The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology

Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) share molecular mechanisms that cause the pathological symptoms they have in common. Here, we review evidence suggesting that hyperactivity of the EGFR/ADAM17 axis plays a role in the development of chronic lung disease in both CF and COPD. The ubiquitous transmembrane protease A disintegrin and metalloprotease 17 (ADAM17) forms a functional unit with the EGF receptor (EGFR), in a feedback loop interaction labeled the ADAM17/EGFR axis. In airway epithelial cells, ADAM17 sheds multiple soluble signaling proteins by proteolysis, including EGFR ligands such as amphiregulin (AREG), and proinflammatory mediators such as the interleukin 6 coreceptor (IL-6R). This activity can be enhanced by injury, toxins, and receptor-mediated external triggers. In addition to intracellular kinases, the extracellular glutathione-dependent redox potential controls ADAM17 shedding. Thus, the epithelial ADAM17/EGFR axis serves as a receptor of incoming luminal stress signals, relaying these to neighboring and underlying cells, which plays an important role in the resolution of lung injury and inflammation. We review evidence that congenital CFTR deficiency in CF and reduced CFTR activity in chronic COPD may cause enhanced ADAM17/EGFR signaling through a defect in glutathione secretion. In future studies, these complex interactions and the options for pharmaceutical interventions will be further investigated

Second-order electronic correlation effects in a one-dimensional metal

The Pariser-Parr-Pople (PPP) model of a single-band one-dimensional (1D) metal is studied at the Hartree-Fock level, and by using the second-order perturbation theory of the electronic correlation. The PPP model provides an extension of the Hubbard model by properly accounting for the long-range character of the electron-electron repulsion. Both finite and infinite version of the 1D-metal model are considered within the PPP and Hubbard approximations. Calculated are the second-order electronic-correlation corrections to the total energy, and to the electronic-energy bands. Our results for the PPP model of 1D metal show qualitative similarity to the coupled-cluster results for the 3D electron-gas model. The picture of the 1D-metal model that emerges from the present study provides a support for the hypothesis that the normal metallic state of the 1D metal is different from the ground state.Comment: 21 pages, 16 figures; v2: small correction in title, added 3 references, extended and reformulated a few paragraphs (detailed information at the end of .tex file); added color to figure

Axial Strength of Purlins Attached to Standing Seam Roof Panels

The purpose of this research was to determine the axial load capacity of Z-purlins with one flange attached to a standing seam roof system. The axial load capacity was determined by developing a relationship between the flexural uplift buckling strength and the axial buckling strength in the Z-purlin. This relationship was investigated using finite element models and by conducting a parametric study. At the conclusion of the parametric study, confirmatory tests were conducted to verify the finite element results. A relationship has been provided that relates the axial buckling strength in the Z-purlin to the flexural uplift buckling strength. This paper is a condensed version of the MBMA Research Report 99-02 (MBMA 2001)

The abducens nerve: its topography and anatomical variations in intracranial course with clinical commentary

Background: The sixth cranial nerve (CN VI) — or the abducens nerve — in humans supplies only the lateral rectus muscle. Due to its topographic conditions, including angulations and fixation points along its course from the brainstem to the lateral rectus muscle, the CN VI is vulnerable to injury. Every case of CN VI palsy requires precise diagnostics, which is facilitated by an understanding of the anatomy. The present article’s aims include a detailed study of the intracranial course of the CN VI, determination of occurrence of its particular anatomical variations, as well as presentation of some essential anatomical conditions which may conduce to CN VI palsy. Special emphasis was put on the correlation between craniometric measurements and a particular variation of the CN VI, which complements the data that can be found in literature. Materials and methods: Twenty randomly selected specimens of cadaveric heads fixed in a 10% formalin solution were studied. The study used 40 specimens of the CN VI in order to examine its course variations within the section between the pontomedullary sulcus and the superior orbital fissure. Results: Detailed analysis of the CN VI topography and anatomy in its intracranial course revealed 3 anatomical variations of the nerve in the studied specimens. Variation I, found in 70% of cases, covers those cases in which the CN VI was found to be a single trunk. Those cases in which there was a branching of the CN VI exclusively inside the cavernous sinus were classified as variation II, occurring in 20% of cases. Cases of duplication of the CN VI were classified as variation III, found in 10% of the specimens. In 75% of cases of CN VI duplication one of the nerve trunks ran upwards from the petrosphenoidal ligament, outside Dorello’s canal. Conclusions: The CN VI throughout its intracranial course usually runs as a single trunk, however, common variations include also branching of the nerve in the cavernous sinus or duplication. Topographic relations of the CN VI with adjacent structures account for the risk of injuries which may be caused to the nerve as a result of a disease or surgical procedures.

On Conformal Infinity and Compactifications of the Minkowski Space

Using the standard Cayley transform and elementary tools it is reiterated that the conformal compactification of the Minkowski space involves not only the "cone at infinity" but also the 2-sphere that is at the base of this cone. We represent this 2-sphere by two additionally marked points on the Penrose diagram for the compactified Minkowski space. Lacks and omissions in the existing literature are described, Penrose diagrams are derived for both, simple compactification and its double covering space, which is discussed in some detail using both the U(2) approach and the exterior and Clifford algebra methods. Using the Hodge * operator twistors (i.e. vectors of the pseudo-Hermitian space H_{2,2}) are realized as spinors (i.e., vectors of a faithful irreducible representation of the even Clifford algebra) for the conformal group SO(4,2)/Z_2. Killing vector fields corresponding to the left action of U(2) on itself are explicitly calculated. Isotropic cones and corresponding projective quadrics in H_{p,q} are also discussed. Applications to flat conformal structures, including the normal Cartan connection and conformal development has been discussed in some detail.Comment: 38 pages, 8 figures, late

ADAM17 and EGFR regulate IL-6 receptor and amphiregulin mRNA expression and release in cigarette smoke-exposed primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD)

Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, and epidermal growth factor receptor (EGFR) has been suggested to contribute to chronic obstructive pulmonary disease (COPD) development and progression. The aim of this study was to investigate the role of these proteins in activation of primary bronchial epithelial cells differentiated at the air–liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing cells from COPD patients with non-COPD. CS exposure of ALI-PBEC enhanced ADAM17-mediated shedding of the IL-6 receptor (IL6R) and the EGFR agonist amphiregulin (AREG) toward the ba

Civillity in the Legal Profession: A Survey of the Texas Judiciary.

Abstract Forthcoming

Civillity in the Legal Profession: A Survey of the Texas Judiciary.

Abstract Forthcoming