Galois theory in monoidal categories

The Galois theory of Chase and Sweedler [11], for commutative rings, is generalized to encompass commutative monoids in an arbitrary symmetric, closed, monoidal category with finite limits and colimits. The primary tool is the Morita theory of Pareigis [35, 36, 37], which also supplies a suitable definition for the concept of a “finite” object in a monoidal category. The Galois theory is then extended by an examination of “normal” sub-Hopf-monoids, and examples in various algebraic and topological categories are considered. In particular, symmetric, closed, monoidal structures on various categories of topological vector spaces are studied with respect to the existence of “finite” objects

Multi-Level Kinetic Model of mRNA Delivery via Transfection of Lipoplexes

Recent work on the use of mRNA lipoplexes for gene delivery demonstrates the need for a mathematical model that simulates and predicts kinetics and transfection efficiency. The small copy numbers involved make it necessary to use stochastic models and include statistical analysis of the variation observed in the experimental data. The modeling requirements are further complicated by the multi-level nature of the problem, where mRNA molecules are contained in lipoplexes, which are in turn contained in endosomes, where each of these entities displays a behavior of its own. We have created a mathematical model that reproduces both the time courses and the statistical variance observed in recent experiments using single-cell tracking of GFP expression after transfection. By applying a few key simplifications and assumptions, we have limited the number of free parameters to five, which we optimize to match five experimental determinants by means of a simulated annealing algorithm. The models demonstrate the need for modeling of nested species in order to reproduce the shape of the dose-response and expression-level curves

Multi-Level Kinetic Model of mRNA Delivery via Transfection of Lipoplexes

Recent work on the use of mRNA lipoplexes for gene delivery demonstrates the need for a mathematical model that simulates and predicts kinetics and transfection efficiency. The small copy numbers involved make it necessary to use stochastic models and include statistical analysis of the variation observed in the experimental data. The modeling requirements are further complicated by the multi-level nature of the problem, where mRNA molecules are contained in lipoplexes, which are in turn contained in endosomes, where each of these entities displays a behavior of its own. We have created a mathematical model that reproduces both the time courses and the statistical variance observed in recent experiments using single-cell tracking of GFP expression after transfection. By applying a few key simplifications and assumptions, we have limited the number of free parameters to five, which we optimize to match five experimental determinants by means of a simulated annealing algorithm. The models demonstrate the need for modeling of nested species in order to reproduce the shape of the dose-response and expression-level curves

Single-cell mRNA transfection studies: Delivery, kinetics and statistics by numbers

AbstractIn artificial gene delivery, messenger RNA (mRNA) is an attractive alternative to plasmid DNA (pDNA) since it does not require transfer into the cell nucleus. Here we show that, unlike for pDNA transfection, the delivery statistics and dynamics of mRNA-mediated expression are generic and predictable in terms of mathematical modeling. We measured the single-cell expression time-courses and levels of enhanced green fluorescent protein (eGFP) using time-lapse microscopy and flow cytometry (FC). The single-cell analysis provides direct access to the distribution of onset times, life times and expression rates of mRNA and eGFP. We introduce a two-step stochastic delivery model that reproduces the number distribution of successfully delivered and translated mRNA molecules and thereby the dose–response relation. Our results establish a statistical framework for mRNA transfection and as such should advance the development of RNA carriers and small interfering/micro RNA-based drugs.From the Clinical EditorThis team of authors established a statistical framework for mRNA transfection by using a two-step stochastic delivery model that reproduces the number distribution of successfully delivered and translated mRNA molecules and thereby their dose-response relation. This study establishes a nice connection between theory and experimental planning and will aid the cellular delivery of mRNA molecules

Rope trauma, sedation, disentanglement, and monitoring-tag associated lesions in a terminally entangled North Atlantic right whale (Eubalaena glacialis)

Author Posting. © Society for Marine Mammalogy, 2012. Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms. The definitive version was published in Marine Mammal Science 29 (2013): E98–E113, doi:10.1111/j.1748-7692.2012.00591.x.A chronically entangled North Atlantic right whale, with consequent emaciation was sedated, disentangled to the extent possible, administered antibiotics, and satellite tag tracked for six subsequent days. It was found dead 11 d after the tag ceased transmission. Chronic constrictive deep rope lacerations and emaciation were found to be the proximate cause of death, which may have ultimately involved shark predation. A broadhead cutter and a spring-loaded knife used for disentanglement were found to induce moderate wounds to the skin and blubber. The telemetry tag, with two barbed shafts partially penetrating the blubber was shed, leaving barbs embedded with localized histological reaction. One of four darts administered shed the barrel, but the needle was found postmortem in the whale with an 80º bend at the blubber-muscle interface. This bend occurred due to epaxial muscle movement relative to the overlying blubber, with resultant necrosis and cavitation of underlying muscle. This suggests that rigid, implanted devices that span the cetacean blubber muscle interface, where the muscle moves relative to the blubber, could have secondary health impacts. Thus we encourage efforts to develop new tag telemetry systems that do not penetrate the subdermal sheath, but still remain attached for many months.Funding from NOAA Cooperative Agreement NA09OAR4320129, PO EA133F09SE4792, M. S. Worthington Foundation, North Pond Foundation, Sloan and Hardwick Simmons, and Woods Hole Oceanographic Institution Marine Mammal Center

Host Reproductive Phenology Drives Seasonal Patterns of Host Use in Mosquitoes

Seasonal shifts in host use by mosquitoes from birds to mammals drive the timing and intensity of annual epidemics of mosquito-borne viruses, such as West Nile virus, in North America. The biological mechanism underlying these shifts has been a matter of debate, with hypotheses falling into two camps: (1) the shift is driven by changes in host abundance, or (2) the shift is driven by seasonal changes in the foraging behavior of mosquitoes. Here we explored the idea that seasonal changes in host use by mosquitoes are driven by temporal patterns of host reproduction. We investigated the relationship between seasonal patterns of host use by mosquitoes and host reproductive phenology by examining a seven-year dataset of blood meal identifications from a site in Tuskegee National Forest, Alabama USA and data on reproduction from the most commonly utilized endothermic (white-tailed deer, great blue heron, yellow-crowned night heron) and ectothermic (frogs) hosts. Our analysis revealed that feeding on each host peaked during periods of reproductive activity. Specifically, mosquitoes utilized herons in the spring and early summer, during periods of peak nest occupancy, whereas deer were fed upon most during the late summer and fall, the period corresponding to the peak in births for deer. For frogs, however, feeding on early- and late-season breeders paralleled peaks in male vocalization. We demonstrate for the first time that seasonal patterns of host use by mosquitoes track the reproductive phenology of the hosts. Peaks in relative mosquito feeding on each host during reproductive phases are likely the result of increased tolerance and decreased vigilance to attacking mosquitoes by nestlings and brooding adults (avian hosts), quiescent young (avian and mammalian hosts), and mate-seeking males (frogs)

Ultraconserved Elements in the Olig2 Promoter

. basal promoter and found that it represses expression in undifferentiated embryonic stem cells. expression during development

Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

BACKGROUND: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. METHODOLOGY: We developed and implemented an optimized mutation profiling platform ("OncoMap") to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. CONCLUSIONS: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents

Female-Biased Dispersal and Gene Flow in a Behaviorally Monogamous Mammal, the Large Treeshrew (Tupaia tana)

Background: Female-biased dispersal (FBD) is predicted to occur in monogamous species due to local resource competition among females, but evidence for this association in mammals is scarce. The predicted relationship between FBD and monogamy may also be too simplistic, given that many pair-living mammals exhibit substantial extra-pair paternity. Methodology/Principal Findings: I examined whether dispersal and gene flow are female-biased in the large treeshrew (Tupaia tana) in Borneo, a behaviorally monogamous species with a genetic mating system characterized by high rates (50%) of extra-pair paternity. Genetic analyses provided evidence of FBD in this species. As predicted for FBD, I found lower mean values for the corrected assignment index for adult females than for males using seven microsatellite loci, indicating that female individuals were more likely to be immigrants. Adult female pairs were also less related than adult male pairs. Furthermore, comparison of Bayesian coalescent-based estimates of migration rates using maternally and bi-parentally inherited genetic markers suggested that gene flow is female-biased in T. tana. The effective number of migrants between populations estimated from mitochondrial DNA sequence was three times higher than the number estimated using autosomal microsatellites. Conclusions/Significance: These results provide the first evidence of FBD in a behaviorally monogamous species without mating fidelity. I argue that competition among females for feeding territories creates a sexual asymmetry in the costs an