The Challenge of Pulmonary Emphysema

I feel very privileged to be invited to be your Stoneburner Lecturer for this year. When I came to consider what I really wanted to say and what might interest people in widely different areas of medicine, there really was little choice. I perhaps can claim to be able to talk about emphysema from a rather broad standpoint than some other physicians. Not because I suffer from it, which is sometimes a good reason for talking about a disease, but because I have been trained both in England and in America, and the outlook on this disease has differed in Europe and in the States

The Modern Treatment of Respiratory Failure

I suppose it is appropriate that we come to respiratory failure at the end of a longish day. The definition of respiratory failure has an interesting history. Barcroft, 30 to 40 years ago, understood respiratory failure as a tissue phenomenon. He would have described cyanide poisoning to you as an example of respiratory failure. Ventilatory failure came into fashion but is not a very good term because total ventilation may be fine but gas exchange may be very poor. Europeans have invented various terms like global insufficiency, which sounds very impressive in German, but always sounds to me more like a term from the Pentagon than a medical or physiological definition. I prefer to use the term respiratory failure to mean everything related to disordered gas tensions; but if you attempt a precise definition, you run into unexpected difficulties

Toroidal Vortices in Resistive Magnetohydrodynamic Equilibria

Resistive steady states in toroidal magnetohydrodynamics (MHD), where Ohm's law must be taken into account, differ considerably from ideal ones. Only for special (and probably unphysical) resistivity profiles can the Lorentz force, in the static force-balance equation, be expressed as the gradient of a scalar and thus cancel the gradient of a scalar pressure. In general, the Lorentz force has a curl directed so as to generate toroidal vorticity. Here, we calculate, for a collisional, highly viscous magnetofluid, the flows that are required for an axisymmetric toroidal steady state, assuming uniform scalar resistivity and viscosity. The flows originate from paired toroidal vortices (in what might be called a ``double smoke ring'' configuration), and are thought likely to be ubiquitous in the interior of toroidally driven magnetofluids of this type. The existence of such vortices is conjectured to characterize magnetofluids beyond the high-viscosity limit in which they are readily calculable.Comment: 17 pages, 4 figure

Strong Shift Equivalence of C∗C^*-correspondences

We define a notion of strong shift equivalence for $C^*$-correspondences and show that strong shift equivalent $C^*$-correspondences have strongly Morita equivalent Cuntz-Pimsner algebras. Our analysis extends the fact that strong shift equivalent square matrices with non-negative integer entries give stably isomorphic Cuntz-Krieger algebras.Comment: 26 pages. Final version to appear in Israel Journal of Mathematic

Two Centered Black Holes and N=4 Dyon Spectrum

The exact spectrum of dyons in a class of N=4 supersymmetric string theories is known to change discontinuously across walls of marginal stability. We show that the change in the degeneracy across the walls of marginal stability can be accounted for precisely by the entropy of two centered small black holes which disappear as we cross the walls of marginal stability.Comment: LaTeX file, 12 pages; v3: added footnote 2 regarding overall sign of the index, expanded footnote 3, added reference

The p68 and p72 DEAD box RNA helicases interact with HDAC1 and repress transcription in a promoter-specific manner

BACKGROUND: p68 (Ddx5) and p72 (Ddx17) are highly related members of the DEAD box family and are established RNA helicases. They have been implicated in growth regulation and have been shown to be involved in both pre-mRNA and pre-rRNA processing. More recently, however, these proteins have been reported to act as transcriptional co-activators for estrogen-receptor alpha (ERα). Furthermore these proteins were shown to interact with co-activators p300/CBP and the RNA polymerase II holoenzyme. Taken together these reports suggest a role for p68 and p72 in transcriptional activation. RESULTS: In this report we show that p68 and p72 can, in some contexts, act as transcriptional repressors. Targeting of p68 or p72 to constitutive promoters leads to repression of transcription; this repression is promoter-specific. Moreover both p68 and p72 associate with histone deacetylase 1 (HDAC1), a well-established transcriptional repression protein. CONCLUSIONS: It is therefore clear that p68 and p72 are important transcriptional regulators, functioning as co-activators and/or co-repressors depending on the context of the promoter and the transcriptional complex in which they exist

Activation of Notch signalling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway

© 2019 the American Physiological Society. The Notch ligand delta-like ligand 4 (Dll4), upregulated by VEGF, is a key regulator of vessel morphogenesis and function, controlling tip and stalk cell selection during sprouting angiogenesis. Inhibition of Dll4 results in hypersprouting, nonfunctional, poorly perfused vessels, suggesting a role for Dll4 in the formation of mature, reactive, functional vessels, with low permeability and able to restrict fluid and solute exchange. We tested the hypothesis that Dll4 controls transvascular fluid exchange. A recombinant protein expressing only the extracellular portion of Dll4 [soluble Dll4 (sDll4)] induced Notch signaling in endothelial cells (ECs), resulting in increased expression of vascular-endothelial cadherin, but not the tight junctional protein zonula occludens 1, at intercellular junctions. sDll4 decreased the permeability of FITC-labeled albumin across EC monolayers, and this effect was abrogated by coculture with the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester. One of the known molecular effectors responsible for strengthening EC-EC contacts is PKA, so we tested the effect of modulation of PKA on the sDll4-mediated reduction of permeability. Inhibition of PKA reversed the sDll4-mediated reduction in permeability and reduced expression of the Notch target gene Hey1. Knockdown of PKA reduced sDLL4-mediated vascular-endothelial cadherin junctional expression. sDll4 also caused a significant decrease in the hydraulic conductivity of rat mesenteric microvessels in vivo. This reduction was abolished upon coperfusion with the PKA inhibitor H89 dihydrochloride. These results indicate that Dll4 signaling through Notch activation acts through a cAMP/PKA pathway upon intercellular adherens junctions, but not tight junctions, to regulate endothelial barrier function. NEW & NOTEWORTHY Notch signaling reduces vascular permeability through stimulation of cAMP-dependent protein kinase A

The development of sentence-interpretation strategies in monolingual German-learning children with and without specific language impairment

Previous research on sentence comprehension conducted with German-learning children has concentrated on the role of case marking and word order in typically developing children. This paper compares, the performance of German-learning children with language impairment (age 4-6 years) and without language impairment (aged 2-6, 8-9 years) in two experiments that systematically vary the cues animacy, case marking; word-order, and subject-verb agreement. The two experiments differ with regard to the choice of case marking: in the first it is distinct but in the second it is neutralized. The theoretical framework is the competition model developed by Bates and Mac Whinney and their collaborators, a variant of the parallel distributed processing models. It is hypothesized that children of either population first appreciate the cue animacy that can be processed locally, that is, "on the spot," before they turn to more distributed cues leading ultimately up to subject-verb agreement, which presupposes the comparison of various constituents before an interpretation can be established. Thus agreement is more "costly" in processing than animacy or the (more) local cue initial NP. In experiment I with unambiguous case markers it is shown that the typically developing children proceed from animacy to the nominative (predominantly in coalition with the initial NP) to agreement, while in the second experiment with ambiguous case markers these children turn from animacy to the initial NP and then to agreement. The impaired children also progress from local to distributed cues. Yet, in contrast to the control group, they do not acknowledge the nominative in coalition with the initial NP in the first experiment but only in support of agreement. However, although they do not seem to appreciate distinct case markers to any large extent in the first experiment, they are irritated if such distinctions are lacking: in experiment II all impaired children turn to. animacy (some in coalition with the initial NP and/or particular word orders). In the discussion, the relationship between short-term memory and processing as well as the relationship between production and comprehension of case markers and agreement are addressed. Further research is needed to explore in more detail "cue costs" in sentence comprehension

Living Cellular Construct for Increasing the Width of Keratinized Gingiva: Results From a Randomized, Within‐Patient, Controlled Trial

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142206/1/jper1414.pd

Identification of an unusual Brucella strain (BO2) from a lung biopsy in a 52 year-old patient with chronic destructive pneumonia

<p>Abstract</p> <p>Background</p> <p>Brucellosis is primarily a zoonotic disease caused by <it>Brucella </it>species. There are currently ten <it>Brucella </it>spp. including the recently identified novel <it>B. inopinata </it>sp. isolated from a wound associated with a breast implant infection. In this study we report on the identification of an unusual <it>Brucella</it>-like strain (BO2) isolated from a lung biopsy in a 52-year-old patient in Australia with a clinical history of chronic destructive pneumonia.</p> <p>Results</p> <p>Standard biochemical profiles confirmed that the unusual strain was a member of the <it>Brucella </it>genus and the full-length 16S rRNA gene sequence was 100% identical to the recently identified <it>B. inopinata </it>sp. nov. (type strain BO1^T). Additional sequence analysis of the <it>recA, omp2a </it>and <it>2b </it>genes; and multiple locus sequence analysis (MLSA) demonstrated that strain BO2 exhibited significant similarity to the <it>B. inopinata </it>sp. compared to any of the other <it>Brucella </it>or <it>Ochrobactrum </it>species. Genotyping based on multiple-locus variable-number tandem repeat analysis (MLVA) established that the BO2 and BO1^Tstrains form a distinct phylogenetic cluster separate from the other <it>Brucella </it>spp.</p> <p>Conclusion</p> <p>Based on these molecular and microbiological characterizations, we propose that the BO2 strain is a novel lineage of the newly described <it>B. inopinata </it>species.</p