The Jackprot Simulation Couples Mutation Rate with Natural Selection to Illustrate How Protein Evolution Is Not Random

Protein evolution is not a random process. Views which attribute randomness to molecular change, deleterious nature to single-gene mutations, insufficient geological time, or population size for molecular improvements to occur, or invoke “design creationism” to account for complexity in molecular structures and biological processes, are unfounded. Scientific evidence suggests that natural selection tinkers with molecular improvements by retaining adaptive peptide sequence. We used slot-machine probabilities and ion channels to show biological directionality on molecular change. Because ion channels reside in the lipid bilayer of cell membranes, their residue location must be in balance with the membrane’s hydrophobic/philic nature; a selective “pore” for ion passage is located within the hydrophobic region. We contrasted the random generation of DNA sequence for KcsA, a bacterial two-transmembrane-domain (2TM) potassium channel, from Streptomyces lividans, with an under-selection scenario, the “jackprot,” which predicted much faster evolution than by chance. We wrote a computer program in JAVA APPLET version 1.0 and designed an online interface, The Jackprot Simulation http://faculty.rwu.edu/cbai/JackprotSimulation.htm, to model a numerical interaction between mutation rate and natural selection during a scenario of polypeptide evolution. Winning the “jackprot,” or highest-fitness complete-peptide sequence, required cumulative smaller “wins” (rewarded by selection) at the first, second, and third positions in each of the 161 KcsA codons (“jackdons” that led to “jackacids” that led to the “jackprot”). The “jackprot” is a didactic tool to demonstrate how mutation rate coupled with natural selection suffices to explain the evolution of specialized proteins, such as the complex six-transmembrane (6TM) domain potassium, sodium, or calcium channels. Ancestral DNA sequences coding for 2TM-like proteins underwent nucleotide “edition” and gene duplications to generate the 6TMs. Ion channels are essential to the physiology of neurons, ganglia, and brains, and were crucial to the evolutionary advent of consciousness. The Jackprot Simulation illustrates in a computer model that evolution is not and cannot be a random process as conceived by design creationists

Expression of human soluble tumor necrosis factor (TNF)-related apoptosis-inducing ligand in transplastomic tobacco

The soluble extracellular domain of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (sTRAIL) can, as the whole length TRAIL protein, bind with its receptors and specifically induce the apoptosis of cancer cells; therefore, it has been developed as a potential therapeutic agent for various cancer treatments. As it has become an attractive technology for foreign protein production, especially for production of biopharmaceuticals, chloroplast engineering was applied in this study to express human sTRAIL protein in tobacco. Two transplastomic lines were obtained. Southern blot showed that sTRAIL gene was inserted into the right site of the tobacco chloroplast genome. RT-PCR results also confirmed that the foreign gene is transcribed in both lines. However, western blot showed that only one line accumulated sTRAIL protein stably, while the other line lost the ability to accumulate this protein after several rounds of subcultures. The possible reason for this unexpected phenomenon is discussed.Key words: Chloroplast transformation, sTRAIL, pharmaceutical protein, expression, tobacco chloroplast

Corporate Acquisitions and Firm-level Uncertainty: Domestic versus Cross-Border Deals

This paper studies the impact of corporate acquisitions on the uncertainty faced by acquiring firms. We use data for UK public companies from 2004 to 2017 and employ a matching estimator combined with difference-in-differences to control for the endogenous selection of firms into acquiring status. Acquisitions exert a large and persistent effect on the volatility of stock returns of acquirers and is characterized by a pecking order: domestic takeovers lead to a reduction in the uncertainty faced by the acquirer, while cross-border acquisitions|particularly those involving target firms in emerging markets|engender a positive response in acquirers' volatility

Quadratic ideals and Rogers–Ramanujan recursions

We give an explicit recursive description of the Hilbert series and Gröbner bases for the family of quadratic ideals defining the jet schemes of a double point. We relate these recursions to the Rogers–Ramanujan identity and prove a conjecture of the second author, Oblomkov and Rasmussen

On the Quantum Chromodynamics of a Massive Vector Field in the Adjoint Representation

In this paper, we explore the possibility of constructing the quantum chromodynamics of a massive color-octet vector field without introducing higher structures like extended gauge symmetries, extra dimensions or scalar fields. We show that gauge invariance is not enough to constraint the couplings. Nevertheless the requirement of unitarity fixes the values of the coupling constants, which otherwise would be arbitrary. Additionally, it opens a new discrete symmetry which makes the coloron stable and avoid its resonant production at a collider. On the other hand, a judicious definition of the gauge fixing terms modifies the propagator of the massive field making it well-behaved in the ultra-violet limit. The relation between our model and the more general approach based on extended gauge symmetries is also discussed.Comment: Subsection 2.1 rewritten in order to make it more pedagogical. This version match the text accepted in IJMP

Correcting for Motion between Acquisitions in Diffusion MR Imaging

The diffusion tensor (DT) and other diffusion models assume that each voxel corresponds to the same anatomical location in all the measurements. Movements and distortions violate this assumption and typically the images are realigned before model fitting. We propose a set of model-based methods to improve motion correction and avoid the errors that the traditional method introduces. The new methods are based on a three-step procedure to register DWI datasets, and use different reference images for DWIs with different gradient directions for registration, so the registrations take into account the contrast differences of measurements. Performance of the model-based registration techniques depends critically on outlier rejection. We develop new methods for fitting the diffusion tensor to diffusion MRI measurements in the presence of outliers by drawing on the RANSAC algorithm from computer vision. We compareone popularly used outlier rejection method RESTORE in the diffusion MRI literature with our new method. Then, we combine outlier rejection methods with model-based registration schemes, and compare the performance of motion correction with other methods. After aligning the dataset, we also update diffusion gradients for the registered datasets from both traditional and our methods, according to the transformations used in registrations. We develop and discuss a variety of registration evaluation methods using both synthetic and human-brain diffusion MRI datasets. Experiments demonstrate both quantitative and qualitative improvements using our new model-based methods