Minimally Invasive Mitral Valve Surgery II: Surgical Technique and Postoperative Management.

Techniques for minimally invasive mitral valve repair and replacement continue to evolve. This expert opinion, the second of a 3-part series, outlines current best practices for nonrobotic, minimally invasive mitral valve procedures, and for postoperative care after minimally invasive mitral valve surgery

Management of Forehead Scars

This article provides an overview of scar management within the forehead region. It addresses the unique challenges specific to the treatment of forehead wounds. A logical, stepwise approach is used. A subsite based treatment algorithm is provided along with a review of current best practices. Pertinent case examples are included for demonstration purposes

A Biochemical Approach to Characterize a Divergent Trypanosoma brucei Mitochondrial DNA Polymerase, POLIB

Trypanosoma brucei is a single-celled parasitic protist that causes African sleeping sickness in people and nagana in cattle in sub-Saharan Africa. T. brucei and related trypanosomatid parasites contain an unusual catenated mitochondrial genome known as kinetoplast DNA (kDNA) composed of dozens of 23 kb maxicircles and thousands of 1 kb minicircles. The kDNA structure and replication mechanism are divergent from other eukaryotes and essential for parasite survival. POLIB is one of three Family A DNA polymerases that are independently essential to maintain the kDNA network, and has been implicated in minicircle replication. However, the division of labor among the paralogs, particularly which might be a replicative, proofreading enzyme remains enigmatic. De novo modelling of POLIB suggested a structure that is divergent from all other Family A polymerases in which the thumb subdomain contains a 369 amino acid insertion with homology to DEDDh DnaQ family 3\u27-5\u27 exonucleases. In chapter 2, we explore the polymerase and exonuclease activity of POLIB using purified his-tagged v recombinant variants that have been truncated and codon optimized for expression in E. coli. Using this recombinant protein variants we demonstrated that the 3\u27-5\u27 exonuclease activity of recombinant POLIB prefers DNA vs. RNA substrates and prefers singlestranded vs. double-stranded substrates. POLIB exonuclease activity prevails over polymerase activity on DNA substrates at pH 8.0, while DNA primer extension is favored at pH 6.0. Mutations that ablate POLIB polymerase activity slow the exonuclease rate suggesting crosstalk between the domains. We show that POLIB extends an RNA primer more efficiently than a DNA primer in the presence of dNTPs but does not incorporate rNTPs efficiently using either RNA or DNA primers. Immunoprecipitation of Pol I-like paralogs from T. brucei corroborate the pH selectivity and RNA primer preferences of POLIB and revealed that the other paralogs efficiently extend a DNA primer. We also show that overexpression of the exonuclease-ablated variant of POLIB in T. brucei results in a loss of fitness and impacts kDNA replication. We postulate that this unique enzyme and the machinery associated with it in the process of kDNA replication could be excellent drug targets worthy of further study

Single top-quark production by strong and electroweak supersymmetric flavor-changing interactions at the LHC

(Abridged) We report on a complete study of the single top-quark production by direct supersymmetric flavor-changing neutral-current (FCNC) processes at the LHC. The total cross section for pp(gg)->t\bar{c}+\bar{t}c is computed at the 1-loop order within the unconstrained Minimal Supersymmetric Standard Model (MSSM). The present study extends the results of the supersymmetric strong effects (SUSY-QCD), which were advanced by some of us in a previous work, and includes the computation of the full supersymmetric electroweak corrections (SUSY-EW). Our analysis of pp(gg)->t\bar{c}+\bar{t}c in the MSSM has been performed in correspondence with the stringent low-energy constraints from b->s gamma. In the most favorable scenarios, the SUSY-QCD contribution can give rise to production rates of around 10^5 events per 100 fb^{-1} of integrated luminosity. Furthermore, we show that there exist regions of the MSSM parameter space where the SUSY-EW correction becomes sizeable. In the SUSY-EW favored regions, one obtains lower, but still appreciable, event production rates that can reach the 10^3 level for the same range of integrated luminosity. We study also the possible reduction in the maximum event rate obtained from the full MSSM contribution if we additionally include the constraints from B^0_s-\bar{B}^0_s. In view of the fact that the FCNC production of heavy quark pairs of different flavors is extremely suppressed in the SM, the detection of a significant number of these events could lead to evidence of new physics -- of likely supersymmetric origin.Comment: LaTex, 35 pages, typos corrected. Version accepted in JHE

Variational Methods for Biomolecular Modeling

Structure, function and dynamics of many biomolecular systems can be characterized by the energetic variational principle and the corresponding systems of partial differential equations (PDEs). This principle allows us to focus on the identification of essential energetic components, the optimal parametrization of energies, and the efficient computational implementation of energy variation or minimization. Given the fact that complex biomolecular systems are structurally non-uniform and their interactions occur through contact interfaces, their free energies are associated with various interfaces as well, such as solute-solvent interface, molecular binding interface, lipid domain interface, and membrane surfaces. This fact motivates the inclusion of interface geometry, particular its curvatures, to the parametrization of free energies. Applications of such interface geometry based energetic variational principles are illustrated through three concrete topics: the multiscale modeling of biomolecular electrostatics and solvation that includes the curvature energy of the molecular surface, the formation of microdomains on lipid membrane due to the geometric and molecular mechanics at the lipid interface, and the mean curvature driven protein localization on membrane surfaces. By further implicitly representing the interface using a phase field function over the entire domain, one can simulate the dynamics of the interface and the corresponding energy variation by evolving the phase field function, achieving significant reduction of the number of degrees of freedom and computational complexity. Strategies for improving the efficiency of computational implementations and for extending applications to coarse-graining or multiscale molecular simulations are outlined.Comment: 36 page

Electromigration modeling and layout optimization for advanced VLSI

textElectromigration (EM) is a critical problem for interconnect reliability in advanced VLSI design. Because EM is a strong function of current density, a smaller cross-sectional area of interconnects can degrade the EM-related lifetime of IC, which is expected to become more severe in future technology nodes. Moreover, as EM is governed by various factors such as temperature, material property, geometrical shape, and mechanical stress, different interconnect structures can have distinct EM issues and solutions to mitigate them. For example, one of the most prominent technologies, die stacking technology of three-dimensional (3D) ICs, can have different EM problems from that of planer ICs, due to their unique interconnects such as through-silicon vias (TSVs). This dissertation investigates EM in various interconnect structures, and applies the EM models to optimize IC layout. First, modeling of EM is developed for chip-level interconnects, such as wires, local vias, TSVs, and multi-scale vias (MSVs). Based on the models, fast and accurate EM-prediction methods are proposed for the chip-level designs. After that, by utilizing the EM-prediction methods, the layout optimization methods are suggested, such as EM-aware routing for 3D ICs and EM-aware redundant via insertion for the future technology nodes in VLSI. Experimental results show that the proposed EM modeling approaches enable fast and accurate EM evaluation for chip design, and the EM-aware layout optimization methods improve EM-robustness of advanced VLSI designs.Electrical and Computer Engineerin

Knock-in of Human BACE1 Cleaves Murine APP and Reiterates Alzheimer-like PhenoTypes

Footnotes We thank Roemex and the College for Life Science and Medicine at the University of Aberdeen for their generous support. The authors declare no competing financial interests.Peer reviewedPublisher PD