Model validation for a noninvasive arterial stenosis detection problem

Copyright @ 2013 American Institute of Mathematical SciencesA current thrust in medical research is the development of a non-invasive method for detection, localization, and characterization of an arterial stenosis (a blockage or partial blockage in an artery). A method has been proposed to detect shear waves in the chest cavity which have been generated by disturbances in the blood flow resulting from a stenosis. In order to develop this methodology further, we use both one-dimensional pressure and shear wave experimental data from novel acoustic phantoms to validate corresponding viscoelastic mathematical models, which were developed in a concept paper [8] and refined herein. We estimate model parameters which give a good fit (in a sense to be precisely defined) to the experimental data, and use asymptotic error theory to provide confidence intervals for parameter estimates. Finally, since a robust error model is necessary for accurate parameter estimates and confidence analysis, we include a comparison of absolute and relative models for measurement error.The National Institute of Allergy and Infectious Diseases, the Air Force Office of Scientific Research, the Deopartment of Education and the Engineering and Physical Sciences Research Council (EPSRC)

Lung Science Conference highlights 2023: Post-viral lung diseases – from basic immunology to clinical phenotypes and therapy

The presentations offered a comprehensive understanding of the current research landscape in this area, stressing the need for ongoing investigation and collaboration among scientists and clinicians. It also included a specific session directed at early career delegates, focusing on career development. Early career delegates were involved in several activities, from participating in oral/poster communication sessions as presenters and/or chairs, to mentoring and networking opportunities, as presented in a previous Early Career Forum article [1]. This paper summarises some of the outstanding sessions of the Lung Science Conference 2023, written by early career delegates attending the sessions.info:eu-repo/semantics/publishedVersio

Expression pattern of the aspartyl-tRNA synthetase DARS in the human brain

Translation of mRNA into protein is an evolutionarily conserved, fundamental process of life. A prerequisite for translation is the accurate charging of tRNAs with their cognate amino acids, a reaction catalyzed by specific aminoacyl-tRNA synthetases. One of these enzymes is the aspartyl-tRNA synthetase DARS, which pairs aspartate with its corresponding tRNA. Missense mutations of the gene encoding DARS result in the leukodystrophy hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) with a distinct pattern of hypomyelination, motor abnormalities, and cognitive impairment. A thorough understanding of the DARS expression domains in the central nervous system is essential for the development of targeted therapies to treat HBSL. Here, we analyzed endogenous DARS expression on the mRNA and protein level in different brain regions and cell types of human post mortem brain tissue as well as in human stem cell derived neurons, oligodendrocytes, and astrocytes. DARS expression is significantly enriched in the cerebellum, a region affected in HBSL patients and important for motor control. Although obligatorily expressed in all cells, DARS shows a distinct expression pattern with enrichment in neurons but only low abundance in oligodendrocytes, astrocytes, and microglia. Our results reveal little homogeneity across the different cell types, largely matching previously published data in the murine brain. This human gene expression study will significantly contribute to the understanding of DARS gene function and HBSL pathology and will be instrumental for future development of animal models and targeted therapies. In particular, we anticipate high benefit from a gene replacement approach in neurons of HBSL mouse models, given the abundant endogenous DARS expression in this lineage cell

Clearance of picoplankton-sized particles and formation of rapidly sinking aggregates by the euthecosomatous pteropod, Limacina retriversa

Findings from experiments showed that the web-feeding euthecosomatous pteropod, Limacina retroversa, can produce rapidly sinking, mucous aggregates. It is suggested that, by adhesion, these aggregates scavenged picoplankton-sized particles, which were thus effectively cleared from the medium. In contrast, Calanus finmarchicusw as not able to clear these particles in our experiments. Sedimentation velocities of 10 aggregates measured in vivo were up to 1000 m day1, with an average of —300 m day-1 (not including two aggegates with neutral buoyancy). Mean velocities measured for feces of C.finmarchicus, Calanus hyperboreus and Thysanoessa sp. were considerably lower. We suggest that the sedimentation of L.retroversa aggregates was the source of mucous floes collected in sediment traps (Bathmann et al., Deep-Sea Res., 38,1341-1360,1991) and at the sea floor at 1200 m depth in the southern Norwegian Sea. This process may be an important mediator of sedimentation to the deep sea, when these pteropods are present in surface waters in large abundance

A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions

Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m$^{2}$) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic In VItro Cell-stretch (CIVIC) “breathing” lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o$^{-}$) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35% PCL and 6.34% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung

Acute Phase Response as a Biological Mechanism-of-Action of (Nano)particle-Induced Cardiovascular Disease

Inhaled nanoparticles constitute a potential health hazard due to their size-dependent lung deposition and large surface to mass ratio. Exposure to high levels contributes to the risk of developing respiratory and cardiovascular diseases, as well as of lung cancer. Particle-induced acute phase response may be an important mechanism of action of particle-induced cardiovascular disease. Here, the authors review new important scientific evidence showing causal relationships between inhalation of particle and nanomaterials, induction of acute phase response, and risk of cardiovascular disease. Particle-induced acute phase response provides a means for risk assessment of particle-induced cardiovascular disease and underscores cardiovascular disease as an occupational disease

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<p>Translation of mRNA into protein is an evolutionarily conserved, fundamental process of life. A prerequisite for translation is the accurate charging of tRNAs with their cognate amino acids, a reaction catalyzed by specific aminoacyl-tRNA synthetases. One of these enzymes is the aspartyl-tRNA synthetase DARS, which pairs aspartate with its corresponding tRNA. Missense mutations of the gene encoding DARS result in the leukodystrophy hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) with a distinct pattern of hypomyelination, motor abnormalities, and cognitive impairment. A thorough understanding of the DARS expression domains in the central nervous system is essential for the development of targeted therapies to treat HBSL. Here, we analyzed endogenous DARS expression on the mRNA and protein level in different brain regions and cell types of human post mortem brain tissue as well as in human stem cell derived neurons, oligodendrocytes, and astrocytes. DARS expression is significantly enriched in the cerebellum, a region affected in HBSL patients and important for motor control. Although obligatorily expressed in all cells, DARS shows a distinct expression pattern with enrichment in neurons but only low abundance in oligodendrocytes, astrocytes, and microglia. Our results reveal little homogeneity across the different cell types, largely matching previously published data in the murine brain. This human gene expression study will significantly contribute to the understanding of DARS gene function and HBSL pathology and will be instrumental for future development of animal models and targeted therapies. In particular, we anticipate high benefit from a gene replacement approach in neurons of HBSL mouse models, given the abundant endogenous DARS expression in this lineage cell.</p