Diffusion determines the recurrent graph

We consider diffusion on discrete measure spaces as encoded by Markovian semigroups arising from weighted graphs. We study whether the graph is uniquely determined if the diffusion is given up to order isomorphism. If the graph is recurrent then the complete graph structure and the measure space are determined (up to an overall scaling). As shown by counterexamples this result is optimal. Without the recurrence assumption, the graph still turns out to be determined in the case of normalized diffusion on graphs with standard weights and in the case of arbitrary graphs over spaces in which each point has the same mass. These investigations provide discrete counterparts to studies of diffusion on Euclidean domains and manifolds initiated by Arendt and continued by Arendt/Biegert/ter Elst and Arendt/ter Elst. A crucial step in our considerations shows that order isomorphisms are actually unitary maps (up to a scaling) in our context.Comment: 30 page

Unconventional superfluid order in the FF-band of a bipartite optical square lattice

We report on the first observation of bosons condensed into the energy minima of an $F$-band of a bipartite square optical lattice. Momentum spectra indicate that a truly complex-valued staggered angular momentum superfluid order is established. The corresponding wave function is composed of alternating local $F_{2x^3-3x} + i F_{2y^3-3y}$-orbits and local $S$-orbits residing in the deep and shallow wells of the lattice, which are arranged as the black and white areas of a checkerboard. A pattern of staggered vortical currents arises, which breaks time reversal symmetry and the translational symmetry of the lattice potential. We have measured the populations of higher order Bragg peaks in the momentum spectra for varying relative depths of the shallow and deep lattice wells and find remarkable agreement with band calculations.Comment: 4 pages, 3 figure

Acute gallbladder perforation with gallstones spillage in a cirrhotic patient

Gallbladder perforation is a rare complication of cholecystitis and cholelithiasis. The high morbidity and mortality rates associated with this condition are due to delays in diagnosis and treatment since signs and symptoms of perforation do not differ significantly from those of uncomplicated cholecystitis. We report on a patient who was affected by Child-Pugh A alcoholic liver cirrhosis and who developed an acute gallbladder perforation with spillage of stones into the peritoneal cavity and give a review of the current literature

On the geometry of geodesics in discrete optimal transport

We consider the space of probability measures on a discrete set X, endowed with a dynamical optimal transport metric. Given two probability measures supported in a subset Y⊆X, it is natural to ask whether they can be connected by a constant speed geodesic with support in Y at all times. Our main result answers this question affirmatively, under a suitable geometric condition on Y introduced in this paper. The proof relies on an extension result for subsolutions to discrete Hamilton-Jacobi equations, which is of independent interest

Experimentelle Untersuchungen zum Einfluß der Temperatur während der Präparation auf die Osteoinduktivität von Bone Morphogenetic Gelatin und zur knöchernen Einheilung von Bone Morphogenetic Gelatin im Vergleich zu einer Kombination einer Hydroxylapatitkeramik mit Bone Morphologic Gelatin

Große knöcherne Defekte machen den Einsatz eines Knochenersatzmaterials notwendig. Autogene Spongiosa ist das in jeder Hinsicht unübertroffene Transplantat. Ihre Verfügbarkeit ist jedoch begrenzt. Die Entnahme autogener Spongiosa erfordert meist eine mit zusätzlichen Risiken behaftete und daher zusätzlicher Morbidität verbundene Zweitoperation. Allogene Knochenmatrixgelatine als Weiterverarbeitungsprodukt der demineralisierten Knochenmatrix ist ein osteoinduktives Implantat. Allogene BMG fördert die Regeneration knöcherner Substanzdefekte und kann durch Knochenbanken ständig in ausreichender Menge zur Verfügung gestellt werden. Die verwendete BMG ist ein avitales, vollständig demineralisiertes, antigenfreies Implantat mit günstiger Oberflächenstruktur und guter Bioverträglichkeit. Die Hydroxylapatitkera-mik Endobon® ist eine durch dosierte Verbrennung und Sinterung von boviner Spongiosa hergestellte True Bone Ceramic mit einer organisierten Trabekelstruktur und interkonnek-tierenden Poren. Das Ziel dieser Arbeit war, in vergleichenden Untersuchungen im orthotopen Modell den Einfluß der während der Präparation der BMG herrschenden Temperatur auf die Osteoinduktivität zu erfassen,am Minischwein die knöcherne Regeneration unter dem Einfluß von BMG im Vergleich zur Kombination aus BMG mit der Hydroxylapatitkeramik Endobon® zu untersuchen und dabei gleichzeitigden zeitlichen Verlauf der Knochenbildung beim Heilungsprozeß quantitativ zu erfassen. Die Untersuchung der Temperaturabhängigkeit erfolgte am Trepanationsdefekt bei Wistar- Ratten. Als Negativkontrolle diente der Leerdefekt. Die Heilung des Defekts wurde deskriptiv histologisch und mittels der biochemischen Marker Alkalische Phosphatase, Kalziumgehalt und Hydroxyprolin erfaßt. Die in diesem Versuch verwendete BMG wurde bei 4°C bzw. 22°C hergestellt. Untersuchungszeiträume waren 1, 2, 4, 6 und 12 Wochen. Folgende Ergebnisse wurden erzielt: Beide BMG-Präparationen produzierten eine vollständige Defektheilung nach 12 Wochen.Bei der histologischen Untersuchung konnte zu keinem der Untersuchungszeitpunkte ein Unterschied im Fortschritt der Defektregeneration zwischen beiden Vergleichsgruppen beobachtet werden.Die Aktivität der Alkalischen Phosphatase ist nach der zweiten und der vierten Wochen in der BMG 22°C-Gruppe signifikant (p=0.042 bzw. 0.012) erhöht. Der Kalzium-und Hydroxyprolingehalt werden aus Gründen, die im einzelnen im Kapitel 2.3. diskutiert werden, in diesem Versuch nicht als universell geeignete Parameter zur Erfassung der Osteogenese angesehen. Die Untersuchung der Heilung von Knochendefekten unter dem Einfluß von allogener BMG im Vergleich zu einer Kombination aus BMG mit einer Hydroxylapatitkeramik wurde an Minischweinen durchgeführt. Die zeitliche Dynamik des Knocheneinwuchses wurde anhand histologischer Fluoreszenzübersichten erfaßt. Die tägliche Markierung der Tiere mit Fluorochromen machte die Bestimmung der Knocheneinheilungsrate möglich. Detailhistologien zeigten die Qualität der knöchernen Einheilung. Mittels computergesteuerter Bildanalyse wurde die Quantität des Knocheneinwuchses gemessen. In diesem Versuch wurden folgende Ergebnisse erzielt: Allogene BMG allein hatte keine stimulative Wirkung auf die knöcherne Heilung im ersatzstarken Lager. Der Defekt war auch nach 12 Wochen noch nicht knöchern durchbaut.Der flächenmäßige Anteil neugebildeten Knochens bei Keramik+BMG lag nach 12 Wochen bei 80 % gegenüber 33 % bei alleiniger Implantation von BMG.Keramik mit BMG zeigte eine signifikante Förderung der knöchernen Regeneration und Integration (p=0.0004) mit Bildung einiger separater Osteogenesezentren im Defektzentrum. Die osteokonduktiven Eigenschaften der BMG sind nicht stark genug ausgeprägt, um bei Minischweinen die Heilung ossärer Defekte im ersatzstarken Lager zu beschleunigen. Die Kombination von BMG mit einer Hydroxylapatitkeramik erscheint wegen der signifikanten Beschleunigung des Knocheneinwuchses bei stabiler Fixation als geeignet für die klinische Anwendung. In der Literatur ist gut belegt, daß es sich bei BMG um ein osteoinduktives Implantat handelt. Wird ein klinischer Einsatz von BMG beabsichtigt, ist die vorherige Sterilisation eine unabdingbare Voraussetzung. Die Osteoinduktivität wird durch eine Reihe von Sterilisationsverfahren drastisch reduziert. Für den Verlust der Osteoinduktivität der hier verwendeten BMG kommt als wahrscheinlichste Ursache die Sterilisation im Peressigsäure- Unterdruck- Verfahren in Frage. Der wissenschaftliche Beweis dafür steht noch aus. Die Temperatur während der Präparation hat keinen signifikanten Einfluß auf die osteoinduktive Kapazität der BMG.Osteoinductive bone replacement substances, particularly the Bone Morphogenetic Proteins (BMP), have long been the subject of scientific interest. However, even though the temperature stability of BMP up to 60 degrees Celsius it is well documented, the procedures for the preparation of demineralized bone matrix, Bone Morphogenetic Gelatin (BMG), and the extraction of BMP called for temperatures of 2 - 4 degrees Celsius. This results in considerable costs. It was previously shown that BMP rapidly loses its osteoinductivity when left in a postmortem milieu at room temperatures. To test the hypothesis that the conditions during the preparation of BMG at room temperature do not lead to a degradation of osteoinductivity, BMG was prepared at 4 centigrade and at room temperature. BMG was then implanted in calvaria defects of 6 mm diameter in Wistar rats. Defects were evaluated at 1, 2, 4, 6, and 12 weeks. Alkaline phosphatase activity, calcium, and hydroxyproline were employed as biochemical markers of osteoneogenesis. Descriptive histology showed no differences between the two implant materials. A control group gave proof that the defects did not heal without BMG. In a second experiment, the repair of bony defects in miniature pigs after implantation of BMG was compared to a combination of BMG with a hydroxyapatite ceramic. The defects measured 9.4 mm in diameter and were located in the patellar joint surface of both distal femurs. Each animal had one defect filled with BMG and one defect filled with a pressfit implanted cylindrical hydroxyapatite ceramic and BMG. Polychromic sequential dye marking allowed the quantification of bone healing at their respective time intervals. The defect repair was evaluated at 6 and 12 weeks using X-ray-documentation, fluorescence microscopy and computer assisted histomorphometry. Defects filled with a combination of BMG with pressfit implanted hydroxyapatite cylinder showed a significantly higher degree of healing as measured in terms of radius and area of bony ingrowth. CONCLUSIONS: BMG does not lose its osteoinductive capacity when prepared at room temperature. This translates into a considerable reduction in costs.The combination of the osteoinductive properties of BMG with osteoconductive biocompatible ceramics is superior over the defect repair produced by the sole implantation of BMG only

Ubiquitination and Ubiquitin-Like Modifications in Multiple Myeloma: Biology and Therapy

Multiple myeloma is a genetically heterogeneous plasma cell malignancy characterized by organ damage and a massive production of (in-)complete monoclonal antibodies. Coping with protein homeostasis and post-translational regulation is therefore essential for multiple myeloma cells to survive. Furthermore, post-translational modifications such as ubiquitination and SUMOylation play key roles in essential pathways in multiple myeloma, including NFκB signaling, epigenetic regulation, as well as DNA damage repair. Drugs modulating the ubiquitin-proteasome system, such as proteasome inhibitors and thalidomide analogs, are approved and highly effective drugs in multiple myeloma. In this review, we focus on ubiquitin and ubiquitin-like modifications in the biology and current developments of new treatments for multiple myeloma

Quantitative Characterization of Tetraspanin 8 Homointeractions in the Plasma Membrane

The spatial distribution of proteins in cell membranes is crucial for signal transduction, cell communication and membrane trafficking. Members of the Tetraspanin family organize functional protein clusters within the plasma membrane into so-called Tetraspanin-enriched microdomains (TEMs). Direct interactions between Tetraspanins are believed to be important for this organization. However, studies thus far have utilized mainly co-immunoprecipitation methods that cannot distinguish between direct and indirect, through common partners, interactions. Here we study Tetraspanin 8 homointeractions in living cells via quantitative fluorescence microscopy. We demonstrate that Tetraspanin 8 exists in a monomer-dimer equilibrium in the plasma membrane. Tetraspanin 8 dimerization is described by a high dissociation constant (Kd = 14 700 ± 1100 Tetraspanin8/µm2), one of the highest dissociation constants measured for membrane proteins in live cells. We propose that this high dissociation constant, and thus the short lifetime of the Tetraspanin 8 dimer, is critical for Tetraspanin 8 functioning as a master regulator of cell signaling

Protein pocket and ligand shape comparison and its application in virtual screening

Understanding molecular recognition is one major requirement for drug discovery and design. Physicochemical and shape complementarity between two binding partners is the driving force during complex formation. In this study, the impact of shape within this process is analyzed. Protein binding pockets and co-crystallized ligands are represented by normalized principal moments of inertia ratios (NPRs). The corresponding descriptor space is triangular, with its corners occupied by spherical, discoid, and elongated shapes. An analysis of a selected set of sc-PDB complexes suggests that pockets and bound ligands avoid spherical shapes, which are, however, prevalent in small unoccupied pockets. Furthermore, a direct shape comparison confirms previous studies that on average only one third of a pocket is filled by its bound ligand, supplemented by a 50 % subpocket coverage. In this study, we found that shape complementary is expressed by low pairwise shape distances in NPR space, short distances between the centers-of-mass, and small deviations in the angle between the first principal ellipsoid axes. Furthermore, it is assessed how different binding pocket parameters are related to bioactivity and binding efficiency of the co-crystallized ligand. In addition, the performance of different shape and size parameters of pockets and ligands is evaluated in a virtual screening scenario performed on four representative target

SwissBioisostere: a database of molecular replacements for ligand design

The SwissBioisostere database (http://www.swissbioisostere.ch) contains information on molecular replacements and their performance in biochemical assays. It is meant to provide researchers in drug discovery projects with ideas for bioisosteric modifications of their current lead molecule, as well as to give interested scientists access to the details on particular molecular replacements. As of August 2012, the database contains 21 293 355 datapoints corresponding to 5 586 462 unique replacements that have been measured in 35 039 assays against 1948 molecular targets representing 30 target classes. The accessible data were created through detection of matched molecular pairs and mining bioactivity data in the ChEMBL database. The SwissBioisostere database is hosted by the Swiss Institute of Bioinformatics and available via a web-based interfac

Impacts of urban real-world labs

Ways of evaluating the societal impact of real-world labs as a transdisciplinary and transformative research format are under discussion. We present an evaluation approach rooted in structuration theory, with a focus on structure-agency dynamics at the science-society interface. We applied the theory with its four modalities (interpretation schemes, norms, allocative and authoritative resources) to the case of the Mirke neighbourhood in Wuppertal, Germany. Six projects promoted the capacity for co-productive city-making. The effects of the projects were jointly analysed in a co-evaluation process. Previously proposed subcategories of the modalities as an empirical operationalisation were tested and confirmed as being applicable. Five new subcategories were generated. The use of the modalities seems appropriate for co-evaluation processes. The tool is practical, focused on real-world effects, and suitable for transdisciplinary interpretation processes. We encourage further empirical testing of the tool, as well as development of the subcategories.</p