Unilateral Carotid Body Resection in Resistant Hypertension:A Safety and Feasibility Trial

SummaryAnimal and human data indicate pathological afferent signaling emanating from the carotid body that drives sympathetically mediated elevations in blood pressure in conditions of hypertension. This first-in-man, proof-of-principle study tested the safety and feasibility of unilateral carotid body resection in 15 patients with drug-resistant hypertension. The procedure proved to be safe and feasible. Overall, no change in blood pressure was found. However, 8 patients showed significant reductions in ambulatory blood pressure coinciding with decreases in sympathetic activity. The carotid body may be a novel target for treating an identifiable subpopulation of humans with hypertension

Probabilistic Integrity and Risk Assessment of Turbine Engines, Phase II

15-G-016This grant supported the efforts of the Federal Aviation Administration (FAA) to develop an enhanced life management process, based on probabilistic damage tolerance principles, to address the threat of material or manufacturing anomalies in high-energy rotating components of aircraft engines. Major research products included formal verification and validation of Design Assessment of Reliability With INspection (DARWIN\uae) stress-intensity factor solutions; enhanced DARWIN capabilities for manual and automatic fracture mechanics modeling, probabilistic methods, and fleet risk methods. Substantial improvements in the speed and robustness of DARWIN for large finite element (FE) models; streamlined methods for deterministic life calculations; a DARWIN Python module to facilitate scripting of multiple DARWIN runs; options to specify or limit optional features or default values available in DARWIN; new advanced visualization capabilities enabling users to define and manipulate regions within three-dimensional FE models; multiple new versions of the DARWIN computer code for technology transfer to industry and the FAA, and a large DARWIN training workshop are also included. The efforts facilitate implementation of official advisory material for axial blade slots, titanium hard alpha anomalies, and circular holes, while also developing improved analysis methods for other applications of deterministic and probabilistic damage tolerance to engine safety

Multisensory visual–tactile object related network in humans: insights gained using a novel crossmodal adaptation approach

Neuroimaging techniques have provided ample evidence for multisensory integration in humans. However, it is not clear whether this integration occurs at the neuronal level or whether it reflects areal convergence without such integration. To examine this issue as regards visuo-tactile object integration we used the repetition suppression effect, also known as the fMRI-based adaptation paradigm (fMR-A). Under some assumptions, fMR-A can tag specific neuronal populations within an area and investigate their characteristics. This technique has been used extensively in unisensory studies. Here we applied it for the first time to study multisensory integration and identified a network of occipital (LOtv and calcarine sulcus), parietal (aIPS), and prefrontal (precentral sulcus and the insula) areas all showing a clear crossmodal repetition suppression effect. These results provide a crucial first insight into the neuronal basis of visuo-haptic integration of objects in humans and highlight the power of using fMR-A to study multisensory integration using non-invasinve neuroimaging techniques

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Steady crack growth through ductile metals: Computational studies

This thesis examines the crack-front response during sustained ductile tearing in structural metals at quasi-static rates using high resolution finite element computations. At load levels approaching the steady-growth regime, well-established computational methods that model material damage break down numerically as vanishingly small load increments produce increasingly large amounts of crack extension. The computational model adopted here determines the deformation history of a steadily advancing crack directly without the need for a priori (transient) analysis that considers blunting of the pre-existing stationary crack and subsequent growth through the associated initial plastic zone. Crack extension occurs at the remotely applied, fixed loading without the need for a local growth criteria. This numerical scheme utilizes a streamline integration technique to determine the elastic-plastic fields, generalized from a two-dimensional to a fully three-dimensional setting and implemented within mixed Matlab/C++/F-90 based software. Modifications of the conventional finite element formulation lead to an efficient procedure -- readily parallelized -- and determine the invariant near-front fields, representative of steady-state growth, on a fixed mesh in a boundary-layer framework. In the small-scale yielding regime, the crack front does not sense the existence of remote boundaries, and computational results retain a strong transferability among various geometric configurations where near-front, plastic deformation remains entirely enclosed by the surrounding linear-elastic material. The global stress intensity factor (KI) and imposed T-stress fully specify displacement constraints along the far-field boundary, and in a three-dimensional setting, the panel thickness reflects the only natural length scale. The initial studies in this work consider steady crack advance within the small-scale yielding context under plane-strain conditions and mode I loading. These analyses focus on steady crack growth within a hydrogen-charged material to explore primary features of the streamline integration methodology while providing new results relevant to hydrogen embrittlement at engineering scales. Ductile crack propagation occurs through a homogeneous, high solubility material characteristic of niobium and through a steel weld in the presence of hydrogen. The constitutive model includes the influence of hydrogen on elastic-plastic regimes of material response at the continuum level, \emph{e.g.} hydrogen-induced material softening, based on the hydrogen-enhanced, localized plasticity (HELP) mechanism, and reflects the amount of hydrogen in the material under stress and the intensity of hydrogen-induced softening in the material. Achievements using this two-dimensional framework encouraged further extensions of the research to a fully three-dimensional setting. Subsequent work, and the focal point of this thesis, develops a finite element formulation to investigate key features of the elastic-plastic fields near a steadily advancing crack under three-dimensional, small-scale yielding conditions. The computational model represents a structurally thin component constructed of a material (e.g. Al and Ti alloys) with flow stress and fracture toughness properties that together limit the size of the in-plane plastic zone during steady growth to no more than several multiples of the plate thickness. These studies consider a straight crack front advancing under local and global mode-I loading in a moderately hardening material. The nonsingular T-stress provides a first-order estimate of geometry and loading mode (e.g. tension vs. bending) effects on elastic-plastic, crack front fields. The T-stress has a marked effect on measured crack-growth resistance curves (J-da) -- trends most computational models confirm using a two-dimensional setting. In the first computations of this type to be modeled, the 3D numerical results here demonstrate similarity scaling of the crack front response -- stresses, strains, and displacements -- in terms of two non-dimensional loading parameters. These fields serve as input to key engineering failure models for brittle and ductile crack growth and provide estimates of the apparent fracture toughness linked to changes of the material flow response, geometry, and applied loading. For the first time in the scientific literature, these studies document 3D analyses of steady-state crack growth and represent a key advance in computational analyses of crack extension

Dynamic and static characterization of compact crack arrest tests of navy and nuclear steels

Recent experimental and computational work by Link and associates has demonstrated that relatively small (W= 150 mm) single edge notched tension specimens (SE(T)) can be used to obtain crack arrest data high in the ductile-to-brittle transition of ferritic structural steel using dynamic computational techniques if a thermal gradient is utilized to aid in the crack arrest. Testing has been reported on two important navy structural steels that clearly defines the relative capability of the two materials to arrest rapidly growing cracks. The HY100 material demonstrated the expected large difference between the initiation and crack arrest toughnesses which has made it impossible in the past to measure crack arrest toughness for this material using the standard ASTM procedure (E1221). The HSLA-100 steel, however demonstrated a much higher crack arrest toughness and a correspondingly smaller drop in toughness below the initiation toughness. This small difference between initiation toughness and arrest toughness suggested that the E1221 procedure, using wedge loaded, compact crack arrest (CCA) specimens would be applicable to this material. Two important issues could then be investigated using this material. First, having completed the expensive and relatively complex testing of the SE(T) specimens using tensile loading and a thermal gradient, a second, quite different geometry could be tested using the E1221 procedure, allowing an important comparison between the crack arrest measurements made using these two distinct geometries. Historically, obtaining crack arrest results using one test configuration has been so difficult, that there have been very few reports of results for the same material using two different test geometries. Transferability of the laboratory results to structural applications has thus been a matter of conjecture. Furthermore, if the E1221 CCA specimens were strain gaged to obtain crack velocity data, and analyzed using the dynamic computational procedure used by Link on the SE(T) specimens, it would be possible to compare the results the E1221 static analysis with the results of the dynamic computation procedure to determine the degree of conservatism present in the E1221 standard procedure. The results of this work have shown that the crack arrest toughness results obtained on these two specimen geometries are similar and hence insensitive to the test geometry and the difference resulting from the application of the complex dynamic computational procedure or the E1221 static analyses is small

On the Extension of the Gurson-Type Porous Plasticity Models for Prediction of Ductile Fracture under Shear-Dominated Conditions

One of the major drawbacks of the Gurson-type of porous plasticity models is the inability of these models to predict material failure under low stress triaxiality, shear dominated conditions. This study addresses this issue by combining the damage mechanics concept with the porous plasticity model that accounts for void nucleation, growth and coalescence. In particular, the widely adopted Gurson–Tvergaard–Needleman (GTN) model is extended by coupling two damage parameters, representing the volumetric damage (void volume fraction) and the shear damage, respectively, into the yield function and flow potential. The effectiveness of the new model is illustrated through a series of numerical tests comparing its performance with existing models. The current model not only is capable of predicting damage and fracture under low (even negative) triaxiality conditions but also suppresses spurious damage that has been shown to develop in earlier modifications of the GTN model for moderate to high triaxiality regimes. Finally the modified GTN model is applied to predict the ductile fracture behavior of a beta-treated Zircaloy-4 by coupling the proposed damage modeling framework with a recently developed J2–J3 plasticity model for the matrix material. Model parameters are calibrated using experimental data, and the calibrated model predicts failure initiation and propagation in various specimens experiencing a wide range of triaxiality and Lode parameter combinations