REVIEW: Selection and work-up for liver transplantation

The evaluation of the liver transplantation candidate is intended to confirm the indication for transplantation, determine the severity of disease, exclude contra-indications, optimise pre-transplantation care and candidate condition, and educate the patient and family on post-procedure expectations. This article is intended as a guide for the appropriate selection and work-up of patients for liver transplantation

Mechanical coupling in flashing ratchets

We consider the transport of rigid objects with internal structure in a flashing ratchet potential by investigating the overdamped behavior of a rod-like chain of evenly spaced point particles. In 1D, analytical arguments show that the velocity can reverse direction multiple times in response to changing the size of the chain or the temperature of the heat bath. The physical reason is that the effective potential experienced by the mechanically coupled objects can have a different symmetry than that of individual objects. All analytical predictions are confirmed by Brownian dynamics simulations. These results may provide a route to simple, coarse-grained models of molecular motor transport that incorporate an object's size and rotational degrees of freedom into the mechanism of transport.Comment: 9 pages, 10 figure

Magnetic reordering in the vicinity of a ferromagnetic/antiferromagnetic interface

The magnetic arrangement in the vicinity of the interface between a ferromagnet and an antiferromagnet is investigated, in particular its dependence on the exchange couplings and the temperature. Applying a Heisenberg model, both sc(001) and fcc(001) lattices are considered and solved by a mean field approximation. Depending on the parameter values a variety of different magnetic configurations emerge. Usually the subsystem with the larger ordering temperature induces a magnetic order into the other one (magnetic proximity effect). With increasing temperature a reorientation of the magnetic sublattices is obtained. For coupled sc(001) systems both FM and AFM films are disturbed from their collinear magnetic order, hence exhibit a similar behavior. This symmetry is absent for fcc(001) films which, under certain circumstances, may exhibit two different critical temperatures. Analytical results are derived for simple bilayer systems.Comment: accepted for publication in Eur. Phys. J.

Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors

Fragments based on the VEGFR2i Semaxanib (SU5416, (vascular endothelial growth factor receptor-2 inhibitor) and the HDACi (histone deacetylase inhibitor) SAHA (suberanilohydroxamic acid) have been merged to form a range of low molecular weight dual action hybrids. Vindication of this approach is provided by SAR, docking studies, in vitro cancer cell line and biochemical enzyme inhibition data as well as in vivo Xenopus data for the lead molecule (Z)-N1-(3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)- N8-hydroxyoctanediamide 6

Theortetical Models of Extrasolar Giant Planets

The recent discoveries of giant planets around nearby stars have galvanized the planetary science community, astronomers, and the public at large. Since {\it direct} detection is now feasible, and is suggested by the recent acquisition of Gl229 B, it is crucial for the future of extrasolar planet searches that the fluxes, evolution, and physical structure of objects from Saturn's mass to 15 Juipter masses be theoretically investigated. We discuss our first attempts to explore the characteristics of extrasolar giant planets (EGPs), in aid of both NASA's and ESA's recent plans to search for such planets around nearby stars.Comment: LaTeX, using espcrc2.sty style files from Elsevier, 10 pages, 4 figures, to be published in the Proceedings of the International Conference on "Sources and Detection of Dark Matter in the Universe," ed. by D. Sanders et al. (Nuclear Physics B Supplement), 199

Cost of porcine reproductive and respiratory syndrome virus at individual farm level – An economic disease model

Porcine reproductive and respiratory syndrome (PRRS) is reported to be among the diseases with the highest economic impact in modern pig production worldwide. Yet, the economic impact of the disease at farm level is not well understood as, especially in endemically infected pig herds, losses are often not obvious. It is therefore difficult for farmers and veterinarians to appraise whether control measures such as virus elimination or vaccination will be economically beneficial for their farm. Thus, aim of this study was to develop an epidemiological and economic model to determine the costs of PRRS for an individual pig farm. In a production model that simulates farm outputs, depending on farm type, farrowing rhythm or length of suckling period, an epidemiological model was integrated. In this, the impact of PRRS infection on health and productivity was estimated. Financial losses were calculated in a gross margin analysis and a partial budget analysis based on the changes in health and production parameters assumed for different PRRS disease severities. Data on the effects of endemic infection on reproductive performance, morbidity and mortality, daily weight gain, feed efficiency and treatment costs were obtained from literature and expert opinion. Nine different disease scenarios were calculated, in which a farrow-to-finish farm (1000 sows) was slightly, moderately or severely affected by PRRS, based on changes in health and production parameters, and either in breeding, in nursery and fattening or in all three stages together. Annual losses ranged from a median of € 75′724 (90% confidence interval (C.I.): € 78′885–€ 122′946), if the farm was slightly affected in nursery and fattening, to a median of € 650′090 (90% C.I. € 603′585–€ 698′379), if the farm was severely affected in all stages. Overall losses were slightly higher if breeding was affected than if nursery and fattening were affected. In a herd moderately affected in all stages, median losses in breeding were € 46′021 and € 422′387 in fattening, whereas costs were € 25′435 lower in nursery, compared with a PRRSV-negative farm. The model is a valuable decision-support tool for farmers and veterinarians if a farm is proven to be affected by PRRS (confirmed by laboratory diagnosis). The output can help to understand the need for interventions in case of significant impact on the profitability of their enterprise. The model can support veterinarians in their communication to farmers in cases where costly disease control measures are justified

Discovery of Stable and Selective Antibody Mimetics from Combinatorial Libraries of Polyvalent, Loop-Functionalized Peptoid Nanosheets.

The ability of antibodies to bind a wide variety of analytes with high specificity and high affinity makes them ideal candidates for therapeutic and diagnostic applications. However, the poor stability and high production cost of antibodies have prompted exploration of a variety of synthetic materials capable of specific molecular recognition. Unfortunately, it remains a fundamental challenge to create a chemically diverse population of protein-like, folded synthetic nanostructures with defined molecular conformations in water. Here we report the synthesis and screening of combinatorial libraries of sequence-defined peptoid polymers engineered to fold into ordered, supramolecular nanosheets displaying a high spatial density of diverse, conformationally constrained peptoid loops on their surface. These polyvalent, loop-functionalized nanosheets were screened using a homogeneous Förster resonance energy transfer (FRET) assay for binding to a variety of protein targets. Peptoid sequences were identified that bound to the heptameric protein, anthrax protective antigen, with high avidity and selectivity. These nanosheets were shown to be resistant to proteolytic degradation, and the binding was shown to be dependent on the loop display density. This work demonstrates that key aspects of antibody structure and function-the creation of multivalent, combinatorial chemical diversity within a well-defined folded structure-can be realized with completely synthetic materials. This approach enables the rapid discovery of biomimetic affinity reagents that combine the durability of synthetic materials with the specificity of biomolecular materials

Evaluation of antigens for the serodiagnosis of kala-azar and oriental sores by means of the indirect immunofluorescence antibody test (IFAT)

Antigens and corresponding sera were collected from travellers with leishmaniasis returning to Germany from different endemic areas of the old world. The antigenicity of these Leishmania strains, which were maintained in Syrian hamsters, was compared by indirect immunofluorescence (IFAT). Antigenicity was demonstrated by antibody titres in 18 sera from 11 patients. The amastigotic stages of nine strains of Leishmania donovani and four strains of Leishmania tropica were compared with each other and with the culture forms of insect flagellates (Strigomonas oncopelti and Leptomonas ctenocephali). Eighteen sera from 11 patients were available for antibody determination with these antigens. The maximal antibody titres in a single serum varied considerably depending on which antigen was used for the test. High antibody levels could only be maintained when Leishmania donovani was employed as the antigen, but considerable differences also occurred between the different strains of this species. The other antigens were weaker. No differences in antigenicity between amastigotes and promastigotes of the same strain were observed. It is important to select suitable antigens. Low titres may be of doubtful specificity and are a poor baseline for the fall in titre which is an essential index of effective treatment.Wir sammelten Parasiten und Seren von Reisenden, die aus verschiedenen endemischen Gebieten der Alten Welt mit einer Leishmaniasis nach Deutschland zurückkehrten. Die Antigenaktivitäten der isolierten und fortlaufend in Goldhamstern gehaltenenLeishmania-Stämme wurden im indirekten Immunofluoreszenztest (IFAT) verglichen. Die Antigenität wurde an Hand von Antikörpertitern in 18 Serumproben von 11 Patienten bewiesen. Neun Stämme desLeishmania donovani-Komplexes und vierLeishmania tropica-Isolate wurden in ihrem amastigoten Stadium miteinander verglichen. Hinzu kamen zwei Insekten-Flagellaten als Kulturformen:Strigomonas oncopelti undLeptomonas ctenocephali. 18 Serumproben von 11 Patienten standen für die Antikörperbestimmung mit diesen Antigenen zur Verfügung. Die maximalen Titerhöhen variierten in ein- und derselben antiserumprobe zum Teil erheblich, je nachdem, welches Antigen für den Test benutzt wurde. Hohe Antikörpertiter konnten nur erhalten werden, wennLeishmania donovani als Antigen vorlag, es ergaben sich aber auch zwischen den einzelnen Stämmen dieser Leishmaniaart erhebliche Unterschiede in der Antigenaktivität. Antigene anderer Art erwiesen sich als wenig wirksam. Zwischen amastigoten und promastigoten Entwicklungsformen einesLeishmania donovani-Stammes konnten keine Unterschiede in der Antigenaktivität erkannt werden. Für den Nachweis möglichst hoher Antikörpertiter im IFAT ist die Auswahl geeigneter Antigene von ausschlaggebender Bedeutung. Niedrige Titer erschweren deren Beurteilung als spezifisch und sind eine schlechte Ausgangsposition für die Beobachtung des obligatorischen Titerabfalles nach erfolgreicher Therapie

DNA origami protection and molecular interfacing through engineered sequence-defined peptoids

DNA nanotechnology has established approaches for designing programmable and precisely controlled nanoscale architectures through specific Watson−Crick base-pairing, molecular plasticity, and intermolecular connectivity. In particular, superior control over DNA origami structures could be beneficial for biomedical applications, including biosensing, in vivo imaging, and drug and gene delivery. However, protecting DNA origami structures in complex biological fluids while preserving their structural characteristics remains a major challenge for enabling these applications. Here, we developed a class of structurally well-defined peptoids to protect DNA origamis in ionic and bioactive conditions and systematically explored the effects of peptoid architecture and sequence dependency on DNA origami stability. The applicability of this approach for drug delivery, bioimaging, and cell targeting was also demonstrated. A series of peptoids (PE1–9) with two types of architectures, termed as “brush” and “block,” were built from positively charged monomers and neutral oligo-ethyleneoxy monomers, where certain designs were found to greatly enhance the stability of DNA origami. Through experimental and molecular dynamics studies, we demonstrated the role of sequence-dependent electrostatic interactions of peptoids with the DNA backbone. We showed that octahedral DNA origamis coated with peptoid (PE2) can be used as carriers for anticancer drug and protein, where the peptoid modulated the rate of drug release and prolonged protein stability against proteolytic hydrolysis. Finally, we synthesized two alkyne-modified peptoids (PE8 and PE9), conjugated with fluorophore and antibody, to make stable DNA origamis with imaging and cell-targeting capabilities. Our results demonstrate an approach toward functional and physiologically stable DNA origami for biomedical applications