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91.
In computational systems biology, the general aim is to derive regulatory models from multivariate readouts, thereby generating predictions for novel experiments. In the past, many such models have been formulated for different biological applications. The authors consider the scenario where a given model fails to predict a set of observations with acceptable accuracy and ask the question whether this is because of the model lacking important external regulations. Real‐world examples for such entities range from microRNAs to metabolic fluxes. To improve the prediction, they propose an algorithm to systematically extend the network by an additional latent dynamic variable which has an exogenous effect on the considered network. This variable''s time course and influence on the other species is estimated in a two‐step procedure involving spline approximation, maximum‐likelihood estimation and model selection. Simulation studies show that such a hidden influence can successfully be inferred. The method is also applied to a signalling pathway model where they analyse real data and obtain promising results. Furthermore, the technique can be employed to detect incomplete network structures.Inspec keywords: biology computing, RNA, splines (mathematics), maximum likelihood estimation, approximation theory, biochemistryOther keywords: latent dynamic components, biological systems, computational system biology, regulatory models, multivariate readouts, biological applications, external regulations, real‐world examples, microRNA, metabolic fluxes, latent dynamic variables, variable time course, two‐step procedure, spline approximation, maximum‐likelihood estimation, model selection, signalling pathway model, real data, incomplete network structures 相似文献
92.
Theranostic USPIO‐Loaded Microbubbles for Mediating and Monitoring Blood‐Brain Barrier Permeation
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Twan Lammers Patrick Koczera Stanley Fokong Felix Gremse Josef Ehling Michael Vogt Andrij Pich Gert Storm Marc van Zandvoort Fabian Kiessling 《Advanced functional materials》2015,25(1):36-43
Efficient and safe drug delivery across the blood‐brain barrier (BBB) remains one of the major challenges of biomedical and (nano‐) pharmaceutical research. Here, it is demonstrated that poly(butyl cyanoacrylate)‐based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles within their shell, can be used to mediate and monitor BBB permeation. Upon exposure to transcranial ultrasound pulses, USPIO‐MB are destroyed, resulting in acoustic forces inducing vessel permeability. At the same time, USPIO are released from the MB shell, they extravasate across the permeabilized BBB and they accumulate in extravascular brain tissue, thereby providing non‐invasive R 2*‐based magnetic resonance imaging information on the extent of BBB opening. Quantitative changes in R 2* relaxometry are in good agreement with 2D and 3D microscopy results on the extravascular deposition of the macromolecular model drug fluorescein isothiocyanate (FITC)‐dextran into the brain. Such theranostic materials and methods are considered to be useful for mediating and monitoring drug delivery across the BBB and for enabling safe and efficient treatment of CNS disorders. 相似文献
93.
We report about the current performance of crystalline silicon thin-film (cSiTF) solar cells that are a very attractive alternative to conventional wafer-based silicon solar cells if sufficiently high cell efficiencies are achieved at acceptable cost of production. Applying a standard cell process (diffused POCl3 emitter, front contacts by photolithography, no surface texture) to thin-films deposited with a lab-type reactor, specifically designed for high-throughput photovoltaic applications, on highly-doped Cz substrates we routinely obtain efficiencies above 16%. On 1 Ω cm FZ material substrates we reach efficiencies up to 18.0%, which is among the highest thin-film efficiencies ever reported. Additionally, a comparison to microelectronic-grade epitaxially grown cSiTF material underlines the excellent electrical quality of the epitaxial layers deposited. 相似文献
94.
Cancer Treatment: Photothermal Killing of Cancer Cells by the Controlled Plasmonic Coupling of Silica‐Coated Au/Fe2O3 Nanoaggregates (Adv. Funct. Mater. 19/2014)
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95.
Marianne E. Mertens Alina Hermann Anne Bühren Leon Olde‐Damink Diana Möckel Felix Gremse Josef Ehling Fabian Kiessling Twan Lammers 《Advanced functional materials》2014,24(6):754-762
Non‐invasive imaging holds significant potential for implementation in tissue engineering. It can be used to monitor the localization and function of tissue‐engineered implants, as well as their resorption and remodelling. Thus far, however, the vast majority of effort in this area of research have focused on the use of ultrasmall super‐paramagnetic iron oxide (USPIO) nanoparticle‐labeled cells, colonizing the scaffolds, to indirectly image the implant material. Reasoning that directly labeling scaffold materials might be more beneficial (enabling imaging also in the case of non‐cellularized implants), more informative (enabling the non‐invasive visualization and quantification of scaffold degradation), and easier to translate into the clinic (cell‐free materials are less complex from a regulatory point‐of‐view), three different types of USPIO nanoparticles are prepared and incorporated both passively and actively (via chemical conjugation; during collagen crosslinking) into collagen‐based scaffold materials. The amount of USPIO incorporated into the scaffolds is optimized, and correlated with MR signal intensity, showing that the labeled scaffolds are highly biocompatible, and that scaffold degradation can be visualized using MRI. This provides an initial proof‐of‐principle for the in vivo visualization of the scaffolds. Consequently, USPIO‐labeled scaffold materials seem to be highly suitable for image‐guided tissue engineering applications. 相似文献
96.
V McGrath TC Fabian MA Croce G Minard FE Pritchard 《Canadian Metallurgical Quarterly》1998,64(12):1136-1141
Principles of rectal wound management, including routine diversion, injury repair, presacral drainage and distal washout, evolved from World War II and the Vietnam conflict and have been questioned in recent years. We believe significant confusion arises because of imprecise definition of injury location relative to retroperitoneal involvement. Our 5-year experience with penetrating rectal injuries at a Level I trauma center was analyzed. Injuries to the anterior and lateral surfaces of the upper two-thirds of the rectum were classified as intraperitoneal (IP, serosalized), and those of the posterior surface extraperitoneal (EP, no serosa); injuries to the lower one-third were EP. A total of 58 injuries were managed (92% gunshot wounds). Of these, 16 were IP, and 42 had some EP component. Ten patients underwent repair without diversion (6 IP, 4 EP); there were no leaks. Ten septic complications occurred in the remaining population: 2 necrotizing fasciitis, 5 abdominal abscess, and 3 presacral infections (PIs) (2 presacral abscesses and 1 wound tract infection). PI is the only complication that can be specifically associated with EP rectal injuries relative to management; as associated injury confounds interpretation of the other complications. The operative management in the 38 patients with diverted EP wounds with respect to presacral infection (PI) demonstrated the following: repair injury (n = 10), 0 PI versus no repair (n = 28), 3 PI (P = 0.55); washout (n = 33), 2 PI versus no washout (n = 5), 1 PI (P = 0.35); presacral drain (n = 30), 1 PI versus no drain (n = 8), 2 PI (P = 0.11). We conclude that most IP injuries can be managed with primary repair. EP wounds to the upper two-thirds of the rectum should usually be repaired. EP wounds to the lower one-third, which are explored and repaired, do not require drainage. EP wounds that are not explored should be managed with presacral drainage to minimize the incidence of presacral abscess. 相似文献
97.
Ryan O’Hayre Tibor Fabian Shawn Litster Fritz B. Prinz Juan G. Santiago 《Journal of power sources》2007
The behavior of an air breathing fuel cell (ABFC) operated on dry-hydrogen in dead-ended mode is studied using theoretical analysis. A one-dimensional, non-isothermal, combined heat and mass transport model is developed that captures the coupling between water generation, oxygen consumption, self-heating and natural convection at the air breathing cathode. The model is validated against planar ABFC experimental measurements over a range of ambient temperatures. The model confirms the strong effect of self-heating on the water balance within passive ABFCs. Model analysis provides several conclusions: (1) thermal runaway caused by inadequate heat rejection predominantly limits ABFC performance. (2) The natural convection boundary layer represents a significant barrier to cathode mass and heat transfer. (3) Because the mass and heat transport numbers associated with natural convection are small, even slight forced convection dramatically affects cell behavior. (4) Performance optimization requires maximizing heat rejection while minimizing flooding. Decoupling the latter two phenomena is challenging due to the exponential relationship between water vapor saturation and temperature. 相似文献
98.
TE Dever R Sripriya JR McLachlin J Lu JR Fabian SR Kimball LK Miller 《Canadian Metallurgical Quarterly》1998,95(8):4164-4169
Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2alpha kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2alpha phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA-regulated (PKR), an eIF2alpha kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains. 相似文献
99.
Michael Ryvkin Moshe B. Fuchs Fabian Lipperman Leonid Kucherov 《International Journal of Fracture》2004,128(1-4):215-221
The periodic structure of some natural and especially man-made materials can be manifested not only on an atomic but also on a larger scale. Investigation of mechanical properties of these materials usually hinges on well-developed homogenization methods. On the other hand, these methods are not suitable for fracture analysis where the knowledge of the local stress-strain fields near a flaw (a crack) is required. The result is obtained by the use of the representative cell method based on the discrete Fourier transform. This method enables one to determine the exact stress distribution in a periodic structure subjected to arbitrary loading. Direct application of the method is impossible since the crack violates the translational symmetry defined by the material microstructure. This obstacle is overcome by application of the fictitious loading to the uncracked body at the line where the crack is to be located. The amplitude of the loading is adjusted in order to fulfill the boundary conditions imposed on the crack faces. The compatibility equation for deriving this amplitude is obtained by the use of the corresponding Green function, which is found in a closed form. Fracture problems for the two types of materials with a periodic microstructure are considered. The first one is a composite material consisting of dissimilar isotropic elastic layers arranged periodically. The second periodic microstructure is a 2D infinite beam lattice modeling a cellular material. The analysis of the failure process in the latter case shows that in contrast to the case of homogeneous material, the crack propagation path is not defined by the condition of zero Mode II stress intensity factor. 相似文献
100.
JH Patton TC Fabian MA Croce G Minard FE Pritchard KA Kudsk 《Canadian Metallurgical Quarterly》1996,41(2):231-6; discussion 236-7
The efficacy of prophylactic vena caval filters (VCF) in reducing morbidity and mortality from pulmonary embolism (PE) in high-risk trauma patients has been shown, but minimal follow-up data is currently available. VCFs were prophylactically placed in 110 patients between August 1991 and June 1995. There was an early VCF complication rate of 7%. Twenty-two patients died; the remaining 88 patients formed the basis for the follow-up study. Forty-five patients were located and interviewed by phone, and 30 of these patients (34%) returned for evaluation. The mean follow-up time was 18 months (range, 4-42 months). There was no incidence of caval thrombosis on follow-up. Eleven patients had physical findings, and duplex evidence consistent with postphlebitic syndrome. An additional three patients had evidence of old deep venous thrombosis (DVT) by duplex, but no significant symptomatology. VCF are effective in preventing PE related deaths and have few major complications. The long-term morbidity associated with posttraumatic venous thrombosis is significant. This morbidity is related not to PE or VCF, but to the underlying DVT. Improved strategies against DVT are necessary. 相似文献