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The impact of surgical staplers on tissues has been studied mostly in an empirical manner. In this paper, finite element method was used to clarify the mechanics of tissue stapling and associated phenomena. Various stapling modalities and several designs of circular staplers were investigated to evaluate the impact of the device on tissues and mechanical performance of the end-to-end colorectal anastomosis. Numerical simulations demonstrated that a single row of staples is not adequate to resist leakage due to non-linear buckling and opening of the tissue layers between two adjacent staples. Compared to the single staple row configuration, significant increase in stress experienced by the tissue at the inner staple rows was observed in two and three rows designs. On the other hand, adding second and/or third staple row had no effect on strain in the tissue inside the staples. Variable height design with higher staples in outer rows significantly reduced the stresses and strains in outer rows when compared to the same configuration with flat cartridge.
Spontaneous language has rarely been subjected to neuroimaging studies. This study therefore introduces a newly developed method for the analysis of linguistic phenomena observed in continuous language production during fMRI.
Most neuroimaging studies investigating language have so far focussed on single word or — to a smaller extent — sentence processing, mostly due to methodological considerations. Natural language production, however, is far more than the mere combination of words to larger units. Therefore, the present study aimed at relating brain activation to linguistic phenomena like word-finding difficulties or syntactic completeness in a continuous language fMRI paradigm. A picture description task with special constraints was used to provoke hesitation phenomena and speech errors. The transcribed speech sample was segmented into events of one second and each event was assigned to one category of a complex schema especially developed for this purpose. The main results were: conceptual planning engages bilateral activation of the precuneus. Successful lexical retrieval is accompanied – particularly in comparison to unsolved word-finding difficulties – by the left middle and superior temporal gyrus. Syntactic completeness is reflected in activation of the left inferior frontal gyrus (IFG) (area 44). In sum, the method has proven to be useful for investigating the neural correlates of lexical and syntactic phenomena in an overt picture description task. This opens up new prospects for the analysis of spontaneous language production during fMRI.
With a steady increase of regulatory requirements for business processes, automation support of compliance management is a field garnering increasing attention in Information Systems research. Several approaches have been developed to support compliance checking of process models. One major challenge for such approaches is their ability to handle different modeling techniques and compliance rules in order to enable widespread adoption and application. Applying a structured literature search strategy, we reflect and discuss compliance-checking approaches in order to provide an insight into their generalizability and evaluation. The results imply that current approaches mainly focus on special modeling techniques and/or a restricted set of types of compliance rules. Most approaches abstain from real-world evaluation which raises the question of their practical applicability. Referring to the search results, we propose a roadmap for further research in model-based business process compliance checking.
Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line
(2012)
The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(−/−)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(−/−) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2.
Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.
Disruption experiments targeted at the Bacillus licheniformis degSU operon and GFP-reporter analysis provided evidence for promoter activity immediately upstream of degU. pMutin mediated concomitant introduction of the degU32 allele – known to cause hypersecretion in Bacillus subtilis – resulted in a marked increase in protease activity. Application of 5-fluorouracil based counterselection through establishment of a phosphoribosyltransferase deficient Δupp strain eventually facilitated the marker-free introduction of degU32 leading to further protease enhancement achieving levels as for hypersecreting wild strains in which degU was overexpressed. Surprisingly, deletion of rapG – known to interfere with DegU DNA-binding in B. subtilis – did not enhance protease production neither in the wild type nor in the degU32 strain. The combination of degU32 and Δupp counterselection in the type strain is not only equally effective as in hypersecreting wild strains with respect to protease production but furthermore facilitates genetic strain improvement aiming at biological containment and effectiveness of biotechnological processes.
In this article, we report on the heat-transfer resistance at interfaces as a novel, denaturation-based method to detect single-nucleotide polymorphisms in DNA. We observed that a molecular brush of double-stranded DNA grafted onto synthetic diamond surfaces does not notably affect the heat-transfer resistance at the solid-to-liquid interface. In contrast to this, molecular brushes of single-stranded DNA cause, surprisingly, a substantially higher heat-transfer resistance and behave like a thermally insulating layer. This effect can be utilized to identify ds-DNA melting temperatures via the switching from low- to high heat-transfer resistance. The melting temperatures identified with this method for different DNA duplexes (29 base pairs without and with built-in mutations) correlate nicely with data calculated by modeling. The method is fast, label-free (without the need for fluorescent or radioactive markers), allows for repetitive measurements, and can also be extended toward array formats. Reference measurements by confocal fluorescence microscopy and impedance spectroscopy confirm that the switching of heat-transfer resistance upon denaturation is indeed related to the thermal on-chip denaturation of DNA.
Heterogeneous Composites on the Basis of Microbial Cells and Nanostructured Carbonized Sorbents
(2012)
The fact that microorganisms prefer to grow on liquid/solid phase surfaces rather than in the surrounding aqueous phase was noticed long time ago [1]. Virtually any surface – animal, mineral, or vegetable – is a subject for microbial colonization and subsequent biofilm formation. It would be adequate to name just a few notorious examples on microbial colonization of contact lenses, ship hulls, petroleum pipelines, rocks in streams and all kinds of biomedical implants. The propensity of microorganisms to become surface-bound is so profound and ubiquitous that it vindicates the advantages for attached forms over their free-ranging counterparts [2]. Indeed, from ecological and evolutionary standpoints, for many microorganisms the surface-bound state means dwelling in nutritionally favorable, non-hostile environments [3]. Therefore, in most of natural and artificial ecosystems surface-associated microorganisms vastly outnumber organisms in suspension and often organize into complex communities with features that differ dramatically from those of free cells [4].