto-optic trap-steering, two independent detection channels, and a real-time digital controller was built. A numerical simulation and a theoretical study was performed to assess the signal-to-noise ratio in a constant-force molecular motor stepping experiment. Real-time feedback control of optical tweezers was explored in three studies. Position-clamping was implemented and compared to theoretical models using both proportional and predictive control. A force-clamp was implemented and tested with a DNA-tether in presence of the enzyme lambda exonuclease. The results of the study indicate that the presented models describing signal-to-noise ratio in constant-force experiments and feedback control experiments in optical tweezers agree well with experimental data. The effective trap stiffness can be increased by an order of magnitude using the presented position-clamping method. The force-clamp can be used for constant-force experiments, and the results from a proof-of-principle experiment, in which the enzyme lambda exonuclease converts double-stranded DNA to single-stranded DNA, agree with previous research. The main objective of the thesis was thus achieved. The developed instrument and presented results on feedback control serve as a stepping stone for future contributions to the growing field of single molecule biology.Molekylära biologiska mekanismer involverar 0-100 pN krafter och rörelser från under en nanometer till flera mikrometer. Mikromekaniska experiment strävar till att förklara hur dessa mekanismer/maskiner fungerar genom direkt mätning av rörelser och krafter. Bland flera komplementära enmolekyls-tekniker är den optiska pincetten populär pga. dess höga platsresolution och lämpliga styvhet. En optisk pincett använder laserljus för att ta tag i och mäta krafter/rörelser hos dielektriska partiklar. I enmolekyls experiment binds biomolekyler kemiskt till plastbollar som hålls i pincetten och fungerar som 'handtag' till mikro-världen. Huvudmålet med denna avhandling var att utveckla och bygga ett laserpincett instrument som möjliggör enmolekyls experiment som förklarar molekylära mekanismer samt biofysiken i protein/nukleinsyra-växelverkningar. Ett laserpincett instrument med två pincetter, den ena styrbar, position/kraft mätning i båda pincetterna med hög resolution, samt en realtids kontroller byggdes. Avhandlingen består av fyra artiklar och ett sammandrag. Den första artikeln analyserar signal/brusförhållandet (SNR) i ett enmolekyls experiment. I mikro-skala påverkas det biologiska system som undersöks samt plastbollarna av värmerörelse, vilket försämrar SNR. Artikeln visar vilka förhållanden (molekylens längd, styvhet, spänning, osv.) leder till hög SNR och experiment som kan observera enskilda steg hos molekylära maskiner (steglängden varierar från 0,34 nm för t.ex. DNA-polymeras, till 36 nm för t.ex. myosin). I den andra och tredje artikeln användes realtids-kontrollern för att fixera en plastboll i pincetten, värmerörelsen till trots. Pincetten styrdes 200 000 gånger per sekund på basen av bollens mätta position. Pincettens effektiva styvhet kunde ökas ca. 10-faldigt. I den fjärde artikeln användes kontrollern för att upprätthålla en konstant 3.4 pN spänning i en DNA-molekyl. Molekylen fördes till en lösning innehållande enzymet lambda exonukleas som konverterar dubbel-strängat DNA till en-strängat. Vid 3.4 pN spänning är en-strängat DNA signifikant kortare än dubbel-strängat, och molekylens krympande från ~14 μm till ~8 μm längd observerades under ca 20 min. Detta experiment visar att huvudmålet för avhandlingen uppnåddes. Det utvecklade instrumentet lämpar sig för enmolekylsexperiment och kan användas för framtida kontributioner inom enmolekyls biofysik

Sequence-based study of two related proteins with different folding behaviors

ZSPA-1 is an engineered protein that binds to its parent, the three-helix-bundle Z domain of staphylococcal protein A. Uncomplexed ZSPA-1 shows a reduced helix content and a melting behavior that is less cooperative, compared with the wild-type Z domain. Here we show that the difference in folding behavior between these two sequences can be partly understood in terms of an off-lattice model with 5-6 atoms per amino acid and a minimalistic potential, in which folding is driven by backbone hydrogen bonding and effective hydrophobic attraction.Comment: 12 pages, 5 figure

Microsoft and the European Union Face Off Over Internet Privacy Concerns

Amidst what appears to be a multi-faceted attack by the European Union on Microsoft, the newest angle is the European Commission\u27s announcement last month that it was considering a formal investigation of Microsoft\u27s .Net Passport data processing system for possible violations of the European Union Data Privacy Directive. This iBrief explores the European Data Privacy Directive and seeks to explain why the European Commission believes .Net Passport may be in violation of its privacy policies and a case for further investigation

Medical Waste Regulation: Recommendations for Cleaning Up the Mess

In many applications, design or analysis is performed over a finite frequency range of interest. The importance of the H2/robust H2 norm highlights the necessity of computing this norm accordingly. This paper provides different methods for computing upper bounds on the robust finite-frequency H2 norm for systems with structured uncertainties. An application of the robust finite-frequency H2 norm for a comfort analysis problem of an aero-elastic model of an aircraft is also presented