From Solution Into the Gas Phase: Studying Protein Hydrogen Exchange and Electrospray Ionization Using Molecular Dynamics Simulation

Here, we apply Molecular Dynamics (MD) simulations to investigate fundamental aspects of structural mass spectrometry (MS). We first examine microscopic phenomena underlying Hydrogen/Deuterium exchange (HDX). HDX interrogates structural dynamics of proteins by measuring the rate of Deuterium uptake into backbone amides. We perform microsecond MD simulations on ubiquitin to investigate this process. We find that HDX protection often cannot be explained by H‑bonding or solvent accessibility considerations. These findings caution against non-critical use of HDX data in structural contexts. We next use MD to examine the Electrospray ionization (ESI) mechanism of proteins. ESI is a soft ionization technique resulting in the production of gaseous protein ions. The mechanism of ion formation from nanometer sized droplets is unclear. We apply a trajectory stitching MD approach to simulate protein-containing nanodroplets, finding that natively‑folded proteins remain solvated as droplets shrink. Residual charge carriers remain following desolvation, consistent with Dole’s charged residue model

A clinical and pathological study of genito-urinary tuberculosis

A brief note has been given of the earlier work on genito-urinary tuberculosis and its diagnosis by specialised methods.The etiology and pathology of the disease has been discussed at some length. It is maintained that only by an accurate knowledge of the genesis of tuberculosis can we hope to be successful in our treatment.The clinical manifestations described are based on personal observations made over a period of twenty-six years. Recent methods of diagnosis are mentioned.A brief outline is given of treatment particularly in regard to the giving of tuberculin, and a plea is put forward for its more extensive use in the disease. The relationship of surgery to genito-urinary tuberculosis is discussed

The baboon endogenous virus genome. II. Provirus sequence variations in baboon cell DNA

Restriction analysis of the approximately 100 integrated baboon endogenous virus (BaEV) proviruses in baboon cells and tissues has revealed two major sequence variations, both in the gag gene region of the genome. One, a 150 nucleotide pair insert, is present in a small proportion of the proviral DNAs of some baboons, but is present in the majority of the proviral DNAs of other baboons. The second, a Bam HI recognition sequence located 2.25 kb from the proviral 5' end, is missing or modified in approximately one-half of the integrated genomes. We consider the possibility that accumulation of proviruses not containing the 0.15 kb insert is correlated with viral activation and expression since it is this form that is a replication intermediate in freshly infected permissive cells. It is evident from these initial studies that the organization of the multiple BaEV proviruses in baboon DNA has undergone modification during evolution

Federal Environmental Law in the \u27New Federalism\u27 Era

As we wrote last year, the U.S. Supreme Court has shown considerable interest during the past decade in reconsidering many constitutional doctrines regarding federalism and congressional power. In a series of important decisions, always decided with the same five justices in the majority, the Court has begun to redefine the federal-state relationship and the scope of federal authority. The past term generally continued that trend, with one important commerce power decision, one significant Eleventh Amendment/Fourteenth Amendment decision, and a number of decisions that involve or affect federalism and the scope of federal power, although the Court sometimes relied on statutory interpretation to avoid serious constitutional issues. Part I of this article describes the most recent decisions

Federal Environmental Law in the \u27New Federalism\u27 Era

As we wrote last year, the U.S. Supreme Court has shown considerable interest during the past decade in reconsidering many constitutional doctrines regarding federalism and congressional power. In a series of important decisions, always decided with the same five justices in the majority, the Court has begun to redefine the federal-state relationship and the scope of federal authority. The past term generally continued that trend, with one important commerce power decision, one significant Eleventh Amendment/Fourteenth Amendment decision, and a number of decisions that involve or affect federalism and the scope of federal power, although the Court sometimes relied on statutory interpretation to avoid serious constitutional issues. Part I of this article describes the most recent decisions

State Liability for Environmental Violations: The U.S. Supreme Court’s \u27New\u27 Federalism

This article examines whether the Supreme Court’s decisions in Alden v. Maine, College Savings Bank v. Florida Prepaid Postsecondary Education Expense Board, and Florida Prepaid Postsecondary Education Expense Board v. College Savings Bank, restrict the ability of Congress to regulate state compliance with federal environmental statutes. The article discusses the various enforcement mechanisms identified in Alden v. Maine and that remain valid, notwithstanding any Eleventh Amendment or constitutional immunity the States may retain. The article concludes that the Supreme Court’s federalism decisions will likely have limited practical impact upon Congress’ authority to enact and ensure the enforcement of environmental statutes

Distributionally Robust Model Predictive Control: Closed-loop Guarantees and Scalable Algorithms

We establish a collection of closed-loop guarantees and propose a scalable, Newton-type optimization algorithm for distributionally robust model predictive control (DRMPC) applied to linear systems, zero-mean disturbances, convex constraints, and quadratic costs. Via standard assumptions for the terminal cost and constraint, we establish distribtionally robust long-term and stage-wise performance guarantees for the closed-loop system. We further demonstrate that a common choice of the terminal cost, i.e., as the solution to the discrete-algebraic Riccati equation, renders the origin input-to-state stable for the closed-loop system. This choice of the terminal cost also ensures that the exact long-term performance of the closed-loop system is independent of the choice of ambiguity set the for DRMPC formulation. Thus, we establish conditions under which DRMPC does not provide a long-term performance benefit relative to stochastic MPC (SMPC). To solve the proposed DRMPC optimization problem, we propose a Newton-type algorithm that empirically achieves superlinear convergence by solving a quadratic program at each iteration and guarantees the feasibility of each iterate. We demonstrate the implications of the closed-loop guarantees and the scalability of the proposed algorithm via two examples.Comment: 34 pages, 6 figure

The Australian Barrineans and Their Relationship to Southeast Asian Negritos: An Investigation using Mitochondrial Genomics

The existence of a short-statured Aboriginal population in the Far North Queensland (FNQ) rainforest zone of Australia’s northeast coast and Tasmania has long been an enigma in Australian anthropology. Based on their reduced stature and associated morphological traits such as tightly curled hair, Birdsell and Tindale proposed that these Barrinean peoples were closely related to negrito peoples of Southeast Asia and that their ancestors had been the original Pleistocene settlers of Sahul, eventually displaced by taller invaders. Subsequent craniometric and blood protein studies, however, have suggested an overall homogeneity of indigenous Australians, including Barrineans. To confirm this finding and determine the degree of relatedness between Barrinean people and Southeast Asian negritos, we compared indigenous Australian mitochondrial DNA (mtDNA) sequences in populations from the FNQ rainforest ecozone and Tasmania with sequences from other Australian Aboriginal populations and from Southeast Asian negrito populations (Philippines Batek and Mamanwa, and mainland Southeast Asian Jahai, Mendriq, and Batak). The results confirm that FNQ and Tasmanian mtDNA haplogroups cluster with those of other Australian Aboriginal populations and are only very distantly related to Southeast Asian negrito haplogroups

Baboon endogenous virus genome: Molecular cloning and structural characterization of nondefective viral genomes from DNA of a baboon cell strain

Several heterogeneities in the baboon endogenous virus (BaEV) genomes that are present in the DNA of normal baboon tissues and the baboon cell strain BEF-3 have been described previously. To study these genomes, we cloned BaEV proviruses from BEF-3 cellular DNA into the vector Charon 4A. Of the four full-length clones isolated, one was nondefective as determined by transfection. The sequence of a portion of this clone was found to code for amino acids 61-91 in the p30 region of the gag gene. This identification allowed us to align the restriction map with the BaEV genetic map. One heterogeneity, a BamHI site 2.4 kilobases (kb) from the proviral 5' end, was located close to the gag-pol junction; another, a BamHI site 1.4 kb from the 5' end of the genome, corresponded to the gag p30 coding sequence for amino acids 32-34; and a third, a Xho I site, was near the 3' end of the pol gene. To select the nondefective BaEV genomes from BEF-3 cells, we infected permissive cells with virus produced by BEF-3 cells and also transfected BEF-3 cellular DNA into permissive cells. The BaEV genomes in the permissive recipient cultures were then analyzed by restriction enzyme analysis. These nondefective genomes were found to be heterogeneous with respect to the gag-pol BamHI site and the Xho I site, but all were found to contain the BamHI site 1.4 kb from the 5' end of the genome