Energy-momentum conservation in pre-metric electrodynamics with magnetic charges

A necessary and sufficient condition for energy-momentum conservation is proved within a topological, pre-metric approach to classical electrodynamics including magnetic as well as electric charges. The extended Lorentz force, consisting of mutual actions by F=(E, B) on the electric current and G=(H, D) on the magnetic current, can be derived from an energy-momentum "potential" if and only if the constitutive relation G=G(F) satisfies a certain vanishing condition. The electric-magnetic reciprocity introduced by Hehl and Obukhov is seen to define a complex structure on the tensor product of 2-form pairs (F,G) which is independent of but consistent with the Hodge star operator defined by any Lorentzian metric. Contrary to a recent claim in the literature, it does not define a complex structure on the space of 2-forms itself.Comment: 8 pages, 1 fugur

The Dirac-Nambu-Goto p-Branes as Particular Solutions to a Generalized, Unconstrained Theory

The theory of the usual, constrained p-branes is embedded into a larger theory in which there is no constraints. In the latter theory the Fock-Schwinger proper time formalism is extended from point-particles to membranes of arbitrary dimension. For this purpose the tensor calculus in the infinite dimensional membrane space M is developed and an action which is covariant under reparametrizations in M is proposed. The canonical and Hamiltonian formalism is elaborated in detail. The quantization appears to be straightforward and elegant. No problem with unitarity arises. The conventional p-brane states are particular stationary solutions to the functional Schroedinger equation which describes the evolution of a membrane's state with respect to the invariant evolution parameter tau. A tau-dependent solution which corresponds to the wave packet of a null p-brane is found. It is also shown that states of a lower dimensional membrane can be considered as particular states of a higher dimensional membrane.Comment: 28 page

Creating Porcine Biomedical Models Through Recombineering

Recent advances in genomics provide genetic information from humans and other mammals (mouse, rat, dog and primates) traditionally used as models as well as new candidates (pigs and cattle). In addition, linked enabling technologies, such as transgenesis and animal cloning, provide innovative ways to design and perform experiments to dissect complex biological systems. Exploitation of genomic information overcomes the traditional need to choose naturally occurring models. Thus, investigators can utilize emerging genomic knowledge and tools to create relevant animal models. This approach is referred to as reverse genetics. In contrast to ‘forward genetics’, in which gene(s) responsible for a particular phenotype are identified by positional cloning (phenotype to genotype), the ‘reverse genetics’ approach determines the function of a gene and predicts the phenotype of a cell, tissue, or organism (genotype to phenotype). The convergence of classical and reverse genetics, along with genomics, provides a working definition of a ‘genetic model’ organism (3). The recent construction of phenotypic maps defining quantitative trait loci (QTL) in various domesticated species provides insights into how allelic variations contribute to phenotypic diversity. Targeted chromosomal regions are characterized by the construction of bacterial artificial chromosome (BAC) contigs to isolate and characterize genes contributing towards phenotypic variation. Recombineering provides a powerful methodology to harvest genetic information responsible for phenotype. Linking recombineering with gene-targeted homologous recombination, coupled with nuclear transfer (NT) technology can provide ‘clones’ of genetically modified animals

The causal structure of spacetime is a parameterized Randers geometry

There is a by now well-established isomorphism between stationary 4-dimensional spacetimes and 3-dimensional purely spatial Randers geometries - these Randers geometries being a particular case of the more general class of 3-dimensional Finsler geometries. We point out that in stably causal spacetimes, by using the (time-dependent) ADM decomposition, this result can be extended to general non-stationary spacetimes - the causal structure (conformal structure) of the full spacetime is completely encoded in a parameterized (time-dependent) class of Randers spaces, which can then be used to define a Fermat principle, and also to reconstruct the null cones and causal structure.Comment: 8 page

Altered hippocampal epigenetic regulation underlying reduced cognitive development in response to early life environmental insults

The hippocampus is involved in learning and memory and undergoes significant growth and maturation during the neonatal period. Environmental insults during this developmental timeframe can have lasting effects on brain structure and function. This study assessed hippocampal DNA methylation and gene transcription from two independent studies reporting reduced cognitive development stemming from early life environmental insults (iron deficiency and porcine reproductive and respiratory syndrome virus (PRRSv) infection) using porcine biomedical models. In total, 420 differentially expressed genes (DEGs) were identified between the reduced cognition and control groups, including genes involved in neurodevelopment and function. Gene ontology (GO) terms enriched for DEGs were associated with immune responses, angiogenesis, and cellular development. In addition, 116 differentially methylated regions (DMRs) were identified, which overlapped 125 genes. While no GO terms were enriched for genes overlapping DMRs, many of these genes are known to be involved in neurodevelopment and function, angiogenesis, and immunity. The observed altered methylation and expression of genes involved in neurological function suggest reduced cognition in response to early life environmental insults is due to altered cholinergic signaling and calcium regulation. Finally, two DMRs overlapped with two DEGs, VWF and LRRC32, which are associated with blood brain barrier permeability and regulatory T-cell activation, respectively. These results support the role of altered hippocampal DNA methylation and gene expression in early life environmentally-induced reductions in cognitive development across independent studies.</p

Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets

<p>Abstract</p> <p>Background</p> <p>To gain insight into host-microbe interactions in a piglet model, a functional genomics approach was used to address the working hypothesis that transcriptionally regulated genes associated with promoting epithelial barrier function are activated as a defensive response to the intestinal microbiota. Cesarean-derived germfree (GF) newborn piglets were colonized with adult swine feces, and villus and crypt epithelial cell transcriptomes from colonized and GF neonatal piglets were compared using laser-capture microdissection and high-density porcine oligonucleotide microarray technology.</p> <p>Results</p> <p>Consistent with our hypothesis, resident microbiota induced the expression of genes contributing to intestinal epithelial cell turnover, mucus biosynthesis, and priming of the immune system. Furthermore, differential expression of genes associated with antigen presentation (pan SLA class I, <it>B2M</it>, <it>TAP1 </it>and <it>TAPBP</it>) demonstrated that microbiota induced immune responses using a distinct regulatory mechanism common for these genes. Specifically, gene network analysis revealed that microbial colonization activated both type I (IFNAR) and type II (IFNGR) interferon receptor mediated signaling cascades leading to enhanced expression of signal transducer and activator of transcription 1 (STAT1), STAT2 and IFN regulatory factor 7 (IRF7) transcription factors and the induction of IFN-inducible genes as a reflection of intestinal epithelial inflammation. In addition, activated RNA expression of NF-kappa-B inhibitor alpha (<it>NFκBIA</it>; a.k.a I-kappa-B-alpha, IKBα) and toll interacting protein (<it>TOLLIP</it>), both inhibitors of inflammation, along with downregulated expression of the immunoregulatory transcription factor GATA binding protein-1 (<it>GATA1</it>) is consistent with the maintenance of intestinal homeostasis.</p> <p>Conclusion</p> <p>This study supports the concept that the intestinal epithelium has evolved to maintain a physiological state of inflammation with respect to continuous microbial exposure, which serves to sustain a tight intestinal barrier while preventing overt inflammatory responses that would compromise barrier function.</p

A Genetic Porcine Model of Cancer

The large size of the pig and its similarity in anatomy, physiology, metabolism, and genetics to humans make it an ideal platform to develop a genetically defined, large animal model of cancer. To this end, we created a transgenic oncopig line encoding Cre recombinase inducible porcine transgenes encoding KRASG12D and TP53R167H, which represent a commonly mutated oncogene and tumor suppressor in human cancers, respectively. Treatment of cells derived from these oncopigs with the adenovirus encoding Cre (AdCre) led to KRASG12D and TP53R167H expression, which rendered the cells transformed in culture and tumorigenic when engrafted into immunocompromised mice. Finally, injection of AdCre directly into these oncopigs led to the rapid and reproducible tumor development of mesenchymal origin. Transgenic animals receiving AdGFP (green fluorescent protein) did not have any tumor mass formation or altered histopathology. This oncopig line could thus serve as a genetically malleable model for potentially a wide spectrum of cancers, while controlling for temporal or spatial genesis, which should prove invaluable to studies previously hampered by the lack of a large animal model of cancer