Computational Investigations of Biomolecular Motions and Interactions in Genomic Maintenance and Regulation

The most critical biochemistry in an organism supports the central dogma of molecular biology: transcription of DNA to RNA and translation of RNA to peptide sequence. Proteins are then responsible for catalyzing, regulating and ensuring the fidelity of transcription and translation. At the heart of these processes lie selective biomolecular interactions and specific dynamics that are necessary for complex formation and catalytic activity. Through advanced biophysical and computational methods, it has become possible to probe these macromolecular dynamics and interactions at the molecular and atomic levels to tease out their underlying physical bases. To the end of a more thorough understanding of these physical bases, we have performed studies to probe the motions and interactions intrinsic to the function of biomolecular complexes: modeling the dual-base flipping strategy of alkylpurine glycosylase D, dynamically tracing evolution and epistasis in the 3-ketosteroid family of nuclear receptors, discovering the allosteric and conformational aspects of transcription regulation in liver receptor homologue 1, leveraging specific contacts in tyrosyl-DNA phosphodiesterase 2 for the development of novel inhibitor scaffolds, and detailing the experimentally observed connection between solvation and sequence-specific binding affinity in PU.1-DNA complexes at the atomic level. While each study seeks to solve system-specific problems, the collection outlines a general and broadly applicable description of the biophysical motivations of biochemical processes

Penetration of cefuroxime into the cerebrospinal fluid of patients with traumatic brain injury

Cefuroxime levels were measured in cerebrospinal fluid (CSF) and serum of four patients with traumatic brain injury following the implantation of intraventricular catheters. The levels ranged from 0.15 to 2.03 μg/mL in CSF and from 1.8 to 66.9 μg/mL in serum. No ventriculostomy related infections were detecte

Acrolein Dimer as a Marker for Direct Detection of Acrolein in Wine

Acrolein is highly toxic and its presence in wine has been correlated with the development of bitterness.Analytical detection and quantification in aqueous solutions are challenging due to high reactivityand problems with chemical derivative analysis. Here we demonstrate the potential of a naturalderivative, formed under conditions prevailing in wine, as a marker for acrolein detection. Solid-phasemicroextraction (SPME) coupled with gas chromatograph mass spectrometry (GC-MS) was validated asa technique for direct detection of the acrolein dimer. Conventional GC-MS analysis using a quadrupolemass spectrometer did not provide sufficient chromatographic resolution for the separation of the targetanalyte from interfering compounds. Accurate mass measurements with time-of-flight (TOF)-MS, on theother hand, allowed qualitative and quantitative measurements of the acrolein dimer. This work lays theanalytical foundation for studies on the evolution of acrolein and its dimer in solution

XML Reconstruction View Selection in XML Databases: Complexity Analysis and Approximation Scheme

Query evaluation in an XML database requires reconstructing XML subtrees rooted at nodes found by an XML query. Since XML subtree reconstruction can be expensive, one approach to improve query response time is to use reconstruction views - materialized XML subtrees of an XML document, whose nodes are frequently accessed by XML queries. For this approach to be efficient, the principal requirement is a framework for view selection. In this work, we are the first to formalize and study the problem of XML reconstruction view selection. The input is a tree $T$, in which every node $i$ has a size $c_i$ and profit $p_i$, and the size limitation $C$. The target is to find a subset of subtrees rooted at nodes $i_1,\cdots, i_k$ respectively such that $c_{i_1}+\cdots +c_{i_k}\le C$, and $p_{i_1}+\cdots +p_{i_k}$ is maximal. Furthermore, there is no overlap between any two subtrees selected in the solution. We prove that this problem is NP-hard and present a fully polynomial-time approximation scheme (FPTAS) as a solution

Carbon partitioning and export in transgenic Arabidopsis thaliana with altered capacity for sucrose synthesis grown at low temperature: a role for metabolite transporters

We investigated the role of metabolite transporters in cold acclimation by comparing the responses of wild-type (WT) Arabidopsis thaliana (Heynh.) with that of transgenic plants over-expressing sucrose-phosphate synthase (SPSox) or with that of antisense repression of cytosolic fructose-1,6-bisphosphatase (FBPas). Plants were grown at 23 degrees C and then shifted to 5 degrees C. We compared the leaves shifted to 5 degrees C for 3 and 10 d with new leaves that developed at 5 degrees C with control leaves on plants at 23 degrees C. At 23 degrees C, ectopic expression of SPS resulted in 30% more carbon being fixed per day and an increase in sucrose export from source leaves. This increase in fixation and export was supported by increased expression of the plastidic triose-phosphate transporter AtTPT and, to a lesser extent, the high-affinity Suc transporter AtSUC1. The improved photosynthetic performance of the SPSox plants was maintained after they were shifted to 5 degrees C and this was associated with further increases in AtSUC1 expression but with a strong repression of AtTPT mRNA abundance. Similar responses were shown by WT plants during acclimation to low temperature and this response was attenuated in the low sucrose producing FBPas plants. These data suggest that a key element in recovering flux through carbohydrate metabolism in the cold is to control the partitioning of metabolites between the chloroplast and the cytosol, and Arabidopsis modulates the expression of AtTPT to maintain balanced carbon flow. Arabidopsis also up-regulates the expression of AtSUC1, and to lesser extent AtSUC2, as down-stream components facilitate sucrose transport in leaves that develop at low temperatures.info:eu-repo/semantics/publishedVersio

Intermanifold similarities in partial photoionization cross sections of helium

Using the eigenchannel R-matrix method we calculate partial photoionization cross sections from the ground state of the helium atom for incident photon energies up to the N=9 manifold. The wide energy range covered by our calculations permits a thorough investigation of general patterns in the cross sections which were first discussed by Menzel and co-workers [Phys. Rev. A {\bf 54}, 2080 (1996)]. The existence of these patterns can easily be understood in terms of propensity rules for autoionization. As the photon energy is increased the regular patterns are locally interrupted by perturber states until they fade out indicating the progressive break-down of the propensity rules and the underlying approximate quantum numbers. We demonstrate that the destructive influence of isolated perturbers can be compensated with an energy-dependent quantum defect.Comment: 10 pages, 10 figures, replacement with some typos correcte

Phallus glutinolens

Phallus glutinolens is a species endemic to Brazil, occurring in fragments of Atlantic Forest in southern and southeastern regions. Up to now, there are only a few records of the species from six different sites. The total population is estimated at around 4,800 mature individuals, in one subpopulation. Based on the habitat decline within the area, we suspect a population decline around 10% in the last three generations (20 years). Phallus glutinolens is, therefore, assessed as Vulnerable C2a(ii).Fil: Trierveiler Pereira, Larissa. Universidade de Sao Paulo; BrasilFil: Vieira de Miranda, M.. Universidade de Sao Paulo; BrasilFil: Hernández Caffot, María Luciana. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Baltazar, J. M.. Universidade Federal do São Carlos; BrasilFil: Martins da Cuña, K.. Universidade Federal do Rio Grande do Sul; BrasilFil: Alves Silva, G.. Universidade de Sao Paulo; BrasilFil: Kossmann, T.. Universidade Federal de Santa Catarina; BrasilFil: Palacio, M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Drechsler Santos, E. R.. Universidade Federal de Santa Catarina; Brasi

Accurate ab initio spin densities

We present an approach for the calculation of spin density distributions for molecules that require very large active spaces for a qualitatively correct description of their electronic structure. Our approach is based on the density-matrix renormalization group (DMRG) algorithm to calculate the spin density matrix elements as basic quantity for the spatially resolved spin density distribution. The spin density matrix elements are directly determined from the second-quantized elementary operators optimized by the DMRG algorithm. As an analytic convergence criterion for the spin density distribution, we employ our recently developed sampling-reconstruction scheme [J. Chem. Phys. 2011, 134, 224101] to build an accurate complete-active-space configuration-interaction (CASCI) wave function from the optimized matrix product states. The spin density matrix elements can then also be determined as an expectation value employing the reconstructed wave function expansion. Furthermore, the explicit reconstruction of a CASCI-type wave function provides insights into chemically interesting features of the molecule under study such as the distribution of $\alpha$- and $\beta$-electrons in terms of Slater determinants, CI coefficients, and natural orbitals. The methodology is applied to an iron nitrosyl complex which we have identified as a challenging system for standard approaches [J. Chem. Theory Comput. 2011, 7, 2740].Comment: 37 pages, 13 figure

Threshold Laws for the Break-up of Atomic Particles into Several Charged Fragments

The processes with three or more charged particles in the final state exhibit particular threshold behavior, as inferred by the famous Wannier law for (2e + ion) system. We formulate a general solution which determines the threshold behavior of the cross section for multiple fragmentation. Applications to several systems of particular importance with three, four and five leptons (electrons and positrons) in the field of charged core; and two pairs of identical particles with opposite charges are presented. New threshold exponents for these systems are predicted, while some previously suggested threshold laws are revised.Comment: 40 pages, Revtex, scheduled for the July issue of Phys.Rev.A (1998