Computational methodology to determine fluid related parameters on non regular three-dimensional scaffolds

The application of three-dimensional (3D) biomaterials to facilitate the adhesion, proliferation, and differentiation of cells has been widely studied for tissue engineering purposes. The fabrication methods used to improve the mechanical response of the scaffold produce complex and non regular structures. Apart from the mechanical aspect, the fluid behavior in the inner part of the scaffold should also be considered. Parameters such as permeability (k) or wall shear stress (WSS) are important aspects in the provision of nutrients, the removal of metabolic waste products or the mechanically-induced differentiation of cells attached in the trabecular network of the scaffolds. Experimental measurements of these parameters are not available in all labs. However, fluid parameters should be known prior to other types of experiments. The present work compares an experimental study with a computational fluid dynamics (CFD) methodology to determine the related fluid parameters (k and WSS) of complex non regular poly(L-lactic acid) scaffolds based only on the treatment of microphotographic images obtained with a microCT (lCT). The CFD analysis shows similar tendencies and results with low relative difference compared to those of the experimental study, for high flow rates. For low flow rates the accuracy of this prediction reduces. The correlation between the computational and experimental results validates the robustness of the proposed methodology.The authors gratefully acknowledge research support from the Spanish Ministry of Science and Innovation through research project DPI2010-20399-C04-01. The Instituto de Salud Carlos III (ISCIII) through the CIBER initiative and the Platform for Biological Tissue Characterization of the Centro de Investigacion Biomedica en Red en Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN) are also gratefully acknowledged.Acosta Santamaría, VA.; Malvé, M.; Duizabo, A.; Mena Tobar, A.; Gallego Ferrer, G.; García Aznar, J.; Doblare Castellano, M.... (2013). Computational methodology to determine fluid related parameters on non regular three-dimensional scaffolds. Annals of Biomedical Engineering. 41(11):2367-2380. https://doi.org/10.1007/s10439-013-0849-8S236723804111Acosta Santamaría, V., H. Deplaine, D. Mariggió, A. R. Villanueva-Molines, J. M. García-Aznar, J. L. Gómez Ribelles, M. Doblaré, G. Gallego Ferrer, and I. Ochoa. Influence of the macro and micro-porous structure on the mechanical behavior of poly(l-lactic acid) scaffolds. J. Non-Cryst. Solids 358(23):3141–3149, 2012.Adachi, T., Y. Osako, M. Tanaka, M. Hojo, and S. J. Hollister. 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Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome

Background: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. Methodology/Principal Findings: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased. Conclusions/Significance: We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals.Chelsee A. Hewitt, King-Hwa Ling, Tobias D. Merson, Ken M. Simpson, Matthew E. Ritchie, Sarah L. King, Melanie A. Pritchard, Gordon K. Smyth, Tim Thomas, Hamish S. Scott and Anne K. Vos

Surveying the Down syndrome mouse model resource identifies critical regions responsible for chronic otitis media

Chronic otitis media (OM) is common in Down syndrome (DS), but underlying aetiology is unclear. We analysed the entire available mouse resource of partial trisomy models of DS looking for histological evidence of chronic middle-ear inflammation. We found a highly penetrant OM in the Dp(16)1Yey mouse, which carries a complete trisomy of MMU16. No OM was found in the Dp(17)1Yey mouse or the Dp(10)1Yey mouse, suggesting disease loci are located only on MMU16. The Ts1Cje, Ts1RhR, Ts2Yah, and Ts65Dn trisomies and the transchomosomic Tc1 mouse did not develop OM. On the basis of these findings, we propose a two-locus model for chronic middle-ear inflammation in DS, based upon epistasis of the regions of HSA21 not in trisomy in the Tc1 mouse. We also conclude that environmental factors likely play an important role in disease onset

NanoSIMS Analysis of Bacillus Spores for Forensics

The threat associated with the potential use of radiological, nuclear, chemical and biological materials in terrorist acts has resulted in new fields of forensic science requiring the application of state-of-the-science analytical techniques. Since the anthrax letter attacks in the United States in the fall of 2001, there has been increased interest in physical and chemical characterization of bacterial spores. While molecular methods are powerful tools for identifying genetic differences, other methods may be able to differentiate genetically identical samples based on physical and chemical properties, as well as provide complimentary information, such as methods of production and approximate date of production. Microanalysis has the potential to contribute significantly to microbial forensics. Bacillus spores are highly structured, consisting of a core, cortex, coat, and in some species, an exosporium. This structure provides a template for constraining elemental abundance differences at the nanometer scale. The primary controls on the distribution of major elements in spores are likely structural and physiological. For example, P and Ca are known to be abundant in the spore core because that is where P-rich nucleic acids and Cadipicolinic acid are located, respectively. Trace elements are known to bind to the spore coat but the controls on these elements are less well understood. Elemental distributions and abundances may be directly related to spore production, purification and stabilization methodologies, which are of particular interest for forensic investigation. To this end, we are developing a high-resolution secondary ion mass spectrometry method using a Cameca NanoSIMS 50 to study the distribution and abundance of trace elements in bacterial spores. In this presentation we will review and compare methods for preparing and analyzing samples, as well as review results on the distribution and abundance of elements in bacterial spores. We use NanoSIMS to directly image samples as well as depth profile samples. The directly imaged samples are sectioned to present a flat surface for analysis. We use focused ion beam (FIB) milling to top-cut individual spores to create flat surfaces for NanoSIMS analysis. Depth profiling can be used on whole spores, which are consumed in the process of analysis. The two methods generate comparable results, with the expected distribution of P and Ca. Ca-compatible elements, such as Mg and Mn, are found to follow the distribution of Ca. The distribution of other elements will be discussed. We envision the first application of this methodology will be to sample matching for trace samples. Towards this end, we are generating a baseline data set for samples produced by multiple laboratories. Preliminary results suggest that this method provides significant probative value for identifying samples produced by the same method in the same laboratory, as well as coming from the same initial production run. The results of this study will be presented

Noble gases, stable isotopes, and radiocarbon as tracers of flow in the Dakota aquifer, Colorado and Kansas

A suite of chemical and isotope tracers (dissolved noble gases, stable isotopes of water, radiocarbon, and CI) have been analyzed along a flow path in the Dakota aquifer system to determine likely recharge sources, ground water residence times, and the extent of mixing between local and intermediate flow systems, presumably caused by large well screens. Three water types were distinguished with the tracers, each having a very different history. Two of the water types were found in south-eastern Colorado where the Dakota is poorly confined. The tracer data suggest that the first group recharged locally during the last few thousand years and the second group was composed of ground water that recharged earlier during a cooler climate, presumably during the last glacial period (LGP) and mixed aged water. The paleotemperature record archived in this groundwater system indicates that south-eastern Colorado was about 5°C cooler during the LGP than during the late Holocene. Similar temperature changes derived from dissolved noble gases in other aquifer systems have been reported earlier for the south-western United States. The third water type was located down gradient of the first two in the confined Dakota in western and central Kansas. Groundwater residence time of this water mass is on the order of 104-105 yrs and its recharge location is near the Colorado and Kansas border down gradient of the other water types. The study shows the importance of using multiple tracers when investigating ground water systems

Late-Quaternary recharge determined from chloride in shallow groundwater in the central Great Plains

An extensive suite of isotopic and geochemical tracers in groundwater has been used to provide hydrologic assessments of the hierarchy of flow systems in aquifers underlying the central Great Plains (southeastern Colorado and western Kansas) of the United States and to determine the late Pleistocene and Holocene paleotemperature and paleorecharge record. Hydrogeologic and geochemical tracer data permit classification of the samples into late Holocene, late Pleistocene-early Holocene, and much older Pleistocene groups. Paleorecharge rates calculated from the Cl concentration in the samples show that recharge rates were at least twice the late Holocene rate during late Pleistocene-early Holocene time, which is consistent with their relative depletion in 16O and D. Noble gas (Ne, Ar, Kr, Xe) temperature calculations confirm that these older samples represent a recharge environment approximately 5°C cooler than late Holocene values. These results are consistent with the global climate models that show a trend toward a warmer, more arid climate during the Holocene. (C) 2000 University of Washington

Late-Quaternary recharge determined from chloride in shallow groundwater in the central Great Plains

An extensive suite of isotopic and geochemical tracers in groundwater has been used to provide hydrologic assessments of the hierarchy of flow systems in aquifers underlying the central Great Plains (southeastern Colorado and western Kansas) of the United States and to determine the late Pleistocene and Holocene paleotemperature and paleorecharge record. Hydrogeologic and geochemical tracer data permit classification of the samples into late Holocene, late Pleistocene-early Holocene, and much older Pleistocene groups. Paleorecharge rates calculated from the Cl concentration in the samples show that recharge rates were at least twice the late Holocene rate during late Pleistocene-early Holocene time, which is consistent with their relative depletion in 16O and D. Noble gas (Ne, Ar, Kr, Xe) temperature calculations confirm that these older samples represent a recharge environment approximately 5°C cooler than late Holocene values. These results are consistent with the global climate models that show a trend toward a warmer, more arid climate during the Holocene. (C) 2000 University of Washington

A geochemical study of the impact of irrigation and aquifer lithology on groundwater in the Upper Yakima River Basin, Washington, USA

The Yakima River, a major tributary of the Columbia River, is currently overallocated in its surface water usage in part because of large agricultural water use. As a result, groundwater availability and surface water/groundwater interactions have become an important issue in this area. In several sub-basins, the Yakima River water is diverted and applied liberally to fields in the summer creating artificial recharge of shallow groundwater. Major ion, trace element, and stable isotope geochemistry of samples from 26 groundwater wells from a transect across the Yakima River and 24 surface waters in the Kittitas sub-basin were used to delineate waters with similar geochemical signatures and to identify surface water influence on groundwater. Major ion chemistry and stable isotope signatures combined with principal component analysis revealed four major hydrochemical groups. One of these groups, collected from shallow wells within the sedimentary basin fill, displays temporal variations in NO3 and SO4 along with high δ18O and δD values, indicating significant contribution from Yakima River and/or irrigation water. Two other major hydrochemical groups reflect interaction with the main aquifer lithologies in the basin: the Columbia River basalts (high-Na groundwaters), and the volcaniclastic rocks of the Ellensburg Formation (Ca–Mg–HCO3 type waters). The fourth major group has interacted with the volcaniclastic rocks and is influenced to a lesser degree by surface waters. The geochemical groupings constrain a conceptual model for groundwater flow that includes movement of water between underlying Columbia River basalt and deeper sedimentary basin fill and seasonal input of irrigation water