Towards a New Spatial Representation of Bone Remodeling

Irregular bone remodeling is associated with a number of bone diseases such as osteoporosis and multiple myeloma. Computational and mathematical modeling can aid in therapy and treatment as well as understanding fundamental biology. Different approaches to modeling give insight into different aspects of a phenomena so it is useful to have an arsenal of various computational and mathematical models. Here we develop a mathematical representation of bone remodeling that can effectively describe many aspects of the complicated geometries and spatial behavior observed. There is a sharp interface between bone and marrow regions. Also the surface of bone moves in and out, i.e. in the normal direction, due to remodeling. Based on these observations we employ the use of a level-set function to represent the spatial behavior of remodeling. We elaborate on a temporal model for osteoclast and osteoblast population dynamics to determine the change in bone mass which influences how the interface between bone and marrow changes. We exhibit simulations based on our computational model that show the motion of the interface between bone and marrow as a consequence of bone remodeling. The simulations show that it is possible to capture spatial behavior of bone remodeling in complicated geometries as they occur \emph{in vitro} and \emph{in vivo}. By employing the level set approach it is possible to develop computational and mathematical representations of the spatial behavior of bone remodeling. By including in this formalism further details, such as more complex cytokine interactions and accurate parameter values, it is possible to obtain simulations of phenomena related to bone remodeling with spatial behavior much as \emph{in vitro} and \emph{in vivo}. This makes it possible to perform \emph{in silica} experiments more closely resembling experimental observations.Comment: Math. Biosci. Eng., 9(2), 201

Manufacturing requirements

In recent years, natural laminar flow (NLF) has been proven to be achievable on modern smooth airframe surfaces over a range of cruise flight conditions representative of most current business and commuter aircraft. Published waviness and boundary layer transition measurements on several modern metal and composite airframes have demonstrated the fact that achievable surface waviness is readily compatible with laminar flow requirements. Currently, the principal challenge to the manufacture of NLF-compatible surfaces is two-dimensional roughness in the form of steps and gaps at structural joints. Results of recent NASA investigations on manufacturing tolerances for NLF surfaces, including results of a flight experiment are given. Based on recent research, recommendations are given for conservative manufacturing tolerances for waviness and shaped steps

Modeling and Simulation of the Effects of Cyclic Loading on Articular Cartilage Lesion Formation

We present a model of articular cartilage lesion formation to simulate the effects of cyclic loading. This model extends and modifies the reaction-diffusion-delay model by Graham et al. 2012 for the spread of a lesion formed though a single traumatic event. Our model represents "implicitly" the effects of loading, meaning through a cyclic sink term in the equations for live cells. Our model forms the basis for in silico studies of cartilage damage relevant to questions in osteoarthritis, for example, that may not be easily answered through in vivo or in vitro studies. Computational results are presented that indicate the impact of differing levels of EPO on articular cartilage lesion abatement

Sound exposure level as a metric for analyzing and managing underwater soundscapes

The auditory frequency weighted daily sound exposure level (SEL) is used in many jurisdictions to assess possible injury to the hearing of marine life. Therefore, using daily SEL to describe soundscapes would provide baseline information about the environment using the same tools used to measure injury. Here, the daily SEL from 12 recordings with durations of 18-97days are analyzed to: (1) identify natural soundscapes versus environments affected by human activity, (2) demonstrate how SEL accumulates from different types of sources, (3) show the effects of recorder duty cycling on daily SEL, (4) make recommendations on collecting data for daily SEL analysis, and (5) discuss the use of the daily SEL as an indicator of cumulative effects. The autocorrelation of the one-minute sound exposure is used to help identify soundscapes not affected by human activity. Human sound sources reduce the autocorrelation and add low-frequency energy to the soundscapes. To measure the daily SEL for all marine mammal auditory frequency weighting groups, data should be sampled at 64kHz or higher, for at least 1min out of every 30min. The daily autocorrelation of the one-minute SEL provides a confidence interval for the daily SEL computed with duty-cycled data. (C) 2019 Acoustical Society of America

Stereochemical studies on protonated bridgehead amines. ^1H NMR determination of cis and trans B-C ring-fused structures for salts of hexahydropyrrolo [2,1-a] isoquinolines and related C ring homologs. Capture of unstable ring-fused structures in the solid state

Acid-addition salts of tricyclic isoquinolines 2a/b, 3a/b, 4a-4c, 5, 6a/b, 7, 8a/b, 9a/b, and 17a/b were studied by high-field ^1H NMR in CDCl_3 solution. Cis (e.g., 14 and 15 in Figure 1) and trans (e.g., 13)B-C ring-fused structures were identified by using the vicinal ^3J(CH-NH) coupling constants, which demonstrate a Karplus-like behavior. In some cases, we initially observed a trans form, which converted to a cis A form by N H proton exchange. For 4c.HBr, the exchange process was slowed by addition of trifluoroacetic acid. In many cases, cis A and cis B structures were preferred in solution. The pendant phenyl group exerted a strong influence on the preferred solution structure. Observation of the initial, unstable trans-fused structures was related to their capture in the solid state and release intact on dissolution. X-ray diffraction was performed on the HBr salts of 2a (B-C cis), 2b (B-C cis), and 4c (B-C trans). The result for 4c.HBr confirmed the connection between the initial trans form in solution and the solid state. For 17b.HCI two conformers, associated with hindered rotation about the bond connecting the 2,6-disubstituted phenyl group to the tricyclic array, were detected at ambient probe temperature; however, rotamers were not observed for either of the two forms (trans and cis A) of 17a.HBr. Two conformers were also found for 16b.HBr. Temperature-dependent behavior was recorded in the ^1H NMR spectra of 17b.HBr and 16b.HBr; the activation free energy for interconversion of conformers was estimated to be in the vicinity of 17 kcal/mol for the former and 14-15 kcal/mol for the latter. The ^1H NMR spectrum of butaclamol hydrochloride (20.HC1), a potent neuroleptic agent, in Me_2SO-d_6 revealed two species in a ratio of 81:19, which were assigned as trans and cis A forms, respectively. ^1H NMR data for various free bases are also presented and discussed. Empirical force field calculations on three model hydrocarbons are discussed from a perspective of finding an explanation for the configurational/conformational behavior of the bridgehead ammonium salts. Diverse literature examples of structures for protonated bridgehead amines are also discussed. A tentative rationale is suggested for the preference of cis A forms in some protonated tetrahydroisoquinoline derivatives

Separation of river network–scale nitrogen removal among the main channel and two transient storage compartments

Transient storage (TS) zones are important areas of dissolved inorganic nitrogen (DIN) processing in rivers. We assessed sensitivities regarding the relative impact that the main channel (MC), surface TS (STS), and hyporheic TS (HTS) have on network denitrification using a model applied to the Ipswich River in Massachusetts, United States. STS and HTS connectivity and size were parameterized using the results of in situ solute tracer studies in first‐ through fifth‐order reaches. DIN removal was simulated in all compartments for every river grid cell using reactivity derived from Lotic Intersite Nitrogen Experiment (LINX2) studies, hydraulic characteristics, and simulated discharge. Model results suggest that although MC‐to‐STS connectivity is greater than MC‐to‐HTS connectivity at the reach scale, at basin scales, there is a high probability of water entering the HTS at some point along its flow path through the river network. Assuming our best empirical estimates of hydraulic parameters and reactivity, the MC, HTS, and STS removed approximately 38%, 21%, and 14% of total DIN inputs during a typical base flow period, respectively. There is considerable uncertainty in many of the parameters, particularly the estimates of reaction rates in the different compartments. Using sensitivity analyses, we found that the size of TS is more important for DIN removal processes than its connectivity with the MC when reactivity is low to moderate, whereas TS connectivity is more important when reaction rates are rapid. Our work suggests a network perspective is needed to understand how connectivity, residence times, and reactivity interact to influence DIN processing in hierarchical river systems

Face the Nation - Senator Edmund S. Muskie Interviewed for CBS News

Senator Edmund S. Muskie interview for CBS News\u27 Face the Nation. Topics include the 1972 campaign, the Nixon Administration, the U.S. economy, Vietnam

Comprehensive analysis of Hox gene expression in the amphipod crustacean Parhyale hawaiensis.

Hox genes play crucial roles in establishing regional identity along the anterior-posterior axis in bilaterian animals, and have been implicated in generating morphological diversity throughout evolution. Here we report the identification, expression, and initial genomic characterization of the complete set of Hox genes from the amphipod crustacean Parhyale hawaiensis. Parhyale is an emerging model system that is amenable to experimental manipulations and evolutionary comparisons among the arthropods. Our analyses indicate that the Parhyale genome contains a single copy of each canonical Hox gene with the exception of fushi tarazu, and preliminary mapping suggests that at least some of these genes are clustered together in the genome. With few exceptions, Parhyale Hox genes exhibit both temporal and spatial colinearity, and expression boundaries correlate with morphological differences between segments and their associated appendages. This work represents the most comprehensive analysis of Hox gene expression in a crustacean to date, and provides a foundation for functional studies aimed at elucidating the role of Hox genes in arthropod development and evolution