Analysis of Reaction Network Systems Using Tropical Geometry

We discuss a novel analysis method for reaction network systems with polynomial or rational rate functions. This method is based on computing tropical equilibrations defined by the equality of at least two dominant monomials of opposite signs in the differential equations of each dynamic variable. In algebraic geometry, the tropical equilibration problem is tantamount to finding tropical prevarieties, that are finite intersections of tropical hypersurfaces. Tropical equilibrations with the same set of dominant monomials define a branch or equivalence class. Minimal branches are particularly interesting as they describe the simplest states of the reaction network. We provide a method to compute the number of minimal branches and to find representative tropical equilibrations for each branch.Comment: Proceedings Computer Algebra in Scientific Computing CASC 201

A geometric method for model reduction of biochemical networks with polynomial rate functions

Model reduction of biochemical networks relies on the knowledge of slow and fast variables. We provide a geometric method, based on the Newton polytope, to identify slow variables of a biochemical network with polynomial rate functions. The gist of the method is the notion of tropical equilibration that provides approximate descriptions of slow invariant manifolds. Compared to extant numerical algorithms such as the intrinsic low dimensional manifold method, our approach is symbolic and utilizes orders of magnitude instead of precise values of the model parameters. Application of this method to a large collection of biochemical network models supports the idea that the number of dynamical variables in minimal models of cell physiology can be small, in spite of the large number of molecular regulatory actors

Einfluss von Komorbiditäten auf die Mortalität bei internistischen Intensivpatienten mit schwerer Sepsis und septischen Schock

Fragestellung: Trotz Verbesserungen der Therapie von Pat. mit schwerer Sepsis/septischen Schock liegt die Krankenhaus-Mortalität immer noch bei 30-50%. Ziel der Studie war es, die Bedeutung der Komorbiditäten als Todesursache bei Pat. mit Sepsis zu untersuchen. Methoden: Analyse von allen für eine Qualitätsstudie über fünf Jahre prospektiv erfassten 235 Pat. einer Internistischen Intensivstation mit schwerer Sepsis/septischem Schock. Beurteilung der Komorbiditäten durch hinsichtlich der Erkrankungsschwere, -häufigkeit modifizierten Charlson Score of the Severity of Comorbidities (CSSC). Zusätzlich wurden Sepsis Severity Score (SSS), SAPS II u. SOFA sowie der Knaus Score als Maß der Alltagsfunktionalität erhoben. Bei jedem Verstorbenen teilten vier Begutachter (Doktorand, internistischer & anästhesiologischer Intensivmediziner sowie internistische Grundbehandler) auf Basis der Patientendokumentation den Einfluss der Komorbiditäten auf das Versterben in eine von vier Kategorien ein. Ergebnisse: Die Krankenhaus-Mortalität betrug 33.2% (78/235) bei einer SMR von 0.65 (SSS). Die Mortalitätsrate lag zwischen 15.6% bei Pat. mit niedrigem CSSC (0-1, n=24) u. 56.3% bei Pat. mit hohen CSSC (>10, n=22). Die AUC des CSSC betrug 0.57 u. des Charlson Comorbidity Index 0.55. Alter <50J war mit einer niedrigeren Mortalität (21.6%) assoziiert. Eine Immunsuppression hatten 40% aller Pat. u. 50% der Verstorbenen. Die höchste Mortalität wiesen Pat. mit schwerer chron. pulm. Erkrankung/pulm. Hypertonie (52.9%, n=9/17), schwerer maligner Erkrankung (48.6%, n=17/35) u. schwerer Lebererkrankung (47.6%, n=10/21) auf. Der Gesundheitszustand vor KH-aufnahme war bei 5.1% der Verstorbenen normal (Knaus A), bei 41% stark eingeschränkt (Knaus D). Sepsis als alleinige Todesursache wurde in 6.4- 11.5% der Fälle eingestuft, Sepsis als führende Todesursache mit rel. Komorbiditäten in 15.4-52.6%, Sepsis u. Komorbiditäten gleichermaßen in 20.5- 44.9% u. Komorbiditäten als führende Todesursache in 17.9- 39.7% der Fälle. Die Beurteilerübereinstimmung lag bei einem Kappa von 0.26. Schlussfolgerung: Schwere Komorbiditäten waren bei Sepsis-Pat. einer Internistischen Intensivstation sehr häufig u. wurden durch vier Begutachter überwiegend als führender Faktor für das Versterben angesehen. Gemessen an der niedrigen Beurteilerübereinstimmung durch hinsichtlich Methoden scheint eine objektive Einschätzung jedoch nur schwer möglich

Sustainable Land Use and Rural Development in Southeast Asia: Innovations and Policies for Mountainous Areas

Sustainable Development; Landscape/Regional and Urban Planning; Agricultur

Increasing the sensitivity of reverse phase protein arrays by antibody-mediated signal amplification

<p>Abstract</p> <p>Background</p> <p>Reverse phase protein arrays (RPPA) emerged as a useful experimental platform to analyze biological samples in a high-throughput format. Different signal detection methods have been described to generate a quantitative readout on RPPA including the use of fluorescently labeled antibodies. Increasing the sensitivity of RPPA approaches is important since many signaling proteins or posttranslational modifications are present at a low level.</p> <p>Results</p> <p>A new antibody-mediated signal amplification (AMSA) strategy relying on sequential incubation steps with fluorescently-labeled secondary antibodies reactive against each other is introduced here. The signal quantification is performed in the near-infrared range. The RPPA-based analysis of 14 endogenous proteins in seven different cell lines demonstrated a strong correlation (r = 0.89) between AMSA and standard NIR detection. Probing serial dilutions of human cancer cell lines with different primary antibodies demonstrated that the new amplification approach improved the limit of detection especially for low abundant target proteins.</p> <p>Conclusions</p> <p>Antibody-mediated signal amplification is a convenient and cost-effective approach for the robust and specific quantification of low abundant proteins on RPPAs. Contrasting other amplification approaches it allows target protein detection over a large linear range.</p

Revisiting the limits of photon momentum based optical power measurement method, employing the case of multi-reflected laser beam

In this work, we review the viability and precision of the photon-momentum-based optical power measurement method that employs an amplification effect caused by a multi-reflected laser beam trapped in an optical cavity. Measuring the total momentum transfer of the absorbed and re-emitted photons from a highly reflective surface (reflection of the laser beam from an optical mirror) as a force provides the possibility of measuring the optical power with direct traceability to SI units. Trial measurements were performed at two different metrology laboratories: the laboratory for mass/force at the Technical University of Ilmenau, and the clean room laser radiometry laboratory at PTB, with a portable force measurement setup consisting of two electromagnetic force compensation balances. We compared the results of the optical power measurements performed with the force measurement setup, via the photon-momentum-based method, with those performed using a calibrated reference standard detector traceable to PTB's primary standard for optical power, the cryogenic radiometer. The comparison was carried out for an optical power range between 1 W and 10 W at a wavelength of 532 nm, which corresponds to a force of approximately 2000 nN at the upper limit, yielding approximately 2.3% relative standard uncertainty in the case of 33 reflections. Thus, conflating the high-precision force metrology technique at [my]N to nN levels with the optical setup required to achieve specular multi-reflection configuration of the laser beam, where a macroscopic optical cavity with ultra-high reflective mirrors (>99.995%) can adjustably be suspended from the force sensors, depending on required geometry of reflections, we show that the uncertainty of the optical power measurements upon further increase of the nominally applied optical power, the number of laser beam reflections, or the reflectivity coefficient of the mirrors can be markedly reduced

Effects of broccoli extract and various essential oils on intestinal and faecal microflora and on xenobiotic enzymes and the antioxidant system of piglets

Objective: Since the ban of antibiotics as growth promoting feed additives in the EU in 2006 research in alternatives has gained importance. Phytogenic feed additives represent a heterogenous class of different plant derived substances that are discussed to improve the health of farm animals by direct and indirect antioxidant effects and by influencing microbial eubiosis in the gastrointestinal tract. Consequently our study aimed to investigate the influence of broccoli extract and the essential oils of tur- meric, oregano, thyme and rosemary, as selected individual additives, on intestinal and faecal microflora, on xenobiotic enzymes, and on the antioxidant system of piglets. Methods: 48 four weeks old male weaned piglets were assigned to 6 groups of 8. The piglets were housed individually in stainless steel pens with slatted floor. The control group (Con) was fed a diet without an additive for 4 weeks. The diet of group BE contained 0.15 g/kg sulforaphane in form of a broccoli extract. 535, 282, 373 and 476 mg/kg of the essential oils of turmeric (Cuo), oregano (Oo), thyme (To) and rosemary (Ro) were added to the diets of the remaining 4 groups to stan-dardise supplementation to 150 mg/kg of the oils’ key terpene compounds ar-turmerone, carvacrol, thymol and 1,8-cineole. The composition of bacterial microflora was examined by cultivating samples of jejeunal and colonic mucosa and of faeces under specific conditions. The mRNA expression of xenobiotic and antioxidant enzymes was determined by reversing transcrip- tase real time detection PCR (RT-PCR). Total antioxidant status was assayed using the Trolox Equivalent Antioxidant Capacity (TEAC), and lipid peroxidation was determined by measuring thiobarbioturic acid reactive substances (TBA- RS). Results: Compared to Con piglets all additives positively influenced weight gain and feed conversion in week 1. Over the whole trial period no significant differences in performance parameters existed between the experimental groups. Compared to group Con performance of Ro piglets was, however, slightly impaired. Com- pared to Con piglets Cuo, Oo and To increased the ratio of Lactobacilli:E. coli attached to the jejunal mucosa, whereas BE and Ro impaired this ratio slightly. In contrast in colonic mucosa Ro improved Lactobacilli:E. coli ratio. In faecal samples an improvement of Lactobacilli:E. coli ratio could be analysed for To and Ro. Ro was the only additive that reduced the incidence rate of piglets tested positive for enterotoxic E. coli (ETEC). All additives significantly increased jejunal TEAC and reduced TBA-RS. In the liver BE, Cuo, Oo and To increased TEAC in tendency and Ro significantly. Liver TBA-RS were slightly reduced by all additives compared to Con piglets. Whereas the influence of BE, To and Ro on jejunal TEAC mainly was derived from the induction of xenobiotic and antioxidant enzymes (indirect antioxidant effects), Cuo and Oo influenced TEAC by direct antioxidant effects. Discussion and Conclusions: Our results have shown: That within the labiatae oils Oo and To have the potential to improve performance slightly. That phytogenic substances have a small but not sig- nificant influence on intestinal microflora. That phytogenic feed additives up-regulate the anti- oxidant system of piglets either by direct or by indirect antioxidant effects and that they may thereby improve health status. That within the labiatae oils Oo has a high direct antioxidant potential whereas Ro potently induces xenobiotic and antioxidant enzymes. That broccoli extract is an attractive new phytogenic additive, improving antioxidant status by indirect antioxidant effects. That defined combinations of selected phytogenic substances may produce additive effects. That health promoting effects of phytogenic additives in the future should be studied systematically under the challenge with pathogenic microorganisms or food derived to-xins

Predicting pathway membership via domain signatures

Motivation: Functional characterization of genes is of great importance for the understanding of complex cellular processes. Valuable information for this purpose can be obtained from pathway databases, like KEGG. However, only a small fraction of genes is annotated with pathway information up to now. In contrast, information on contained protein domains can be obtained for a significantly higher number of genes, e.g. from the InterPro database