293 research outputs found
Receipt for medical services, To: Patrick Barry Hayes, From: Dr. Cornelius Boyle, January 1861.
No full textThe Use of Virtual Reality for Surgical Guidance in a Two-Staged Combined Petrosal Approach for Resection of a Petroclival Meningioma: A Case Report
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Extreme Far Lateral Approach for the Resection of the C1 Transverse Process to Relieve Symptomatic Jugular Stenosis
No full textComputational Modeling of the DYW-Deaminase Domain Supports a Zinc-Dependent Deamination Mechanism and Structural Similarities for Related Variants Linked U-to-C Editing
No full textRNA editing changes the primary sequence of many RNAs post-transcriptionally and is a form of mRNA processing utilized by most eukaryotes. Eukaryotes possess a variety of RNA editing enzymes, and typically rely on irreversible hydrolytic deamination mechanisms to convert cytidine to uridine (C-to-U) and adenosine to inosine (A-to-I). C-to-U RNA editing, while present in humans, is pervasive in the organelles of most land plants. Some ferns and nonvascular plants also perform site specific U-to-C editing, but the catalytic mechanism is not known. Plants and protists utilize nuclear-encoded PPR proteins that bind with high specificity to their RNA targets. A C-terminal DYW-deaminase motif that is present at the C-terminus of many PPR editing factors functions as the catalyst for C-to-U deamination. Confounding early biochemical analysis, several recombinant proteins with DYW domains catalyzed ribonuclease cleavage, the catalytic mechanism or native function for the hydrolysis of the sugar phosphate backbone is unresolved. A variant of the DYW domain called the GRP domain has also recently been linked to uridine to cytidine (U-to-C) editing in hornworts through a bioinformatic analysis of the predicted binding of the PPR domains. Since zinc-dependent nucleotide deamination is thermodynamically irreversible it is unclear how the relatively small number of amino acid differences observed between the DYW and GRP domains could support the thermodynamically unfavorable U-to-C reverse editing reaction. Therefore, the DYW-deaminase and GRP-deaminase either utilize a common but hitherto unknown reversible mechanism, or the reverse editing does not occur through a direct amination mechanism. After the structure of the DYW-deaminase was solved, a curious zinc-gated shutter mechanism was projected that involved conformational changes to and from an autoinhibitory ground state and an active state. In this thesis, I have used de novo structural modeling programs and find similar RMSD values for comparisons between DYW-deaminases responsible for C-to-U RNA editing and the GRP domain linked to U-to-C editing and the solved crystal structure suggesting a common structure and catalytic mechanism. I have also explored the proposed gating mechanism in a subset of DYWs and the GRP DYW-variants from a diverse range of plant species and discovered nearly identical predicted structures. Finally, I have used molecular dynamic (MD) simulations of a DYW domain to model the thermodynamically stable active and inactive structures. The MD simulations reveal two vastly different but stable catalytic active sites. The active site of the "active" conformation has features consistent with other zinc-dependent deaminases validating the canonical view of the editing mechanism. Docking of nucleosides and putative transition state analogs support an irreversible deamination mechanism. The "inactive" conformation does not support docking of nucleosides into the canonical active site and is unlikely to support deamination of bases. The "inactive" conformation could by computationally docked with a preference for ribose toward the active site with the base flipped away. Also, MD simulations revealed a trapped hydroxide ion of unknown function when the epsilon nitrogen of the active site histidine is protonated. From the last two observations we posit a model where the DYW "inactive" conformation preferentially supports ribonuclease cleavage but not base deamination
China: Shadow WTO agricultural domestic support notifications
No full text"This paper reviews recent agricultural policy changes in China and presents estimates of domestic support for the period 1996-2005. A set of relevant alternative subsidy-definition scenarios and their effects on the calculated levels of support are analyzed, and a projection of domestic support through 2013 is presented. The paper concludes with a discussion of new WTO rules that may be negotiated in the Doha Round and their implications for China. Based on standard WTO subsidy calculation methods, our results indicated that China's domestic support for the period 1996-2005 has been well below the limits agreed at its WTO accession. The market price support (MPS) component of the aggregate measure of support (AMS) in China has been below zero, and this has dwarfed the relatively small but positive non-product specific AMS and led to a zero current total AMS after de minimis. China has no AMS commitments but can provide trade-distorting domestic support to agricultural producers up to 8.5 percent of the value of production (or RMB561 billion). Thus there appears to be substantial room for China to extend its amber box subsidy measures through heavy use of the de minimis provision. We project domestic support notifications through 2013 based on specified assumptions about domestic policies, including changes in administered prices and commodity program coverage. New rules potentially negotiated in the Doha Round are expected to provide more constraints on subsidies. Due to China's developing country status, with no AMS commitments under the Uruguay Round Agreement on Agriculture the impacts of these new constraints are shown to be limited, although our projections indicate that China may exceed its WTO commitment levels under certain price and commodity coverage scenarios." from authors' abstractAgricultural policies, WTO Doha round, WTO compliance, Notification of domestic support, China agricultural support policies, Globalization, Markets,
Down-regulation of the histone methyltransferase EZH2 contributes to the epigenetic programming of decidualizing human endometrial stromal cells
No full textDifferentiation of human endometrial stromal cells (HESC) into decidual cells represents a highly coordinated process essential for embryo implantation. We show that decidualizing HESC down-regulate the histone methyltransferase enhancer of Zeste homolog 2 (EZH2), resulting in declining levels of trimethylation of histone 3 on lysine 27 (H3K27me3) at the proximal promoters of key decidual marker genes PRL and IGFBP1. Loss of H3K27me3 was associated with a reciprocal enrichment in acetylation of the same lysine residue, indicating active remodeling from repressive to transcriptionally permissive chromatin. Chromatin immunoprecipitation coupled with DNA microarray analysis demonstrated that decidualization triggers genome-wide changes in H3K27me3 distribution that only partly overlap those observed upon EZH2 knockdown in undifferentiated HESC. Gene ontology revealed that gain of the repressive H3K27me3 mark in response to decidualization and upon EZH2 knockdown in undifferentiated cells was enriched at the promoter regions of genes involved in transcriptional regulation and growth/cell proliferation, respectively. However, loss of the H3K27me3 mark (indicating increased chromatin accessibility) in decidualizing cells and upon EZH2 knockdown occurred at selective loci enriched for genes functionally implicated in responses to stimulus. In agreement, EZH2 knockdown in undifferentiated HESC was sufficient to augment the induction of decidual marker genes in response to cyclic AMP and progesterone signaling. Thus, loss of EZH2-dependent methyltransferase activity in the endometrium is integral to the process of chromatin remodeling that enables the transition from a proliferative to a decidual phenotype in response to differentiation cues
Minimally Invasive Bilateral Duo-Keyhole Approach for Giant Falcine Meningioma: 2 Dimensional Operative Video.
No full textOne of the key concepts behind minimally invasive keyhole cranial surgery is that as the operative corridor deepens, it also widens. The corridor should therefore be designed parallel to the long-axis of the tumor to optimize visualization.1 These ideas were applied in a duo-keyhole operation for a falcine meningioma. The patient is a 79-year-old woman diagnosed with a large falcine meningioma compressing both frontal lobes. Her tumor was oriented with the long-axis, perpendicular to the superior sagittal sinus, and has bulbous extensions on both sides of the falx. Incisions on the falx, anterior and posterior to the tumor, in addition to a cut between it and the undersurface of the superior sagittal sinus, would render it practically devascularized and free-floating.2 One keyhole was insufficient, but one anterior and another posterior to the tumor would make the falcine cuts feasible. The operation was performed with the above scheme and the posterior keyhole to the left and anterior one to the right of midline to facilitate surface vascular detachment on both sides. The patient recovered well and was discharged home after 4 days. This procedure highlights that flexible application of the principles of minimally invasive keyhole. Neurosurgery can tailor-make an operation to precisely fit the unique features of a patient and the tumor. The procedure was performed under the ethical guidelines of our hospital. No Institutional Review Board consent was required or sought because the patient gave specific consent to the procedure and publication of her image
Improving Inaccuracies in Augmented Reality Neuronavigation during Anterior Petrosectomy by Recalibrating Using Fixed Bony Landmarks
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