506 research outputs found
Correction: Early management of isolated severe traumatic brain injury patients in a hospital without neurosurgical capabilities: a consensus and clinical recommendations of the World Society of Emergency Surgery (WSES) (World Journal of Emergency Surgery, (2023), 18, 1, (5), 10.1186/s13017-022-00468-2)
No full textFollowing publication of the original article [1], in this article the author name Gregory W. J. Hawryluk was incorrectly written as Gregory W. J. Hawrylux. The original article has been corrected
Vernon Toilers baseball team with their 1929-1930 championship trophy
No full textB (L-R): J. Hawryluk, Frank Netzel, J. Roberts, L. Antilla, C. Ward, L. Hofeld, E. Hankey, R. Hofeld. M (L-R): E.G. Sherwood, E. Henschke, F. Henschke, C.J. Whiten (Vice-President). Front: Gordie Henschke (mascot/batboy)
Intracranial pressure: current perspectives on physiology and monitoring
No full textIntracranial pressure (ICP) monitoring is now viewed as integral to the clinical care of many life-threatening brain insults, such as severe traumatic brain injury, subarachnoid hemorrhage, and malignant stroke. It serves to warn of expanding intracranial mass lesions, to prevent or treat herniation events as well as pressure elevation which impedes nutrient delivery to the brain. It facilitates the calculation of cerebral perfusion pressure (CPP) and the estimation of cerebrovascular autoregulatory status. Despite advancements in our knowledge emanating from a half century of experience with this technology, important controversies remain related even to fundamental aspects of ICP measurements, including indications for monitoring, ICP treatment thresholds, and management of intracranial hypertension. Here, we review the history of ICP monitoring, the underlying pathophysiology as well as current perspectives on why, when and how ICP monitoring is best used. ICP is typically assessed invasively but a number of emerging, non-invasive technologies with inherently lower risk are showing promise. In selected cases, additional neuromonitoring can be used to assist in the interpretation of ICP monitoring information and adapt directed treatment accordingly. Additional efforts to expand the evidence base relevant to ICP monitoring, related technologies and management remain a high priority in neurosurgery and neurocritical care
Structural and functional characterization of the p62 complex, a subcomplex of the nuclear pore complex
No full textThe nuclear pore complex (NPC) is a highly conserved eukaryotic protein complex, which perforates
the nuclear envelope and regulates nucleocytoplasmic transport of cargos between the cytoplasm and nucleus. The structure and function of NPCs were examined in recent years by different molecular and structural biology techniques, such as immunoprecipitation, RNA interference, or electron- and fluorescence microscopy, allowing deeper insights into the molecular mechanisms underlying nucleocytoplasmic
transport. In this introduction, I will highlight recent developments in understanding the organization of four subcomplexes of the central region of the NPC, namely, the p62 complex, the Nup93 complex, the Nup107-160 complex, and the Nup155 complex as well as their impact on nucleocytoplasmic transport. In addition, I will discuss the role of these subcomplexes in cell cycle regulation and their impact
on human diseases. Furthermore, the molecular interactions between different transport receptors, cargos, and components of the NPC are described.
The nuclear pore complex (NPC) is the only known gateway for exchange of macromolecules between the cytoplasm and nucleus of eukaryotic cells. One key compound of the NPC is the p62 subcomplex,
which consists of the nucleoporins p62, p54, and p58/p45 and is supposed to be involved in nuclear protein import and export. In this study we show the localization of different domains of the p62 complex by immuno-electron microscopy using isolated nuclei from Xenopus oocytes. To determine the exact position of the p62 complex, we examined the localization of the C- and N-terminal domains of p62 by immunolabeling using domain-specific antibodies against p62. In addition, we expressed epitope-
tagged versions of p62, p54, and p58 in Xenopus oocytes and localized the domains with antibodies against the tags. This first systematic analysis of the domain topology of the p62 complex within the NPC revealed that the p62 complex is anchored to the cytoplasmic face of the NPC most likely by the coiled-coil domains of the three nucleoporins. Furthermore, we found the phenylalanine-glycine (FG)-repeat domain of p62, but not of p58 and p54, to be mobile and flexible nature.
Nuclear pore complexes (NPCs) are large protein complexes, which are embedded in the nuclear envelope (NE) and control the traffic of proteins and RNAs between the nucleus and the cytoplasm in a signal-dependent manner. Transport receptors bind cargos and interact particularly with certain nucleoporins.
Phenylalanine-glycine (FG) repeat motifs were found in about a third of the nucleoporins, functioning as a major docking site for soluble transport receptors. The p62 complex, which contains several FG repeat domains, was previously described to be involved in protein import and to interact directly with soluble transport receptors. To examine the localization of this docking site and to find out how antibodies against single components of the p62 complex influence nucleocytoplasmic transport, we performed in vitro transport assays using nucleoplasmin-GFP as cargo. This cargo was used in transport assays with digitonin-permeabilized HeLa cells, which were treated with antibodies against the p62 complex components, or was directly conjugated to colloidal gold in ultrastructural transport assays, using isolated nuclei from Xenopus oocytes. Our data suggest that antibodies against the components of the p62 complex inhibit or reduce transport of cargos through the NPC. The ultratructural transport studies revealed that the second docking site for cargo/receptor complexes is masked when p62 complex antibodies are used in the transport assay.
During the past few years, evidence accumulated that distinct nuclear pore complex proteins do not only function in the nucleocytoplasmic transport, but also in the regulation of other cellular processes, such as mitosis. To study the function of the p62-complex (i.e. p62, p54, and p58) in a cellular context, we depleted its components from HeLa cells by RNA interference, which led to an arrest in cell growth and an increase of apoptotic cells as analyzed by fluorescence activated cell sorting. In vitro transport studies of p62- and p54-depleted HeLa cells further showed that the depletion of these p62 complex components had a significant inhibitory effect on nuclear protein import. Taken together, these results indicate that the p62 complex is not only critical for mediating nuclear protein import, but also for cell growth and cell division.
To determine the location of different domains of the p62 complex within the 3D structure of the NPC, we localized the different FG-repeat and coiled-coil domains of this subcomplex with immuno-EM. Previous immuno-EM showed controversial results concerning the anchoring sites and the localization of the p62 complex within the 3D structure of the NPC. Our new data revealed that the p62 complex is anchored with its coiled-coil domains to the cytoplasmic side of the NPC and that its FG-repeat domains show differences in their flexibility and their distribution within the 3D architecture of the NPC. Thus, the FG-repeat domain of the nucleoporin p62 could be found at the cytoplasmic as well as at the nuclear
side of the NPC, whereas the FG-repeat domains of p54 and p58 were restricted to the cytoplasmic side. This might be due to different anchoring sites of the distint FG-repeat domains, the varied length of the FG-repeat domains of the complex, and differences in the biophysical behavior of the FG-repeat domains.
Recently, a complementary technique to immuno-EM was established to observe FG-repeat domains
in vitro by AFM. Lim et al. examined the biophysical behavior of the FG-repeat domain of Nup153, immobilized to a gold dot, by AFM simulating nuclear import by adding importin β.and RanGTP (Lim, Fahrenkrog et al. 2007). The immobilized FG-repeat domains formed a polymer brush with a certain height, which collapsed after addition of importin β. This collapse could be reversed after addition of RanGTP, demonstrating a new biophysical principle for nucleocytoplasmic transport. The AFM-studies were attended by immuno-EM-studies with isolated nuclei of Xenopus oocytes, which showed that, after addition of importin β, the FG-repeat domains of Nup153 collapse to their anchoring sites at the nuclear basket.
It would be interesting to use the same experimental approach equally for the different FG-repeat domains of the p62 complex in order to examine if the FG-repeat domains can form polymer brushes similar to the ones formed by the FG-repeat domains of Nup153. Beyond that, it would be worth to uncover
the anchoring sites of the FG-repeat domains of the p62 complex by immuno-EM after addition of importin β (Lim, Fahrenkrog et al. 2007). In the near future, progress in EM tomography will facilitate the localization of antibodies against certain nucleoporins without the use of gold particles, which would reveal the exact binding sites of the antibodies to structural elements of the NPC
Miss Gemmell regrets : anatomy of a PR campaign
No full textNikki Gemmel's 'outing' as the author of The Bride Stripped Bare and her subsequent fall from grace is dissected in this article
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An American Neoromantic: David Maslanka's Concerto for Clarinet and Wind Ensemble: Analysis, Insights to the Composer's Performance Intentions, and Discussion of the Commissioning Process
No full textThis examination of David Maslanka's Concerto for Clarinet and Wind Ensemble will assist in performers' preparation of the concerto through analysis of Maslanka's American Neoromantic compositional techniques, rehearsal suggestions, and firsthand insight of the composer's intent for its performance. The author will elaborate on performance practice, ensemble seating, and rehearsal suggestions that were revealed while collaborating with the composer in preparation for the premiere performance.
The author applies Walter Simmons's discussion of American Neoromanticism to understand Maslanka's compositional style. Maslanka's use of classical forms, heightened importance of rhythmic drive, and expanded functional harmony lead to the characterization of this concerto as fitting within the American Neoromantic compositional spectrum.
This study outlines the commissioning of this concerto through the process of building a consortium. The author delineates steps that may be used by other artists and educators. Through this discussion, the author provides a historical discourse on the concerto's germination.
Finally, this study provides firsthand documentation and insight to the composer's intentions for its performance. The author worked closely with Maslanka in the preparation leading to the premiere performance of the concerto
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A Tutorial on Basic Principles of Microwave Reflectometry Applied to Fluctuation Measurements in Fusion Plasmas
No full textMicrowave reflectometry is now routinely used for probing the structure of magnetohydrodynamic and turbulent fluctuations in fusion plasmas. Conditions specific to the core of tokamak plasmas, such as small amplitude of density irregularities and the uniformity of the background plasma, have enabled progress in the quantitative interpretation of reflectometer signals. In particular, the extent of applicability of the 1-D [one-dimensional] geometric optics description of the reflected field is investigated by direct comparison to 1-D full wave analysis. Significant advances in laboratory experiments are discussed which are paving the way towards a thorough understanding of this important measurement technique. Data is presented from the Tokamak Fusion Test Reactor [R. Hawryluk, Plasma Physics and Controlled Fusion 33 (1991) 1509] identifying the validity of the geometric optics description of the scattered field and demonstrating the feasibility of imaging turbulent fluctuations in fusion scale devices
Call waiting
No full textThis thesis examines the life and career of Bret Easton Ellis, and the influences of his work on the author's development as a writer. Part one encapsulates a novel written specifically for this thesis. 'Call waiting' is a harsh look at modern friendships, the role of work in these relationships and the proliferation of shallow communication through the advent of email. A critical reflection follows, examining the process that led to the novel's creation. Three specific areas are focussed on: the direct influence of Ellis' novel 'The rules of attraction' on the overall themes of 'Call waiting', the realisation of the project and the various editing changes and narrative developments that arose during the writing of the novel, and an examination of the inspiration behind the novel's creation. Part two considers Ellis' role in the literary world of the 1980s, his own complicity in the creation of a career as a celebrity author, and the carefully manufactured persona Ellis presents to the world. In Part three the thesis is concluded with a close analysis of the publication of Ellis' controversial novel 'American psycho'. This chapter explores the negative publicity the novel attracted and the possible causes of the ensuing backlash against the author
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Review of D-T Experiments Relevant to Burning Plasma Issues
No full textProgress in the performance of tokamak devices has enabled not only the production of significant bursts of fusion energy from deuterium-tritium (D-T) plasmas in the Tokamak Fusion Test Reactor (TFTR) and the Joint European Torus (JET) but, more importantly, the initial study of the physics of burning magnetically confined plasmas. The TFTR and JET, in conjunction with the worldwide fusion effort, have studied a broad range of topics including magnetohydrodynamic stability, transport, wave-particle interactions, the confinement of energetic particles, and plasma boundary interactions. The D-T experiments differ in three principal ways from previous experiments: isotope effects associated with the use of deuterium-tritium fuel, the presence of fusion-generated alpha particles, and technology issues associated with tritium handling and increased activation. The effect of deuterium-tritium fuel and the presence of alpha particles is reviewed and placed in the perspective of the much large r worldwide database using deuterium fuel and theoretical understanding. Both devices have contributed substantially to addressing the scientific and technical issues associated with burning plasmas. However, future burning plasma experiments will operate with larger ratios of alpha heating power to auxiliary power and will be able to access additional alpha-particle physics issues. The scientific opportunities for extending our understanding of burning plasmas beyond that provided by current experiments is described
Comparison of steady-state and perturbative transport coefficients in TFTR
No full textSteady-state and perturbative transport analysis are complementary techniques for the study of transport in tokamaks. These techniques are applied to the investigation of auxiliary-heated L-mode and supershot plasmas in the tokamak fusion test reactor (TFTR) [R. J. Hawryluk et al., Plasma Physics and Controlled Nuclear Fusion Research, Proceedings of the 11th International Conference, Kyoto, 1986 (IAEA, Vienna, 1987), Vol. 1, p. 51.]. In the L mode, both steady-state and perturbative transport measurements reveal a strong temperature dependence that is consistent with electrostatic microinstability theory and the degradation of confinement with neutral beam power. Steady-state analysis of the ion heat and momentum balance in supershots indicates a reduction and a significant weakening of the power-law dependence on the transport in the center of the discharge. © 1991 American Institute of Physics
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